calcitonin and Fractures--Bone

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

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

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

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

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

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

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

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

Osteoporosis is a 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

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

With the aim of preventing postfracture osteopenia, we randomized 24 patients with internally fixed ankle fractures to 3 months of treatment with placebo or 200 IU nasal salmon calcitonin (sCT) in a prospective, double-blind design. 3 patients were excluded, leaving 11 patients in the placebo group and 10 in the sCT group for study. Bilateral measurements of bone mineral content (BMC) in the coronal plane of the proximal tibia were performed by dual photon absorptiometry (DPA) postoperatively within 7 days of the fracture and after 1.5, 3 and 6 months. 3 months after the fracture, BMC in the injured legs had decreased by 14% in the placebo group and 2.1% in the sCT group. This difference was not statistically significant. In the healthy legs, a statistically significant intergroup difference was seen 6 weeks after the fracture, caused by a tendency towards a decrease in BMC of 4.6% in the placebo group, while BMC in the sCT group had increased by 7.4%. Nasal sCT may to some extent, but in this study not significantly, reduce postfracture osteopenia, and cause a significant effect on BMC in the healthy leg.

Topics: Absorptiometry, Photon; Administration, Intranasal; Adult; Ankle Injuries; Bone Density; Bone Diseases, Metabolic; Calcitonin; Double-Blind Method; Female; Fracture Fixation, Internal; Fracture Healing; Fractures, Bone; Humans; Male; Middle Aged; Prospective Studies; Radionuclide Imaging; Tibia; Time Factors

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

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

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

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

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

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

One hundred and four patients with Paget's disease of bone received treatment with a calcium/thiazide regimen, salmon calcitonin, or ethane-1-hydroxy-1, 1-diphosphonate (EHDP). Most patients commenced therapy with the calcium/thiazide regimen; in 67% of these, the disease was satisfactorily controlled for some years. When the response was unsatisfactory, calcitonin was given. This was frequently effective, but produced troublesome nausea in 28% of patients. When these side effects were unacceptable, or the response was not adequate, EHDP was given, unless the patient appeared to be at risk of fracture. It is suggested that the calcium/thiazide regimen has a place in the management of Paget's disease; that calcitonin is more frequently effective, but has a high incidence of unpleasant, though not serious, side effects; and that EHDP is a useful agent in the treatment of Paget's disease, but must be administered with care, and does carry a small risk of pathological fracture.

Topics: Aged; Alkaline Phosphatase; Calcitonin; Calcium; Chlorthalidone; Dose-Response Relationship, Drug; Etidronic Acid; Female; Fractures, Bone; Humans; Kinetics; Male; Middle Aged; Nausea; Osteitis Deformans; Risk