calcitonin and Osteoporosis

The objective of this meta-analysis was to compare the efficacy and safety of teriparatide versus salmon calcitonin for the treatment of osteoporosis in Asian patients and to investigate whether the results of global studies could be applicable to Asian patients.. PubMed, OVID, Cochrane Central Register of Controlled Trials (CENTRAL) and EMBASE up to December 2018 were searched. Eligible randomized controlled trials (RCTs) that compared teriparatide versus salmon calcitonin in Asian osteoporosis population were included. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for data synthesis, and Cochrane Collaboration software Review Manager 5.3 was used to analyze the pooled data.. Three RCTs involving 529 patients were included (mean age 68.7 yr; 93.4% females; mean follow-up 6 months); outcome measures included bone mineral density (BMD) of the femoral neck, total hip and lumbar spine; bone markers and adverse events. We found that the period of 6-months of teriparatide treatment was helpful for the improvement of the BMD of lumbar vertebra, however, the improvement of BMD was not significant in the femoral neck and total hip joint. There was a positive correlation between bone-specific alkaline phosphatase (BSAP) and osteocalcin (OCN) and the response of Asian patients to subcutaneous injection of 20 micrograms per day of teriparatide. The proportion of the occurrence of adverse effects was more obvious in the teriparatide group compared with salmon calcitonin, but there was no significant difference.. Results suggested that the use of teriparatide could improve the lumbar BMD by shortterm (six months) application in Asian osteoporosis patients, which is beneficial to the patients who cannot tolerate adverse events of long-term treatment. The BSAP and OCN bone markers could be useful to monitor the responses of Asian osteoporosis patients to teriparatide treatment. Finally, both of teriparatide and salmon calcitonin were well tolerated by Asian patients.

Topics: Asia; Bone Density; Bone Density Conservation Agents; Calcitonin; Humans; Osteoporosis; Randomized Controlled Trials as Topic; Teriparatide; Treatment Outcome

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

To evaluate the strength of evidence supporting a possible association between salmon calcitonin (SCT) use and cancer incidence.. Searches of MEDLINE/PubMed, MEDLINE/OVID, and EMBASE (January 1973 to September 2013) were performed using the key search terms salmon calcitonin, humans, nasal calcitonin, and (for EMBASE only) randomized controlled trial. We also performed a manual review of data reviewed by the US Food and Drug Administration (FDA) committee in 2013.. All articles identified from the data sources were evaluated and all information deemed relevant was included for this review.. Intranasal and injectable SCT are FDA-approved for the treatment of postmenopausal osteoporosis. After a safety signal suggested a possible link between SCT use and prostate cancer, the European Medicines Agency and FDA regulatory agencies conducted analyses of SCT randomized controlled trial data to assess cancer-related adverse events and to readdress the approval status of SCT. Eighteen studies were found that compared nasal or oral SCT and placebo. In 15 of the 18 studies, the percentage of malignancy was greater in the SCT arm. The studies varied in quality, outcomes, and length. Most of the studies had poor-quality methods to assess new cancer cases.. Current evidence may suggest an association between SCT use and cancer incidence based on studies with poor-quality cancer assessment methods. However, considering the lack of demonstrated efficacy of SCT to reduce fractures, clinicians should consider discontinuing its use for osteoporosis treatment regardless of the FDA's final approval decision.

Topics: Calcitonin; Humans; Neoplasms; Osteoporosis; Risk

Oral delivery of proteins has been hampered by an array of difficulties. However, promising novel oral delivery systems have been developed. 5-CNAC, formulated with the peptide salmon calcitonin, is in phase III clinical trials for the treatment of osteoporosis or osteoarthritis and could become the first marketed oral peptide. This article reviews key findings and implications from studies undertaken to date with this oral formulation. Findings include these: (1) the optimal calcitonin tablet dose is 0.8 mg; (2) 0.8 mg of oral calcitonin is rapidly absorbed, reaching maximum concentration in 15 to 30 minutes, and is eliminated from plasma with a short half-life-9 to 15 minutes; (3) the 0.8-mg tablet is more highly absorbed than the marketed nasal formulation, with biomarker levels indicating significantly greater efficacy in suppression of bone resorption; (4) drug absorption is increased with dosing at least 10 minutes before a meal rather than postprandially and also with 50 mL of water; (5) the optimal timing of dosing for osteoporosis therapy is in the evening to mitigate the circadian peak in bone resorption; and (6) the oral formulations of synthetic and recombinant calcitonin have similar pharmacokinetic and pharmacodynamic properties. These key findings may aid researchers in the development of other oral formulations.

Topics: Administration, Oral; Bone Density Conservation Agents; Bone Resorption; Calcitonin; Food-Drug Interactions; Gastric Emptying; Humans; Osteoporosis; Peptide Fragments; Tablets

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

Topics: Absorptiometry, Photon; Aged; Alendronate; Calcitonin; Calcium; Estrogen Replacement Therapy; Female; Humans; Male; Osteoporosis; Raloxifene Hydrochloride; Risk Factors; Selective Estrogen Receptor Modulators

Osteoporosis is a prevalent condition among elderly women and is associated with an increased risk for fractures. With the burgeoning size of the elderly population, a practitioner is likely to face many questions regarding the evaluation and management of postmenopausal osteoporosis. This review discusses and compares available therapies. All women should have adequate calcium and vitamin D intake. Women diagnosed as having osteoporosis should be evaluated for secondary causes of osteoporosis and risk factors for falls. For women with postmenopausal osteoporosis, therapy with hormone replacement, bisphosphonates (alendronate sodium or risedronate sodium), raloxifene hydrochloride, or calcitonin should be considered. The results of ongoing studies will help refine the strategies used for management of postmenopausal osteoporosis.

Topics: Aged; Algorithms; Bone Density; Calcitonin; Calcium; Diphosphonates; Estrogens; Female; Fractures, Bone; Humans; Osteoporosis; Postmenopause; Raloxifene Hydrochloride; Risk Factors; Selective Estrogen Receptor Modulators; United States; Women's Health

We have investigated the pharmacokinetics and pharmacodynamics of nasal SCT in the dose range of 50-200 IU. When evaluated by AUC, it appeared that the absorption through the nasal mucosa was dose dependent. The resulting plasma levels of SCT were highly variable between individuals. A hypocalcemic effect accompanied by an increase of s-PTH was seen 2-3 hours after administration of a single dose of 200 IU to healthy male adults, but not after administration to postmenopausal women. When evaluated by changes in biochemical markers of bone remodeling nasal SCT 200 IU decreased bone resorption in the magnitude of 15% after a single dose as well as after a multiple daily dosing regimen. No tachyphylaxis of the antiresorptive effect of nasal SCT was noted. The histomorphometric analysis revealed a decrease of erosion depth as the major antiresorptive action on the bone remodeling system of nasal SCT. We were unable to demonstrate an anabolic effect of nasal SCT on bone formation. There was a tendency towards a dose dependent increase in lumbar BMD, but not even in the group receiving 200 IU daily did the increase reach statistical significance when compared to placebo. BMD in the distal forearm as well as in the hip was unaffected by nasal SCT.

Topics: Absorption; Administration, Intranasal; Adult; Bone and Bones; Calcitonin; Calcium; Double-Blind Method; Female; Humans; Male; Osteoporosis; Randomized Controlled Trials as Topic

Topics: Analgesics; Animals; Calcitonin; Clinical Trials as Topic; Humans; Osteoporosis

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

Topics: Animals; Bone and Bones; Bone Density; Calcitonin; Disease Models, Animal; Female; Fractures, Spontaneous; Humans; Male; Osteoblasts; Osteoporosis; Spinal Fractures

Calcitonin (CT) constitutes one of the major choices for the pharmacologic treatment of postmenopausal and senile osteoporosis. In postmenopausal osteoporosis, CT, analogous to estrogens, determines increase of bone mass, improvement of intestinal calcium absorption and a positivization of calcium balance. Patients treated with CT can also benefit from the analgesic effect of the hormone. Unlike estrogens, these beneficial effects of CT occur with minimal risk and require no routine gynecological monitoring. In addition, CT is completely devoid of toxicity. The only limitations to the use of CT are linked to the frequent parenteral injections and the occurrence of side effects. These limitations can now be overcome by the availability of the new nasal spray preparation, which has been developed for synthetic salmon calcitonin (sCT). The introduction of this new form increases the patients' compliance, and the different pharmacokinetic curtails the side effects, compared to the parenteral administration. At present, one-year controlled studies have been reported, showing a beneficial effect of sCT on bone mass in patients with established osteoporosis. Also, shorter studies demonstrate the analgesic activity of sCT treatment in patients with vertebral crush fractures and bone pain. The improvement in the patients' compliance and the reduction of side effects allow this new CT preparation to be used in the prevention of postmenopausal osteoporosis.

Topics: Administration, Intranasal; Aged; Bone and Bones; Calcitonin; Female; Fractures, Spontaneous; Humans; Middle Aged; Minerals; Osteoporosis; Spinal Injuries

Topics: Bone and Bones; Bone Resorption; Calcitonin; Drug Therapy, Combination; Female; Humans; Osteoporosis

This study aimed to evaluate the effects of salmon calcitonin, and calcium and vitamin D treatment on bone mineral density, serum and synovial fluid bone formation and resorption markers in patients with osteoporosis.. The study was completed with twenty-five osteoporosis patients divided into two groups: The 15 patients comprising Group I (1 male and 14 females; mean age: 67.0±12.0) were administered calcitonin treatment in addition to calcium and vitamin D. The 10 patients in Group II (3 males and 7 females; mean age 68.0±16.0) were administered calcium and vitamin D only. Serum and synovial fluid calcium phosphorus, alkaline phosphatase, calcitonin, C-telopeptide (CTx), N-telopeptide (NTx) and sialoprotein levels, and bone densitometries were determined at the beginning and at the end of one year of treatment.. In the calcitonin and calcium and vitamin D treatment group (Group I), femoral neck density scores were decreased and vertebrae scores were increased after one-year treatment. Both scores were increased in the non-calcitonin group (Group II). In Group I, synovial fluid levels of calcitonin, sialoprotein and NTx were decreased, and synovial fluid CTx levels showed no change. The only decrease that was statistically significant was that in calcitonin levels. In Group II, synovial fluid calcitonin levels were decreased, synovial fluid CTx levels were increased and synovial fluid NTx and sialoprotein level were unchanged. These changes were not statistically significant. Serum changes in the parameters were not statistically significant in either group.. In osteoporosis, salmon calcitonin treatment affects synovial fluid bone formation and absorption marker levels. Advanced studies are needed to evaluate the mechanisms by which this takes place, and to explain the relationship between osteoporosis and articular cartilage metabolism.

Topics: Biomarkers; Bone Density; Bone Density Conservation Agents; Calcitonin; Female; Humans; Male; Middle Aged; Osteogenesis; Osteoporosis; Posture; Protein Precursors; Radiography; Synovial Fluid; Treatment Outcome

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

This study aimed to investigate calcitonin as an effective therapy for osteoporosis in patients with bone pain during the anastrozole treatment of breast cancer. Ninety-one patients, who were on anastrozole treatment for breast cancer and also suffered anastrozole-induced bone pain, were randomly divided into two groups: the calcitonin group received salmon calcitonin and Caltrate D, and the control group received Caltrate D. All patients were evaluated by the visual analogue scale (VAS) and underwent the dual energy x-ray absorptiometry test for bone mineral density (BMD), and serum osteocalcin (BGP), alkaline phosphatase (ALP), calcium (Ca), and phosphorus (P) were measured at three months before and after the treatment. Significant differences in serum Ca, P, BGP, and ALP were found in each group between before and after treatment (P < 0.05), while no differences between the calcitonin and control groups were found. No difference was observed in femur BMD between the two groups, or between before and after treatment in each group. There was a significant difference in spine BMD between before and after treatment in the control group (P < 0.05) but not in the calcitonin group, while no difference was found between the calcitonin and control groups. Futhermore, VAS score significantly declined in each group after treatment (P < 0.05), but much more in the calcitonin group than the control group (P < 0.05). Our finding suggests that calcitonin may alleviate bone pain during the anastrozole treatment of breast cancer but has no effect on bone loss during cancer treatment.

Topics: Absorptiometry, Photon; Aged; Alkaline Phosphatase; Anastrozole; Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Bone Density; Bone Density Conservation Agents; Breast Neoplasms; Calcitonin; Calcium; Female; Femur; Humans; Middle Aged; Nitriles; Osteocalcin; Osteoporosis; Pain; Phosphorus; Spine; Triazoles

To explore the reasonable treatment scheme of salmon calciteonin in the treatment of elderly women with type 2 diabetes complicated with osteoporosis, patients were randomly divided into Group A, B and C, and they were given the salmon calcitonin every time 50 IU, subcutaneous injection. The Group A were 1 time a day, for 15 days; Group B were 1 time every 2 days, for 30 days; Group C, one time three days for 90 days. Then to observe the symptoms have efficiency, bone density T value change, incidence rate, incidence of side effects and treatment of loss rate of fracture. Efficiency of symptoms: Group A is lower and there is no difference in Group B and C. T Degree: Group C was significantly increased and Group A was the lowest. Fracture incidence of Group B and C were significantly lower than Group A, and there is no difference in Group B and C. Turnover rate: Group A was significantly lower than B and C, and there is no difference in Group B and C. There is low incidence of side effects in the three groups and they three have no significant difference. It is effective and safe to use salmon calcitonin in the treatment of elderly women with type 2 diabetes complicated with osteoporosis. 50 IU each time, subcutaneous injection, 1 time every 3 days, for 3 months is a reasonable solution.

Topics: Aged; Bone Density Conservation Agents; Calcitonin; Diabetes Mellitus, Type 2; Female; Humans; Osteoporosis

Loosening of a hip prosthesis after total arthroplasty is related to periprosthetic bone loss. Calcitonin has been used in the treatment of bone loss in osteoporosis and prevention of fractures. The main purposes of the study were firstly to evaluate the effect of calcitonin on periprosthetic bone after total hip arthroplasty, secondly investigate possible loosening of the prosthesis and thirdly examine further clinical outcome.. 60 patients who underwent total hip arthroplasty using cemented Exeter prosthesis were randomized in the treatment group (salmon calcitonin 200 IU nasal spray daily + calcium 500 mg) and the placebo group (inactive nasal spray + calcium 500 mg) for six months. Bone mineral density (BMD) was measured from different locations at the time of discharge and after six and 12 months. Dynamic histomorphometry on bone biopsies taken from femoral collum was performed. Serum bone-specific alkaline phosphatase (BAP), serum osteocalcine (OC) and cross-linked N-telopeptides (NTX) were measured after one week, one month, three months and 12 months. Clinical manifestations and the incidence of fractures and loosening of the prosthesis were followed up to eight years.. Statistically there was not significant difference in bone histomorphometry between the groups. In both groups there was a significant BMD decrease in periprosthetic bone. However, the difference between the groups was not statistically significant. In the biochemical analysis NTX increased more in the Miacalcic group than in the placebo group (p = 0.013). There were no significant differences between the groups in serum BAP or OC even though the changes within the groups were statistically significant. No loosening of the prosthesis was seen during the follow-up and there was no need for revision of any reason. Four fractures were recorded in three patients. One patient sustained a periprosthetic fracture. All the patients with fractures were allocated in the placebo group.. Nasal salmon calcitonin 200 IU on a daily basis does not promote any additional value on calcium substitution to prevent bone loss after hip replacement. The durability of the Exeter prosthesis was good.

Topics: Arthroplasty, Replacement, Hip; Bone Density Conservation Agents; Calcitonin; Drug Administration Schedule; Female; Follow-Up Studies; Hip Prosthesis; Humans; Incidence; Male; Nasal Sprays; Osteoporosis; Periprosthetic Fractures; Postoperative Complications; Prosthesis Failure; Treatment Outcome

Oral delivery of proteins has been hampered by an array of difficulties. However, promising novel oral delivery systems have been developed. 5-CNAC, formulated with the peptide salmon calcitonin, is in phase III clinical trials for the treatment of osteoporosis or osteoarthritis and could become the first marketed oral peptide. This article reviews key findings and implications from studies undertaken to date with this oral formulation. Findings include these: (1) the optimal calcitonin tablet dose is 0.8 mg; (2) 0.8 mg of oral calcitonin is rapidly absorbed, reaching maximum concentration in 15 to 30 minutes, and is eliminated from plasma with a short half-life-9 to 15 minutes; (3) the 0.8-mg tablet is more highly absorbed than the marketed nasal formulation, with biomarker levels indicating significantly greater efficacy in suppression of bone resorption; (4) drug absorption is increased with dosing at least 10 minutes before a meal rather than postprandially and also with 50 mL of water; (5) the optimal timing of dosing for osteoporosis therapy is in the evening to mitigate the circadian peak in bone resorption; and (6) the oral formulations of synthetic and recombinant calcitonin have similar pharmacokinetic and pharmacodynamic properties. These key findings may aid researchers in the development of other oral formulations.

Topics: Administration, Oral; Bone Density Conservation Agents; Bone Resorption; Calcitonin; Food-Drug Interactions; Gastric Emptying; Humans; Osteoporosis; Peptide Fragments; Tablets

To investigate the prevalence of osteoporosis in patients undergoing maintenance dialysis and explore the safety and efficacy of salmon calcitonin in maintenance dialysis patients underwent with osteoporosis.. Double-energy X-ray bone density meter was used on 256 patients undergoing maintenance dialysis, 126 males and 130 females, aged 60 +/- 14 (22 -79), to measure the bone mineral density (BMD) at the lumbar spine and femoral neck. 108 of them with the T values < -2.5 s were diagnosed as with osteoporosis, and then were randomly divided into 2 equal groups matched in baseline age, sex, mode of dialysis, and levels of iPTH, ALP, and BMD: control group receiving oral administration of calcium carbonate 1500 mg tid and rocaltrol 0.25 microg qn for 18 months, and experimental group, received subcutaneous injection of salmon calcitonin (50 U) three times a week in addition. The BMD levels of lumbar spine and femoral neck, and serum intact parathyroid hormone (iPTH), calcium, phosphorus, and alkaline phosphatase (ALP) were assessed before treatment and 3, 6, 12, and 18 months after treatment.. (1) The osteoporosis rate of the 256 maintenance dialysis patients was 42.19%. (2) The osteoporosis rate of the 201 patients undergoing maintenance hemodialysis (MHD) was 47.76%, significantly higher than that of the 55 patients undergoing maintenance peritoneal dialysis (21.82%, P < 0.01). (3) At the end of the trial, there was a significant increase of BMD of lumbar spine and femoral neck in the experiment group compared with the control group. (4) Compared with the control group, the serum ALP, iPTH, and BGP levels 3, 6, 12, and 18 months after treatment were all significantly lower than the baseline level and those of the corresponding control groups (all P < 0.01). The serum calcium of the control group at the end of experiment increased significantly in comparison with baseline level (P < 0.05). (5) No adverse events were found after the treatment of salmon calcitonin.. Salmon calcitonin effectively increases the BMD of the maintenance dialysis patients and is well tolerated.

Topics: Absorptiometry, Photon; Adult; Aged; Alkaline Phosphatase; Bone Density; Bone Density Conservation Agents; Calcitonin; Calcium; Case-Control Studies; Female; Humans; Injections, Subcutaneous; Male; Middle Aged; Osteoporosis; Phosphorus; Renal Dialysis; Time Factors; Treatment Outcome; Young Adult

Bone resorption displays marked diurnal variation. Reversible inhibition of bone resorption may result in best possible efficacy when bone resorption peaks. The aim of the study was to assess the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of 0.8 mg of oral salmon calcitonin (sCT) and the effect of timing of drug intake.. The study was a randomized, double-blind, double-dummy, placebo-controlled, phase I study to assess the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of 0.8 mg of oral sCT in healthy postmenopausal women. Totally 81 subjects were included, aimed at investigation of a morning dose given at 8:00 (n = 42), a pre-dinner dose given at 17:00 (n = 20), and an evening dose given at 22:00 (n = 19). Plasma sCT concentrations and bone resorption (C-terminal-telopeptide of collagen type I (CTX-I)) was assessed.. Morning and pre-dinner dosing led to comparable concentration of sCT of 45 pg/ml, whereas there was a tendency towards lower Cmax for the evening dosing having a mean of 24 pg/ml. The maximum difference from placebo was observed 1 to 3 hours post-dose with a 40 to 50% suppression consequent to morning dose, and about 75% suppression after pre-dinner and evening dose, due to the increase bone resorption as a result of circadian variation.. The study suggests that orally administered 0.8 mg of salmon calcitonin was effective in suppression of serum CTX irrespective of time of dosing. The pre-dinner dosing resulted in optimum efficacy response corresponding to an overall suppression of bone resorption by 25%.

Topics: Administration, Oral; Aged; Bone Resorption; Calcitonin; Circadian Rhythm; Double-Blind Method; Drug Delivery Systems; Female; Humans; Middle Aged; Osteoporosis; Treatment Outcome

The aim of this study was to examine the effect of intranasal salmon calcitonin therapy on bone mineral density (BMD) in idiopathic male osteoporosis without vertebral fractures. We conducted a randomized, open label, controlled trial in 71 male patients (mean age 59 +/- 6 years) suffering from idiopathic osteoporosis (femoral neck T-score < -2.5) without vertebral deformity. Patients in the control group (n = 31) received 400 IU Vitamin D + 1000 mg elemental calcium daily while the treatment group (n = 40) received 400 IU Vitamin D, 1000 mg elemental calcium plus 200 IU calcitonin nasal spray daily during alternate months. The study period was 18 months. Compared to controls, nasal calcitonin was associated with significant increases in bone mineral density at the lumbar spine (+3.5 +/- (-4.3%) vs. +0.83 +/- 6.4%, P = 0.04) and the femoral neck (+3.2 +/- 3.9% vs. +0.68 +/- 5.7%, P = 0.004). No significant difference was observed at the radius between the treatment groups (+1.4 +/- 8.8% vs. +1.4 +/- 10.9%, P = 0.98). Treatment was well tolerated with no premature discontinuations or significant side effects compared to the control group. We conclude that 200 IU salmon calcitonin nasal spray used daily, intermittently proved to be an effective and safe therapy in male idiopathic osteoporosis.

Topics: Administration, Intranasal; Aged; Bone Density; Calcitonin; Humans; Male; Middle Aged; Osteoporosis

We aimed to investigate different treatment drugs for the prevention of post-transplant bone loss.. Sixty adult male recent renal transplant recipients were enrolled into the study. Patients were randomized into 4 groups: group I received daily alfacalcidol 0.5 microg PO; group II received oral alendronate 5 mg/day; group III received intranasal salmon calcitonin 200 IU every other day; and group IV was considered a control group. Every patient was supplemented with daily 500 mg oral calcium carbonate. Parameters of bone metabolism were measured before and at 12 months after starting treatment. Bone mineral density (BMD) was measured by (DEXA) at lumber spine, femoral neck, and forearm before and after treatment period.. BMD was increased at lumber spine by 2.1%, 0.8%, 1.7%, by 1.8%, 0.6%, 1.6% at femoral neck, and by 3.2%, 1.9%, 2.6% at forearm in groups I, II, and III, respectively, while it decreased by 3.2%, 3.8%, and 1.8% at the same sites, respectively, in control group (P= <0.05). iPTH level decreased significantly in group I, while the decrease was insignificant in other groups (P= 0.003). All other parameters were not statistically significant between treatment groups. Apart from transient hypocalcaemia in 3 patients in group II, and 2 patients in group III, no other significant adverse effects were noted.. This study proves that early bone loss that occurs during the first 12 months after renal transplantation could be prevented by alfacalcidol, calcitonin, or alendronate. Among the treatment groups, alfacalcidol significantly improved the hyperparathyroidism. All treatment drugs are safe and tolerable.

Topics: Adult; Alendronate; Bone Density; Calcitonin; Calcium Carbonate; Humans; Hydroxycholecalciferols; Kidney Transplantation; Male; Osteoporosis; Parathyroid Hormone; Prospective Studies; Single-Blind Method

In a 12-month 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. Twenty-eight men with idiopathic osteoporosis aged 27-74 years (mean, 52.4 years) were randomized to receive either nasal SCT (200 IU) or a nasal placebo daily for a period of 1 year. All the men received a daily supplement of 0.5 g of calcium. The men who received SCT had a mean (+/-SEM) increase in BMD of 7.1 +/- 1.7% at the lumbar spine. In contrast, the men who received the placebo had an increase of 2.4 +/- 1.5% (p > 0.05) for the comparison with baseline. The increase in lumbar BMD in the calcitonin group was significantly greater than that in the placebo group (p < 0.05). There were no significant changes in the femoral neck, trochanter, or Ward's triangle relative to both baseline and placebo after 12 months. Treatment with nasal SCT resulted in a significantly pronounced suppression of bone resorption markers (urinary deoxypyridinoline [DPD], type I cross-linked N-telopeptide [NTX], and type I cross-linked C-telopeptide [CTX]) and to a lesser extent in bone formation markers (serum bone-specific alkaline phosphatase [BALP], osteocalcin [OC], serum C-terminal procollagen type I extension peptides [PICP], and serum N-termnal procollagen type I extension peptides [PINP]), whereas the placebo did not. Therapy was tolerated well and there were no treatment-related adverse events. We conclude that intranasal SCT (200 IU daily) is safe and effective in increasing lumbar BMD and reducing bone turnover in men with idiopathic osteoporosis.

Topics: Adult; Aged; Amino Acids; Biomarkers; Bone Density; Bone Remodeling; Bone Resorption; Calcitonin; Collagen; Collagen Type I; Double-Blind Method; Humans; Male; Middle Aged; Osteoporosis; Peptides

Topics: Absorptiometry, Photon; Bone and Bones; Bone Density; Bone Remodeling; Calcitonin; Fractures, Bone; Humans; Magnetic Resonance Imaging; Osteoporosis; Risk Factors; Tomography, X-Ray Computed; Ultrasonography

The aim of this study was to examine the effect of intranasal administration of salmon calcitonin to a group of 24 postmenopausal women with severe, established osteoporosis (t score < -2.5 SD) and more than one vertebral fracture. The patients were treated with 200 IU of nasal salmon calcitonin daily for 2 months with a subsequent pause of 2 months (3 cycles) and 500 mg calcium daily over a total of 12 months in an open randomized study. The patients were compared with an age matched control group of 18 women of a similar clinical status who were treated with calcium and vitamin D only. In the nasal calcitonin treatment group an increase in the trabecular axial bone density of 2.8% was achieved, as well as increase in trabecular appendicular (forearm) bone density of 1.6%, together with a cortical bone density increase of 1.8% axial and 1% appendicular. Initially, elevated values of urinary deoxypyridinoline were found in 12 women in the nasal calcitonin treatment group; these levels returned to normal under salmon calcitonin nasal therapy and documented the inhibition of increased osteoclastic activity. Cyclic intermittent calcitonin nasal therapy led to a general increase in trabecular and cortical axial and appendicular bone density, marked alleviation of the subjective sensation of pain, and a reduction in the daily dose of accompanying nonsteroidal anti-inflammatory drugs by 50%.

Topics: Administration, Intranasal; Amino Acids; Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arm; Biomarkers; Bone Density; Bone Resorption; Calcitonin; Calcium; Female; Humans; Immunoenzyme Techniques; Middle Aged; Osteoporosis; Pain Measurement; Pilot Projects; Salmon; Spinal Fractures; Spine; Tomography, X-Ray Computed; Vitamin D

To evaluate the analgesic efficacy of calcitonin suppositories (200 IU) in comparison with bed rest and paracetamol tablets, as a rescue analgesic.. A prospective, double-blind, randomized, placebo-controlled, clinical trial.. Forty patients (8 men and 32 postmenopausal women), who had recently (within the last 5 days) suffered a nontraumatic osteoporotic vertebral fracture.. All patients were admitted to the hospital, divided randomly into two groups and received either one calcitonin or placebo suppository once a day, respectively, for 28 days. All patients were allowed to take paracetamol tablets (500 mg), with a maximum dose of six tablets daily.. Spinal pain evaluation was performed at the beginning of the study (before the initiation of treatment) and then daily until the end of the study (day 28) using the Huskinsson's visual analog scale (VAS) and a painmeter device, by direct pressure on the fractured vertebra. Pain was evaluated with the patients attempting or performing four different locomotor functions, e.g., bed rest, sitting, standing, and walking functions. Biochemical urine and plasma measurements were carried out before the initiation of treatment and on days 14 and 28.. All calcitonin-treated patients experienced an overall statistically significant (all p values < 0.001) decrease of spinal pain as assessed by the VAS and the painmeter device. Pain relief allowed for early mobilization and the gradual restoration of the locomotive functions in the calcitonin-treated group. Placebo-treated patients remained in bed for almost the whole of the observation period. At the end of the study (28th day), fasting osteocalcin, hydroxyproline/creatinine, and calcium/creatinine ratio values were statistically significantly (all p values < 0.001), lower in the calcitonin-treated than in the placebo-treated patients. In the placebo group these values showed a gradual increase. In the calcitonin-treated group side effects mainly included dizziness and enteric irritation caused by the suppositories. Enteric irritation was also present in the placebo-treated group.. Salmon calcitonin suppositories (200 IU daily) caused a dramatic decrease in spinal pain in patients with recent osteoporotic vertebral fractures and influenced the early mobilization and the gradual restoration of their locomotor functions.

Topics: Acute Disease; Aged; Aged, 80 and over; Analgesics; Calcitonin; Female; Humans; Male; Middle Aged; Osteoporosis; Pain; Pain Measurement; Placebos; Prospective Studies; Spinal Fractures; Suppositories; Walking

Salmon calcitonin is frequently used in the treatment of osteoporosis. Via specific receptors on osteoclasts it reduces bone absorption and has also an osteogenic effect. Treatment with calcitonin leads to an increase in bone density, drop of markers of bone turnover and reduction of risk fractures. In the submitted trial the authors investigated the influence of nasal calcitonin administered in amounts of 100 IU in three-month intervals, on bone density. The group comprised 59 patients, mean age 64 years. The mean period of treatment was 2.5 years. Treatment led to a significant increase of bone density in the region of the lumbar spine and neck of the femur. Treatment was well tolerated and the authors did not record new manifest fractures or side-effects of treatment.

Topics: Administration, Intranasal; Adult; Aged; Aged, 80 and over; Bone Density; Calcitonin; Female; Humans; Male; Middle Aged; Osteoporosis

The objectives were to determine the efficacy and safety of nasal salmon calcitonin 200 IU daily in the prevention of corticosteroid-induced osteoporosis. A minimized, double-blind, placebo-controlled trial was carried out in corticosteroid-treated patients with polymyalgia rheumatica. The setting was a tertiary care university-affiliated hospital and a total of 31 patients were enrolled. The primary outcome measure was the percentage change in bone mineral density of the lumbar spine in the two treatment groups from baseline to 1 yr of follow-up. The mean +/- S.D. bone mineral density of the lumbar spine in the calcitonin-treated group decreased by 1.29 +/- 6.76% and in the placebo group by 4.95 +/- 3.50% after 12 months. The observed difference of 3.65 +/- 2.10% between groups is statistically significant (P < 0.05). Nasal salmon calcitonin prevented loss of bone in the lumbar spine as measured by dual-energy X-ray absorptiometry.

Topics: Absorptiometry, Photon; Administration, Inhalation; Aged; Analgesics; Bone and Bones; Bone Density; Calcitonin; Double-Blind Method; Female; Glucocorticoids; Humans; Lumbar Vertebrae; Male; Osteoporosis; Polymyalgia Rheumatica; Prednisone; Safety

Patients treated with high-dose or long-term corticosteroids are at risk of accelerated osteoporosis and spontaneous vertebral and traumatic fractures. To assess the efficacy of salmon calcitonin in preventing corticosteroid- induced osteoporosis, 48 patients with newly diagnosed polymyalgia rheumatica, temporal arteritis, and other vasculitides were enrolled in a 2-year, double-blind, randomized, controlled trial. Patients were randomized to receive subcutaneous injections t.i.w. of either 100 IU of salmon calcitonin (25 patients) or placebo (23 patients). After 2 years, 19 and 21 patients, respectively, were evaluable. All patients also received supplemental calcium carbonate (1500 mg daily in divided doses) and vitamin D3 (400 IU daily). Baseline and serial radiologic assessments included dual-energy X-ray absorptiometry (DXA) of the lumbar spine and hip, and spine radiographs to detect vertebral fractures. There were no significant baseline differences between the two study groups. The mean within-subject percentage change in DXA lumbar spine density in the two groups over the 2-year period of the study was only -0.1% (calcitonin plus calcium) versus -0.2% (placebo plus calcium) a nonsignificant difference despite the high mean cumulative corticosteroid doses of 5371 mg and 4680 mg, respectively (NS). The incidence of vertebral fracture was 12.5% (calcitonin plus calcium: 11%, versus placebo plus calcium: 14%, NS), with four fractures in the first year and one fracture in the second year. Higher cumulative cortico-steroid dose was associated with a greater loss in bone density. In rheumatic disease patients starting high-dose, long-term corticosteroids, salmon calcitonin with calcium and vitamin D3 provided no greater bone preservation than that observed with calcium and vitamin D3 alone.

Topics: Absorptiometry, Photon; Adrenal Cortex Hormones; Aged; Aged, 80 and over; Bone Density; Bone Resorption; Calcitonin; Cohort Studies; Double-Blind Method; Female; Fractures, Bone; Giant Cell Arteritis; Humans; Incidence; Lumbar Vertebrae; Male; Middle Aged; Osteoporosis; Polymyalgia Rheumatica; Spinal Injuries

Osteopenia is a major complication of orthotopic liver transplantation (OLT). However, no effective therapy for bone disease has been defined. We have studied vertebral bone mineral density (VMD) and fasting serum markers of bone formation [bone gla protein (BGP), procollagen I carboxyterminal peptide (PICP)] and metabolism (serum Ca, P, intact parathyroid hormone (iPTH), 25OHD3 and 1,25(OH)2D3) in 120 patents after OLT. VMD was measured by dual-energy X-ray absorptiometry (DXA) using a Hologic QDR 1000 densitometer on two occasions, 12 months apart. Patients with OLT had a VBD significantly lower compared with age- and sexed-matched Spanish controls (P < 0.05). Prevalence of osteoporosis (Z score below -2 SD) was 35.8%. Serum BGP (8.6 +/- 0.7 ng/ml) and PICP (222.9 +/- 81.9 ng/dl) were higher than those of controls. However, serum calcium, phosphorus, iPTH, 25OHD3, and 1,25(OH)2D3 were within normal range. Patients with osteoporosis were randomly treated with 40 IU/day of calcitonin i.m. (Diatin, Ferrer Int. Laboratories) (n = 17) or 400 mg p.o., 15 days every 3 months, of sodium ethiodronate (Difosfen, Rubio Laboratories) (n = 23). All patients received 500 mg/12 hours of elemental calcium p.o. After 12 months of treatment, a significant increment of vertebral mineral density (VMD) was observed (6.4% and 8.2%, respectively). Serum BGP and PICP values remained elevated without a difference between the two drugs. Our results indicate that antiresorptive drugs may be of benefit in the high turnover osteoporosis of OLT recipients.

Topics: Adult; Bone Density; Bone Diseases, Metabolic; Calcitonin; Etidronic Acid; Female; Humans; Liver Transplantation; Male; Middle Aged; Osteoporosis; Postoperative Complications

Topics: Administration, Rectal; Aged; Calcitonin; Female; Humans; Middle Aged; Osteoporosis; Time Factors

Cyclical treatments of osteoporosis utilizing a skeletal Activator of bone remodelling, and sequential therapy with a Depressor to selectively block the resulting phase of osteoclastic resorption have been dubbed 'ADFR' therapy; there is usually a treatment Free interval while the activated bone multicellular units complete the remodelling cycle before the protocol is Repeated. In this report an ADFR protocol was developed in which all patients received synthetic hPTH (1-38) for the first 14 days of a 100 day cycle. Half the patients received no other therapy (Group 1), but were followed closely with repeated vertebral bone mineral measurements over two full cycles. The remaining patients (Group 2) were randomly allocated to receive salmon calcitonin, at an average dose of 79 units per day for a 56 day depressor period immediately following each phase of activation. Detailed bone histomorphometry was performed on iliac biopsies obtained before treatment and at the end of the second cycle (Day 200). In Group 1, the serum alkaline phosphatase (Alk. P'ase) increased by 23 +/- 12% (P less than 0.01) and by 18 +/- 16% (P less than 0.03) of the baseline values following PTH treatment during the first and second cycles, respectively. The overall changes in serum Alk. P'ase across time were significantly less (P less than 0.04) in Group 2; however this parameter also increased by 15 +/- 15% during the first cycle and 8 +/- 6% during the second cycle. Vertebral BMC increased by 13% in Group I (P less than 0.01), but forearm BMC decreased by 11% (P less than 0.05) over the two cycles of therapy. There were no significant changes in bone mineral measurements in Group 2, but the differences between the two groups were not significant. Eighteen paired biopsies were available for histomorphometric analysis. There were no significant changes in static parameters measuring total bone tissue, osteoclastic function or osteoid formation after two cycles of treatment. Individual bone formation rates (surface referent) were not significantly different between the two groups; the pooled data for all biopsies showed a small but insignificant increase from 0.030 +/- 0.018 to 0.035 +/- 0.028 mm3/mm2/day. However there was a significant increase in the activation frequency (the probability of a remodelling event occurring on queiscent cancellous surface) from 13 +/- 7 to 27 +/- 26/day x 10(-4) (P less than 0.05) when calculated for the pooled data from both groups.(ABSTRACT TRUNCA

Topics: Aged; Alkaline Phosphatase; Biopsy; Bone Density; Calcitonin; Female; Humans; Male; Middle Aged; Osteogenesis; Osteoporosis; Parathyroid Hormone; Peptide Fragments

Fifty-nine consecutive patients (19 men, 40 women, mean age 60.8 [27-80] years) with primary osteoporosis were studied to see if there was any significant gain in bone mass after treatment with salmon calcitonin. All the patients were given 1 g calcium by mouth every morning. Group 1 (n = 20) received no other specific medication while group 2 (n = 19) were given 100 I.U. calcitonin subcutaneously every second evening and group 3 (n = 20) received the same dose every evening. The pain reported by the patients was subdivided into four severity grades, and analgesic consumption was recorded. In group 1 there was a nonsignificant decrease in pain, but in groups 2 and 3 there was a highly significant diminution in pain (P less than 0.005) and in analgesic intake (P less than 0.01). Measurements of bone density carried out by photon absorption at the end of 12 months showed a 5.5% increase in the distal radius in group 2 (P = 0.0001) and a 7.1% increase in group 3 (P = 0.0001), while in group 1 mineral content had decreased by 4.3% (nonsignificant). These results show that a significant gain in bone mass can be achieved by administration of calcitonin, either daily or on alternate days. The incidence of extravertebral fractures and of new or progressive vertebral deformity tended to be lower in groups 2 and 3 than in group 1.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Bone Density; Calcitonin; Calcium; Creatinine; Dose-Response Relationship, Drug; Female; Fractures, Spontaneous; Humans; Injections, Subcutaneous; Male; Middle Aged; Osteoporosis; Phosphorus; Randomized Controlled Trials as Topic; Spinal Injuries

In women suffering from post-menopausal osteoporosis, we evaluated the effectiveness of two cyclic treatments with synthetic salmon calcitonin over a whole year, using an average daily dose of 16 and 32 IU, respectively. This treatment was compared with treatment with oral calcium carbonate. The results, evaluated by peripheral densitometry of the radius, showed a 3.2% loss of bone mineral content (BMC) in the women treated only with calcium carbonate, a loss of 1% in those treated with an average dose of 16 IU/day of calcitonin and an increase of 4% in the women treated with an average dose of 32 IU/day (an increase just above the statistically significant limit using the paired t-test). An average dose of 32 IU/day probably represents the minimum effective dose of calcitonin required to produce a significant increase in bone mineral mass, when used according to a sequential scheme.

Topics: Aged; Aging; Alkaline Phosphatase; Bone and Bones; Calcitonin; Calcium Carbonate; Densitometry; Female; Humans; Hydroxyproline; Middle Aged; Osteoporosis

79 women who had been menopausal for less than 36 months and who had not received any form of treatment to prevent bone loss were randomly assigned to a 12-month regimen of calcium 500 mg/day or calcium 500 mg plus intranasal salmon calcitonin 50 IU/day for 5 days per week. After 12 months of treatment bone mineral density had decreased in the calcium-only group by a mean of 3.16 (SEM 0.6)% (p less than 0.01) but had increased in the calcium plus calcitonin group by 1.38 (0.8)% (NS). The difference in response between the two treatment groups was also highly significant (p less than 0.01), as was the difference between values for hydroxyprolinuria/creatininuria (p less than 0.01). Endogenous calcitonin levels rose significantly in the calcium group but remained unchanged in calcitonin-treated patients. Treatment by calcitonin and calcium was not followed by increased secretion of parathyroid hormone. The findings suggest that intranasal calcitonin can counteract early postmenopausal bone loss.

Topics: Administration, Intranasal; Bone and Bones; Calcitonin; Calcium; Clinical Trials as Topic; Creatinine; Drug Therapy, Combination; Female; Humans; Hydroxyproline; Minerals; Osteoporosis; Radionuclide Imaging; Random Allocation; Tablets; Time Factors

Fourteen women with postmenopausal osteoporosis, all having at least one vertebral crush fracture, were randomly assigned to two treatment arms, each lasting 24 months. The coherence treatment group (7 patients) was treated in the following sequence: human growth hormone (hGH) 7 IU subcutaneously daily for 2 months, followed by 3 months of salmon calcitonin (CT), 100 MRC units every other day. After a 3 month rest period, this sequence was repeated twice. The contrast group (7 patients) was treated intermittently with salmon CT given in the same time periods and at the same dose as in the coherence treatment group. Bone mass was measured every 4 months by neutron activation analysis for total body calcium (TBCa) and by single photon absorptiometry for bone mineral content (BMC) of the distal radius. Although there were no significant differences between the two groups (two-way ANOVA), the rate of change in TBCa in the coherence treatment group was significantly different from zero (F = 3.8, P less than .05) and was +2.3%/year. The increase in bone mass appeared to be sustained throughout the 2 year study, in contrast with previous studies where a plateau effect was observed with calcitonin given alone or continuously with growth hormone. No significant change was found in bone histomorphometric values measured before and after treatment in 4 patients from each group.

Topics: Aged; Bone and Bones; Calcitonin; Calcium; Drug Therapy, Combination; Female; Growth Hormone; Humans; Menopause; Middle Aged; Minerals; Osteoporosis

There is uncertainty about the best treatment for steroid-induced osteoporosis. Thirty-six patients with steroid-dependent, chronic obstructive lung disease and associated steroid osteoporosis have been studied, of whom 18 were treated with salmon calcitonin and the other 18 served as controls. Treatment lasted for 6 months and consisted of 100 I.U.s.c. every other day. In the controls there were significant decrements of 1.4% and 3.5%, respectively, in cortical and cortical and trabecular bone mineral content, whereas in subjects on calcitonin there were increments of 2.6% and 2.7%, respectively. Additional evidence of positive effect of calcitonin was derived from the reduced incidence of new fractures occurring during the observation period. A significant reduction in back pain was a further consequence of the hormone therapy.

Topics: Adrenal Cortex Hormones; Adult; Aged; Bone and Bones; Calcitonin; Clinical Trials as Topic; Female; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Minerals; Osteoporosis; Random Allocation

In this paper we present the results of a 12-month double-blind clinical multicenter study assessing the effects of synthetic salmon calcitonin (CT) administration in a group of white postmenopausal osteoporotic women. Treated patients were given 100 MRC units of synthetic salmon CT injected i.m. in the morning every other day. Control patients received a placebo injection. All patients received 500 mg of elementary calcium p.o., b.i.d. Bone mineral content (BMC) was measured at the extreme distal radius of the nondominant arm by a dual photon bone densitometer which utilizes two radionuclides, 241Am and 125I, with energies of about 60 keV and 30 keV respectively. Biochemical parameters of calcium-phosphorus metabolism were also measured. After 12 months of treatment a significant mean increment of BMC and nondialyzable OHPr/creatinine values and a significant decrease of total OHPr/creatinine values were observed in the treated group, while controls showed a significant decrease in BMC values. These results, together with the observation that in some patients the decrease in total OHPr/creatinine values was not accompanied by an increment of BMC, show that long-term salmon CT treatment may be of benefit in postmenopausal osteoporosis and that the effects of CT on bone mass may be due not only to the inhibition of bone resorption but also to the stimulation of bone formation.

Topics: Aged; Bone and Bones; Calcitonin; Calcium; Clinical Trials as Topic; Creatinine; Double-Blind Method; Female; Humans; Hydroxyproline; Menopause; Middle Aged; Minerals; Osteoporosis

Topics: Calcitonin; Clinical Trials as Topic; Double-Blind Method; Female; Gastrointestinal Diseases; Humans; Menopause; Osteoporosis; Patient Compliance

A composite separable microneedles (MNs) system consisting of silk fibroin (SF) needle tips and hyaluronic acid (HA) base is developed for transdermal delivery of salmon calcitonin (sCT) for therapy of osteoporosis. Poly(ethylene glycol) (PEG) is used to modulate the conformation structure of SF to achieve controllable sustained release of sCT. The prepared MNs can effectively penetrate the skin stratum corneum. After application to the skin, the HA base is dissolved within 2 min, allowing these SF drug depots to be implanted into the skin for controllable sustained release of sCT. The release kinetics of sCT can be controlled by regulating the conformation of SF with PEG and the interaction between sCT peptide and SF proteins. Compared with traditional needle injection, delivery of sCT using optimized HA-PEG/SF MNs shows better trabecular bone repair for ovariectomized-induced osteoporosis in mice. The proposed MNs system provides a new noninjection strategy for therapy of osteoporosis.

Topics: Administration, Cutaneous; Animals; Calcitonin; Delayed-Action Preparations; Drug Delivery Systems; Mice; Needles; Osteoporosis

Osteoporosis therapy consists of inhibiting the osteoclasts' activity and promoting osteoblasts' osteogenesis. Salmon calcitonin (sCT) could realize both requirements, however, it is limited by the low bioavailability caused by fibrillation. Supramolecular assembly of sCT and biocompatible agents into nanoassemblies provides an opportunity to overcome these shortcomings. Herein, we used a facile method to fabricate salmon calcitonin-aspartame (sCT-APM) nanoassemblies. Supramolecular interactions could not only delay fibrillation time (from 36.9 h to 50.4 h), but also achieve sustained sCT release. Moreover, sCT-APM showed good biocompatibility and higher osteoinductive capacity than free sCT, revealing an osteogenesis improvement effect. Moreover, in vivo studies showed that sCT-APM has enhanced relative bioavailability (2.42-fold of sCT) and increased relative therapeutic efficacy (3.55-fold of sCT) through subcutaneous injection. These findings provide a convenient alternative strategy for osteoporosis therapy via supramolecular assemblies.

Topics: Aspartame; Calcitonin; Humans; Osteogenesis; Osteoporosis

We present salmon calcitonin (SCT) loaded Hydroxyapatite nanoparticles (HAP-NPs) for sublingual osteoporosis therapy. Surface stabilized HAP-NPs were prepared by aqueous precipitation. SCT was loaded by ionic complexation, as confirmed by FTIR. SCT-HAP-NPs exhibited high loading efficiency (~85%), average size (~100 nm), and zeta potential (~ -25 mv). Stability of SCT was established by circular dichroism spectroscopy and HPLC analysis. Confocal laser scanning microscopy confirmed deep penetration of SCT-HAP-NPs into the mucosa with >4-fold enhancement in permeability relative to SCT solution. Sublingual SCT-HAP-NPs revealed relative bioavailability of ~15% compared to the subcutaneous injection in rabbits (200 IU). Significant and comparable improvement in serum biomarkers with increase in bone mass and mechanical strength and decreased bone erosion compared to subcutaneous SCT was confirmed in ovariectomized (OVX) osteoporosis rat model. Such comparable pharmacodynamic effect at the same dose suggested targeted bone delivery and promise of sublingual SCT-HAP-NPs as a non-invasive alternative to the injection.

Topics: Animals; Bone Density; Calcitonin; Chromatography, High Pressure Liquid; Circular Dichroism; Durapatite; Female; Microscopy, Confocal; Microscopy, Electron, Scanning; Nanoparticles; Osteoporosis; Ovariectomy; Rabbits; Rats; Rats, Sprague-Dawley; Spectroscopy, Fourier Transform Infrared; Swine

The high level of bone metabolism associated with osteopenia and multifocal skeletal fracture remains a challenging clinical problem in osteoporosis patients. Salmon calcitonin (sCT), as a peptide medicine, is able to inhibit osteoclast activity and stimulate osteoblast growth. However, calcitonin receptors (CTRs) are widely distributed in vivo, limiting the specificity and therapeutic effects. Here, we report a bone-seeking hexapeptide (Asp6)-conjugated sCT (sCT-Mal-Asp6) for the targeted treatment of osteoporosis. The sCT-Mal-Asp6 was synthesized via a disulfide re-bridge reaction with high specificity and purity. It was demonstrated that the adsorption of sCT-Mal-Asp6 on hydroxyapatite (HA) was about 5.4 times higher than that of sCT. It was demonstrated a prolonged circulation time and 3-fold higher femur tissue accumulation of sCT-Mal-Asp6. In ovariectomized (OVX) models, sCT-Mal-Asp6 significantly increased the ability to attenuate hypercalcemia and reconstruct the trabecula. Our work provides an efficient approach to targeted and effective osteoporosis treatment.

Topics: Animals; Aspartic Acid; Bone and Bones; Bone Density Conservation Agents; Calcitonin; Drug Delivery Systems; Durapatite; Female; Femur; Humans; Maleimides; Oligopeptides; Osteoporosis; Rats; Rats, Sprague-Dawley; Tissue Distribution

We investigated the role of the calcitonin (Miacalcin) in the progression of osteoarthritis (OA) and in nociceptive behavior in an experimental rat model of OA and osteoporosis. OA was induced by anterior cruciate ligament transection (ACLT) of the right knee and by bilateral ovariectomy (OVX) in Wistar rats. Nociceptive behaviors (secondary mechanical allodynia and weight-bearing distribution of the hind paws) were analyzed prior to surgery and every week, beginning at 12 weeks after surgery, up to 20 weeks. At 20 weeks, histopathological studies were performed on the cartilage of the knee joints. Immunohistochemical analysis was performed to examine the effect of calcitonin on transforming growth factor (TGF)-β1 expression in articular cartilage chondrocytes. Rats subjected to ACLT + OVX surgery showed obvious OA changes in the joints. Animals subjected to ACLT + OVX and treated with calcitonin showed significantly less cartilage degeneration and improved nociceptive tests compared with animals subjected to ACLT + OVX surgeries alone. Moreover, calcitonin increased TGF-β1 expression in chondrocytes in ACLT + OVX-affected cartilage. Subcutaneous injection of calcitonin (1) attenuated the development of OA, (2) concomitantly reduced nociception, and (3) modulated chondrocyte metabolism, possibly by increasing cellular TGF-β1 expression.

Topics: Animals; Calcitonin; Cartilage; Cartilage Diseases; Chondrocytes; Immunohistochemistry; Male; Nociception; Osteoarthritis; Osteoporosis; Ovariectomy; Rats; Rats, Wistar; Transforming Growth Factor beta1; Weight-Bearing

The objective of the present study was to assess the effectiveness of combined salmon calcitonin (sCT) and aspirin [acetylsalicylic acid (ASA)] treatment in an ovariectomized (OVX) rat model of postmenopausal osteoporosis. Following 12 weeks of treatment, therapeutic efficacy was assessed by evaluating changes in the biochemical and biophysical properties of bone (n=8 rats per group). Serological markers of bone metabolism were measured by ELISA; bone mineral densities (BMD) by dual energy X-ray absorptiometry; bone biomechanics of the femur and lumbar vertebrae by three-point stress test; trabecular bone morphology of lumbar vertebrae by hematoxylin and eosin staining; messenger RNA expression levels of osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) in bone marrow cells by reverse transcription-quantitative polymerase chain reaction and OPG and RANKL protein expression levels in the proximal tibia were analyzed by immunohistochemistry. Compared with treatment by sCT or ASA alone, combined treatment (sCT+ASA) increased BMD, improved femur bone strength, normalized trabecular network architecture and morphology, and increased mRNA and protein expression of OPG, while reducing the expression of RANKL. Collectively, these results demonstrated that combined treatment (sCT+ASA) of osteoporotic symptoms in OVX rats was more effective than treatment with sCT or ASA alone. Furthermore, these two drugs appeared to alter the expression of two distinct factors in the OPG/RANKL/RANK system, suggesting that their effects may be synergistic. Since sCT and ASA are currently approved for use in humans, the results of the present study suggest that the safety and efficacy of sCT+ASA combined therapy for post-menopausal osteoporosis should be assessed in clinical trials.

Topics: Animals; Aspirin; Biomarkers; Bone Density; Calcitonin; Female; Femur; Immunohistochemistry; Lumbar Vertebrae; Osteoporosis; Osteoprotegerin; Ovariectomy; RANK Ligand; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; RNA, Messenger; Tibia

Topics: Aged; Alendronate; Bone Density Conservation Agents; Calcitonin; Calcium; Cholecalciferol; Humans; Lumbosacral Region; Male; Osteoporosis; Osteoporotic Fractures

The fate of inhaled salmon calcitonin (sCT) at the respiratory epithelial barrier was studied with particular emphasis on enzymatic degradation by trypsin, chymotrypsin, and neutrophil elastase.. Degradation of sCT was assessed by HPLC in cell homogenate, supernatant and intact monolayers of human respiratory epithelial cells (hBEpC, Calu-3, 16HBE14o-, A549) and Caco-2 as comparison at 37°C for 2 h. Breakdown of sCT by trypsin, chymotrypsin and neutrophil elastase was investigated. The presence of enzymes in cell supernatant and homogenate was studied by immunoblot and enzyme activity by model substrate assay. Transport studies across Calu-3 monolayers were performed.. sCT concentration remained unchanged over 2 h, when incubated in supernatant or with cell monolayers, independent of cell type studied. When cell homogenates were used, sCT concentrations were reduced to varying extents. sCT was degraded when incubated with enzymes alone. Western blot revealed abundance of all proteinases in cell homogenates and weaker expression in supernatants. Transport studies indicated net-absorptive sCT translocation; presence of bacitracin resulted in increased amount of sCT in receiver compartments.. Epithelial proteases play a role in the disposition of sCT after pulmonary delivery.

Topics: Administration, Inhalation; Biological Transport; Blood-Air Barrier; Caco-2 Cells; Calcitonin; Cell Line; Chromatography, High Pressure Liquid; Chymotrypsin; Humans; Leukocyte Elastase; Osteoporosis; Respiratory Mucosa; Trypsin

In order to assess the therapeutic efficacy of an antiresorptive drug with imparted bone targeting potential using bisphosphonate (BP) conjugation and an improved pharmacokinetic profile using PEGylation, we synthesized, characterized and evaluated in vivo efficacy of bone-targeting PEGylated salmon calcitonin (sCT) analog (sCT-PEG-BP). sCT-PEG-BP was compared with non-PEGylated bone targeting sCT analog (sCT-BP) and unmodified, commercially available sCT. sCT-PEG-BP conjugates were characterized by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) analysis. The effect of PEG-BP or BP upon sCT secondary structure was examined by Circular Dichroism and sCT-PEG-BP was evaluated for in vitro bone mineral Hydroxyapatite (HA) binding ability and calcium salts specificity using a binding assay for bone HA and several calcium salts. Anti-calcitonin antibody binding ability of these analogs was determined using enzyme-linked immunosorbent assay (ELISA), by reacting bone targeting sCT analogs with calcium phosphate coated Osteologic® plates and detecting the bound sCT using anti-sCT antibody. Potential cytotoxicity of these compounds was evaluated in monocytic RAW 264.7 cells, and sCT bioactivity was evaluated using an in vitro intracellular cAMP stimulation assay in human T47D breast cancer cells. Finally, in vivo efficacy of each compound was evaluated by determining the plasma levels of calcium after s.c. administration in normal rats, and in a rat model of Osteoporosis, secondary to ovariectomy (OVX). In vivo micro-computed tomography (micro-CT) was used to temporally map and quantify alterations in bone volume and bone mineral density (BMD) in the same animals at 1, 4, 8 and 12 weeks after OVX surgery. Sixteen 6 week old virgin female rats underwent OVX surgery followed by the daily s.c. injection of 2.5IU/kg/day sCT or equivalent analogs, and compared to four sham-operated, placebo treated control rats. Our results showed the chemical coupling of PEG-BP or BP to sCT altered its secondary structure without altering its antibody binding ability. sCT analogs retained strong sCT bioactivity, were non-toxic to RAW 264.7 cells in culture and elicited a comparable hypocalcemic effect to that of unmodified sCT in normal rats. Compared to marketed unmodified sCT, sCT-PEG-BP showed significantly improved efficacy in terms of preserving bone volume, BMD and trabecular micro-architecture in osteoporotic rats at the initial dose tested. Bisphosphonat

Topics: Animals; Bone Density; Bone Density Conservation Agents; Calcitonin; Calcium; Calcium Compounds; Cell Line; Cell Survival; Diphosphonates; Durapatite; Female; Mice; Osteoporosis; Ovariectomy; Polyethylene Glycols; Rats; Rats, Sprague-Dawley; Sulfhydryl Compounds

The effects of multivalent metal ions (Cu(2+)/Zn(2+)/Al(3+)) on the aggregation of salmon calcitonin (sCT)--a therapeutic peptide used worldwide in the treatment of osteoporosis and Paget's disease--have been studied in vitro using NMR (both solution state and solid state), TEM, ThT-fluorescence, and FT-IR spectroscopy. Overall, the various results indicated that the metal-ions-induced conformational transitions in the peptide--mostly toward the β-sheet--facilitate the aggregation of sCT in solution. First, the solution NMR has been used to check the interaction between the peptide and the metal ions. Following this, the formation and characterization of calcitonin aggregates has been performed using TEM, solid state NMR, and FT-IR spectroscopy. The TEM and ThT-fluorescence results revealed that the sCT peptide incubated with Cu(2+) and Zn(2+) metal ions (in aqueous environment) forms globular aggregates, while that with Al(3+) ions forms fibrils. The solid state NMR and FT-IR studies revealed the presence of a substantial amount of β-sheet content in sCT aggregates (formed in the presence of these metal ions) compared to the monomeric sCT, indicating that the metal binding is concomitant with conformational changes. The present study becomes crucial while prescribing this drug peptide under physio-pathological conditions associated with an abnormal accumulation of metal ions (Cu(2+)/Zn(2+)/Al(3+)) in the body (i.e., abnormal metal ion homeostasis).

Topics: Aluminum; Amino Acid Sequence; Bone Density Conservation Agents; Calcitonin; Cations; Copper; Humans; Molecular Sequence Data; Nuclear Magnetic Resonance, Biomolecular; Osteitis Deformans; Osteoporosis; Protein Structure, Secondary; Spectroscopy, Fourier Transform Infrared; Zinc

The purpose of this study was to develop a biodegradable triblock copolymer, mPEG-PLGA-mPEG-based delivery system for long-term controlled release of salmon calcitonin (sCT) after single subcutaneous injection.. The delivery system was prepared by dissolving sCT into polymer solution. In vitro release of sCT from the delivery systems was studied in phosphate buffer saline (PBS, pH 7.4) at 37 degrees C. Stability of released sCT and sCT remaining in gel formulation was evaluated using circular dichroism, HPLC and MALDI-TOF mass spectrometry. In vivo absorption and therapeutic efficacy of sCT from the polymeric formulations were examined in female wistar rats and methylprednisolone acetate (MPA)-induced osteoporosis rat model, respectively.. The polymeric formulations of sCT showed long term controlled release (~20 to 40 days) of sCT in its conformationally and chemically stable form. The sCT polymeric formulations controlled the release of sCT over ~20 to 40 days and prevented MPA induced osteoporosis in vivo. The released sCT was biologically active in terms of lowering serum calcium level.. The triblock copolymer delivery systems controlled the release of sCT in vitro and in vivo in chemically and conformationally stable as well as biologically active and therapeutically effective form.

Topics: Absorption; Animals; Biological Availability; Calcitonin; Drug Delivery Systems; Drug Stability; Female; Osteoporosis; Rats; Rats, Wistar; Temperature; Treatment Outcome

The aim of the study was to explore (1) the synthesis of a novel poly(ethylene glycol) modified lipid (PEG-lipid, PL) containing a chemically active tri-block linker, epsilon-maleimido lysine (Mal), and its conjugation with salmon calcitonin (sCT), and (2) the biophysical properties and activity of the resulting conjugate, Mal-PL-sCT, relative to the control, 2PEG-Mal-sCT, which comprises sCT conjugated with alpha-palmitoyl-N-epsilon-maleimido-L-lysine at cysteine 1 and cysteine 7, and PEG moieties at lysine 11 and lysine 18 via a conventional stepwise method.. The PEG-lipid was obtained by condensing palmitic acid derivative of epsilon-maleimido lysine with methoxy poly(ethylene glycol) amine. Under reductive conditions, the PEG-lipid readily reacted with sCT to yield the resultant compound, Mal-PL-sCT.. Dynamic light scattering analyses suggested that Mal-PL-sCT and 2PEG-Mal-sCT exhibited robust helical structures with a high tendency to aggregate in water. Both compounds were more stable against intestinal degradation than sCT, although Mal-PL-sCT was less stable than 2PEG-Mal-sCT. However, 2PEG-Mal-sCT did not possess hypocalcaemic activity while Mal-PL-sCT retained the hypocalcaemic activity of sCT when it was subcutaneously injected in the rat model. Multiple functional groups may be conjugated to a peptide via a tri-block linker without the risk of obliterating the intrinsic bioactivity of the peptide.. The resultant novel PEG-lipid has a potential role to optimize protein and peptide delivery.

Topics: Animals; Calcitonin; Calcium; Circular Dichroism; Digestion; Drug Carriers; Drug Design; Female; Gels; Lysine; Nephelometry and Turbidimetry; Osteoporosis; Particle Size; Polyethylene Glycols; Protein Structure, Secondary; Random Allocation; Rats; Rats, Wistar; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Time Factors

Transient osteoporosis of the hip is a rare clinical disorder of unknown etiology, characterized by hip pain and functional disability that resolves spontaneously in 6-24 months. Despite a benign prognosis, the long clinical course causes prolonged disability. We report on a case of transient osteoporosis of the hip during pregnancy that was rapidly resolved with the use of calcitonin. An accurate diagnosis was made 2 months after the onset of symptoms (4 weeks postpartum) based on findings in the form of bone marrow edema of the right hip by magnetic resonance imaging. The patient received calcitonin for 8 weeks and the beneficial effect was observed after 3 weeks of therapy with full resolution of symptoms after 8 weeks of therapy (4 months after onset of symptoms). We suggest that the use of calcitonin may be considered as a therapeutic intervention to shorten the disease duration.

Topics: Adult; Bone Density Conservation Agents; Calcitonin; Calcium; Cholecalciferol; Diphosphonates; Drug Therapy, Combination; Female; Hip Joint; Humans; Magnetic Resonance Imaging; Organotechnetium Compounds; Osteoporosis; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Third; Puerperal Disorders; Radionuclide Imaging

Osteoporosis is a disease of bone metabolic disorder, the incidence of which increases sharply in old people. Calcitonin (CT) is a peptide hormone containing 32 amino acid that can inhibit osteoclasts activity. Osteogenic Growth Peptide (OGP) is a peptide hormone with 14 amino acid. It is an autocrine mitogen for osteoblastic and firbroblastic cells which has anabolic activiy. Six SCT and OGP DNA segments were chemically synthesized and ligated into a yeast expression vector pPIC9. The recombinant plasmid was transformed into pichia pastoris GS115. Finally, we got two stable SCT-OGP high expression clones after screening. Purifed protein can stimulate the proliferation of osteoblastic and fibroblastic cells, and also stimulate serum ALP activity and decrease serum calcium level using mice as animal models, demonstrating its potential role in oteoporosis therapy.

Topics: Animals; Calcitonin; Calcium; Histones; Intercellular Signaling Peptides and Proteins; Mice; NIH 3T3 Cells; Osteoblasts; Osteoporosis; Rats; Rats, Wistar; Recombinant Fusion Proteins

Ovariectomy induces deterioration of the trabecular structure in the femoral neck of ewes, as depicted by MR microscopic imaging. This structural deterioration is prevented by salmon calcitonin treatment.. This study evaluated the trabecular (Tb) microarchitecture of an ovariectomy (OVX)-induced osteoporotic model in ewes and determined the effects of salmon calcitonin (sCT), an osteoclast inhibitor, on the Tb structure. This is the first report of OVX-induced changes in the Tb structure in the femoral neck in the ewes and effect of sCT on the microarchitecture.. Ewes (5-8 years old, n = 28) were equally allocated into sham (Sham), OVX injected with vehicle, or OVX injected with sCT at 50 or 100 IU, three injections per week. They were killed 6 months after OVX. The femoral neck was examined with an MR imager at 9.4 T in axial, coronal, and sagittal planes. An internal calibration procedure as a means of standardizing image analysis was used to adjust the segmentation threshold. Data from all three planes were averaged.. Compared with Sham, OVX induced significant changes (p < 0.0125) in the MRI-derived femoral neck Tb structure: Tb bone volume fraction (BV/TV), -18%; Tb number, -20%; Tb separation, +23%; number of free ends, +28%; number of nodes, -39%; number of Tb branches, -23%; mean length of Tb branches, -19%. Compared with OVX, treatment of sCT at 100 IU significantly improved all the Tb structural parameters to the Sham level (p < 0.0001 approximately p = 0.0281), whereas 50 IU significantly increased the Tb number and the mean length of the Tb branches. BV/TV explained 74% of the variation of compressive stress of the trabecular cylinder cores of the femoral neck. Combining all structural parameters in a multivariate regression analysis significantly improved the explanation to 84%, and adding BMD further improved the predictive ability of the model to 92%. We conclude that OVX induces deterioration of the MRI-derived Tb microstructure in the femoral neck of ewes. sCT treatment prevents OVX-induced changes. The femoral neck microarchitecture significantly correlates with its biomechanical properties. Combining microstructural parameters with BMD further improves the prediction of bone biomechanical properties. The effects of sCT on OVX ewes may help explain reduced fracture risk in postmenopausal osteoporotic women treated with sCT.

Topics: Animals; Calcitonin; Compressive Strength; Disease Models, Animal; Female; Femur Neck; Magnetic Resonance Imaging; Osteoporosis; Ovariectomy; Sheep

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

Calcitonin is currently used to treat hypercalcemia of many clinical types. However, we encountered a woman who suffered severe hypercalcemia and status epilepticus, both of which developed 8 days after the administration of salmon calcitonin for the treatment of breast cancer. When the patient first presented her serum calcium level was 15.5mg/dl, intact parathyroid hormone level 118 pg/ml, calcitonin <2 pg/ml, magnesium 1.2mg/dl, and phosphate 1mg/dl. Her serum calcium level returned to the reference range within 48 h after correction. At follow-up no hypercalcemia had developed, although the patient had received no further treatment for her breast cancer and multiple metastases were subsequently detected. Her hypercalcemia is ascribed to exogenous calcitonin supplementation. These conflicting events may be due to functionally heterogeneous calcitonin receptors or to activation of 1 alpha-hydroxylase by exogenous calcitonin.

Topics: Bone Neoplasms; Breast Neoplasms; Calcitonin; Female; Humans; Hypercalcemia; Middle Aged; Osteoporosis; Status Epilepticus

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

Salmon calcitonin (sCT)-containing proliposomes were prepared by penetrating a methanol-chloroformic solution of sCT and phosphatidylcholine (PC) into microporous sorbitol particles, followed by vacuum evaporation of the solvent. As a result, sCT proliposomes with free-flowing flowability were obtained. On contact with water, the proliposomes were rapidly converted into a liposomal dispersion, in which a certain amount of sCT was entrapped by the liposomes. The apparent permeability of sCT across Caco-2 cell monolayers was increased as the result of incorporating sCT into the proliposomes, suggesting that the pharmacokinetics of sCT would be modified through the administration of proliposomes. This is the first study that reports the successful loading of sCT, a protein drug, in proliposomes. The development of various dosage forms of sCT, especially solid dosage forms, appears be feasible using proliposomes.

Topics: Caco-2 Cells; Calcitonin; Humans; Liposomes; Microscopy, Electron; Microscopy, Electron, Scanning; Osteoporosis; Particle Size; Pharmaceutic Aids; Phosphatidylcholines; Sorbitol

Topics: Animals; Basement Membrane; Bone Density; Bone Resorption; Calcitonin; Calcium; Hydrocortisone; Male; Mandible; Microscopy, Electron, Scanning; Osteoporosis; Random Allocation; Rats

A collaborative study was undertaken by members of the International Network of Agencies for Health Technology Assessment (INAHTA). The evidence of the effectiveness of bone density measurement and selected treatments in preventing fractures in later life was reviewed. There was fair evidence that bone density measurement can predict risk of fractures and that hormone replacement therapy and intranasal salmon calcitonin preserve bone mass and decrease the risk of fractures. However, it was estimated that only 1-7% of hip fractures would be prevented if these technologies were used in a screening program for menopausal women. Results of the assessment were endorsed by 13 INAHTA members, disseminated widely and provided input to policy and further work in this area. The project demonstrated the feasibility of international collaborative health technology assessment.

Topics: Bone Density; Calcitonin; Canada; Cooperative Behavior; Estrogen Replacement Therapy; Female; Fractures, Bone; Health Policy; Humans; International Cooperation; Middle Aged; Osteoporosis; Outcome Assessment, Health Care; Technology Assessment, Biomedical

To assess the effectiveness of salmon calcitonin in the therapy of male osteoporosis.. Nine male patients aged 20-73 years with vertebral osteoporosis were included in this study. Patients were prescribed 100 units of salmon calcitonin injected subcutaneously three times per week over a period of three months, followed by three months without salmon calcitonin treatment. Thereafter the patients received another salmon calcitonin cycle for three months as described above. All men received calcium supplementation of 1000 mg/day throughout the study period of 12 months. Bone mineral density of the lumbar spine and at the hip was measured at the beginning and the end of the treatment period using DXA (n = 7) or QCT (n = 2).. Baseline evaluation revealed a bone mineral density of the lumbar spine of 0.78 +/- 0.09 g/cm2 and 0.62 +/- 0.09 g/cm2 at the hip. Treatment with salmon calcitonin resulted in a significant increase of vertebral bone mineral density to 0.80 +/- 0.09 g/cm2 (p < 0.015). Femoral bone mineral density also significantly increased after salmon calcitonin therapy to 0.64 +/- 0.11 g/cm2 (p < 0.05).. These results show that calcium and salmon calcitonin increase bone mineral density in male patients with osteoporosis. Calcium and calcitonin may be useful in the treatment of male osteoporosis; however, further studies are necessary before definite recommendations can be made.

Topics: Adult; Aged; Analgesics; Bone Density; Calcitonin; Calcium; Drug Administration Schedule; Drug Therapy, Combination; Follow-Up Studies; Humans; Injections, Subcutaneous; Male; Middle Aged; Osteoporosis; Retrospective Studies

The aim of this study was to assess the effect of calcitonin (CCT) and alendronate (ALN) on bone quality through histomorphometric, histological, densitometric and crystallographic evaluations in an experimental model of osteoporosis obtained in ovariectomized rats.. The animals were randomly assigned to the treatment with CCT (2 IU/kg/day, N-12) or with ALN (6 micrograms/kg/day, N-12) given subcutaneously, starting three months after ovariectomy: treatment lasted 60 days. Six rats untreated after ovariectomy and other 6 non ovariectomized (intact) were taken as controls. At the end of treatment the animals were sacrificed and femurs explanted for laboratory examinations. Results were evaluated by an ANOVA followed by the Tukey's test when appropriate.. The histomorphometric analysis showed a significant increase of the trabecular bone volume and of the cortical bone thickness either with CCT and ALN in comparison with the ovariectomized untreated controls. Optic and electronic microscopy examinations suggest a higher bone remodeling after ALN than after CCT, but accompanied by areas of imperfect mineralization, and more irregular osteon and collagen fibres disposition. The densitometry carried out at the femoral head and diaphysis showed a similar bone mass increase following either CCT and ALN, but significantly higher in comparison to the untreated controls. At the diaphysis level ALN was superior in increasing the bone mass also when compared to the intact rats. The mineralogic exams showed that CCT acted on the re-elaboration of the mineral phase approaching the molar ratio Ca/PO4 to the physiological values typical of senescence, and crystallography revealed that the formation of hydroxyapatite crystals follows a physiological mineral redeposition: those phenomena were not observed for ALN.. In conclusion both CCT and ALN could reduce the bone loss due to osteoporosis, by increasing the bone mass and thickness. Nevertheless the submicroscopic and chemical bone structure are less similar to the physiologic ones after treatment with ALN.

Topics: Alendronate; Analysis of Variance; Animals; Bone and Bones; Bone Density; Calcitonin; Crystallography; Female; Models, Biological; Osteoporosis; Ovariectomy; Rats; Rats, Sprague-Dawley

Topics: Analgesics; Calcitonin; Costs and Cost Analysis; Humans; Legislation, Drug; Osteoporosis

The authors have established that osteoporosis is noted in the age above 70 years old--in 70-80% and above 80 years old--in all of the patients. That's why while treating the fractures of neck of the femur (NF) in the patients aged older than 60 years the osteosynthesis is not recommended. The stump joint endoprosthesis may be a method of choice. It is expedient to prescribe antiresorptive preparations phosamax, myacalcique and preparations of calcium in the complex of treatment.

Topics: Age Factors; Aged; Aged, 80 and over; Alendronate; Analgesics; Calcitonin; Calcium, Dietary; Femoral Neck Fractures; Fracture Fixation, Internal; Humans; Middle Aged; Osteoporosis

It was examined histomorphometrically whether or not and how chronic treatment with nasal salmon calcitonin (SCT) of rats could prevent ovariectomy (OVX)-induced osteoporotic changes in the trabecular bone of tibia. During 7 weeks on a synthetic low Ca diet after OVX, rats developed type 1 osteopenia which was defined by strut analysis as resulting mainly from loss in the connectivity of strut but in the thickness. An intermittent dosing regimen of nasal SCT (10 or 40 U/rat/d, 3 d/week, for 7 weeks) was able to retard development of osteopenia in a dose-dependent manner. The results indicate that the nasal route would be usable for chronic treatment of experimental osteoporosis with SCT and possibly other peptide anti-osteoporotics.

Topics: Animals; Bone Diseases, Metabolic; Calcitonin; Female; Osteoporosis; Ovariectomy; Rats; Rats, Wistar

The activity of a novel calcitonin SB 205614 was compared with salmon calcitonin (sCT) and (Asu1,7)-eel calcitonin (ELC) in six different models of osteoclastic bone resorption in vitro and in vivo. SB 205614 is an ELC analogue that has an acetylenic bridge instead of the natural disulphide bridge, rendering the molecule more stable biologically than sCT and equally stable to ELC. Our aim was to determine whether this structural change compromised biologic activity, and if not, whether the increased stability could be used to exploit novel modes of administration. In the in vitro assays of pit formation by disaggregated rat osteoclasts on cortical bone slices (DROcA) and PTH stimulation of 45Ca-release from prelabeled fetal rat bone, no significant differences in activity were observed between the three calcitonins. In the DROcA, IC50s of 0.003, 0.015 and 0.064 pg/ml for sCT, ELC, and SB 205614, respectively, were determined, with total or near complete inhibition observed at 1 pg/ml (0.3 pM). In the assay of PTH-stimulation of 45Ca release, IC50s were measured of 5.5, 4.8, and 12.9 pM for sCT, ELC, and SB 205614, respectively; in every case maximal inhibition (ca. 80%) was observed at 30 and 100 pM. The internationally approved U.S. Pharmacopoeia bioassay of hypocalcemia in the rat following intravenous (IV) administration indicated that SB 205614 had a greater potency than ELC or sCT. More important, a full dose-hypocalcemic response curve demonstrated significantly increased potency compared to sCT or ELC, as the doses causing 15% lowering of serum calcium (approximately 50% of the maximum effect) were 33.9, 25.2, and 12.9 mg/kg for sCT, ELC, and SB 205614, respectively. As a preliminary means of investigating alternative delivery forms of calcitonin, the time course of the hypocalcemic effect was investigated in the rat and rabbit following IV administration, and was compared with that following intranasal (IN) administration (rat and rabbit), and following intracolonic administration (rat only). Maximal effects were similar, whereas in general the hypocalcemic effect of SB 205614 was of a longer duration than the other two calcitonins; this was reflected in a larger area over the curve (AOC). However, following IN administration in the rabbit, where an aerosol delivery device similar to that used in the clinic was used to administer the calcitonins, SB 205614 (100 IU/kg) induced a highly significant two-fold increase in the AOC compared to ELC or sCT

Topics: Amino Acid Sequence; Animals; Bone Resorption; Calcitonin; Disease Models, Animal; Drug Administration Routes; Evaluation Studies as Topic; Hypocalcemia; In Vitro Techniques; Male; Molecular Sequence Data; Osteoclasts; Osteoporosis; Rabbits; Rats; Rats, Sprague-Dawley; Rats, Wistar

Topics: Aerosols; Calcitonin; Drug Approval; Humans; Osteoporosis

Local immobilization is a good model for studying disuse-induced bone loss and to appreciate the effects of drugs, especially preventive action of antiresorptive therapy. In fact, increased osteoclastic activity is the main point of such a bone loss. The effect of salmon calcitonin was investigated on immobilization-induced osteoporosis in the sheep. Twenty-four nonovariectomized, adult, female, Welsh mountain sheep were submitted, by an external fixator procedure, to hock joint immobilization from the tibia to the the metatarsus for 12 weeks. The sheep were randomized into two groups receiving either an injection of placebo or salmon calcitonin (100 IU) three times per week, for 12 weeks. Histomorphometric analysis was performed on pre- and posttherapeutic transiliac bone biopsies, and on immobilized (left) and nonimmobilized calcanei removed after sacrifice. Results showed a 29% significant decrease of cancellous bone volume in the placebo group due to a significant reduced trabecular thickness when we compared immobilized versus nonimmobilized calcaneus. This structural adaptation appeared to be the consequence of an overall increased bone turnover. In the calcitonin group, same changes were observed, with a 23% reduction of bone mass in the immobilized calcaneus. By comparing calcitonin with placebo groups in both left and right calcanei, no difference was found. On the other hand, a significant increase of mineralization parameters in the iliac crest was only observed in the calcitonin group. In conclusion, salmon calcitonin, at a dose of 100 IU/day three times a week, was ineffective in preventing local disuse osteoporosis in this sheep model.

Topics: Animals; Calcaneus; Calcitonin; Cattle; Disease Models, Animal; Female; Immobilization; Osteoporosis; Sheep

Topics: Adrenal Cortex Hormones; Analgesics; Calcitonin; Gynecomastia; Humans; Male; Middle Aged; Osteoporosis

The anti-osteopenic effect of nasal salmon calcitonin (SCT) was investigated in a type 1 osteoporotic model, Wistar rats which were ovariectomized (OVX) at age of 12 weeks, and compared with that of subcutaneous SCT. It was proved that nasal (5, 10, 20 and 40 U/rat) and subcutaneous (5, 10 and 20 U/kg) administration of SCT on alternate days for 3 weeks, starting a week after OVX, prevented the osteopenic changes of tibia and lumbar vertebra; this was proved by physicochemical parameters and histomorphometrically. A clear dose-dependent effect was seen in the trabecular bone volume of a selected regions of the 5th lumbar vertebra, and the ED50s of nasal and subcutaneous SCT calculated were 7.4 U/rat and 3.5 U/kg, respectively. The results indicate that nasal SCT is absorbed efficiently in rats with increased bone turnover to prevent rapidly developing osteopenia and that the administration route is a suitable standard method for chronically giving biodegradable anti-osteoporotic peptides to rats.

Topics: Administration, Intranasal; Animals; Bone and Bones; Calcitonin; Calcium; Dose-Response Relationship, Drug; Female; Injections, Subcutaneous; Osteoporosis; Ovariectomy; Phosphorus; Rats; Rats, Wistar

A two-site assay was developed by use of the "dissociation and enhancement lanthanide fluoroimmunoassay" (DELFIA) technique for determination of salmon calcitonin (SCT) in serum after administration to osteoporotic patients. Polyclonal antibodies were produced in rabbits immunized with SCT coupled to ovalbumin. After affinity purification, the antibodies were used both as immobilized capture antibodies and as Eu-chelate-labeled signal antibodies. A sensitive assay with a detection limit of 1.1 pmol/L was achieved, and no cross-reaction with human calcitonin was observed. The intra- and interassay CVs were < 12% (n = 10) and < 15% (n = 4), respectively. Analytical recovery of SCT added to serum was 91% +/- 3% (mean +/- SD, n = 4). SCT was measurable in all the samples from eight osteoporotic patients after subcutaneous SCT administration. We conclude that this new sensitive and specific two-site DELFIA can reliably measure SCT in serum.

Topics: Aged; Aged, 80 and over; Calcitonin; Female; Flow Cytometry; Fluoroimmunoassay; Humans; Male; Osteoporosis; Time Factors

Coherence therapy, popularly known by the acronym ADFR (Activate, Depress, Free, Repeat), was designed to increase bone mass in osteopenic patients. Accordingly, we report a case of a hypogonadal male with histologically proven low bone turnover osteoporosis and a progressive vertebral fracture syndrome, who responded favorably to ADFR treatment with the use of salmon calcitonin and inorganic phosphate. Dramatic increments in bone mass were observed during a 68-month period of therapy. Serial quantitative computerized tomography demonstrated a 146% increase from baseline in bone mineral density for the first 30 months of treatment, and dual energy radiography yielded a 36.5% increase for the subsequent 31-68 months. Furthermore, no episode of fracture occurred since coherence therapy was initiated.

Topics: Adult; Bone Density; Calcitonin; Drug Therapy, Combination; Humans; Male; Osteoporosis; Phosphates; Reserpine; Spinal Diseases

Topics: Bone Diseases; Calcitonin; Clinical Trials as Topic; History, 20th Century; Humans; North America; Osteitis Deformans; Osteoporosis

To determine the effect of intranasal administration of salmon calcitonin on glucocorticoid-induced osteoporosis in children with nephrosis, we gave 100 U of calcitonin intranasally on alternate days with 1 alpha-hydroxyvitamin D3 to five children, 8 to 12 years of age, with frequently relapsing nephrosis. Four patients with osteoporosis, 10 to 14 years of age, were treated only with 1 alpha-hydroxyvitamin D3 and served as control subjects. Both groups were treated with an almost equal amount of glucocorticoids previously and during this study period. Bone mineral content of the spine was measured by a quantitative computed tomographic technique. The bone mineral content was preserved in both cortical and spongeous areas of the vertebrae during the 16-month period in the calcitonin-treated group but was decreased significantly in the control group. Urinary hydroxyproline and calcium excretion decreased significantly in the calcitonin-treated group. The serum calcium and phosphorus concentrations and the parathyroid function did not change significantly in either group. We conclude that calcitonin suppressed bone resorption and might be useful for the long-term treatment of osteoporosis, in combination with 1 alpha-hydroxyvitamin D3, in children with nephrosis requiring long-term glucocorticoid therapy.

Topics: Administration, Intranasal; Aerosols; Bone Density; Calcitonin; Child; Drug Therapy, Combination; Glucocorticoids; Humans; Hydroxycholecalciferols; Nephrosis; Osteoporosis; Recurrence; Spine; Tomography, X-Ray Computed

Osteoporosis becomes a common pathologic feature in patients given a long-term corticosteroid treatment: actually, bone formation proves decreased, and bone resorption increased. Said reduced bone formation is ascribable to an inhibited osteoblastic function: on the contrary, increased bone resorption may be ascribed to a suppressed intestinal calcium absorption with a consequent secondary increase in the parathyroid hormone secretion. The present trial had the purpose of assessing the BMC (Bone Mineral Content) in 10 patients with bullous diseases, such as pemphigus and pemphigoid, in the course of treatment with corticosteroid agents and nasal spray salmon calcitonin (sCT). The patients, 3 males and 7 females, mean age 62.9 years (min 33, max 93) were given intranasal sCT at the dosage regimen of 200 IU/day/6 months. No patients had previously received corticosteroid treatment. Six patients were given betamethasone, and 4 methylprednisolone, compared thereafter with hydrocortisone; the minimum dose was 70 mg and the maximum dose 400 mg. To evaluate the BMC, the patients were subjected to a single photon absorption densitometry (SPA). Distal radius determinations were reasonably related with the axial skeleton BMC. Determinations were carried out at the start of the trial, at the 3rd month as well as the end of treatment. At the start of the trial, the mean BMC was 0.765 (+/- SE 0.056) calculated at the radial distal end; at the 6th month of treatment the mean BMC resulted to be 0.847 (+/- SE 0.059). Actually, as reported by various investigators, BMC may attain an over 10% loss in the course of a corticosteroid treatment, an evidence that is not encountered in the case of an intranasal sCT administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Betamethasone; Calcitonin; Female; Humans; Male; Methylprednisolone; Middle Aged; Osteoporosis; Skin Diseases, Vesiculobullous; Time Factors

Topics: Adult; Aged; Aged, 80 and over; Calcitonin; Drug Evaluation; Female; Humans; Male; Middle Aged; Osteoporosis; Product Surveillance, Postmarketing

Topics: Aged; Calcitonin; Densitometry; Female; Humans; Middle Aged; Osteoporosis

Prednisone-induced osteoporosis is very frequent in the long-term treatment of sarcoidosis (sarcoidosis 4:45-48, 1987). The aim of this work is to evaluate if salmon Calcitonin (sCT) is able to prevent osteopenia in the long-term. We have studied 53 patients with chronic histologically-proven sarcoidosis, all needing steroids, in a follow-up of 15 months; 20 of them were protected with sCT (100 I.U. i.m. daily for one month, then every two days for all the time of the study), 33 were unprotected. The two groups were matched for age, sex and total dose of prednisone. In order to overcome the differences of Vertebral Cancellous Mineral Content (VCMC) due to age and sex, we express VCMC in terms of Z score, i.e. the number of standard deviations above or below our normal means: initial Z score was -1.77 +/- 0.16 in the sCT group and -0.99 +/- 0.17 in the other group (P less than .05). For each subject we calculated the Mineral Loss (ML) in % of the initial value. At the end of the study ML% averaged -2.15(+/- 2.27) in the sCT protected group, and -14.11(+/- 2.08) in the unprotected group (P less than .001). We have also analysed the results limited to pts with initial Z score under -1 (19 sCT protected pts vs 18 unprotected). In these subgroups the ML% after 15 months averaged -13.62(+/- 2.9) in the unprotected group and -2.80(+/- 2.29) in the protected one (P less than .01). Finally we have studied another subgroup, i.e. 21 postmenopausal females: 9 were sCT protected, 12 were unprotected.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Calcitonin; Chronic Disease; Female; Humans; Male; Menopause; Middle Aged; Minerals; Osteoporosis; Prednisone; Sarcoidosis; Spine

Topics: Adrenal Cortex Hormones; Adult; Aged; Arthritis, Rheumatoid; Calcitonin; Drug Evaluation; Female; Humans; Male; Menopause; Middle Aged; Osteoporosis; Scleroderma, Systemic; Time Factors

Twenty-five patients with radiological and clinical evidence of osteoporosis were studied. Nineteen patients received oral phosphorus at a dose of 1,000 mg/die for 10 days followed by salmon calcitonin (100 U MRC/die) for 20 days. Six patients received only oral calcium at a dose of 1,000 mg/die). In the first group, a significant increase in serum osteocalcin and parathyroid hormone, after administration of phosphorus and persisting after treatment with salmon calcitonin, was found. No variation in the controls was observed. In a later study, a significant increase in serum 1,25 dihydroxyvitamin D (1,25(OH)2D3), after receiving phosphorus and persisting after salmon calcitonin, was demonstrated. In accordance with the authors' results, phosphorus could be considered a useful activator of bone formation and this stimulus by parathyroid hormone was mediated. Finally, the positive effects of phosphorus on circulating 1,25(OH)2D3 must be considered for a good treatment protocol of osteoporosis.

Topics: Administration, Oral; Aged; Aged, 80 and over; Alkaline Phosphatase; Bone and Bones; Calcitonin; Calcitriol; Calcium; Calcium-Binding Proteins; Drug Therapy, Combination; Female; Humans; Hydroxyproline; Middle Aged; Minerals; Osteocalcin; Osteoporosis; Parathyroid Hormone; Phosphorus

Twenty-one women with primary osteoporosis received an intramuscular injection of 100 IU of salmon calcitonin at 8 AM. Blood samples IU of salmon calcitonin at 8 AM. Blood samples were collected up to 5 h postcalcitonin and urine was collected for 24 h in three periods of 8 h each. A significant fall of the total hydroxyproline excretion (THP) was observed in every period but the maximum effect took place 8-16 h postcalcitonin. The effect was more pronounced in those patients with a greater basal excretion of THP and in those with a more significant diminution of their bone mass. A significant diminution of the urinary excretion of calcium was found 8-24 h postcalcitonin, while phosphate excretion increased throughout the three 8 h periods. The effect of calcitonin in osteoporotic women was compared with the results obtained in 9 patients with Paget's disease. In absolute in 9 patients with Paget's disease. In absolute values the fall of THP excretion was significantly greater in the pagetic patients but the percentage diminution was not significantly different in osteoporotic women and in pagetic patients. Salmon calcitonin induced a significant acute diminution of bone turnover in patients with osteoporosis, as defined by decreases in total urinary hydroxyproline. The calcitonin-induced hypocalcemia does not seem to be an accurate index of the hormone action in osteoporosis.

Topics: Aged; Calcitonin; Calcium; Female; Humans; Hydroxyproline; Middle Aged; Osteitis Deformans; Osteoclasts; Osteoporosis; Phosphates

Prevention of the experimental bone rarefaction which occurs in rats put on a low calcium diet was attempted by using salmon calcitonin and 25 hydroxyvitamin D given with a similar regimen to that used in human disease. Results were compared with the previously reported effects of synthetic anabolic steroids. Statistical analysis was carried out on measurements of cancellous bone mass. No statistically significant increase in the femoral trabecular bone volume occurred in rats put on an hypocalcemic diet plus treatment by calcitonin and vitamin D whereas such an increase had been noted when anabolic steroids were used. Measurement of the trabecular bone volume of proximal and distal epiphyses demonstrated a statistically significant difference between rats on a hypocalcemic diet treated by 25-OH-D3 and rats treated by calcitonin or controls on a normal diet. In rats on a normal diet, 25 hydroxyvitamin D led to an increase in bone mass which did not reach statistical significance but is probably explained by improvement in calcium intestinal absorption.

Topics: Anabolic Agents; Animals; Bone and Bones; Bone Resorption; Calcifediol; Calcitonin; Calcium; Calcium, Dietary; Epiphyses; Female; Osteoporosis; Rats; Rats, Inbred Strains

Topics: Calcitonin; Calcium Carbonate; Drug Therapy, Combination; Female; Humans; Injections, Intramuscular; Injections, Subcutaneous; Menopause; Osteoporosis; Vitamin D

Topics: Arthritis; Calcitonin; Drug Administration Schedule; Humans; Osteoporosis; Pain

Calcitonin has been considered of therapeutic value in osteoporosis because of its effects in tissue culture. In the whole animal, however, the predominant result seems to be hypocalcemia, which might be expected to have the opposite effect of stimulating parathyroid hormone secretion and therefore resorption of bone. Indeed, in a short term study of 3- and 4-month duration in osteoporotic women, this was found to be so. A combination of calcium and calcitonin was therefore considered a more promising therapeutic alternative for this disease. Calcium was given to 26 patients, alone or with vitamin D, for a period of 15 months, and the effects on serum and urine calcium and phosphorus and on bone resorption and formation were evaluated. Calcium and vitamin D decreased serum parathyroid hormone levels, reduced bone resorption, and increased urinary calcium. The addition of calcitonin to the calcium and vitamin D did not seem to change these effects. Neither form of treatment resulted in change of bone mass. Calcium, with or without vitamin D supplements, may prevent the development of osteoporosis, but it seems unlikely that calcitonin has any additional desirable effect in the disease.

Topics: Aged; Bone and Bones; Bone Resorption; Calcitonin; Calcium; Female; Humans; Male; Middle Aged; Osteoporosis; Parathyroid Hormone; Phosphates