calcitonin and Osteoporosis--Postmenopausal

To evaluate the efficacy and safety of intranasal salmon calcitonin in the treatment of osteoporosis.. Eight Chinese and English databases were searched by electronic search (from the establishment of the database to October 2019). The literature was screened according to the inclusion criteria and exclusion criteria, the quality was evaluated according to Cochrane software, and the Review Manager 5.2 software was used for statistical analysis.. A total of 374 documents were retrieved and 12 (12 original studies) were included after the screening, with a total sample capacity of 1068 cases. Meta-analysis showed that the intranasal salmon calcitonin had obvious advantages in reducing blood calcium, improving the ratio of serum creatinine and alkaline phosphatase. In addition, the intranasal salmon calcitonin had no obvious advantages in other indicators. It cannot be illustrated that the combination of intranasal salmon calcitonin and other conventional drugs is more effective than the simple use of conventional drugs.. The intranasal salmon calcitonin is superior to conventional drugs in reducing blood calcium, increasing creatinine ratio, and alkaline phosphatase, but its advantages in other indicators such as improving the bone mineral density (BMD) of lumbar vertebrae and hip have not been confirmed, and it is not clear that the combination of intranasal salmon calcitonin and other conventional drugs is better than the simple conventional drugs.

Topics: Administration, Intranasal; Bone Density Conservation Agents; Calcitonin; Humans; Lumbar Vertebrae; Osteoporosis, Postmenopausal

Salmon calcitonin (sCT) has been used for the treatment of postmenopausal osteoporosis for over 30 years. It is available in injectable and intranasal formulations. Two oral formulations have recently been developed.. The basis for oral sCT's bioavailability rests with a carrier molecule (8-(N-2-hydroxy-5-chloro-benzoyl)-amino-caprylic acid) or an acid-resistant enteric coating (Eudragit® polymer containing citric acid). With these formulations, sCT is resistant to gastric acid, and thus becomes available for absorption at the higher pH of the small intestine. Even though the changes in bone mineral density and bone turnover markers are greater with oral compared to nasal sCT, it shows only minor effects on these surrogate markers.. Oral sCT is attractive in concept as it is would be more convenient to patients than other routes of administration. While there may be other advantages to the oral formulation such as improving bone mineral density to a greater extent than nasal CT, anti-fracture efficacy has not been shown in a recent major clinical trial. Together with the possibility of an association between the drug and cancer and the availability of antiresorptive drug classes that are clearly more efficacious than sCT, successful development of oral sCT as a treatment for postmenopausal osteoporosis is uncertain.

Topics: Administration, Oral; Animals; Biological Availability; Bone Density; Bone Density Conservation Agents; Calcitonin; Drug Design; Female; Humans; Osteoporosis; Osteoporosis, Postmenopausal

In the beginning, that is from the 1960's, when a link between menopause and osteoporosis was first identified; estrogen treatment was the standard for preventing bone loss, however there was no fracture data, even though it was thought to be effective. This continued until the Women's Health Initiative (WHI) study in 2001 that published data on 6 years of treatment with hormone therapy that showed an increase in heart attacks and breast cancer. Even though the risks were small, 1 per 1500 users annually, patients were worried and there was a large drop off in estrogen use. In later analyses the WHI study showed that estrogen reduced fractures and actually prevented heart attacks in the 50-60 year age group. Estrogen alone appeared to be safer to use than estrogen+the progestin medroxyprogesterone acetate and actually reduced breast cancer. At the same time other drugs were being developed for bone that belong to the bisphosphonate group and the first generation of compounds showed moderate potency on bone resorption. The second and third generation compounds were much more potent and in a series of large trials were shown to reduce fractures. For the last 15 years the treatment of osteoporosis belonged to the bisphosphonate compounds, most of which reduce fracture rates by 50 percent. With the exception of gastrointestinal irritation the drugs are well tolerated and highly effective. The sophistication of the delivery systems now allow treatment that can be given daily, weekly, monthly and annually either orally or intravenously. Bone remodeling is a dynamic process that repairs microfractures and replaces old bone with new bone. In the last 10 years there has been a remarkable understanding of bone biology so that new therapies can be specifically designed on a biological basis. The realization that RANKL was the final cytokine involved in the resorption process and that marrow cells produced a natural antagonist called Osteoprotegerin (OPG) quickly led to two lines of therapy. First OPG was used as a therapy to block RANKL was initially successful but later antibodies against OPG developed and this line of treatment had to be discontinued. The next step was to develop a monoclonal antibody against RANKL and this proved to be highly effective in blocking bone resorption. It led to development of a drug Denosumab that successfully reduces fractures and is now one of the therapeutic options for osteoporosis treatment. On the anabolic side bone biology res

Topics: Aged; Aged, 80 and over; Alendronate; Antibodies, Monoclonal, Humanized; Bone Density; Bone Remodeling; Calcitonin; Denosumab; Diphosphonates; Estrogen Replacement Therapy; Female; Fractures, Bone; Humans; Middle Aged; Osteoporosis, Postmenopausal; Osteoprotegerin; RANK Ligand; Risk Factors; Selective Estrogen Receptor Modulators; Teriparatide

Osteoporosis is a slow progressive disease with develops over decades, and where intervention is needed for an extended number of years. This highlights the need for safe intervention possibilities, which have sustained beneficial effects post-treatment.. Articles on salmon calcitonin appearing on Pubmed from 1960 until today, with focus on a newly developed oral formulation showing increased exposure and efficacy compared with nasal formulation is reviewed. The second half focuses on long-term phenomena, such as bone quality and resolution effects. The final part discusses potential additional benefits of salmon calcitonin.. Insight into the clinical development of an orally formulated peptide, as well as a detailed understanding of why this approach could revive salmon calcitonin as a treatment for osteoporosis.. The oral formulation of salmon calcitonin provides additional benefits and increased efficacy on bone based on Phase I and II clinical trials data, as compared with the nasal formulation. Hence, the results on the ongoing Phase III fracture trial are awaited with great interest.

Topics: Administration, Intranasal; Administration, Oral; Aged; Amino Acids; Bone Density Conservation Agents; Bone Resorption; Calcitonin; Circadian Rhythm; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Carriers; Female; Humans; Middle Aged; Osteoclasts; Osteoporosis; Osteoporosis, Postmenopausal; Receptors, Calcitonin

Salmon calcitonin, available as a therapeutic agent for more than 30 years, demonstrates clinical utility in the treatment of such metabolic bone diseases as osteoporosis and Paget's disease, and potentially in the treatment of osteoarthritis. This review considers the physiology and pharmacology of salmon calcitonin, the evidence based research demonstrating efficacy and safety of this medication in postmenopausal osteoporosis with potentially an effect on bone quality to explain its abilities to reduce the risk of spine fracture, the development of an oral salmon calcitonin preparation, and the therapeutic rationale for this preparation's chondroprotective effect in osteoarthritis.

Topics: Adult; Aged; Bone Density; Bone Density Conservation Agents; Bone Resorption; Calcitonin; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Middle Aged; Osteitis Deformans; Osteoporosis, Postmenopausal; Parathyroid Hormone; Spinal Fractures; Treatment Outcome

An intranasal spray formulation of recombinant salmon calcitonin [salcatonin] is in development with Unigene Laboratories as therapy for postmenopausal osteoporosis. Calcitonin is an endogenous polypeptide hormone that regulates calcium and bone metabolism. It is produced by the parafollicular cells of the thyroid gland in humans and other species. Calcitonin inhibits bone loss through the suppression of osteoclast activity. Salmon calcitonin is approximately 40-50 times more potent than natural human calcitonin at inhibiting osteoclast function. It can be obtained naturally from salmon or can be synthesised with the same chemical structure. Calcitonin was originally available only as an injectable formulation, but in recent years more convenient formulations have become available. Unigene is actively seeking to license its intranasal calcitonin product in Europe and other territories outside the US. nigene licensed its intranasal calcitonin product to Upsher-Smith Laboratories in December 2002, under a $US10 million exclusive US licensing agreement. Under the terms of the agreement, Unigene received an upfront payment of $US3 million from Upsher-Smith and will be eligible to receive milestone payments and royalty payments on product sales. Unigene will be responsible for manufacturing the product at its Boonton facility in New Jersey, USA, and will sell finished calcitonin product to Upsher-Smith. Upsher-Smith will package, market and distribute the product nationwide. Unigene granted an exclusive license to Faran Laboratories in September 2003 for its intranasal calcitonin osteoporosis product in Greece. Unigene will sell the finished product to Faran, who will promote and market it throughout the country after Unigene obtains European regulatory approval and local pricing approval. Unigene will receive an upfront payment and is eligible to receive milestone payments prior to product launch. Faran will pay Unigene a fixed price for each unit of product received. Qingdao General Pharmaceutical Company was a licensee for Unigene's injectable and intranasal calcitonin products in the People's Republic of China, and Unigene had received initial payments from Qingdao General Pharmaceutical in 1996. However, in June 2000, Unigene announced that it has entered into a joint venture with Shijiazhuang Pharmaceutical Group Company for the manufacture and distribution of injectable and intranasal calcitonin for the treatment of osteoporosis in China. Unigene initia

Topics: Administration, Intranasal; Calcitonin; Clinical Trials as Topic; Humans; Osteoporosis, Postmenopausal; Recombinant Proteins

Osteoporosis is a systemic skeletal condition characterized by decreased bone strength with consequent increased susceptibility to bone fracture. Fragility fractures in osteoporosis are often painful and result in loss of quality of life and disability. Salmon calcitonin (SCT) is a natural hormone that may assist in the management of osteoporotic patients following fracture by reducing fracture risk and decreasing pain. SCT is an antiresorptive agent which has been shown to reduce the risk of vertebral fractures (by 36%) in postmenopausal women with osteoporosis and previous fractures, with a safety profile comparable to placebo over long-term use. Clinical evidence suggests that SCT (with either subcutaneous and intranasal delivery) is an analgesic for the acute pain following osteoporotic fracture. Pain relief with SCT occurs after 1 week or less of treatment. Associated with this pain relief, vertebral fracture patients receiving SCT have been observed to have earlier mobilization compared with those receiving a placebo. Both preclinical and clinical data suggest a central analgesic effect for SCT. The mechanism(s) by which SCT induces pain relief has (have) not been conclusively shown. Neither a direct receptor-mediated action nor an indirect endorphin-mediated effect can be ruled out.

Topics: Analgesics; Animals; Calcitonin; Controlled Clinical Trials as Topic; Disease Models, Animal; Drug Evaluation, Preclinical; Female; Fractures, Bone; Humans; Osteoporosis, Postmenopausal; Pain

Osteoporosis causes approximately 1.5 million low-trauma fracture per year, and at all ages the incidence of fracture is higher in women than in men. Risk factors for osteoporotic fractures in postmenopausal women include family history of bone fracture, ethnicity, and weight < 127 pounds. Densitometry is used to diagnose osteoporosis and can be performed at intervals to monitor bone density during treatment. The older woman's diet should, in general, include 1,200 to 1,500 mg of calcium and 400 to 800 IU of vitamin D. Estrogens, bisphosphonates, selective estrogen receptor modulators, calcitonin, and exogenous parathyroid hormone are pharmacologic therapy options that can preserve and increase bone mass and reduce the risk of fracture.

Topics: Absorptiometry, Photon; Aged; Aged, 80 and over; Calcitonin; Diphosphonates; Estrogen Replacement Therapy; Exercise; Female; Fractures, Bone; Humans; Osteoporosis, Postmenopausal; Risk Factors; Selective Estrogen Receptor Modulators

To assess the cost effectiveness of nasal calcitonin (Miacalcin) compared with no therapy, alendronate or etidronate in the treatment of postmenopausal women with previous osteoporotic fracture.. Meta-analysis followed by economic analysis.. A Canadian provincial Ministry of Health.. The meta-analysis of randomised controlled clinical trials was based on the recommendations of the Cochrane Collaboration. Economic analysis was conducted within a Markov model using probabilities and costs derived from Canadian sources.. The meta-analysis found evidence of the positive effect of both nasal calcitonin and alendronate in reducing the risks of hip, wrist and vertebral fractures in postmenopausal women. However, there was a lack of evidence of the effect of etidronate on hip and wrist fractures. For a 65-year-old woman, with 5 years' therapy, the incremental cost per quality-adjusted life-year (QALY) gained for nasal calcitonin was 46,500 Canadian dollars ($Can) compared with no therapy and $Can32,600 compared with etidronate (1998 values). Comparison with alendronate was highly sensitive to the inclusion of one specific trial.. Given the results of the analysis, based on current evidence, nasal calcitonin can be considered at the margins of being cost effective when compared with no therapy. Compared with active therapy, nasal calcitonin can be considered more cost effective than etidronate, but its cost effectiveness versus alendronate is inconclusive.

Topics: Aged; Aged, 80 and over; Alendronate; Calcitonin; Cost-Benefit Analysis; Female; Fractures, Bone; Humans; Markov Chains; Middle Aged; Osteoporosis, Postmenopausal; Quality-Adjusted Life Years

Osteoporosis is a common problem among postmenopausal women and is associated with significant morbidity, mortality and costs primarily resulting from osteoporotic fractures. Salcatonin (salmon calcitonin) inhibits osteoclastic bone resorption and is approximately 40 to 50 times more potent than human calcitonin. In most randomised trials in which intranasal salcatonin (usually 50 to 200 IU/day plus oral calcium supplements) was administered for 1 to 5 years to postmenopausal women for prevention of osteoporosis, bone mineral density or content of the lumbar spine increased by approximately 1 to 3% from baseline. In contrast, postmenopausal women receiving only oral calcium supplements typically had reductions in bone mineral density or content of about 3 to 6%. The difference between treatment groups was statistically significant in essentially all studies. Although changes in bone mineral density or content were broadly similar in studies of postmenopausal women with established osteoporosis to those in postmenopausal women receiving therapy for prevention of the disease, studies in women with established osteoporosis did not usually demonstrate statistically significant differences between treatment groups. Also in postmenopausal women with established osteoporosis, intranasal salcatonin reduced pain and/or analgesic consumption in some trials and, in a limited number of studies of relatively short duration (i.e. < or = 2 years), the incidence of osteoporotic fractures. A large multicentre 5-year study with adequate statistical power to confirm the effect of intranasal salcatonin on reducing osteoporotic fracture rates in postmenopausal women is currently under way. The intranasal formulation of salcatonin offers a more convenient and better tolerated alternative to the parenteral formulation of the drug which is administered by regular subcutaneous or intramuscular injections. Adverse events associated with the intranasal formulation are generally mild and transient, usually involving local reactions such as nasal discomfort, rhinorrhoea or rhinitis. Thus, for postmenopausal women unable or unwilling to tolerate long term hormone replacement therapy, intranasal salcatonin is an attractive alternative for the management of osteoporosis.

Topics: Administration, Intranasal; Aged; Bone Density; Bone Resorption; Calcitonin; Calcium; Clinical Trials as Topic; Female; Humans; Osteoporosis, Postmenopausal

Calcitonin (CT) inhibits osteoclast-mediated bone resorption and is being used to treat Paget's disease of bone, hypercalcemia of malignancy and postmenopausal osteoporosis. The formation of antibodies against heterologuous calcitonins like salmon calcitonin (sCT) is common and occurs in 40-70% of the patients treated for more than 4 months. Not all of these patients, however, develop a secondary resistance to sCT, therefore the clinical significance of sCT antibodies is discussed controversially. In vivo and in vitro approaches demonstrate a neutralizing effect in 35 to 60% of the patient sera with antibodies against sCT. These neutralizing antibodies appear to explain most cases of clinically relevant secondary resistance to sCT treatment, which occurs in 25-45% of the patients after treatment periods of 6 months and longer. A positive treatment response to human CT after development of secondary resistance to sCT proves the diagnosis of antibody related resistance. Few cases develop secondary resistance in the absence of sCT binding antibodies, the mechanism of this phenomenon is unclear. Antibody related resistance is a significant problem in long term treatment with sCT. Especially in conditions like postmenopausal osteoporosis, where no readily accessable marker of treatment response is available, the development of sCT antibodies and their possible neutralizing effect has to be considered.

Topics: Animals; Antibodies; Calcitonin; Drug Resistance; Female; Humans; Hypercalcemia; Neoplasms; Osteitis Deformans; Osteoporosis, Postmenopausal

Topics: Administration, Intranasal; Aged; Animals; Calcitonin; Estrogen Replacement Therapy; Female; Humans; Middle Aged; Osteoporosis; Osteoporosis, Postmenopausal

Synthetic salmon calcitonin (SCT) is a potent antiosteoclastic hormone with adjunctive stimulatory effects on osteoblastic function. It is capable of increasing or stabilizing bone mass in osteoporosis and thereby can lessen the risk of fractures. Treatment doses vary from 100 IU daily to 50 IU three times a week, and the duration of treatment is 2 to 5 years. SCT also exerts an analgesic effect on the skeleton that increases its beneficial effect. Side effects, which do not involve organ toxicity, are common but are usually mild and transient. More severe side effects can be managed by maneuvers such as bedtime dosing, premedication, and temporary dose reduction. Primary resistance occurs in approximately 25% of patients and secondary resistance, usually due to neutralizing antibody formation, in 10% to 20% of patients. SCT is indicated in both early and late osteoporosis and is the treatment of choice in the latter.

Topics: Antibody Formation; Back Pain; Bone Density; Calcitonin; Drug Resistance; Female; Humans; Osteoporosis, Postmenopausal; Time Factors

Synthetic calcitonin-salmon is a treatment option for older patients with postmenopausal osteoporotic syndromes. Some clinical trials reveal a simple suppression of annual bone-loss rates with calcitonin therapy, whereas others show significant dose-related increases in vertebral and long-bone mass. Response is greater in patients with high-turnover (type I) osteoporosis than in those with the low/normal (type II) form. Candidates for calcitonin-salmon therapy include older women with established vertebral fractures, those who are osteopenic by bone mass analysis, and those in need of preventive therapy because of an accumulation of risk factors.

Topics: Aged; Calcitonin; Estrogen Replacement Therapy; Female; Humans; Osteoporosis, Postmenopausal; Spinal Fractures; Syndrome

This article reviews several of our studies in which we evaluated the effect of nasal salmon calcitonin in preventing bone loss in normal women just after menopause. In the first study, after treatment with nasal salmon calcitonin, bone loss stopped and, in fact, actually increased slightly. In contrast, the placebo group continued to lose bone mass. On the other hand, bone mass in the forearm, which has more cortical bone, showed no change in response to nasal salmon calcitonin. The effect of salmon calcitonin nasal spray in women with established osteoporosis has also been studied. In one study, bone mass in the forearm was constant in the group receiving nasal salmon calcitonin plus calcium, whereas bone mass in the placebo plus calcium group decreased by roughly 2%. Similarly, patients in the group without any treatment also lost 2%. The effect of nasal salmon calcitonin is probably the result of a reduction in the bone resorption to a level seen in premenopausal females. When women were divided according to their baseline bone turnover or initial bone mass, the women with the highest turnover level (assessed by alkaline phosphatase or fasting urinary hydroxyproline) or the lowest bone mass were the group with the greatest increase in bone mass. In conclusion, treatment with salmon calcitonin nasal spray in patients with established osteoporosis stops bone loss, normalizes bone turnover, and causes no subjective or objective side effects.

Topics: Administration, Intranasal; Calcitonin; Female; Humans; Middle Aged; Osteoporosis, Postmenopausal

This randomized, double-blind, placebo-controlled phase III study was conducted to assess the efficacy and safety of oral calcitonin (SMC021) for the treatment of postmenopausal osteoporosis. A total of 4665 postmenopausal women with osteoporosis were randomized 1:1 to receive calcium and vitamin D plus either SMC021 tablets (0.8mg/d) or placebo for 36months. The primary endpoint was the proportion of patients with a new vertebral fracture. The two groups were well balanced at baseline with regards to demographic and clinical data. No effect of SMC021 on preventing new vertebral fractures was observed, nor was any effect seen on new hip or non-vertebral fractures. Women receiving SMC021 had a mean 1.02% (±0.12%) increase in lumbar spine bone mineral density (BMD) compared with a mean 0.18% (±0.12%) increase in the placebo group by the end of the study (p<0.0001). Similarly, small increases in BMD were observed at the femoral neck and hip in both groups. Levels of the biomarkers of bone turnover, urinary CTX-I and CTX-II, were 15% lower in the SMC021 group than in the placebo arm at 12 and 24months, but not at 36months. No change in quality of life between groups, assessed by the Qualeffo-14 questionnaire, was observed in either group between baseline and month 36. Pharmacokinetics analysis confirmed exposure to SMC021, but the drug levels were markedly lower than expected. Approximately 92% of subjects in each treatment group experienced an adverse event (AE), the majority of which were mild or moderate in intensity. AEs associated with SMC021 were primarily of gastrointestinal origin and included nausea, vomiting and abdominal pain, as well as hot flushes which were the reason for the slightly higher drop-out rate in the active treatment arm compared to placebo. The number of severe AEs was low in both groups. Thirty-five deaths were reported but none were considered treatment-related. Due to the lack of efficacy in preventing fractures, the development of the orally formulated calcitonin was terminated despite the promising results in earlier studies.

Topics: Administration, Oral; Aged; Biomarkers; Bone Density; Bone Remodeling; Calcitonin; Calcium; Demography; Double-Blind Method; Female; Humans; Incidence; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Placebos; Quality of Life; Risk Factors; Treatment Outcome; Vitamin D

In healthy postmenopausal women, nasal salmon calcitonin blunted distal radius and tibia bone microstructure degradation.. Nasal salmon calcitonin (NSC) has been reported to lower vertebral fracture risk by 33%, but to modestly increase spine areal bone mineral density (aBMD) by 1.5%. Thus, NSC may also influence bone microstructure, another known determinant of bone strength.. In a randomized, double-blind, placebo-controlled trial, we investigated the effects of 200 IU/day NSC on distal radius and tibia bone microstructure (by high-resolution 3-dimensional peripheral quantitative computerized tomography), aBMD (by dual-energy X-ray absorptiometry), and serum bone turnover markers in healthy postmenopausal women.. Mean age was 57.6 ± 0.8 (±SEM) and 57.4 ± 0.7 in NSC (n = 45) and placebo groups (n = 45), respectively. Mean femoral neck T-score was in the osteopenic range; prevalent vertebral fracture was 4% in each group. There was no observed between-group difference in the primary outcome distal radius BV/TV (-2.8 ± 0.6% vs. -4.3 ± 1.0%, NS). By 2 years, the decrease in distal radius total density vs. baseline was 4.4 ± 0.7% in controls and 2.1 ± 0.6% in NSC-receiving patients (p < 0.05). Distal radius and tibia cortical thickness decreased by 3.7 ± 1.0 and 2.4 ± 0.5% in placebo (p < 0.05 vs. baseline for both), respectively, but not in the NSC group. Distal radius total density and cortical thickness changes were lower in NSC group than in placebo (p < 0.05 for both) in the subgroup with baseline C-terminal telopeptides (CTX) above the median. By 6 and 12 months, serum CTX decreased by 17.3 ± 6.2 and 19.1 ± 6.6% (both p < 0.05 vs. baseline), respectively, in NSC, but remained stable in controls (NS vs. baseline). There was no difference in aBMD. NSC was well tolerated, with less arthralgia than the placebo group (14 vs. 26, p < 0.05).. Nasal salmon calcitonin blunted the degradation of distal radius and tibia bone microstructure in healthy postmenopausal women.

Topics: Absorptiometry, Photon; Administration, Intranasal; Aged; Bone Density; Bone Density Conservation Agents; Bone Resorption; Calcitonin; Double-Blind Method; Female; Humans; Middle Aged; Osteoporosis, Postmenopausal; Postmenopause; Radius; Tibia; Tomography, X-Ray Computed

To investigate the analgesic effect of nasal salmon calcitonin on the post-fracture period of distal radius fracture.. In this prospective randomized double-blind study, forty-one postmenopausal women with a recent distal radius fracture treated conservatively were randomly assigned to receive either 200 IU of intranasal salmon calcitonin or placebo daily for 3 months following fracture. The assessment of the patient's pain was recorded using the Visual Analogue Scale (VAS).. The average age of the calcitonin group was 67.11 (SD, ±8.68) years and 64.91 (SD, ±7.48) of the placebo group. In the calcitonin group, the mean VAS score improved from 4.05 to 0.53 while in the placebo group from 3.36 to 0.32. A higher decrease of VAS score during the first post-fracture period was observed in the calcitonin group.. In the study, there is a statistically significant calcitonin mediated analgesic effect in the immediate post fracture period (at 10 days) when compared to placebo group. These results are in accordance with literature referring to the analgesic effect of calcitonin in the acute osteoporotic vertebral compression fracture. Thus calcitonin administration could be recommended to a short term course in acute osteoporotic conservatively treated distal radius fractures.

Topics: Administration, Intranasal; Aged; Analgesics; Calcitonin; Double-Blind Method; Female; Humans; Middle Aged; Osteoporosis; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Pain; Pain Measurement; Prospective Studies; Radius Fractures; Treatment Outcome

The effect of an investigational oral calcitonin tablet upon bone mineral density (BMD) of the spine was investigated in postmenopausal women with low bone mass and at increased risk of fracture. Compared to placebo, calcitonin tablets increased lumbar spine BMD. This agent may provide an additional choice for patients.. An investigational oral salmon calcitonin preparation was previously shown to increase lumbar spine BMD in postmenopausal women with osteoporosis. Our objective was to evaluate the use of this agent in postmenopausal women with low bone mass and at increased fracture risk but not meeting BMD criteria for osteoporosis.. Treatment-naïve women were randomized to receive oral recombinant salmon calcitonin tablets or placebo once daily for 1 year. Dual-energy X-ray absorptiometry was performed at baseline and at study weeks 28 and 54. CTx-1, a bone resorption marker, was obtained at the same time points. Subjects returned periodically for tolerability assessment and adverse event (AE) recording.. One hundred twenty-nine women in the USA were randomized, 86 to calcitonin and 43 to placebo. Calcitonin recipients experienced a significant increase from baseline in lumbar spine BMD; the difference compared with placebo was significant. Dosing at bedtime or with dinner was equally effective. CTx-1 was suppressed in calcitonin recipients but not in placebo subjects. Gastrointestinal AEs were common, but the overall safety profile was comparable between groups.. Oral calcitonin may provide a useful therapeutic alternative for some women with low bone mass.

Topics: Absorptiometry, Photon; Administration, Oral; Aged; Biomarkers; Bone Density; Bone Density Conservation Agents; Calcitonin; Collagen Type I; Double-Blind Method; Female; Femur Neck; Hip Joint; Humans; Lumbar Vertebrae; Middle Aged; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Peptides; Single-Blind Method; Treatment Outcome

The Oral Calcitonin in Postmenopausal Osteoporosis (ORACAL) study was a randomized, double-blind, double-dummy, active- and placebo-controlled, multiple-dose, phase 3 study to assess the efficacy and safety of oral recombinant calcitonin for treatment of postmenopausal osteoporosis. A total of 565 women age 46 to 86 (mean 66.5) years were randomized (4:3:2) to receive oral recombinant salmon calcitonin (rsCT) tablets (0.2  mg/d) plus placebo nasal spray, synthetic salmon calcitonin (ssCT) nasal spray (200 IU/d) plus placebo tablets, or placebo (placebo tablets plus placebo nasal spray), respectively for 48 weeks. All women received calcium (≥1000  mg/d) and vitamin D (800 IU/d). Women randomized to oral rsCT had a mean ± SD percent increase from baseline in lumbar spine bone mineral density (BMD) (1.5% ± 3.2%) that was greater than those randomized to ssCT nasal spray (0.78% ± 2.9%) or placebo (0.5% ± 3.2%). Lumbar spine BMD change in those receiving nasal calcitonin did not differ from placebo. Oral rsCT treatment also resulted in greater improvements in trochanteric and total proximal femur BMD than ssCT nasal spray. Reductions in bone resorption markers with oral rsCT were greater than those observed in ssCT nasal spray or placebo recipients. Approximately 80% of subjects in each treatment group experienced an adverse event, the majority of which were mild or moderate in intensity. Gastrointestinal system adverse events were reported by nearly one-half of women in all treatment groups and were the principal reason for premature withdrawals. Less than 10% of women experienced a serious adverse event and no deaths occurred. Overall, oral rsCT was superior to nasal ssCT and placebo for increasing BMD and reducing bone turnover. Oral rsCT was safe and as well tolerated as ssCT nasal spray or placebo. Oral calcitonin may provide an additional treatment alternative for women with postmenopausal osteoporosis.

Topics: Administration, Oral; Aged; Aged, 80 and over; Biomarkers; Bone Density; Bone Density Conservation Agents; Bone Remodeling; Calcitonin; Female; Femur; Femur Neck; Hip; Humans; Lumbar Vertebrae; Middle Aged; Osteoporosis, Postmenopausal; Treatment Outcome

Renal osteodystrophy is one of the commonest complications of chronic renal failure. It may have a severe impact on the quality of life of patients on maintenance dialysis therapy. Besides post-menopausal women and elderly people, the dialysis patients are another high risk group. But at present, there is no research on how to prevent osteoporosis in maintenance dialysis patients. This study was conducted to observe the bone density of maintenance dialysis patients and to evaluate the clinical outcomes and safety of different administration dosage of salmon calcitonin to prevent osteoporosis in maintenance dialysis patients.. One hundred and forty-eight patients on maintenance dialysis were involved in the 12-month, randomized, controlled trial. Fifty patients (experiment I group) received subcutaneous injection of salmon calcitonin (50 U) three times a week for 12 months. Fifty patients (experiment II group) received subcutaneous injection of salmon calcitonin (100 U) three times a week for 12 months. At the same time, both of them received oral calcium carbonate 1500 mg tid and rocaltrol 0.25 microg qn for 12 months. The control group only received oral calcium carbonate 1500 mg tid and rocaltrol 0.25 microg qn for 12 months. The levels of bone mass density (BMD) of the lumbar spine and femoral neck, serum intact parathyroid hormone (iPTH), osteocalcin (OC), calcium, phosphorus, alkaline phosphatase (ALP) were assessed at baseline and then again after 3, 6 and 12 months of treatment.. The values of BMD at the lumbar spine and femoral neck before the treatment were not significantly different from those 3, 6, and 12 months after the treatment in trial groups I and II (all P > 0.05) and there were no significant differences in the BMD values at different time points between trial groups I and II. In the control group, the BMD values at the lumbar spine and femoral neck 3, 6, and 12 months after the beginning of trial were significantly lower than those before the trial, and significantly lower than the corresponding values of trial groups I and II (all P < 0.05). The serum OC 3, 6, and 12 months after the treatment was significantly lower than that before the experiment (all P < 0.05) in the control group. However, there was no significant difference in the value of serum OC before and 3, 6, and 12 months after the treatment in trial groups I and II (all P > 0.05).. The dose of salmon calcitonin 50 U three times a week plus calcium carbonate and active vitamin D can effectively preserve the BMD and prevent bone loss in maintenance dialysis patients, and it is well tolerated by patients on maintenance dialysis.

Topics: Adult; Alkaline Phosphatase; Bone Density; Bone Density Conservation Agents; Calcitonin; Calcium; Calcium Carbonate; Drug Administration Schedule; Female; Femur Neck; Humans; Lumbar Vertebrae; Male; Middle Aged; Osteocalcin; Osteoporosis, Postmenopausal; Parathyroid Hormone; Phosphorus; Renal Dialysis

The purpose of this study was to evaluate the efficacy of calcitonin on beta-endorphin levels in female patients experiencing back pain associated with postmenopausal osteoporosis. The secondary purpose was to assess the pain and quality of life in these patients. There were 30 patients with a mean age of 58.2+/-5.4 years in the treatment group and 26 patients with a mean age of 58.8+/-5.2 years in the placebo group in this randomized, placebo-controlled study. The patients subcutaneously received 100 IU salmon calcitonin or placebo injections and 1,000 mg elementary calcium for 2 weeks. Baseline plasma beta-endorphin levels were measured and repeated after 2 weeks. Patients' pain and quality of life (QOL) were evaluated by using the Visual Analogue Scale, Modified Face Scale, Beck Depression Index, and Nottingham Health Profile. Patients' global assessment of disease activity was also performed at baseline and at the end of the first and second week. We found that plasma beta-endorphin levels in the treatment group were significantly higher than the placebo group at the end of the second week (p<0.001). Although pain and QOL scores were improved at the end of the second week in both groups (p<0.05), the improvement in the treatment group was more significant when compared with the placebo group (p<0.05). Therefore, calcitonin is an analgesic agent, as it increases the plasma beta-endorphin levels in patients with postmenopausal osteoporosis, which consequently improves QOL.

Topics: Aged; Back Pain; beta-Endorphin; Bone Density; Bone Density Conservation Agents; Calcitonin; Female; Humans; Injections, Subcutaneous; Middle Aged; Osteoporosis, Postmenopausal; Placebos; Quality of Life; Single-Blind Method

The aim of this study was to investigate the early effect of nasal salmon calcitonin on a bone-resorption marker, "Crosslaps", in postmenopausal osteoporotic women. In this randomized, single-blind and placebo-controlled study we included 78 postmenopausal women with osteoporosis, between 45 and 65 years of age, with at least 5 years duration of menopause. Patients were randomly divided into two groups, the treatment and the placebo groups. Patients in the treatment group were given 100 IU day(-1) nasal salmon calcitonin, 1,000 mg day(-1) elemental calcium, and 400 IU day(-1) vitamin D. Patients in the placebo group took only 1,000 mg day(-1) elemental calcium, and 400 IU day(-1) vitamin D. The outcome measurements were urinary deoxypyridinoline, serum alkaline phosphatase, osteocalcin, and Crosslaps. The treatment group consisted of 39 patients whose mean age was 60.4 +/- 6 years and the placebo group included 39 patients with a mean age of 60.5 +/- 4.9 years. There was no significant difference between two groups in terms of demographic characteristics. The results of bone marker measurements were analyzed statistically. Crosslaps levels in the treatment group were significantly lower (P < 0.05) than in the placebo group. Other bone marker levels at the end of the study were not significantly lower (P > 0.05) than those at baseline in both treatment and placebo groups, however. Salmon calcitonin affects bone turnover within a few months and bone-resorption markers such as Crosslaps can be used to monitor the effect of nasal salmon calcitonin in the early phase of treatment for postmenopausal osteoporosis.

Topics: Absorptiometry, Photon; Adjuvants, Immunologic; Administration, Intranasal; Aged; Alkaline Phosphatase; Amino Acids; Biomarkers; Bone Density; Bone Resorption; Calcitonin; Calcium; Collagen; Female; Femur; Humans; Lumbar Vertebrae; Middle Aged; Osteocalcin; Osteoporosis, Postmenopausal; Peptide Fragments; Single-Blind Method; Vitamin D

This study compared the clinical efficacy, safety, and tolerability of daily subcutaneous injections of teriparatide and salmon calcitonin in the treatment of postmenopausal women with established osteoporosis in Taiwan. This 6-month, multicenter, randomized, controlled study enrolled 63 women with established osteoporosis. They were randomized to receive either teriparatide 20 microg or calcitonin 100 IU daily in an open-label fashion. Lumber spine, femoral neck, total hip bone mineral density (BMD), and biochemical markers of bone turnover were measured, and adverse events and tolerability were recorded. The results at 6 months showed that patients using teriparatide had larger mean increases in spinal BMD than those who used calcitonin (4.5% vs. 0.1%), but the BMD changes in these two groups at the femoral neck and the total hip were not significant. There were also larger mean increases in bone markers in the teriparatide group than in the calcitonin group (bone specific alkaline phosphatase 142% vs. 37%; osteocalcin 154% vs. 23%). We conclude that teriparatide has more positive effects on bone formation than salmon calcitonin, as shown by the larger increments of lumbar spine BMD and bone formation markers, and caused only mild adverse events and no significant change in liver, kidney or hematological parameters. Compared with the published global results, teriparatide seems to be equally effective and safe to use in this Asian population.

Topics: Aged; Bone Density; Bone Density Conservation Agents; Calcitonin; Chi-Square Distribution; Female; Femur Neck; Follow-Up Studies; Humans; Lumbar Vertebrae; Osteoporosis, Postmenopausal; Taiwan; Teriparatide

A 1-year prospective, open, randomized, controlled trial was conducted as a pilot study to examine the effect of intermittent administration of 200 IU intranasal salmon calcitonin and 1alpha(OH) vitamin D3 [1alpha(OH)D3] on bone mineral density (BMD) of the lumbar spine and hip as well as on the markers of bone metabolism in women with postmenopausal osteoporosis. A total of 102 randomly recruited women received either 200 IU intranasal salmon calcitonin (Miacalcic nasal 200, Novartis, Basel, Switzerland) daily, 1 month on-1 month off, 0.25 mug 1alpha(OH)D3, and 500 mg elemental calcium continuously (n=57 women) or only 0.25 mug 1alpha(OH)D3 and 500 mg calcium (n=45 women) for a period of 1 year. BMD of the lumbar spine and hip plus biochemical markers reflecting calcium (Ca) metabolism and bone turnover [serum Ca, serum phosphorus, intact parathormone (iPTH), total and bone-specific alkaline phosphatase, osteocalcin levels, 24-h urinary Ca, morning fasting urinary Ca/creatinine, and Pyrilinks-D/creatinine ratio] were measured at the beginning of the study before treatment and after 6 and 12 months of treatment. Baseline characteristics of participants, including age, body mass index, lumbar and hip BMD, and biochemical markers were similar between the two groups. A total of 91 patients completed the study (50 in the salmon calcitonin nasal spray group and 41 in the other group). Lumbar BMD increased significantly in the salmon calcitonin group from baseline (3.0%, p=0.005) and in comparison to the non-calcitonin-treated group (p=0.009). The salmon calcitonin group also had a significant increase in femoral neck BMD compared with baseline values (3.1%, p=0.0005) and in comparison to the non-calcitonin-treated group (p=0.0005) in Ward's triangle BMD (2.9% from baseline values, p=0.009) and in comparison to the non-calcitonin-treated group (p=0.005) in trochanteric BMD (3.4% from baseline values, p=0.007) and in comparison to the non-calcitonin-treated group (P=0.01). Urinary Ca/creatinine and Pyrilinks-D/creatinine levels were significantly decreased from baseline in the salmon calcitonin-treated group (-6.1 and -6.3%, respectively, p=0.001). Bone-specific alkaline phosphatase levels were also significantly decreased from baseline in the salmon calcitonin-treated group (-3.6%, p=0.003). In the same group, a significant decrease in iPTH serum levels compared to baseline values (-2.5%, p=0.005) and in comparison to the non-calcitonin-treated group (p=0.005)

Topics: Absorptiometry, Photon; Adjuvants, Immunologic; Administration, Intranasal; Aged; Alkaline Phosphatase; Analgesics; Biomarkers; Bone Density; Calcitonin; Calcium; Creatinine; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Hydroxycholecalciferols; Lumbar Vertebrae; Middle Aged; Osteocalcin; Osteoporosis, Postmenopausal; Pelvic Bones; Prospective Studies; Treatment Outcome

The purpose of this study was to assess the effects of alendronate and intranasal salmon calcitonin (sCT) treatments on bone mineral density and bone turnover in postmenopausal osteoporotic women with rheumatoid arthritis (RA) receiving low-dose glucocorticoids.. Fifty osteoporotic postmenopausal women with RA, who had been treated with low-dose corticosteroids for at least 6 months, were randomized to receive alendronate 10 mg/day or sCT 200 IU/day for a period of 24 months. All patients received calcium supplementation 1,000 mg and vitamin D 400 IU daily. Bone mineral density (BMD) of the lumbar spine, femoral neck, and trochanter was measured annually using dual-energy X-ray absorptiometry. Bone metabolism measurements included urinary deoxypyridinoline (DPD), serum bone alkaline phosphatase (BAP), and serum osteocalcin (OC).. Over 2 years, the lumbar spine (4.34%, P < 0.001), femoral neck (2.52%, P < 0.05), and trochanteric (1.29%, P < 0.05) BMD in the alendronate group increased significantly. The sCT treatment increased lumbar spine BMD (1.75%, P < 0.05), whereas a significant bone loss occurred at the femoral neck at month 24 (-3.76%, P < 0.01). A nonsignificant decrease in the trochanteric region was observed in the sCT group (-0.81%). The difference between the groups with respect to the femoral neck and trochanteric BMD was statistically significant ( P < 0.001 and P < 0.05, respectively). The decreases in urinary DPD (-21.87%, P < 0.001), serum BAP (-10.60%, P < 0.01), and OC (-19.59%, P < 0.05) values were statistically significant in the alendronate group, whereas nonsignificant decreases were observed in the sCT group (-5.77%, -1.96%, and -4.31%, respectively). A significant difference was found in the DPD and BAP levels between the two treatment groups in favor of the alendronate group at all time points ( P = 0.001 and P < 0.05, respectively).. The results of this study demonstrated that alendronate treatment produced significantly greater increases in the femoral neck BMD and greater decreases in bone turnover than intranasal sCT in RA patients receiving low dose glucocorticoids.

Topics: Absorptiometry, Photon; Administration, Inhalation; Administration, Intranasal; Alendronate; Alkaline Phosphatase; Amino Acids; Arthritis, Rheumatoid; Bone and Bones; Bone Density; Bone Density Conservation Agents; Bone Resorption; Calcitonin; Calcium, Dietary; Female; Glucocorticoids; Humans; Middle Aged; Osteocalcin; Osteoporosis, Postmenopausal

The increasing rate of hip fractures is giving rise to a number of socioeconomic problems for the aging community. In addition to being unable to resume their previous living habits, many patients fail to achieve full functional recovery after the fractures. Total hip arthroplasty (THA) is a successful operation for the majority of patients with all forms of hip fractures. Dislocation and aseptic loosening are the major reasons for revisions. An additional problem post-THA is the rate of heterotopic soft tissue calcification after total hip arthroplasty, resulting in severely impaired function, pain, and a reduced range of hip motion. In an open study, 37 women who had undergone cementless total hip arthroplasty after accidental hip fractures were treated twice daily with 200 IU salmon calcitonin nasal spray for 12 months. Simultaneously, the patients received one bag of 1000 mg calcium plus 880 IU vitamin D daily throughout the treatment period of 1 year. A parallel group of 38 women with a similar clinical status in terms of hip fractures and cementless total hip arthroplasty were treated with only one bag of 1000 mg calcium plus 880 IU vitamin D daily through the treatment period. The results of this 12-month clinical trial show that 200 IU salmon calcitonin nasal spray per day promotes general independence from foreign assistance, mobility, and fear of further falls in postmenopausal elderly women following THA. Treatment with a salmon calcitonin nasal spray reduces bone turnover serum markers, loss of further bone density, and pain. Additionally, calcitonin promoted the repair of hip fractures and, as a coincidence finding, was associated with a significantly reduced rate of refractures as well as periprosthetic ossifications.

Topics: Administration, Inhalation; Aged; Analgesics; Arthroplasty, Replacement, Hip; Bone Density; Calcitonin; Calcium; Female; Hip Fractures; Humans; Osteogenesis; Osteoporosis, Postmenopausal; Recurrence; Treatment Outcome; Vitamin D

Oral administration of calcitonin could improve compliance to long-term treatment. Efficacy and safety of a novel oral formulation was assessed on 277 postmenopausal women. The results show (1) effective enteral absorption, (2) marked inhibition of bone resorption with minimal alteration of formation, and (3) reproducibility of responses over 3 months.. We have recently introduced an Eligen technology-based oral formulation of salmon calcitonin (sCT) that effectively delivers the hormone to the circulation. The efficacy and safety during longer-term administration, however, has not been investigated in the target population.. This was a multicenter, randomized, double-blind, placebo-controlled, dose-ranging clinical trial including 277 healthy postmenopausal women 55-85 years of age. Women received treatment with either daily (0.15, 0.4, 1.0, or 2.5 mg) or intermittent doses (1.0 mg, every other day) of sCT combined with the delivery agent (8-[N-2-hydroxi-5-chloro-benzoyl]-amino-caprylic acid, 200 mg) or placebo for 3 months. All participants received 1,000 mg calcium plus 400 IU vitamin D daily throughout the study. Efficacy parameters were the acute and/or pre-dose changes in serum and urinary C-terminal telopeptide of type I collagen (CTx), N-mid osteocalcin (OC), bone-specific alkaline phosphatase (BSALP), calcium, and parathyroid hormone (PTH) measured by established immunoassays.. After the first dose, sCT evoked dose-dependent decreases in serum CTx (-60.8% to -81.8% from baseline) compared with placebo, reaching nadirs 2-3 h after drug intake, after which, gradual increases were observed. The simultaneous acute changes in OC were statistically nonsignificant. Area under the curve (AUC) of serum CTx responses at months 1 and 3 showed strong correlation with those at baseline (both r = 0.78, p < 0.001). At month 3, the placebo-corrected changes in the pre-dose value of serum and urinary CTx were significant only in the 1.0-mg dose group (-18.9% and -20.5%, respectively, p < 0.05). The placebo-corrected change in OC was -8.6 (p = 0.09), whereas the change in BSALP was -7.3 (p = 0.02). The oral formulation was well tolerated, with mild to moderate gastrointestinal and skin manifestations apparent mainly in the high-dose groups.. The results of this 3-month trial show that the novel Eligen technology-based oral formulation of sCT has potential to become a safe and effective treatment for postmenopausal bone loss. Future trials are needed to assess the impact of long-term administration on changes in BMD and fracture risk.

Topics: Administration, Oral; Aged; Aged, 80 and over; Biomarkers; Bone and Bones; Bone Remodeling; Calcitonin; Calcium; Dose-Response Relationship, Drug; Double-Blind Method; Female; Health; Humans; Middle Aged; Osteoporosis, Postmenopausal; Parathyroid Hormone; Postmenopause; Time Factors

Salmon calcitonin is a potent inhibitor of osteoclastic activity. The effect of calcitonin in elderly women with high bone turnover at higher risk of developing osteoporosis has not been studied. To investigate acute effects of calcitonin treatment on bone resorption markers in elderly women, we conducted a randomized trial in women >65 years of age with high bone turnover assessed as urinary N-telopeptide of type-I collagen (NTx) levels 1 SD higher than mean premenopausal levels, which was irrespective of bone density. A total of 98 elderly women were randomly assigned to receive either 200 IU calcitonin nasal spray (n = 75) with calcium (500 mg) and vitamin D (200 IU) or calcium and vitamin D (n = 23) alone for 6 months. Blood and urine samples were collected at 0, 2, 4, and 6 months and analyzed for urinary NTx and serum C-telopeptide of type-1 collagen (CTx). At baseline, mean age was 72.1 +/- 4.7 (mean +/- SD) in the calcitonin group and 72.2 +/- 6 years in the control group. The spine and total hip BMD, serum PTH levels and urinary calcium/creatinine ratios were similar in both groups. Mean BMD was in the osteopenic range in both groups. Calcitonin treatment resulted in significant decreases in serum CTx levels, 2, 4 and 6 months after treatment as compared to baseline, and after 4 and 6 months as compared to controls. A maximum decrease from baseline of 33% was seen at 6 months. The urinary resorption marker, urine NTx, showed a significant decrease in the calcitonin group when compared to baseline only at the 6-month time point. Analysis of least significance change (LSC) showed that 70% of calcitonin patients were categorized as responders using serum CTx after 6 months of treatment. We conclude that 200 IU calcitonin effectively decreases bone resorption within 60 days of therapy, thus preventing further bone loss in elderly women who are at a high risk of developing osteoporosis.

Topics: Aged; Biomarkers; Bone Density; Bone Resorption; Calcitonin; Collagen; Female; Humans; Osteoporosis, Postmenopausal; Time Factors

We conducted a 5-year, double-blind, randomized, placebo-controlled study to determine whether salmon calcitonin nasal spray reduced the risk of new vertebral fractures in postmenopausal women with osteoporosis.. A total of 1,255 postmenopausal women with established osteoporosis were randomly assigned to receive salmon calcitonin nasal spray (100, 200, or 400 IU) or placebo daily. All participants received elemental calcium (1,000 mg) and vitamin D (400 IU) daily. Vertebral fractures were assessed with lateral radiographs of the spine. The primary efficacy endpoint was the risk of new vertebral fractures in the salmon calcitonin nasal spray 200-IU group compared with the placebo group.. During 5 years, 1,108 participants had at least one follow-up radiograph. A total of 783 women completed 3 years of treatment, and 511 completed 5 years. The 200-IU dose of salmon calcitonin nasal spray significantly reduced the risk of new vertebral fractures by 33% compared with placebo [200 IU: 51 of 287, placebo: 70 of 270, relative risk (RR) = 0.67, 95% confidence interval (CI): 0.47- to 0.97, P = 0.03]. In the 817 women with one to five prevalent vertebral fractures at enrollment, the risk was reduced by 36% (RR = 0.64, 95% CI: 0.43- to 0.96, P = 0.03). The reductions in vertebral fractures in the 100-IU (RR = 0.85, 95% CI: 0.60- to 1.21) and the 400-IU (RR = 0.84, 95% CI: 0.59- to 1.18) groups were not significantly different from placebo. Lumbar spine bone mineral density increased significantly from baseline (1% to 1. 5%, P<0.01) in all active treatment groups. Bone turnover was inhibited, as shown by suppression of serum type-I collagen cross-linked telopeptide (C-telopeptide) by 12% in the 200-IU group (P <0.01) and by 14% in the 400-IU group (P<0.01) as compared with placebo.. Salmon calcitonin nasal spray at a dose of 200 IU daily significantly reduces the risk of new vertebral fractures in postmenopausal women with osteoporosis.

Topics: Aged; Analysis of Variance; Bone Density; Calcitonin; Chi-Square Distribution; Double-Blind Method; Female; Fractures, Spontaneous; Humans; Middle Aged; Nasal Cavity; Osteoporosis, Postmenopausal; Reference Values; Secondary Prevention; Spinal Fractures; Treatment Outcome

The usefulness of GH in the treatment of post-menopausal osteoporosis (PMO) is still debated. We have studied the effects of recombinant human GH (rhGH) given alone or in combination with salmon calcitonin (sCT) in the treatment of PMO.. Thirty women with established PMO (aged 61.1 +/- 4.4 years) were divided into 3 groups of 10 and randomly assigned to 3 treatment sequences: rhGH (12IU/day) s.c. for 7 days, followed by sCT (50 IU/day) s.c. for 21 days and by 61 days without treatment (group 1); placebo for 7 days, followed by sCT for 21 days and by 61 days without treatment (group 2); rhGH for 7 days, followed by placebo for 21 days, and by 61 days without treatment (group 3). Each cycle was repeated 8 times (24 months).. At days 0, 8, 29 and 90 of each cycle, serum IGF-I, calcium, phosphate, osteocalcin, alkaline phosphatase and urinary excretion of calcium, hydroxyproline and pyridinoline cross-links (Pyr) were measured. At months 0, 6, 12, 18 and 24, bone mineral density (BMD) was measured by dualphoton absorptiometry (DPA), at lumbar spine (LS), femoral shaft (F) and distal radius (DR).. A significant increase in serum osteocalcin and urinary calcium, hydroxyproline and Pyr was detected after each rhGH period. In group 1, BMD at lumbar spine increased by 2.5% at year 2; in contrast, significant (P < 0.05) decreases in BMD-LS values were found in patients treated with CT and placebo (group 2) and with GH and placebo (group 3). BMD-F did not show any significant change in patients of group 2, but a significant (P < 0.05) decrease was found in groups 1 and 3. BMD-DR did not show any significant change with respect to baseline in any of the three groups. No significant difference between the three groups was found in bone mass at the three different regions.. Our study demonstrates that treatment with rhGH increases bone turnover in postmenopausal osteoporotic women. Combined treatment with rhGH and CT over a period of 24 months is able to maintain bone mass at lumbar spine and distal radius, but induces a decline at femoral shaft; therefore, it does not seem particularly useful in the therapy of post-menopausal osteoporosis.

Topics: Amino Acids; Analgesics; Bone Density; Calcitonin; Calcium; Drug Therapy, Combination; Female; Femur; Human Growth Hormone; Humans; Hydroxyproline; Lumbar Vertebrae; Middle Aged; Osteocalcin; Osteoporosis, Postmenopausal; Placebos; Radius

Calcitriol has been widely used in the management of osteoporosis, but its efficiency is a matter of controversy. It is not known whether combinations of calcitriol and antiresorptive agents such as etidronate and calcitonin are superior to calcitriol alone in the treatment of postmenopausal osteoporosis. To make this determination, 30 Turkish women with postmenopausal osteoporosis between 45 and 68 years of age were randomized to receive either intermittent cyclical etidronate (400 mg/day, for 14 days) followed by 60 days of cyclical calcitriol therapy 0.25 microg twice daily (group 1; n = 10), or calcitriol 0.25 microg twice daily (group 2; n = 10), or calcitriol 0.25 microg/day in combination with 100 IU intranasal salmon calcitonin taken every other day (group 3; n = 10) through a 1-year period. Bone mineral density (BMD) of lumbar spine (L2 to L4) was determined for each patient by dual-photon absorptiometry (153Gd) at baseline, after 6 months, and at the end of the study. There was no significant difference among groups with respect to mean spinal BMD at baseline, after 6, and after 12 months. No significant spinal BMD changes occurred in any group from baseline, after 6 months, and after 12 months. Four patients in groups 1 and 2 and five patients in group 3 developed hypercalcemia at least once during therapy. Hypercalciuria occurred at least once in 9, 10, and 7 patients in groups 1, 2, and 3, respectively. One patient in group 2 developed a renal stone at the end of the study. Mean urine hydroxyproline levels did not change significantly in any group with respect to baseline. The data suggest that one-year treatment with calcitriol, given either alone or in combination with antiresorptive agents, does not improve spinal BMD in Turkish women with postmenopausal osteoporosis, and is associated with a high rate of adverse events.

Topics: Absorptiometry, Photon; Administration, Intranasal; Aged; Analysis of Variance; Biomarkers; Bone Density; Calcitonin; Calcitriol; Drug Synergism; Drug Therapy, Combination; Etidronic Acid; Female; Humans; Hydroxyproline; Lumbar Vertebrae; Middle Aged; Osteoporosis, Postmenopausal; Prospective Studies; Treatment Outcome; Turkey

In a randomized, double-blind, placebo-controlled trial, we have studied the effects of intranasal salmon calcitonin (SCT) on bone mineral density (BMD) and biochemical markers of bone turnover over a period of 2 years. Our study comprised 117 Caucasian postmenopausal women, otherwise healthy apart from reduced bone density. They received either intranasal synthetic SCT (200 IU either three times weekly or daily) or placebo. Compared with placebo, daily intranasal calcitonin resulted in no significant bone loss in the lumbar spine, as assessed by dual photon absorptiometry, over the 2-year study period (P < 0.02). In this group, women more than 5 years postmenopause, with the lowest baseline bone mass, showed the greatest response to this treatment, with a total increase placebo in lumbar spine BMD of 3.1%. Significant spinal bone loss (P < 0.005) occurred in women receiving either placebo or thrice-weekly calcitonin. Although the rates of bone loss in the proximal femur were not significantly different in the three groups, there were differences over time. Whereas bone loss in the daily calcitonin group was insignificant, women who received placebo or thrice-weekly calcitonin experienced significant bone loss (P < 0. 001). No significant changes in biochemical markers were observed in any group. Therapy was well tolerated and there were no significant treatment-related adverse events. We conclude that intranasal SCT 200 IU daily is effective and safe for the prevention of bone loss in postmenopausal women with reduced bone mass.

Topics: Administration, Intranasal; Bone Density; Bone Resorption; Calcitonin; Consumer Product Safety; Double-Blind Method; Female; Femur; Humans; Middle Aged; Osteoporosis, Postmenopausal; Spine

The objective of this study was to determine whether intranasal salmon calcitonin prevents physiological bone loss at perimenopause. A double-blind study of 120 perimenopausal women without present or past disease or medication that could affect bone metabolism were studied. The subjects were randomized in two groups and provided with nasal spray bottles containing either placebo (excipient only) or active compound (excipient plus 50 international units (IU) salmon calcitonin per dose). Subjects took one puff from the nasal spray in each nostril every morning. All subjects took one soluble tablet of calcium (1000 mg) per day. Serum biochemistry, dual-energy X-ray absorptiometry of lumbar spine and proximal femur, quantitative computed tomography of lumbar spine, and single photon attenuation of forearm were used to evaluate bone mineral density (BMD). There were no differences in demographic characteristics or hormone status at entry. No fractures were recorded during the study period. Serum calcium increased and serum dihydroxyvitamin D and osteocalcin decreased in both groups. There was no difference in biochemical parameters between the groups. The BMD of upper femur did not change during the study, but it was decreased in the lumbar spine in both groups. The mineral content of distal radius increased in both groups. In conclusion, nasal salmon calcitonin, 100 IU daily, has no protective effect on bone mass and does not modify bone metabolism at perimenopause.

Topics: Absorptiometry, Photon; Administration, Intranasal; Adult; Analgesics; Biomarkers; Bone Density; Calcitonin; Dihydroxycholecalciferols; Double-Blind Method; Female; Humans; Lumbar Vertebrae; Middle Aged; Osteocalcin; Osteoporosis, Postmenopausal; Premenopause; Tomography, X-Ray Computed

The effect of nasal salmon calcitonin (SCT) on bone has been investigated by densitometry, biochemical markers of bone turnover, and histomorphometry. 62 women (mean age 65 years) who had experienced Colles' fracture after menopause were randomized to receive either nasal salmon calcitonin (SCT) 200 IU or nasal placebo daily for 24 months. All received a daily supplement of 0.5 g calcium. There was a significant increase above baseline in the bone mineral density of the lumbar spine in the SCT group (2.5%; 95% confidence interval 0.9--4.2%) and in the placebo group (1.7%; 95% confidence interval 0.3--3.1%) after 24 months, but the difference between the groups was not significant (0.8%; 95% confidence interval -1.2-3.0%). Serum levels of osteocalcin decreased significantly below baseline in the SCT group, whereas they were unchanged in the placebo group. At months 12 and 24, serum levels of osteocalcin were significantly lower in the SCT group than in the placebo group (p < 0.03). Urinary levels of deoxypyridinoline/creatinine decreased significantly below baseline in the SCT group, whereas only a transient decrease was observed in the placebo group. The differences between the groups were, however, not significant. The erosion depth was significantly lower in the SCT group than in the placebo group after 12 months (median [interquartile range]; 46.9 mu m [10.4] vs. 50.5 mu m [10.7]; p = 0.03), whereas bone volume and activation frequency did not differ between the groups. This study indicates that nasal SCT in a dose of 200 IU daily induces only a minor inhibition of bone resorption and therefore produces only a minor increase in bone mass. Furthermore, it seems that nasal SCT in a dose of 200 IU does not interfere with the recruitment of new bone multicellular units, but preferably decreases ongoing osteoclastic bone resorption.

Topics: Administration, Intranasal; Aged; Biomarkers; Bone and Bones; Bone Density; Bone Remodeling; Calcitonin; Calcium; Double-Blind Method; Female; Humans; Middle Aged; Osteoporosis, Postmenopausal

Intramuscular and intranasal synthetic salmon calcitonin (sCT) has long been used in the treatment of involutional osteoporosis. A new suppository formulation was developed and many studies demonstrated that rectally administered sCT is efficacious and well tolerated. Thirty postmenopausal women, who had a bone mineral density at the lumbar spine below the mean of age-matched women, were enrolled in this study. Using an open balanced, randomized design, the patients were allocated to two groups of treatment: sCT suppositories at the dose of 100 UI/day or 200 UI every other day for six months. Treatment with sCT suppositories caused a statistically significant decrease of pain in both study groups. Bone mineral density at lumbar spine showed an increase in both study groups with significant difference respect the basal value for the patients treated with sCT on alternate day. Based on the results of this study, we can thus conclude that sCT in suppository formulation is effective in reducing pain sintomatology, bone loss and turnover in involutional osteoporosis.

Topics: Aged; Analgesics; Calcitonin; Female; Humans; Middle Aged; Osteoporosis, Postmenopausal; Suppositories; Time Factors

188 patients with high-turnover type post-menopausal osteoporosis were treated for 18 months with 4 different treatment regimens of S-calcitonin nasal spray. For a total of 18 months group 1 was given 100 IU/day, continuously; group 2, 100 IU/day daily for 30 days every other month ("ciclically"); group 3, 200 IU/day continuously, and group 4, 200 IU/day, ciclically. To monitor the effects of treatment, MOC of L2-L4, as well as serum osteocalcin and urinary hydroxyproline: creatinine levels were measured, on initiation of therapy, then at 9, 12 and 18 months, and finally at 6 and 12 months after completion of therapy. Analysis of the results yields the following major points: (A) The peak increase in bone mass occurs at 9 months the continuous therapy groups, and at 18 months in the cyclic therapy groups. In absolute values, the peak are higher in the continuous groups than in the cyclic groups. (B) The long-term increase in bone mass (measured at one year after completion of therapy) does not differ significantly between cyclic and continuous treatment groups at the same dosage. (C) During treatment, a dose-effect relationship exist when comparing dosages of 100 IU/day and 200 IU/day. However, this disappears by one year after completion of therapy. (D) There seems to be a "rebound effect" on osseous turnover after cessation of S-calcitonin therapy. The magnitude and rapidity of onset of this effect appear to correlate directly with the dosage of S-calcitonin administered.

Topics: Calcitonin; Drug Administration Schedule; Female; Humans; Middle Aged; Nebulizers and Vaporizers; Osteoporosis, Postmenopausal

A group (150) of healthy women, who had been menopausal for less than 5 years and who had never received any form of treatment to prevent bone loss were entered into a randomized, controlled study comprising three arms. They were randomly allocated to the double-blind administration of five suppositories per week containing either 100 IU of salmon calcitonin or a placebo, or to a group receiving a suppository containing 200 IU of salmon calcitonin three times per week. All women received 500 mg/day of calcium supplementation. After 12 months, bone mineral density (BMD) of the spine, measured by dual energy X-ray absorptiometry, decreased significantly (P < 0.01) in the placebo group by 3.1% (SD: 3.6%) but did not change in the two calcitonin groups [+1.3% (3.5%) with 100 IU/day and +2.3% (4.0%) with 200 IU 3/week]. The differences in response between the placebo group and the two calcitonin groups were significant (P < 0.05), but the difference between the two regimens of calcitonin administration was not. No differences appeared among the three groups for the response at the level of the hip. Evolution of biochemical markers reflecting bone turnover did not differ significantly among groups. Nearly 40% of the women withdrew prematurely because of local (rectal or intestinal) intolerance to repetitive suppositories, with a nonsignificantly different frequency in the placebo or calcitonin groups. We conclude that rectal calcitonin might be an interesting preventive approach against trabecular postmenopausal bone loss but that long-term acceptability of suppositories should be evaluated in view of each patient's sensibility or cultural background.

Topics: Administration, Rectal; Bone Density; Calcitonin; Calcium; Double-Blind Method; Female; Hip; Humans; Middle Aged; Osteoporosis, Postmenopausal; Spine; Time Factors

We study the effectivity and tolerance of synthetic salmon calcitonin nasally administered (Miacalcic) in the treatment of established postmenopausic osteoporosis. During one year, two randomized groups of postmenopausic women diagnosed of osteoporosis were treated in an outpatient service either with 1 gr of calcium element per day during the whole study or with 100 daily I.U. of salmon synthetic calcitonin nasally administered in patterns of 14 days and the same period of rest, plus a supplement of 500 mgr of calcium element per day. Globally, 43 patients were assessed at the end of the study in the calcitonin plus calcium group and 45 in the group receiving only calcium. The main evaluation parameters were pain and presence of new fractures. At the beginning and at the end of the study, complementary tests of blood biochemistry were conducted, including alkalin phosphatase, calcium, phosphorus and uric acid, as well as calcium, hydroxiprolin and creatinini in the urine. The results showed a significant improvement of pain (p < 0.001) in the group treated with calcitonin, supported by a lower consumption of analgesics. The rate of vertebral fractures determined according to the Meunier's index, was also significantly lower (p < 0.001) in the group treated with calcitonin at the end of the study period. These results suggest that, compared to only calcium, nasally administered calcitonin precludes the formation of new vertebral fractures during one year of treatment and it is effective in terms of pain reduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Intranasal; Aged; Analgesics; Calcitonin; Calcium; Female; Humans; Middle Aged; Osteoporosis, Postmenopausal

Nasal administration of salmon calcitonin (SCT) has been suggested for preventing trabecular bone loss during the first years following the menopause, but no conclusive evidence has appeared about the minimal effective dose. Since nasal calcitonin is highly expensive, it makes sense to define this dose.. We performed a double-blind, placebo-controlled, randomized, single-center study with a 3-arm parallel-group design. The subjects were 251 healthy women who had experienced natural menopause within the past 6 to 72 months and were not affected by any diseases or treatments that interfere with calcium metabolism. They were randomly allocated in groups of 6 to receive intranasal SCT 50 IU (n = 84), SCT 200 IU (n = 84), or placebo (n = 83). All treatments were given on 5 consecutive days per week. Statistical analysis was based on two populations: intention-to-treat (IT) and valid completers (VC). The main assessments performed were bone mineral density of the lumbar spine (LSBMD) and biochemical parameters reflecting bone turnover (serum alkaline phosphatase, urinary calcium/creatinine, and hydroxyproline/creatinine ratios).. Changes over the treatment period were comparable in the IT and VC populations. In the group receiving the placebo, LSBMD decreased from baseline to end point by a mean of 6.28% (95% confidence interval [CI] -7.69 to -4.89) in the IT population and 6.98% (95% CI -8.86 to -5.11) in the VC population (P = 0.0001, end LSBMD versus baseline LSBMD). LSBMD increased slightly with the 50-IU/d dose of SCT, by 0.82% (95% CI -0.26 to 1.89) in the IT population, and 0.51% (95% CI -0.69 to 1.72) in the VC (P = NS, versus baseline). Subjects who received SCT 200 IU/d experienced significant increases of 2.03% (95% CI 0.92 to 3.15) in the IT population and 2.26% (95% CI 1.01 to 3.51) in the VC (both P = 0.001). The difference between the evolution of the combined groups receiving nasal SCT and the group treated with the placebo was highly significant (P = 0.0001). No significant changes were recorded in biochemical parameters reflecting bone turnover.. SCT 50 IU/d administered nasally and intermittently appears to prevent lumbar bone loss in nonobese early postmenopausal women.

Topics: Administration, Intranasal; Alkaline Phosphatase; Animals; Bone Density; Bone Remodeling; Calcitonin; Calcium; Creatinine; Double-Blind Method; Female; Humans; Hydroxyproline; Lumbosacral Region; Middle Aged; Osteoporosis, Postmenopausal; Spine

Seventy-two postmenopausal osteoporotic women having more than one nontraumatic vertebral crush fracture were studied. Thirty-six of them, aged 68.8 +/- 1.2 years (18 +/- 4 YSM-years since menopause), were treated with 100 IU/day of salmon calcitonin i.m. plus 500 mg of elemental calcium for 10 days each month. The remaining 36 patients, aged 69.6 +/- 1.4 years (19 +/- 3 YSM), were given only 500 mg of elemental calcium for 10 days each month. All patients underwent clinical and analytical evaluation every 3 months. Radiological evaluation, assessment of vertebral deformities, and metacarpal radiogrammetry were done every 6 months. Densitometric measurements of total and regional bone mass were made every 12 months. At 24 months, the calcitonin group showed a 60% reduction in the number of new fractures and the group receiving only calcium had a 45% increase (P < 0.001). The incidence of vertebral fractures was 0.07 per patient-year in the group treated with calcitonin and 0.45 per patient-year in the group treated with calcium (P < 0.001). At 2 years, the calcitonin group showed a 12% increase in cortical bone mass on metacarpal radiogrammetry, a 16% increase in the axial skeleton on trunk densitometry, a 3.5% increase in total body bone mineral content, a 30.7% increase in pelvic bone mineral content, and a 6.2% increase in arm bone mineral content (all P < 0.001). In the group treated with calcium alone there was a loss of bone mass in every region. These findings suggest that salmon calcitonin is effective in the treatment of osteoporosis and show that it acts on cortical and trabecular bone.

Topics: Absorptiometry, Photon; Aged; Arm; Biomarkers; Bone Density; Calcitonin; Calcium; Chi-Square Distribution; Female; Follow-Up Studies; Humans; Injections, Intramuscular; Metacarpus; Osteoporosis, Postmenopausal; Pelvic Bones; Prospective Studies; Risk Factors; Spinal Fractures; Spine

The main objective of this study was to determine the effect of daily oral alendronate treatment on bone mass in postmenopausal women affected by osteoporosis. The efficacy of intranasal salmon calcitonin was also examined. Nine centers in Italy enrolled 286 postmenopausal women between the ages of 48 and 76 with spinal bone mineral density > or = 2 SD below adult mean peak in the two-year, double-blind, randomized, placebo-controlled trial. Patients were randomized to one of four treatment arms: double-blind placebo, alendronate 10 mg/day, alendronate 20 mg/day, or open-label intranasal salmon calcitonin 100 IU/day; all patients received 500 mg Ca++ supplements. Bone mass was measured by dual-energy x-ray absorptiometry every six months for two years. Patients who received alendronate 10 or 20 mg experienced significant increases in bone mass at all sites measured. At the end of the second year, the mean percent changes, for alendronate 10 and 20 mg relative to placebo, were 5.2% and 7.3% at the lumbar spine, 3.8% and 4.6% at the femoral neck, and 7.1% and 7.5% at the trochanter, respectively. In contrast, intranasal salmon calcitonin failed to increase bone mineral mass significantly at any site. Both alendronate doses significantly decreased serum alkaline phosphatase, serum osteocalcin, and urinary pyridinolines, markers of bone turnover, whereas placebo and intranasal calcitonin did not. Alendronate was generally well tolerated and no serious adverse events were attributed to its use.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Absorptiometry, Photon; Administration, Intranasal; Administration, Oral; Aged; Analysis of Variance; Biomarkers; Bone and Bones; Bone Density; Calcitonin; Calcium, Dietary; Diphosphonates; Double-Blind Method; Female; Femur; Femur Neck; Humans; Italy; Longitudinal Studies; Lumbar Vertebrae; Middle Aged; Osteoporosis, Postmenopausal; Patient Compliance

We reviewed data on 42 postmenopausal women with established osteoporosis (forearm fracture or a low bone mass) who had been randomly treated for 1 year with either rectal salmon calcitonin (sCT), 100 IU daily (n = 25) or nasal sCT, 200 IU daily (n = 17) applying an estimation algorithm for bone loss rates. Both groups received a daily calcium supplement of 500 mg. A group of 18 age-matched women who received no treatment served as controls. The bone mineral content of the distal forearm (BMCarm) was measured every 3 months by single photon absorptiometry. The individual rates of change during the 1-year period were calculated by linear regression analysis (alpha BMCarm). Bone loss rates were estimated initially and after 1 year of therapy by measurements of serum alkaline phosphatase, plasma bone Gla protein, and fasting urinary hydroxyproline and calcium (both corrected for creatinine excretion) according to the estimation algorithm. Both administration forms revealed significant control group-corrected decreases in serum and urine markers of bone turnover of 15-40% (P < 0.05-0.01) and positive outcomes of 2% in alpha BMCarm (P < 0.01). The estimated effect on bone mass was expressed as the difference between the bone loss estimated after 1 year and initially (delta ESTBIO). A significant correlation was seen between alpha BMCarm and delta ESTBIO (r = 0.5, P < 0.0001). We conclude that the effect of sCT on bone can be followed up by biochemical markers for bone turnover, i.e., by an annual blood and fasting urine sample, applying an estimation algorithm for the rate of bone loss.

Topics: Absorptiometry, Photon; Administration, Intranasal; Administration, Rectal; Biomarkers; Bone and Bones; Bone Density; Calcitonin; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Forearm; Humans; Osteoporosis, Postmenopausal; Reproducibility of Results

We examine the dose-related effect of intranasal salmon calcitonin (sCT) on the early postmenopausal bone loss and bone turnover; a 2-year, prospective, randomized, double-blind, placebo-controlled study was carried out with 134 healthy women who had passed a natural menopause within 6 months to 3 years. The women were allocated randomly to 2 years of treatment with either 100, 200, or 400 IU of sCT given intranasally or placebo. All groups received a calcium supplement of 500 mg. Twenty-one women left the study before its end and 91 complied with the study criteria throughout. Bone mineral content/density of the distal forearm and lumbar spine and biochemical parameters of bone turnover were measured. Although the measurements after 24 months revealed no significant difference between groups in bone mineral density of the lumbar spine, the average changes over time revealed prevention of bone loss in the groups treated with 200 and 400 IU of sCT (0.2 to -0.6%) and declines of 0.8-1.7% in the groups treated with 100 IU of sCT and placebo (P < 0.05-0.01; within-group testing). There was no dose-related response to sCT but there was a significant difference between the pooled groups treated with 200 plus 400 IU of sCT versus the 100 IU sCT and placebo-treated groups (P = 0.030-0.005). The same difference between groups was seen for biochemical parameters of bone turnover (P = 0.022-0.003). The biochemical parameters of bone turnover revealed decreases of 10-20% (P < 0.001; within group testing) in the groups treated with the two highest sCT doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Intranasal; Alkaline Phosphatase; Bone Density; Calcitonin; Calcium, Dietary; Double-Blind Method; Drug Tolerance; Estrogen Replacement Therapy; Female; Forearm; Humans; Lumbar Vertebrae; Middle Aged; Osteocalcin; Osteoporosis, Postmenopausal; Prospective Studies

The aim of this paper was to evaluate the long-term (5 years) efficacy of nasal salmon calcitonin in prevention of trabecular postmenopausal bone loss, which was a follow-up of a previously published study (3 years); a randomized, controlled group comparison. One hundred healthy postmenopausal women were randomly chosen from those (186) having completed the 3 year protocol. The 100 women were allocated to an additional 2 year period (total of 5 years) of treatment with either 500 mg d-1, 5 days week-1 of calcium or the same amount of calcium plus 50 IU d-1, 5 days per week of nasal salmon calcitonin, 87 (87%) women complied with the protocol throughout. The main outcome measures were the bone mineral density of the lumbar spine (1-BMD) (DPA) and biochemical parameters reflecting bone turnover (serum alkaline phosphatases, urinary calcium/creatinine and hydroxyproline/creatinine ratios). The women receiving calcium alone presented a significant decrease in 1-BMD after 6 months [-1.6 (0.5)%] [mean(SEM)] (P < 0.01) and this decrease remained significant after 36 months [-6.1(0.8)%] (P < 0.01) and until the end of the trial [-6.6(1.0)% at t60] (P < 0.01). In women receiving calcium and calcitonin, 1-BMD significantly increased after 36 months [+2(0.7%] (P < 0.01) and 42 months [+2.5(0.7)%] (P < 0.01 and was unchanged at the other times of investigation [+1.1 (1.1)% at t60] (NS). The evolution of BMD in the two groups was highly significantly different (P < 0.001) since the sixth month of the study and remained so until the end of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Absorptiometry, Photon; Alkaline Phosphatase; Bone Density; Calcitonin; Calcium; Calcium, Dietary; Creatinine; Female; Humans; Hydroxyproline; Lumbar Vertebrae; Osteoporosis, Postmenopausal

The objective of this study was to test the efficacy and safety of salmon calcitonin (sCT) suppository in post-menopausal women with previous hip fractures as an inhibitory agent of bone loss. The study was a single blind, randomized, and placebo-controlled trial comparing three parallel groups of patients. Fifty-four healthy women were randomly allocated to 1 year's treatment with either sCT 100 IU/6 times a week, 200 IU/3 times a week, or placebo/6 times a week. All groups received a calcium supplement of 500 mg daily. Fifteen patients left the study before its end, six of those due to adverse events, such as abdominal and rectal pain, nausea, headache, and diarrhea. Bone mineral density of the spine and the femoral neck was measured every 26 weeks, and biochemical markers of bone turnover were measured at baseline and week 12, 26, and 52. There were no significant changes in bone mineral density in the spine and in the hip in any of the treatment groups. No significant changes were observed in serum alkaline phosphatase, serum osteocalcin, urine hydroxyproline, and urine pyridinoline or deoxypyridinoline. Conclusively, we did not observe any significant effect on bone metabolism in women with postmenopausal osteoporosis after 1 year of treatment with sCT suppositories at the doses used.

Topics: Aged; Bone and Bones; Bone Density; Calcitonin; Female; Hip Fractures; Humans; Middle Aged; Osteoporosis, Postmenopausal; Suppositories

The long-term effect of intermittent low-dose nasal salmon calcitonin on trabecular early postmenopausal bone loss was assessed as follow-up to a previously published study. Randomized controlled group comparison was made of 287 healthy women with 6-36 months of natural menopause and no treatment interfering with calcium metabolism at an outpatient clinic for research in bone and cartilage metabolism. The 287 women were randomly allocated to 3 years of treatment with either 500 mg/day, 5 days/week of calcium or the same amount of calcium plus 50 IU/day, 5 days per week of nasal salmon calcitonin. A total of 186 women complied with the study protocol throughout. The main outcome measures were bone mineral density of the lumbar spine (DPA) and biochemical parameters reflecting bone turnover (serum alkaline phosphatases, urinary calcium/creatinine, and hydroxyproline/creatinine ratio). The average changes in bone mineral density after 36 months showed a positive (p < 0.05) outcome (1.8 +/- 5.7%; mean +/- SD) in the group treated with salmon calcitonin and calcium and a significant (p < 0.01) loss (-5.8 +/- 4.8%) in patients receiving calcium alone. The difference between the evolution of the two groups was significantly (p < 0.01) different after 6 months of treatment and remained so until the end of the study. No significant changes were recorded in biochemical parameters reflecting bone turnover. As previously shown during a 1 year follow-up, nasal salmon calcitonin given at low dose and intermittently, in association with calcium, can counteract trabecular postmenopausal bone loss.

Topics: Administration, Intranasal; Bone Density; Calcitonin; Calcium; Drug Synergism; Female; Follow-Up Studies; Humans; Lumbar Vertebrae; Osteoporosis, Postmenopausal

Thirty early postmenopausal women having risk factors for osteoporosis entered and 23 completed a six months double-blind placebo controlled study of the effect of nasal salmon calcitonin (SCT) (100 IU daily) plus oral calcium on bone turnover, cortical bone mass and sex-steroids. After the double-blind study SCT treatment was continued for six months in 20 women in both groups. A six months nasal SCT treatment was found to be effective in significantly increasing cortical bone mass and the gain was maintained following a 12 months treatment. The nasal SCT treatment was effective in significantly reducing parameters of bone turnover, as indicated by osteocalcin pBGP and urinary hydroxyproline levels, while during placebo administration an increasing trend of pBGP suggested a state of increasing bone remodeling. During the study, a small decrease in plasma testosterone not related to cortical bone mass and bone turnover was observed.

Topics: Absorptiometry, Photon; Administration, Intranasal; Administration, Oral; Alkaline Phosphatase; Biomarkers; Bone Resorption; Calcitonin; Calcium; Double-Blind Method; Female; Gonadal Steroid Hormones; Humans; Hydroxyproline; Middle Aged; Osteocalcin; Osteoporosis, Postmenopausal; Risk Factors; Sex Hormone-Binding Globulin

Alendronate sodium (ALN) is a potent amino bisphosphonate which specifically inhibits osteoclastic bone resorption and has been found to reverse bone loss in several animal models. To determine if daily oral ALN treatment could prevent or reverse bone loss in osteoporotic postmenopausal women, and to compare ALN to intranasal salmon calcitonin (CT), a 2-year, double-masked, randomized, placebo-controlled study was initiated at 9 clinical centers in Italy. Two hundred and eighty six postmenopausal women (age 48-76) with spinal bone mineral density (BMD) > or = 2 SD below adult mean peak, with or without vertebral crush fractures, were randomized to one of four treatment arms: ALN 10 mg daily, ALN 20 mg daily or matching placebo (these groups all double-masked), or CT 100 IU daily (open label) for 2 years. All patients received supplemental calcium (as carbonate) 500 mg daily. Bone mass was measured by dual-energy X-ray absorptiometry of the PA lumbar spine (LS) and proximal femur (femoral neck and trochanter) at 6-month intervals. Subject safety was measured through sequential clinical and laboratory evaluation. A planned 1-year interim analysis of this ongoing study was performed centrally in a manner that maintains the double-mask for all subjects receiving oral study drug. Relative to PBO, ALN at either 10 mg or 20 mg daily increased LS BMD by 4.7% and 6.1%, respectively; each increased femoral neck BMD by 3.1% and increased trochanter BMD by 3.3% and 3.8% respectively. In contrast, CT failed to significantly increase BMD of either the spine, femoral neck or trochanter, either relative to baseline or to PBO.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Intranasal; Administration, Oral; Aged; Alendronate; Alkaline Phosphatase; Bone Density; Calcitonin; Diphosphonates; Double-Blind Method; Female; Humans; Middle Aged; Osteoporosis, Postmenopausal

The objective was to study the dose-related response of intranasal salmon calcitonin (Salcatonin) on bone mass and bone turnover and the effect of salcatonin on rates of fracture in elderly women with moderate osteoporosis. A total of 208 healthy women aged 68-72 years, who had a bone mineral content (BMC) of the distal forearm 30% below the mean value for healthy premenopausal women, were examined in a double-blind, placebo-controlled, randomized group comparison study. They were randomized to a two-year daily treatment of either 50 IU, 100 IU, 200 IU Salcatonin or placebo. All received 500 mg calcium daily. In the calcium-(placebo)-treated group the BMC of the spine increased 1%, whereas an increase of 3% was seen in the 200 IU Salcatonin treated group. There was a dose-related response to Salcatonin manifested by an increase in BMC of 1.0%/100 IU. The incidence of new fractures was significantly lower in the women treated with Salcatonin (about one third of that in the non-Salcatonin treated women). In conclusion the results suggest that, compared with calcium alone, Salcatonin given intranasally reduces the rate of fracture by two thirds in elderly women with moderate osteoporosis. Furthermore, it increases spinal bone mass in a dose dependent manner.

Topics: Administration, Intranasal; Aged; Analgesics; Bone Density; Calcitonin; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fractures, Spontaneous; Humans; Osteoporosis, Postmenopausal

The amino acid sequence of salmon calcitonin (SCT) differs considerably from that of the human hormone and specific antibodies (Ab) develop in a significant proportion of patients after parenteral or nasal administration of SCT. Controversy remains regarding the functional importance of these Ab. We report on the development of specific anti-SCT Ab in a population of postmenopausal women receiving nasal SCT for prevention of postmenopausal bone loss, and compare the effects of nasal SCT in women with or without Ab. Thirty-nine per cent of women developed Ab after 6 months of treatment with SCT, 52% after 12 months, and 61% after 18 and 24 months. After 24 months the AB titre was 3.47-17.7 x 10(-9) M/l (mean +/- SD: 13.3 +/- 3.1 x 10(-9) M/l). No significant differences appeared between the changes in lumbar bone mineral density (BMD) measured in the whole population (n = 44) (mean +/- SD: +1.06 +/- 3.9%), the patients without Ab (n = 17) (+0.05 +/- 3.7%) or in those with Ab (n = 27) (+1.7 +/- 4.6%). During the same period, a control population randomly assigned to a 500 mg/day calcium intake showed a significant loss of lumbar BMD (-4.57 +/- 4.9%) (p < 0.01). In conclusion, in healthy postmenopausal women nasal SCT seems to maintain the same preventive effect against bone loss whether or not Ab are present.

Topics: Administration, Intranasal; Antibodies; Bone Density; Calcitonin; Female; Humans; Osteoporosis, Postmenopausal; Postmenopause; Time Factors

Topics: Administration, Intranasal; Adult; Aerosols; Bone and Bones; Bone Density; Calcitonin; Female; Humans; Hydroxyproline; Middle Aged; Osteocalcin; Osteoporosis, Postmenopausal; Time Factors

To study the dose related response of salmon calcitonin (salcatonin) given intranasally on bone mass and bone turnover and the effect of salcatonin on rates of fracture in elderly women with moderate osteoporosis.. Double blind, placebo controlled, randomised group comparison.. Outpatient clinic for research into osteoporosis.. 208 healthy women aged 68-72 years who had a bone mineral content of the distal forearm on average 30% below the mean value for healthy premenopausal women.. The 208 women were allocated randomly in blocks of four to two years of treatment with either salcatonin 50 IU, 100 IU, or 200 IU given intranasally or placebo. All groups received a calcium supplement of 500 mg. 32 of the women left the study before its end and 164 women complied with the study criteria throughout.. Bone mineral content of the distal forearm and lumbar spine and rates of vertebral and peripheral fractures after two years of treatment.. The average changes in bone mineral content of the spine showed positive outcomes of 1% (95% confidence interval -0.1% to 1.5%) in the group treated with calcium (placebo) and 3% (1.8% to 4.2%) in the group treated with salcatonin 200 IU. There was a significant dose related response to salcatonin, manifested by an increase of 1.0%/100 IU (0.2% to 1.7%, p = 0.008). The rate of patients with new fractures was reduced significantly in the women treated with salcatonin to about one third of that in the non-salcatonin treated women (relative risk 0.23 (0.07 to 0.77)).. The results suggest that, compared with calcium alone, salcatonin given intranasally reduces the rates of fracture by two thirds in elderly women with moderate osteoporosis. Furthermore, it increases spinal bone mass in a dose dependent manner.

Topics: Administration, Intranasal; Aged; Bone and Bones; Bone Density; Calcitonin; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fractures, Bone; Humans; Osteoporosis, Postmenopausal; Prospective Studies; Spinal Fractures; Treatment Outcome

In order to devise a convenient and effective therapeutic regimen of intranasal salmon calcitonin (sCT) for the treatment of early postmenopausal bone loss, we studied the effects of a 1-year course of sCT nasal spray on vertebral mineral content (VMC), assessed by dual photon densitometry, and bone turnover in 21 early postmenopausal osteoporotic women. Subjects enrolled in the study had a value above the normal average of at least one index of bone turnover: whole body retention (WBR) of 99mTc-methylene-dichloro-bisphosphonate (99mTc-MDP), serum bone gla protein (BGP), urinary hydroxyproline/creatinine excretion (HOP/Cr). After baseline evaluation, patients were randomized for treatment with either sCT (200 IU every other day) or placebo. Treatment with sCT significantly increased VMC by 2.7 +/- 0.9% at 6 months, and 3.3 +/- 0.8% at 1 year, whereas a progressive decline was observed in the placebo group (-2.6 +/- 0.5%, and -3.5 +/- 0.5% after 6 and 12 months, respectively). These changes were associated with a progressive and significant reduction of all parameters of bone turnover in the sCT-treated patients, whereas no changes were detected in the control group during the study period. The differences between the two groups were significant after 1 year for VMC, BGP, and WBR (P less than 0.05, one-way analysis of variance). Thus, 200 IU intranasal sCT administered on alternate days is adequate to stop the fast bone loss occurring early after the menopause in women with high bone turnover rates. This therapeutical modality represents an important addition to the available pharmacologic spectrum for the prevention and treatment of postmenopausal osteoporosis.

Topics: Administration, Intranasal; Bone Density; Calcitonin; Drug Administration Schedule; Female; Humans; Middle Aged; Osteoporosis, Postmenopausal; Spine

The effectiveness of calcitonin on the vertebral fracture rate in postmenopausal osteoporosis was assessed through the skeletal deformity index (SDI) and the new vertebral fracture rate per 100 patient-years in a group of 32 women with postmenopausal osteoporosis treated by us with 100 IU of salmon calcitonin and 500 mg of elemental calcium for 10 consecutive days each month, and in another group of 28 women with postmenopausal osteoporosis treated with 500 mg of elemental calcium only for 10 consecutive days each month. Both groups were age-matched. The follow-up was a retrospective randomized study over 24 months. Thirty of the 32 women of the calcitonin group and 27 of 28 women of the calcium group finished treatment. The SDI was stabilized after six months in the calcitonin group (0.57 +/- 0.13, 0.62 +/- 0.18, 0.63 +/- 0.16 and 0.64 +/- 0.17, at base line, 6, 12 and 24 months respectively). The calcium group showed a significant increase only at 12 months (P less than 0.01) and 24 months (P less than 0.05) (0.61 +/- 0.16, 0.63 +/- 0.16, 0.69 +/- 0.16, and 0.73 +/- 0.15, at base line, 6, 12 and 24 months respectively). At 24 months, the new vertebral fracture rate decreased by 60% (20%, 14% and 8% at 6, 12 and 24 months respectively) in the calcitonin group and increased by 35% (31%, 33% and 42%, at 6, 12 and 24 months respectively) in the calcium group (P less than 0.025). These results show that calcitonin induced a significant reduction in postmenopausal osteoporotic vertebral fractures.

Topics: Aged; Calcitonin; Female; Follow-Up Studies; Humans; Osteoporosis, Postmenopausal; Retrospective Studies; Spinal Fractures; Syndrome

Sixty postmenopausal women were randomly assigned to three types of treatment with intranasal salmon calcitonin (SCT) plus calcium 500 mg daily (group A: 100 IU daily of SCT; group B: 100 IU daily of SCT for alternate cycles of 2 months with a 1-month interval; group C: 100 IU daily of SCT for alternate cycles of 3 months of treatment followed by a 3-month interval) or calcium 500 mg daily alone (control group). Lumbar density significantly decreased in the control group while it maintained the initial value in both continuously or cyclically treated groups. The bone density of the proximal and distal forearm in treated and control groups did not show significant changes after 12 months.

Topics: Administration, Intranasal; Bone Density; Calcitonin; Calcium; Drug Therapy, Combination; Female; Humans; Lumbar Vertebrae; Middle Aged; Osteoporosis, Postmenopausal; Time Factors

Back pain due to vertebral collapse is the main symptom of postmenopausal osteoporosis. The clinical picture in these crush fractures varies, depending on the type and the location of fracture, but in general, a new vertebral crush fracture gives rise to severe pain that immobilizes the patient and necessitates bedrest. In this double-blind controlled clinical trial, 56 patients who had recently (within the last 3 days) suffered an osteoporotic vertebral fracture were hospitalized for a period of 14 days. Salmon calcitonin (100 IU) or placebo injections were given daily. Pain was rated daily on a 10-point scale by the same observers. Blood and urinary parameters were also evaluated. The results showed a significant (P less than 0.001) difference in pain intensity between the calcitonin group and the placebo group. This beneficial effect was generally apparent from the second day of treatment onward, and over the following 2 weeks, the patients were able to sit and stand, and gradually started to walk again. A significant decrease in urinary hydroxyproline and urinary calcium was also noted in the calcitonin group. It is concluded that calcitonin exerts a beneficial effect on back pain following a vertebral crush fracture.

Topics: Aged; Analgesics; Calcitonin; Calcium; Double-Blind Method; Female; Humans; Hydroxyproline; Osteoporosis, Postmenopausal; Pain; Spinal Fractures

Forty postmenopausal women with a former Colles' fracture were enrolled in a 1-year study to determine the dose-effect relationship of nasal salmon calcitonin (SCT) on bone mass. They were randomized to receive either placebo, 50, 100, or 200 IU per day of SCT given as a nasal spray. The rate of change in the bone mineral content of the lumbar spine was 0.7, 0.2, 1.1, and 2.0 gHA per year, respectively, and the rate of change in the bone mineral content in the forearm was -0.4, -0.1, 0.0, and -0.1 AU per year, respectively. The rate of change in the bone mineral content of the lumbar spine in patients receiving 200 IU of SCT per day differed significantly from zero (P less than 0.01). Except for one patient, who experienced intolerable nausea, no systemic side effects were observed. Seven patients withdrew, two patients from nasal intolerance to the spray. These preliminary data suggest that SCT given by the nasal route has a positive and dose-dependent effect on spinal bone mass, but affects forearm bone mass only minimally.

Topics: Administration, Intranasal; Aged; Bone Density; Calcitonin; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Middle Aged; Osteoporosis, Postmenopausal

To study the effect of salmon calcitonin (salcatonin) given intranasally on calcium and bone metabolism in early postmenopausal women.. Double blind, placebo controlled, randomised group comparison.. Outpatient clinic for research into osteoporosis.. 52 Healthy women who had had a natural menopause two and a half to five years previously.. The 52 women were allocated randomly to two years of treatment with either salcatonin 100IU given intranasally (n = 26) or placebo (n = 26). Both groups received a calcium supplement of 500 mg daily. Seven of the women receiving salcatonin and six of those receiving placebo left the study before its end.. Bone mineral content in the spine, the total skeleton, and the forearms after two years of treatment.. Bone mineral content in the spine was significantly higher in the women who had received salcatonin than in those who had received placebo both after one year and after two years of treatment. After one year the difference was 3.8% (95% confidence interval 0.0 to 7.6%) and after two years it was 8.2% (3.8 to 12.6%). In contrast, the bone mineral content in the distal and proximal forearms and in the total skeleton declined similarly in both groups by about 2% each year, and after two years of treatment the differences between the groups were not significant. Biochemical estimates of bone turnover were not affected by salcatonin.. The results suggest that salcatonin given intranasally in the dose used prevents bone loss in the spine of early post menopausal women but does not affect the peripheral skeleton.

Topics: Administration, Intranasal; Bone and Bones; Calcitonin; Double-Blind Method; Female; Humans; Middle Aged; Minerals; Osteoporosis, Postmenopausal; Randomized Controlled Trials as Topic; Spine

Eleven women with primary osteoporosis (mean age, 63.1 years; range, 57-78) received in a random schema: placebo, 200 and 400 IU of salmon calcitonin nasal spray (sCT-NS) during 3 successive days. Total and ionized calcium and phosphate in serum were determined before and 5 h after calcitonin. Total hydroxyproline (THP) and creatinine excretion were measured in urine in three periods of 8 h each after calcitonin administration. The THP excretion after placebo administration showed a circadian rhythm with peak excretion during the night. This rhythm was not altered by sCT-NS administration at 8 a.m. but a sustained diminution of the THP/creatinine excretion was observed. The average decrease after 400 IU of sCT-NS was 9, 16 and 6% during the first, second and third periods of urine collection. Although the average effect of the 200 and 400 IU doses was similar, only the diminution induced by the latter dose on the 24-h period was statistically significant: placebo, 24.8 +/- 2.9; 200 IU, 20.8 +/- 2.9 (P n.s.); 400 IU, 20.1 +/- 2.2 mg/24 h (P less than 0.01). No significant changes were observed on serum except a fall provoked by the 400 IU dose upon ionized calcium (4.44 +/- 0.08 to 4.37 +/- 0.06 mg/dl; P less than 0.05). The administration of 200 or 400 IU of sCT-NS provoked a sustained but moderate decrease of bone resorption on osteoporotic females of a lesser degree than the one observed in a previous study after the parenteral administration of 100 IU.

Topics: Administration, Intranasal; Aged; Calcitonin; Calcium; Creatinine; Female; Humans; Hydroxyproline; Middle Aged; Osteoporosis, Postmenopausal; Phosphates; Random Allocation

Thirty-seven women with established osteoporosis completed a one-year double-blind, placebo-controlled study with the primary aim of examining the effect of nasal salmon calcitonin (200 IU daily) on bone and calcium metabolism. All the women received a daily calcium supplement of 500 mg. For comparison we also report data from an age-matched group of healthy women who did not receive calcium supplementation. The bone mineral measured in the forearm (single photon absorptiometry) and spine (dual photon absorptiometry) showed a similar pattern during treatment. The calcitonin group (n = 17) did not lose bone mineral in comparison with the placebo (n = 20) and the control groups (n = 19) (P less than 0.01). The biochemical estimates of both bone resorption and bone formation decreased highly significantly in the calcitonin group (P less than 0.001) and were unchanged in the control group, whereas the placebo (calcium) group showed intermediate values. Neither subjective nor objective side-effects occurred in any of the groups. We conclude that nasal calcitonin is a realistic treatment of established osteoporosis.

Topics: Administration, Intranasal; Aged; Bone and Bones; Bone Density; Calcitonin; Calcium; Double-Blind Method; Female; Humans; Middle Aged; Osteoporosis, Postmenopausal; Randomized Controlled Trials as Topic

The aim of this project was to perform an empirical evaluation of the impact of on site source data verification (SDV) on the data quality in a clinical trial database to guide an informed decision on selection of the monitoring approach.. We used data from three randomized phase III trials monitored with a combination of complete SDV or partial SDV. After database lock, individual subject data were extracted from the clinical database and subjected to post hoc complete SDV. Error rates were calculated with focus on the degree of on study monitoring and relevance and analyzed for potential impact on end points.. Data from a total of 2566 subjects including more than 3 million data fields were 100% source data verified post hoc. An overall error rate of 0.45% was found. No sites had 0% errors. 100% SDV yielded an error rate of 0.27% as compared with partial SDV having an error rate of 0.53% (P < 0.0001). Comparing partly and fully monitored subjects, minor differences were identified between variables of major importance to efficacy or safety.. The findings challenge the notion that a 0% error rate is obtainable with on site monitoring. Data indicate consistently low error rates across the three trials analyzed. The use of complete vs. partial SDV offers a marginal absolute error rate reduction of 0.26%, i.e. a need to perform complete SDV of about 370 data points to avoid one unspecified error and does not support complete SDV as a means of providing meaningful improvements in data accuracy.

Topics: Calcitonin; Clinical Trials, Phase III as Topic; Data Accuracy; Databases, Factual; Electronic Health Records; Female; Forms and Records Control; Humans; Osteoarthritis, Knee; Osteoporosis, Postmenopausal; Randomized Controlled Trials as Topic

Synthetic analogues of the peptide hormone calcitonin have been used in medicine as biologic drug therapies for decades, to treat pathological conditions of excessive bone turnover, such as osteoporosis, where more bones are removed than replaced during bone remodeling. Osteoporosis and other chronic skeletal diseases, including inflammatory arthritis, exact a substantial and growing toll on aging populations worldwide however they respond poor to synthetic biologic drug therapy, due in part to the rapid half-life of elimination, which for calcitonin is 43 minutes. To address those shortcomings, we have developed and synthesized bone-targeting variants of calcitonin as a targeted drug delivery strategy, by conjugation to bisphosphonate drug bone-seeking functional groups in highly specific reaction conditions. To evaluate their in vivo efficacy, bisphosphonate-mediated bone targeting with PEGylated (polyethylene glycol conjugated) and non-PEGylated salmon calcitonin analogues were synthesized and dose escalation was performed in female rats developing Osteoporosis. The bone-targeting calcitonin analogues were also tested in a separate cohort of male rats developing adjuvant-induced arthritis. Ovariectomized female rats developing Osteoporosis were administered daily sub-cutaneous injection of analogues equivalent to 5, 10 and 20 IU/kg of calcitonin for 3 months. Adjuvant arthritis was developed in male rats by administering Mycobacterium butyricum through tail base injection. Daily sub-cutaneous injection of analogues equivalent to 20 IU/kg of calcitonin was administered and the rats were measured for visible signs of inflammation to a 21 day endpoint. In both studies, the effect of drug intervention upon bone volume and bone mineral density (BMD) was assessed by measuring the trabecular bone volume percentage and BMD at the proximal tibial metaphysis using in vivo micro-computed tomography. With dose escalation studies, only bone targeting analogue dosed groups showed a trend towards increased BMD and bone volume at 4, 8 and 12 weeks. Significant preservation of bone volume and BMD as evidenced by nonsignificant (P<0.05) loss of bone volume and BMD at the end of 3 month study endpoint was seen in animals dosed with 20 IU/kg of calcitonin compounds. Similarly, in case of adjuvant-induced arthritis rats, there was a significant increase (P<0.05) in bone volume and BMD in calcitonin-bisphosphonate and calcitonin-PEG-bisphosphonate treated groups at 21 days

Topics: Animals; Ankle Joint; Arthritis, Experimental; Bone Density; Bone Density Conservation Agents; Bone Remodeling; Calcitonin; Chemistry, Pharmaceutical; Diphosphonates; Drug Carriers; Female; Humans; Injections, Subcutaneous; Male; Mycobacterium; Osteoporosis, Postmenopausal; Ovariectomy; Polyethylene Glycols; Rats, Sprague-Dawley; Technology, Pharmaceutical; Tibia; Time Factors; X-Ray Microtomography

Topics: Bone Density Conservation Agents; Calcitonin; Contraindications; Drug Approval; Female; Humans; Male; Neoplasms; Osteoporosis, Postmenopausal

Topics: Administration, Inhalation; Animals; Calcitonin; Female; Humans; Neoplasms; Osteoporosis, Postmenopausal

The aim of this study was to assess clinical efficacy of intranasal salmon calcitonin (Miacalcic, Novartis pharma) treatment in women with established postmenopausal osteoporosis. 30 women of the main group with established postmenopausal osteoporosis(T-score < -2,5) were treated with intranasal salmon calcitonin: 200 IU daily for 2 months with subsequent pause of 2 months (3 cycles), 12 months in total. Age matched control group was formed by 25 postmenopausal women with similar clinical status. SOS (speed of sound) of cortical bone was measured in the middle of the tibia by ultrasound densitometer--Sound Scan Compact (Myriad-Israel). Patients of both groups received 500 mg Ca and 200 IU vit.D3 (CaD3 Nycomed) two times daily in the same regimen (two months treatment--two months pause). Our results showed that intranasal treatment with 200 IU daily effectively influence the back pain, reduces bone turnover and significantly increases cortical BMD. Significant changes were not observed in patients of the control group, who received only CaD3 Nycomed, that showed that Calcium and vitamin D supplementation is more effective for prevention of bone lose in postmenopausal women, rather for treatment of established osteoporosis.

Topics: Administration, Intranasal; Adult; Aged; Analgesics; Bone Density; Calcitonin; Calcium; Densitometry; Female; Follow-Up Studies; Humans; Middle Aged; Osteoporosis, Postmenopausal; Phosphorus; Treatment Outcome

The unique noninvasive MRI technique was used to assess trabecular microarchitecture at multiple skeletal sites in 91 postmenopausal osteoporotic women receiving nasal spray salmon calcitonin (CT-NS) or placebo over 2 years. In the distal radius and lower trochanter of the hip, individuals treated with CT-NS exhibited significant preservation of trabecular bone microarchitecture compared with placebo, where significant deterioration was shown. MRI analyses of os calcis or microCT/histomorphometric analyses of bone biopsies did not reveal consistent differences in architecture between CT-NS and placebo.. It is postulated that the reduction in osteoporotic fracture risk in response to certain antiresorptive osteoporosis therapies is caused less by effects on bone quantity than on bone quality (specifically trabecular microarchitecture). To test this hypothesis, the QUEST study was conducted to assess the effects of nasal spray salmon calcitonin (CT-NS) or placebo on parameters of trabecular microarchitecture at multiple skeletal sites using noninvasive MRI technology and iliac crest bone biopsies by microCT/histomorphometry.. Ninety-one postmenopausal osteoporotic women were followed for 2 years (n = 46 for CT-NS, n = 45 for placebo); all women received 500 mg calcium daily. MRI measurements at distal radius, hip (T2 relaxation time [T2*]), and os calcis (obtained yearly), iliac crest bone biopsies with 2D histomorphometry and 3D microCT (obtained at study onset and conclusion), DXA-BMD at spine/hip/wrist/os calcis (obtained yearly), and markers of bone turnover (obtained at 2-week to 12-month intervals) were analyzed, with an analysis of covariance model used to assess treatment effect for parameters of interest.. MRI assessment of trabecular microarchitecture at individual regions of the distal radius revealed significant improvement, or preservation (no significant loss), in the CT-NS-treated group compared with significant deterioration in the placebo control group, as reflected in apparent BV/TV (p < 0.03), apparent trabecular number (p < 0.01), and apparent trabecular spacing (p < 0.01). Also, at the hip, the CT-NS group exhibited preservation of trabecular microarchitecture at the lower trochanter (p < 0.05) as determined by T2* MRI technology. Significant deterioration of trabecular bone architecture was noted in the placebo group at the femoral neck, Ward's triangle, and lower trochanteric sites. Apart from a significant increase in apparent trabecular number in the CT-NS group, significant changes within or between groups were not noted at the os calcis. Combined microCT/histomorphometric analysis of iliac crest bone biopsies did not reveal significant differences between treated and placebo groups. In the CT-NS group, regardless of the change in BMD (gain or loss) at the spine, hip, or distal radius, preservation of parameters of trabecular microarchitecture was noted, whereas in the placebo group, regardless of the change in BMD (gain or loss) at the spine, hip, or distal radius, loss or preservation was noted; however, changes in DXA/BMD (of the spine, hip, wrist, os calcis) between CT-NS and placebo groups were not significant. Serum C-telopeptide (S-CTx), a specific bone resorption marker, was reduced by 22.5% at 24 months (p = 0.056). The results of the QUEST study suggest therapeutic benefit of CT-NS compared with placebo in maintaining trabecular microarchitecture at multiple skeletal sites and support the use of MRI technology for assessment of trabecular microarchitecture in clinical research trials. However, the results also highlight site specific differences in response to antiresorptive therapies and the importance of sufficiently large sampling volumes (areas) to obtain reliable assessment of bone architecture.

Topics: Aged; Analgesics; Animals; Biopsy; Bone and Bones; Bone Density; Bone Resorption; Calcitonin; Double-Blind Method; Female; Fracture Healing; Hip; Humans; Lumbar Vertebrae; Magnetic Resonance Imaging; Models, Statistical; Osteoporosis; Osteoporosis, Postmenopausal; Placebos; Postmenopause; Risk; Salmon; Time Factors; Tomography, X-Ray Computed; Treatment Outcome

Topics: Alendronate; Bone and Bones; Bone Density; Bone Density Conservation Agents; Calcitonin; Dietary Supplements; Female; Fractures, Bone; Hip Fractures; Humans; Male; Osteoporosis; Osteoporosis, Postmenopausal; Spinal Fractures; Teriparatide; Vitamin D; Vitamin D Deficiency

Topics: Administration, Intranasal; Adult; Aged; Bone Density; Bulgaria; Calcitonin; Female; Humans; Middle Aged; Osteoporosis, Postmenopausal; Treatment Outcome

Monitoring treatments of osteoporosis is required to identify patients not responding to the treatment in a way that reflects mechanism of action of the antiresorption drug on bone. Neither bone mineral measurement nor the available biochemical markers of bone remodeling can be used to monitor efficacy of treatment with nasal spray salmon calcitonin (sCT) since the changes in individual patients are modest and do not exceed the least significant change.. The novel calcitonin load test (CLT) was developed to assess the biological response to sCT in postmenopausal osteoporotic women. The CLT is based on the time course and an extent of suppression of serum C-terminal telopeptide of types I collagen (CTX) after the intranasal and subcutaneous administration of sCT. The CLT was conducted in 30 untreated postmenopausal osteoporotic women (control group, mean age, 67.7+/-8.4 years), and in 120 postmenopausal osteoporotic women (mean age, 68.5+/-8.1 years) treated with 200 IU of sCT (Miacalcic Nasal, Novartis, Switzerland), for up to 8.4 years (mean, 3.5+/-2.1 years).. After 90 min from the intranasal administration of 400 IU of sCT, a decrease (p<0.01) in serum CTX by 58+/-11% was found in the control group, and by 60+/-11% in 74% of the treated patients. In the remaining treated patients, the decrease in CTX did not exceed the least significant change. The number of patients not responding to the CLT increased with duration of the treatment up to 34% in patients treated for over 4 years. Of the non-responders to the nasal spray sCT, 63% failed to respond to the subcutaneous administration of 10 IU of sCT. In the treated group, a significant negative correlation has been found between the percentual changes in CTX from its baseline levels detected during the CLT, and a rate of changes in the femoral neck BMD (p<0.01).. The CLT can be used as a tool to identify patients that respond to administration of CT, and will profit from a continued treatment with sCT.

Topics: Administration, Cutaneous; Administration, Intranasal; Aged; Aged, 80 and over; Biomarkers; Bone Density; Calcitonin; Collagen Type I; Female; Humans; Middle Aged; Osteoporosis, Postmenopausal; Peptide Fragments; Radioimmunoassay; Regression Analysis; Time Factors

Topics: Bone Density; Calcitonin; Female; Fractures, Bone; Humans; Middle Aged; Osteoporosis, Postmenopausal

Topics: Aged; Aged, 80 and over; Alendronate; Calcitonin; Dosage Forms; Drug Interactions; Female; Femur; Humans; Lumbar Vertebrae; Middle Aged; Osteoporosis, Postmenopausal; Raloxifene Hydrochloride; Randomized Controlled Trials as Topic; Selective Estrogen Receptor Modulators

The study was designed to compare the skeletal effects of intermittent and continuous administration of calcitonin (CT) in ovariectomized (OVX) rats. Female rats were sham operated or OVX at 3 months of age and treated for 6 weeks with vehicle or salmon CT. Sham-operated control rats were injected subcutaneously with vehicle on alternate days. One group of OVX rats was treated with vehicle intermittently by subcutaneous injection or continuously via Alzet osmotic minipumps. The remaining OVX rats were treated with CT by either subcutaneous injections (16 U/kg) on alternate days or by continuous infusion via minipumps at a daily dose of 8 U/kg. OVX rats treated with CT continuously were mildly hypocalcemic compared with all other groups. The proximal tibial metaphyses of vehicle-treated OVX rats were osteopenic with a cancellous bone volume at only 28% of the vehicle-treated control level. This bone loss was associated with increased indices of bone turnover such as osteoclast surface, osteoblast surface, and bone formation rate. Cancellous bone volume in OVX rats treated with CT either intermittently or continuously was significantly higher than that of vehicle-treated OVX rats, but lower than that of vehicle-treated control rats. Treatment of OVX rats with intermittent or continuous CT significantly decreased all indices of bone turnover compared with vehicle-treated OVX rats. However, osteoclast and osteoblast surfaces of OVX rats treated with CT continuously were still significantly higher than those of vehicle-treated control rats. These results indicate that intermittent and continuous administration of CT had similar skeletal effects in OVX rats. Both treatment regimens depressed bone turnover and partially prevented cancellous bone loss in the estrogen-deplete skeleton.

Topics: Analysis of Variance; Animals; Bone Density; Bone Development; Bone Diseases, Metabolic; Calcitonin; Calcium; Disease Models, Animal; Female; Humans; Infusion Pumps, Implantable; Injections, Subcutaneous; Osteoclasts; Osteoporosis, Postmenopausal; Ovariectomy; Random Allocation; Rats; Rats, Sprague-Dawley; Tibia

Only two medications, estrogen and injectable salmon calcitonin, are currently approved by the FDA for the treatment of osteoporosis. Oral etidronate has been investigated but not approved for osteoporosis therapy. We compared the three available anti-resorptive medications in untreated osteoporotic women.. A nonrandomized, open label trial. After baseline biochemistry and bone mineral density (BMD) determinations, subjects self-selected therapy based on descriptions of the three drugs which were similar for all patients. Bone densitometry of the lumbar spine, femoral neck and distal and proximal forearm sites was repeated every 6 months.. Twenty-one patients chose estrogen, 20 chose etidronate and 11 chose calcitonin. Fear of breast cancer was the most common reason given for not choosing estrogen therapy. Mean age was slightly lower and spine and hip bone densities slightly higher in the estrogen group compared with both the etidronate and calcitonin groups. In the lumbar spine, all three agents resulted in similar small increments (mean increments 1.2-4.4% at 2 years). In the estrogen group, there was no change in femoral neck density while there were significant losses in both calcitonin and etidronate groups (3.1-4.9%). In the forearm, there was either no change (distal site) or an increment (proximal site) in the estrogen group, while both etidronate and calcitonin groups demonstrated a mean loss at both sites over the 2-year observation period.. These preliminary results suggest that all three agents appear equally effective at maintaining or increasing BMD of the lumbar spine, while estrogen appeared more effective at maintaining or increasing BMD of the appendicular skeleton. This study underscores the need for an alternative to estrogen therapy which is equally effective and can be given orally for those in whom estrogen is either contraindicated or undesirable.

Topics: Aged; Aged, 80 and over; Bone Density; Calcitonin; Choice Behavior; Estrogen Replacement Therapy; Etidronic Acid; Female; Follow-Up Studies; Fractures, Spontaneous; Humans; Middle Aged; Osteoporosis, Postmenopausal; Patient Participation; Risk Factors; Treatment Outcome

To evaluate the efficacy of salmon calcitonin (sCT) suppositories in inhibiting postmenopausal bone demineralization and the tolerability of this formulation, we treated ten women oophorectomized in reproductive age with intrarectal sCT at the dose of 200 IU/day for 12 months postoperatively. Modifications of calcium and phosphate metabolism were quantified by measurements of vertebral and peripheral bone mineral content, serum alkaline phosphatase, and hydroxyprolinuria at baseline and at 6 and 12 months of treatment. Tolerability was assessed by recording the appearance of local or systemic side-effects. sCT suppositories were demonstrated to inhibit post-oophorectomy calcium loss, and tolerability was good.

Topics: Adult; Bone Density; Calcitonin; Female; Humans; Middle Aged; Osteoporosis, Postmenopausal; Ovariectomy; Pilot Projects; Suppositories

The authors evaluate the efficacy of salmon calcitonin and aminosuberic analogue of eel calcitonin in the prevention of post-oophorectomy osteoporosis in rats. Both drugs, administered at the same dosage, are equally effective in preventing oophorectomy bone loss in rats. Besides, plasma biochemical evaluations demonstrate that calcitonins reduce bone turnover in treated rats, compared with control oophorectomized ones.

Topics: Absorptiometry, Photon; Alkaline Phosphatase; Animals; Biomarkers; Bone Resorption; Calcitonin; Calcium; Female; Humans; Osteocalcin; Osteoporosis, Postmenopausal; Ovariectomy; Phosphorus; Rats; Rats, Sprague-Dawley

The use of calcitonin (CT) is established as a treatment of Paget's disease of bone and postmenopausal osteoporosis (PMO). Salmon calcitonin (sCT), which differs in 14 of the 32 amino acids from human calcitonin, has found a wider distribution world wide, although antibody formation against sCT has been reported in more than 70% of the patients on continuous sCT treatment. The clinical significance of these antibodies has been discussed controversially, because the occurrence of antibodies is not always associated with the development of secondary resistance. Using an in vitro bioassay, based on the CT-mediated increase of the cyclic AMP (cAMP) production of the human breast cancer cell line T 47 D we could identify a neutralizing activity against sCT in the serum of a subset of patients with formation of antibodies against sCT which was related to the development of secondary resistance. Antibody formation against human calcitonin (hCT) has been reported only once before. Binding and neutralizing antibodies were now observed in 1 of 33 patients with PMO treated with hCT. Due to a low neutralizing activity, clinical sequelae were not to be expected in this patient. The formation of neutralizing antibodies against calcitonin is common after treatment with salmon but a rare phenomenon after treatment with human calcitonin. We recommend monitoring of patients with postmenopausal osteoporosis and Paget's disease of bone on long term treatment with sCT or hCT for neutralizing antibody formation in order to evaluate the therapeutic effect of treatment.

Topics: Antibodies; Antibody Formation; Breast Neoplasms; Calcitonin; Cyclic AMP; Drug Resistance; Female; Humans; Iodine Radioisotopes; Osteitis Deformans; Osteoporosis, Postmenopausal; Receptors, Calcitonin; Tumor Cells, Cultured

We studied 21 women with postmenopausal osteoporosis, treated with salmon calcitonin nasal spray (100 IU/daily) and calcium (1 g/daily) for six months. Bone mineral content (BMC), measured before and at the end of therapy with lumbar dual photon absorptiometry, showed a significant increase (p < 0.01). At the end of the study, there was also a clear improvement of osteoporotic pain. Among biochemical markers of bone turnover, there was a significant (p < 0.01) reduction of urinary excretion of hydroxyproline. No side effect was registered and all patients had a good compliance to therapy.

Topics: Absorptiometry, Photon; Administration, Inhalation; Aerosols; Bone and Bones; Calcitonin; Calcium; Female; Humans; Hydroxyproline; Middle Aged; Osteoporosis, Postmenopausal; Pain

The aim of this study was to acquire further knowledge relative to the local tolerability of synthetic salmon Calcitonin, administered by the intranasal route. The Authors have evaluated several olfactometry parameters in a group of patients treated for twelve months with the drug. The Wright matrix test and the olfacto-respiratory reflex test were performed. An evaluation regarding mucociliary transport time was additionally effected. No interference on the part of the drug was reported regarding the functional parameters of the nasal mucosa. The excellent local tolerability of intranasal salmon Calcitonin, as already indicated by other Authors, was confirmed, even in terms of specific parameters relative to the olfactory functions.

Topics: Administration, Intranasal; Calcitonin; Female; Humans; Middle Aged; Olfactory Mucosa; Osteoporosis, Postmenopausal; Reflex; Smell; Time Factors

Topics: Bone Diseases; Calcitonin; Calcium; Female; Humans; Hypercalcemia; Male; Osteitis Deformans; Osteoporosis, Postmenopausal

Menopausal osteoporotic women (age: 49-69, mean: 59.5 years) with crush fractures of the spine were treated with low doses of calcitonin (Miacalcic, 350 U/month), or with calcitonin + anabolic steroid (Retabolil, 50 mg/month). Efficacy of the therapy was controlled by single foton absorptiometry of midshaft and distal radius, by X-ray morphometry and by registering new crush fractures of the spine. Calcitonin monotherapy stopped further bone loss for two years, but at the end of the third year both absorptiometric values, as well as the radiomorphometrical index of the lumbar spine decreased significantly. In patients on calcitonin+anabolic steroid the decrease was just significant and only at radius midshaft, while at the other measured sites it was not. Two new crush fractures per 1396 patient-months occurred. Intermittent administration of low-dose calcitonin, especially together with an anabolic steroid seems to be a safe and effective therapy in established osteoporosis.

Topics: Aged; Calcitonin; Drug Therapy, Combination; Female; Fractures, Spontaneous; Humans; Middle Aged; Nandrolone; Nandrolone Decanoate; Osteoporosis, Postmenopausal; Spinal Fractures

Calcitonin has been observed to have an analgesic effect on painful bone conditions. A case illustrating the antinociceptive effect of calcitonin on bone pain caused by osteoporotic vertebral compression fracture is presented. There is increasing clinical evidence supporting this phenomenon, though few rigorously controlled studies exist. Calcitonin may have an advantage over other analgesics in the treatment of bone pain resulting from an osteoporotic compression fracture, because, in addition to the observed analgesic effect, it is useful in treating the underlying disorder.

Topics: Aged; Analgesics; Calcitonin; Female; Humans; Osteoporosis, Postmenopausal; Pain; Spinal Fractures; Thoracic Vertebrae

Nineteen patients with postmenopausal osteoporosis were treated with 200 u (15 nmol) synthetic salmon calcitonin (sCT) intranasally per day for 15 months. Six months after the start of the nasal administration of sCT, antibodies were recognized in 7, and after 15 months in 10 of the 19 patients studied. The half-maximal dilution of serum binding to 60 pmol/l [125I]sCT (dilution-50) ranged from 2 to 490, and half-maximal inhibition of [125I]sCT binding (60 pmol/l) from 91 to 221 pmol/l sCT. In a cultured breast cancer cell line (T47D) cAMP production was stimulated by sCT (EC50 70 pmol/l). Stimulated cAMP production by sCT (50 pmol/l) was reduced to between 4% and 23% in the presence of serum from patients with antibody dilution-50 of [125I]sCT binding exceeding 32. In patients with lower titer antibodies cAMP production was only marginally suppressed. The values of patients with postmenopausal osteoporosis were in the range of those of earlier studied patients with Paget's disease and clinical resistance to sCT. There was a linear relation between the antibody dilution-50 and the serum dilution required for half-maximal inhibition of cAMP production (P less than 0.01). In conclusion, neutralizing antibodies to sCT may contribute to the decreased responsiveness of bone mineral loss during prolonged treatment with sCT.

Topics: Administration, Intranasal; Aged; Antibody Formation; Calcitonin; Female; Humans; Middle Aged; Neutralization Tests; Osteitis Deformans; Osteoporosis, Postmenopausal