Calcitonin

Calcitonin is a 32-amino acid polypeptide secreted by the parafollicular cells of the thyroid. Effects on bone include inhibition of osteoclasts, thus preventing bone resorption, as well as increased renal calcium excretion. Salmon calcitonin is often used therapeutically because it is more potent and has a longer duration of action compared with human calcitonin. Calcitonin also possesses analgesic properties. The mechanism of its analgesic effect is unknown but is thought to involve inhibition of prostaglandins and stimulation of β-endorphins. Most of the clinical data in postmenopausal osteoporosis involves the use of salmon calciton in nasal spray. Clinical trials have demonstrated a reduction in the risk of vertebral fractures and increased bone mineral density. Studies examining nonvertebral fractures have shown mixed results, some indicating a nonsignificant risk In general, calcitonin is inferior to bisphosphonates (BPs) in reducing fracture risk. Calcitonin is effective in the treatment of osteopathic pain. It has also been used in glucocorticoid-induced osteoporosis. Parenteral calcitonin is generally associated with more frequent side effects compared with intranasal calcitonin. Injectable administration can cause flushing, tingling, nausea, and injection site and allergic reactions. Side effects with intranasal use are usually limited to local effects (nasal congestion and irritation). Recent phase I trials with a new oral dosage form show promise in terms of efficacy and tolerability for treating patients who prefer this route of administration. This review of pertinent literature on calcitonin indicates that this remains a viable, though second-or third-line, agent for osteoporotic patients who refuse or cannot tolerate other treatments (e.g., BPs, raloxifene, and estrogen).     

Calcitonin for prevention and treatment of postmenopausal osteoporosis

Prolonged calcitonin administration (intramuscular, subcutaneous, or intranasal) can prevent postmenopausal trabecular bone loss. Nasal administration constitutes a particularly attractive option for women who cannot tolerate or benefit from estrogen replacement therapy. The optimal schedule of administration still has to be precised, but 100 U/day of nasal calcitonin, combined with calcium supplements, can currently be recommended. Interrupted regimens are maybe favourable. Calcitonin can also prevent further bone loss in established osteoporosis particularly if bone turnover is increased. The anti-fracture efficacy of calcitonin is suggested by different types of studies but has not been formally demonstrated. Lastly, its analgesic efficacy in cases of painful vertebral compression fractures has been demonstrated in controlled studies.     

Calcitonin Therapy in Osteoporosis

Osteoporosis is the most prevalent metabolic bone disease and is characterized by diminished bone strength predisposing to an increased risk of fracture. Its incidence is particularly high in postmenopausal women but it can also affect other groups, such as men and patients receiving corticosteroid therapy. Calcitonin is a naturally occurring peptide which acts via specific receptors to strongly inhibit osteoclast function. It has been used in the treatment of osteoporosis for many years. Historically, calcitonin was administered as a parenteral injection, but the intranasal formulation is now the most widely used because of its improved tolerability. New approaches are currently being investigated to enhance the bioavailability and effects of calcitonin, including oral, pulmonary, and transdermal routes of administration, and novel allosteric activators of the calcitonin receptor. Several controlled trials have reported that calcitonin stabilizes and in some cases produces a short-term increase in bone density at the lumbar spine level. The most relevant clinical trial to evaluate the effect of calcitonin in the prevention of fractures was the Prevent Recurrence of Osteoporotic Fractures (PROOF) study, a 5-year double-blind, randomized, placebo-controlled trial showing that salmon calcitonin nasal spray at a dosage of 200 IU/day can reduce the risk of vertebral osteoporotic fractures by 33% (relative risk [RR] = 0.67; 95% CI 0.47, 0.97; p = 0.03). However, the 100 and 400 IU/day dosages did not significantly reduce vertebral fracture risk. Effects on nonvertebral fractures were not significant (RR = 0.80; 95% CI 0.59, 1.09; p = 0.16). There is mounting evidence to show that calcitonin diminishes bone pain in osteoporotic vertebral fractures, which may have clinical utility in vertebral crush fracture syndrome. A recent study suggests that nasal salmon calcitonin appears to be a promising therapeutic approach for the treatment of men with idiopathic osteoporosis, although long-term trials are necessary to confirm these results and evaluate fracture rate as an endpoint in men. The role of calcitonin in corticosteroid-induced osteoporosis remains controversial, hence it can only be considered a second-line agent for the treatment of patients with low bone mineral density who are receiving long-term corticosteroid therapy.     

Bisphosphonate treatment of osteoporosis

Bisphosphonates represent the agents of choice for most patients with osteoporosis. They are the best studied of all agents for the prevention of bone loss and reduction in fractures. They increase BMD, primarily at the lumbar spine, but also at the proximal femur. In patients who have established osteoporosis, bisphosphonates reduce the risk of vertebral fractures, and are the only agents in prospective trials to reduce the risk of hip fractures and other nonvertebral fractures. Bisphosphonates reduce the risk of fracture quickly. The risk of radiographic vertebral deformities is reduced after 1 year of treatment with risedronate [68]. The risk of clinical vertebral fractures is reduced after 1 year of treatment with alendronate [69] and just 6 months' treatment with risedronate [157]. The antifracture effect of risedronate has been shown to continue through 5 years of treatment [158]. Alendronate and risedronate are approved by the FDA for prevention of bone loss in recently menopausal women, for treatment of postmenopausal osteoporosis, and for prevention (risedronate) and treatment (alendronate and risedronate) of glucocorticoid-induced osteoporosis. Alendronate is also approved for treatment of osteoporosis in men. Other bisphosphonates (etidronate for oral use, pamidronate and zoledronate for intravenous infusion) are also available and can be used off label for patients who cannot tolerate approved agents. Although bisphosphonates combined with estrogen or raloxifene produce greater gains in bone mass compared with single-agent treatment, the use of two antiresorptive agents in combination cannot be recommended because the benefit on fracture risk has not been demonstrated and because of increased cost and side effects.     

Treatment of osteoporosis with bisphosphonates

Bisphosphonates are safe and effective agents for treatment and prevention of osteoporosis. Alendronate and risedronate are the best studied of all agents for osteoporosis in terms of efficacy and safety. They increase bone mass. In patients who have established osteoporosis, they reduce the risk of vertebral fractures. They are the only agents shown in prospective trials to reduce the risk of hip fractures and other nonvertebral fractures. They are approved by the US FDA for prevention of bone loss in recently menopausal women, for treatment of postmenopausal osteoporosis, and for management of glucocorticoid-induced bone loss. Other bisphosphonates (e.g., etidronate for oral use, pamidronate for intravenous infusion) are also available and can be used off-label for patients who cannot tolerate approved agents. Bisphosphonates combined with estrogen produce greater gains in bone mass compared with either agent used alone; whether there is a greater benefit of combination therapy on fracture risk is not clear. Combining a bisphosphonate with raloxifene or calcitonin is probably safe, although data on effectiveness are lacking.     

Role of bisphosphonates and calcitonin in the prevention and treatment of osteoporosis

Bisphosphonates have been shown to increase bone mineral density in patients with established osteoporosis as well as those with osteopenia. The evidence conclusively shows a reduction in fracture rates in patients on the more potent nitrogen containing bisphosphonates. Indeed, significant vertebral fracture rate reduction has been demonstrated after only 1 year of therapy. Alendronate, a second-generation bisphosphonate, and risedronate, a third-generation bisphosphonate, are first line medications for the treatment of osteoporosis given their efficacy in preventing both vertebral and non-vertebral fractures. There is evidence that vertebral fractures may be prevented by intermittent cyclic therapy with etidronate. All three have been shown to increase bone mineral density in the spine, with alendronate and risedronate producing significant increases in hip bone density. Calcitonin has demonstrated the ability to reduce vertebral fracture rates with minimal changes in bone density. Calcitonin is also beneficial in reducing the bone pain associated with fractures.     

Aging bone and osteoporosis: strategies for preventing fractures in the elderly

As the older population increases, the incidence of osteoporotic fractures is expected to dramatically rise during the next few decades. Older patients are much more susceptible to fracture at any given bone mineral density (BMD) than are younger patients because of various factors, including the quality of aging bone, which involves more than BMD. Suppression of increased bone turnover by antiresorptive therapies, even with only small changes in BMD, can reduce fracture risk, especially in the lumbar spine. Bisphosphonate treatment can significantly reduce vertebral and nonvertebral fractures, including hip fractures, even in the very elderly. Prospective analyses show that risedronate therapy consistently and significantly reduces the risk of new morphometric vertebral fractures after 1 year in postmenopausal women. Post hoc analyses report significant reductions in the risk of 1 new clinical vertebral fracture after 6 months of risedronate therapy and after 1 year of alendronate therapy. Oral raloxifene therapy and salmon calcitonin nasal spray therapy have been shown to reduce the risk of vertebral fracture after 3 and 5 years, respectively, and post hoc data show a significant reduction in clinical vertebral fracture risk at 1 year with raloxifene use. However, neither raloxifene therapy nor calcitonin therapy reduce the risk of nonvertebral and hip fractures at currently approved doses. Bisphosphonates have been shown to be safe and efficacious with 7 years' risedronate sodium and 10 years' alendronate sodium data published, and bisphosphonates reduce bone turnover and increase BMD to a greater degree than raloxifene and calcitonin, which may partly account for their nonvertebral and hip fracture reduction effect. Therefore, bisphosphonate therapy with risedronate or alendronate should be considered in patients with low BMD at the hip and in older patients with osteoporosis and osteopenia, particularly those with an existing fracture.     

Treatment of osteoporosis and Paget's disease

Osteoporosis is a major public health problem. In women, the estimated lifetime risks of hip and vertebral fractures are 15% and 25%, respectively. The development of accurate and reproducible methods of assessing bone mineral density has enabled identification of persons at risk of fracture and assessment of response to treatment. Estrogen replacement therapy is effective in the prophylaxis of postmenopausal osteoporosis, and is the only therapy with well-proven antifracture efficacy. Fluoride can dramatically increase bone density, although a recent large, controlled study has demonstrated no effect on vertebral fractures. Bisphosphonates are emerging as a likely effective therapy for both idiopathic and glucocorticoid-induced osteoporosis. Calcium, vitamin D, calcitonin, and anabolic steroids may still have a role. Parathyroid hormone is a promising development that will need further study. Paget's disease is also common, affecting more than 3% of people over 40 years old. Calcitonin is an established therapy, although the bisphosphonates are a promising alternative.     

Corticosteroid-Induced Osteoporosis

Corticosteroid-induced osteoporosis is the leading cause of secondary osteoporosis and a significant cause of morbidity in both men and women. Long-term use of even low-dose corticosteroids has been associated with increased risk of bone loss. Recent large randomized controlled trials have generated new knowledge on treatment strategies for patients with corticosteroid-induced osteoporosis. However, the majority of individuals receiving corticosteroids are not receiving prophylaxis for osteoporosis. Calcium and vitamin D should be recommended to patients initiating therapy with corticosteroids (and should be adequate for those receiving corticosteroids for less than 3 months). For those receiving corticosteroids for greater than 3 months, bisphosphonates are the therapy of choice, with both alendronate (alendronic acid) and risedronate (risedronic acid) approved by the US FDA for use in this indication. Calcitonin can be considered a second-line agent and should be reserved for patients who are intolerant of bisphosphonates or who are experiencing pain from a vertebral fracture. Hormone replacement therapy or testosterone therapy may be offered to those individuals on long-term corticosteroid treatment who are hypogonadal. Teriparatide (recombinant human parathyroid hormone 1-34) shows promise as a future anabolic agent for the prevention and treatment of patients with corticosteroid-induced osteoporosis.     

Calcitonin

Calcitonin reduces the risk of vertebral fracture in postmenopausal women with osteoporosis. Calcitonin produces small increments in the bone mass of the spine and modestly reduces bone turnover in women with osteoporosis. No significant effect on nonvertebral fractures has been observed. Calcitonin may have analgesic benefit.     

Current trend of nasal calcitonin spray

Nasal calcitonin spray is a newly approved treatment for osteoporosis. This treatment increases lumbar spine bone mass and well tolerated. In one recent study nasal calcitonin is reduced the rate of vertebral fracture. In Japan clinical sturdy (phase III) of nasal calcitonin was performed. But this study is suspended. However nasal calcitonin has been permitted in other 50 countries.     

Drug insight: Existing and emerging therapies for osteoporosis

Osteoporosis is a major public health problem that is characterized by microarchitectural deterioration, low bone mass, and increased risk of fractures. Currently, many women and men affected with this disease are not diagnosed or treated. As osteoporosis is often clinically silent, risk-factor assessment and measurement of BMD are needed to identify those who may benefit from osteoporosis therapy. Although adequate daily intake of calcium and vitamin D, and regular weight-bearing exercise are important for skeletal health, they are not adequate treatments for individuals with osteoporosis. Therapies approved for treatment and/or prevention of osteoporosis in the United States include oral bisphosphonates (alendronate, ibandronate and risedronate), calcitonin, estrogens, teriparatide (parathyroid hormone fragment [1-34]), and raloxifene. For most patients, oral bisphosphonates are the treatment of choice, given the large-scale randomized-trial data demonstrating efficacy in fracture reduction, although bisphosphonates that reduce spine and nonspine fractures (e.g. alendronate and risedronate) are preferred. For high-risk patients (those with very low bone density, or with fractures), teriparatide therapy for 2 years should be considered. The treatment paradigm for osteoporosis will evolve further as promising new treatments progress through clinical development.     

Osteoporosis. Pathogenesis, diagnosis, and treatment in older adults

Osteoporosis is a major cause of disability and excess mortality in older men and women. Hip fracture incidence accelerates approximately 10 years after menopause in women and after age 70 in men. Approximately 1 million Americans suffer fragility fractures each year at a cost of over 14 billion dollars. The disability, mortality, and cost of hip and vertebral fractures are substantial in the rapidly growing, aging population so that prevention of osteoporosis is a major public health concern. BMD is used to make the diagnosis of osteoporosis before incident fracture and predict fracture risk. Recommendations for treatment and prevention of osteoporosis based on BMD score have been published by the World Health Organization and the National Osteoporosis Foundation. In a process that continues throughout life, bone repairs itself by the coupled action of bone resorption followed by bone formation, sometimes referred to as bone turnover. Osteoblasts and osteoclasts are the primary cells involved in bone formation and resorption, respectively. The process of bone turnover is regulated by hormones, such as PIH and local factors such as IL-1 and prostaglandins. Following attainment of peak bone mass at age 25, bone loss begins, accelerates in women at menopause and slows again but continues into advanced years at a rate of 1% to 2% per year, similar to premenopausal bone loss rate. The leading theories of the mechanism of bone loss in older individuals is calcium deficiency leading to secondary hyperparathyroidism and sex hormone deficiency. Risk factors such as age, gender, ethnic background, smoking, exercise, and nutrition, and medical conditions associated with osteoporosis should be evaluated and modified when possible to prevent further bone loss. Osteoporosis treatment and prevention include weight-bearing exercise, calcium and vitamin D supplementation, estrogen replacement, bisphosphonates, selective estrogen receptor antagonists, and calcitonin. Although there is no currently approved treatment for osteoporosis in men, many of the treatments approved for osteoporosis in women hold promise to be beneficial in men.     

Parathyroid hormone

Parathyroid hormone (PTH) is the most recently approved agent for osteoposis treatment. It differs from other therapies that act by inhibiting bone resorption, because it stimulates bone formation. The resultant increases in bone mineral density are therefore greater than those associated with therapy with bisphosphonates (BPs), selective estrogen receptor modulators, or calcitonin. Despite being available for at least 2 yr. PTH has not been exten sively studied. Although some existing data support its use for reducing the risk of vertebral fractures in women. data are still limited with regard to nonvertebral fracture prevention in women and fracture prevention in men. Preliminary studies have demonstrated a potential role in the management of patients with glucocorticoid-induced osteoporosis, but more data are needed. PTH is administered daily by subcutaneous injection for a maximum of 24 mo. Common adverse effects include pain with injection, arthralgia, and nausea. PTH caused an increase in osteosarcoma in rats and therefore, its use should be avoided in patients at increased risk of osteosarcoma, such as those with Paget's disease, unexplained baseline elevations of alkaline phosphatase, open epiphyses, or previous skeletal radiation exposure. At this time. PTH should not be combined with other agents, but a 2-yr treatment period may be sequentially followed by a BP. Because of high cost, the need for parenteral administration and potential for adverse effects, PTH use should be reserved for patients with severe osteoporosis who fail BP therapy.     

Treating osteoporosis to prevent fractures: current concepts and future developments

Antiresorptive drugs, such as the bisphosphonates and the RANKL inhibitor denosumab, are currently the most widely used osteoporosis medications. These drugs increase bone mineral density (BMD) and reduce the risk of vertebral (by 40–70%), nonvertebral (by 25–40%) and hip fractures (by 40–53%) in postmenopausal women with osteoporosis. Due to the risk of rare side‐effects, the use of bisphosphonates has been limited to up to 10 years with oral bisphosphonates and 6 years with intravenous zoledronic acid. Despite their well‐proven efficacy and safety, few women at high risk of fracture are started on treatment. Case finding strategies, such as fracture risk‐based screening in primary care using the fracture risk assessment tool (FRAX) and Fracture Liaison Services, have proved effective in increasing treatment rates and reducing fracture rates. Recently, anabolic therapy with teriparatide was demonstrated to be superior to the bisphosphonate risedronate in preventing vertebral and clinical fractures in postmenopausal women with vertebral fracture. Treatment with the sclerostin antibody romosozumab increases BMD more profoundly and rapidly than alendronate and is also superior to alendronate in reducing the risk of vertebral and nonvertebral fracture in postmenopausal women with osteoporosis. For patients with severe osteoporosis and high fracture risk, bisphosphonates alone are unlikely to be able to provide long‐term protection against fracture and restore BMD. For those patients, sequential treatment, starting with a bone‐building drug (e.g. teriparatide), followed by an antiresorptive, will likely provide better long‐term fracture prevention and should be the golden standard of future osteoporosis treatment.     

How to manage postmenopausal osteoporosis?

Osteoporosis is characterized by reduced bone mass and disruption of bone architecture, resulting in increased fracture risk. Several therapeutic agents are now available to treat postmenopausal osteoporosis and prevent fractures. Combined calcium and vitamin D supplementation reduce the relative risk of non-vertebral fractures by about 18%. Hormone replacement therapy (HRT) should not be prescribed for osteoporosis in women who do not experience menopausal symptoms. The marked benefits of raloxifene on the reduction in invasive breast cancer and vertebral fracture risk are partially counterbalanced by a lack of effect on non-vertebral fracture risk, and an increased risk of venous thromboembolism and stroke. All four bisphosphonates available in Belgium, except ibandronate, have been shown to reduce the risk of vertebral, non-vertebral and hip fractures in prospective, placebo-controlled trials. Globally, the incidence of vertebral fractures is reduced by 41%-70%, and the incidence of non-vertebral fractures by 25%-39%. The anti-fracture efficacy of weekly or monthly doses of oral bisphosphonates has not been directly shown but is assumed from bridging studies based on BMD changes. To date, the various bisphosphonates have not been studied in head-to-head comparative trials with fracture endpoints. There are potential concerns that long-term suppression of bone turnover associated with bisphosphonate treatment may eventually lead to adverse effects, especially atypical femoral fractures and osteonecrosis of the jaw, but these cases are extremely rare. Teri-paratide (recombinant human 1-34 PTH) administered by daily subcutaneous injections decreases by 65% the relative risk of new vertebral fractures in patients with severe osteoporosis. Pivotal trials with strontium ranelate have shown a 41% reduction in new vertebral fractures and a 16% reduction in non-vertebral fractures over 3 years. Denosumab is a fully human monoclonal antibody to RANK Ligand that is administered as a 60-mg subcutaneous injection every 6 months. In the pivotal phase III trial, there was a 68% reduction in the incidence of new vertebral fractures, whereas the incidence of non-vertebral fractures was reduced by 20%. Several new approaches are being explored, including antibodies to sclerostin, cathepsin K inhibitors, src kinase inhibitors, and drugs that act on calcium sensing receptors.     

Selective estrogen-receptor modulators

Tamoxifen is useful for adjuvant treatment of breast cancer and in some women for the prevention of breast cancer. The risk-benefit ratio in regard to the skeleton and perhaps other organ systems may very well be different for postmenopausal versus premenopausal women. In postmenopausal women, tamoxifen (20 mg/d) increased BMD in the spine and perhaps the hip; however, the effect on fracture risk is unclear. Therefore, for postmenopausal women with osteoporosis, consideration should be given to the addition of an agent that is shown to have efficacy against fractures (such as bisphosphonates), even while these women are on tamoxifen. For women at only modest or moderate risk, with bone density above the osteoporosis range (T score above -2.5) and no major fracture history, tamoxifen is probably adequate for 5 years of use. Potentially serious adverse effects include venous thromboembolism, uterine cancer, benign uterine disease, and cataracts. Raloxifene (60 mg/d) protects against vertebral fractures over 4 years in women with osteoporosis, produces small increases in bone mass of the spine, hip, and total body, and reduces bone turnover in postmenopausal women with or without osteoporosis. No significant effect has yet been demonstrated on nonvertebral fractures after 4 years of treatment. Raloxifene has the additional benefit of substantially reducing the risk of ER-positive invasive breast cancer and does not increase the risk of uterine disease. Raloxifene increases the risk of venous thromboembolic disease to the same degree as tamoxifen and estrogen. Therefore, SERMS and estrogens are generally contraindicated in women with a previous history of venous thromboembolism or those who are at significantly increased risk. Raloxifene is probably most useful in women who have osteoporosis (T score = -2.5) or who are at risk (T score less than -1.5 with clinical risk factors) in the middle menopausal period (age 55-65) or in the early menopausal period in women who have no significant hot flashes. At this stage in life, vertebral fractures are common, but hip fractures are not. Therefore, women who take raloxifene can expect a reduction in the likelihood of having a vertebral fracture, and possibly breast cancer. The lack of definitive efficacy against hip fracture is not a major deterrent to use of this agent in this age group because hip fracture risk is very low. Raloxifene might not be the treatment of choice for elderly women who are at particularly high risk of hip fracture.     

Anabolic Agents for Osteoporosis

Antiresorptive agents for osteoporosis are a cornerstone of therapy, but anabolic drugs have recently widened our therapeutic options. By directly stimulating bone formation, anabolic agents reduce fracture incidence by improving other bone qualities in addition to increasing bone mass. Teriparatide (human parathyroid hormone[1-34]) has clearly emerged as a major approach for selected patients with osteoporosis. Teriparatide increases bone mineral density and bone turnover, improves bone microarchitecture, and changes bone size. The incidence of vertebral and non-vertebral fractures is reduced. Teriparatide is approved in many countries throughout the world for the treatment of both postmenopausal women and men with osteoporosis who are at high risk for fracture. Another anabolic agent, strontium ranelate, may both promote bone formation and inhibit bone resorption. Clinical trials support the use of strontium ranelate as a treatment for postmenopausal osteoporosis and have shown that strontium ranelate reduces the frequency of vertebral and non-vertebral fractures. Other potential anabolic therapies for osteoporosis, including other forms of parathyroid hormone, growth hormone, and insulin-like growth factor-I, have been examined, although less data are currently available on these approaches.     

Fragility fractures and the osteoporosis care gap: an international phenomenon

OBJECTIVES: To describe practice patterns in the management of osteoporosis after fragility fracture. METHODS: Systematic review of articles in MEDLINE, EMBASE, Cochrane, and CINAHL databases (1996 to February 2005). Diagnostic outcomes included clinical osteoporosis diagnoses, laboratory tests, and bone density scans. Treatment outcomes included initiation of calcium, vitamin D, hormone replacement therapy, bisphosphonates, calcitonin, raloxifene and falls assessments. RESULTS: Thirty-five studies met our inclusion criteria and demonstrated that adults who experience fragility fracture are not receiving osteoporosis management. An osteoporosis diagnosis was reported in 1 to 45% of patients with fractures; laboratory tests were ordered for 1 to 49% and 1 to 32% of patients had bone density scans. Calcium/vitamin D and pharmacological therapy was reported in 2 to 62% and 1 to 65% of patients, respectively. Osteoporosis treatment was recommended more often in women than men, and more often in patients with vertebral fractures than in patients with nonvertebral fractures. Older patients were more likely to be diagnosed with osteoporosis, but treatment was more likely in younger patients. A history of prior fracture was reported in 7 to 67% of patients. Between 1 and 22% of patients had a subsequent fracture during follow-up periods of 6 months to 5 years. Falls assessments were not often reported; when they were, they were infrequently performed. A greater proportion of patients were diagnosed/treated during follow-up studies than in studies evaluating diagnosis/treatment on discharge from acute care. CONCLUSIONS: The majority of individuals who sustain fragility fractures are not receiving adequate osteoporosis management. Future research should address barriers to appropriate management and the efficacy of implementation strategies designed to close the osteoporosis care gap. RELEVANCE: This article is of particular importance to health care professionals who provide care for patients with fragility fracture.     

The role of selective estrogen receptor modulators in the prevention and treatment of osteoporosis

Osteoporosis can affect almost everyone in the population, and although clinical outcome of fracture is manifested in late life, the disease process begins in the early postmenopausal years in women. The pharmacologic agents currently available for osteoporosis prevention and treatment act by inhibiting bone resorption, and include estrogen or hormone replacement therapy (estrogen with progestin), bisphosphonates, salmon calcitonin nasal spray, and selective estrogen receptor modulators (SERMs). Raloxifene is a benzothiophene SERM that has estrogen against effects in bone and on serum lipid metabolism and estrogen antagonist effects on breast and uterine tissue. This article summarizes the effects of these antiresorptive agents, as measured by changes in bone mineral density, biochemical markers of bone turnover, and incident fractures in postmenopausal osteoporosis.