Etidronate and alendronate in the treatment of postmenopausal osteoporosis.

OBJECTIVE: To review the clinical trials evaluating the efficacy of etidronate and alendronate in the treatment of established postmenopausal osteoporosis. DATA SOURCE: A MEDLINE search was performed (from 1966 through September 1998) using the search terms bisphosphonates, etidronate, alendronate, and postmenopausal osteoporosis. English-language articles were considered for review. STUDY SELECTION AND DATA EXTRACTION: Prospective, randomized, double-blind, placebo-controlled clinical trials using fracture as an end point were selected to review the efficacy of etidronate and alendronate in the treatment of postmenopausal osteoporosis. Results for the outcomes of bone mineral density (BMD) and fracture are summarized. DATA SYNTHESIS: Etidronate and alendronate increase spinal BMD in postmenopausal women with osteoporosis. In one study, etidronate decreased the number of women sustaining new radiographic vertebral fractures over two years, but this effect was lost after three years of treatment. Alendronate reduces the number of radiographic vertebral fractures in postmenopausal women with a low bone mass. In women with preexisting fractures, alendronate decreases the number of patients with radiographic vertebral fractures, clinical (i.e., symptomatic vertebral and nonvertebral) fractures, and hip fractures. A significant reduction in the overall number of nonvertebral fractures has not been demonstrated in clinical trials evaluating either alendronate or etidronate. CONCLUSIONS: No studies have directly compared the efficacy of alendronate and etidronate and the results of long-term clinical trials (i.e., >5 y) have not been published. Based on the results obtained in clinical trials using fracture as an end point, alendronate appears to be the bisphosphonate of choice. Safety profiles and cost should also be considered in the choice of etidronate or alendronate for the treatment of postmenopausal osteoporosis.     

Pharmacologic prevention of osteoporotic fractures

Osteoporosis is characterized by low bone mineral density and a deterioration in the microarchitecture of bone that increases its susceptibility to fracture. The World Health Organization defines osteoporosis as a bone mineral density that is 2.5 standard deviations or more below the reference mean for healthy, young white women. The prevalence of osteoporosis in black women is one half that in white and Hispanic women. In white women 50 years and older, the risk of osteoporotic fracture is nearly 40 percent over their remaining lifetime. Of the drugs that have been approved for the prevention or treatment of osteoporosis, the bisphosphonates (risedronate and alendronate) are most effective in reducing the risk of vertebral and nonvertebral fractures. Risedronate has been shown to reduce fracture risk within one year in postmenopausal women with osteoporosis and in patients with glucocorticoid-induced osteoporosis. Hormone therapy reduces fracture risk, but the benefits may not outweigh the reported risks. Teriparatide, a recombinant human parathyroid hormone, reduces the risk of new fractures and is indicated for use in patients with severe osteoporosis. Raloxifene has been shown to lower the incidence of vertebral fractures in women with osteoporosis. Salmon calcitonin is reserved for use in patients who cannot tolerate bisphosphonates or hormone therapy.     

Pharmacologic and nonpharmacologic management of osteoporosis

Fractures that occur as a result of osteoporosis are associated with significant morbidity, mortality, and cost. A treatment regimen consisting of both nonpharmacologic and pharmacologic interventions can be used to decrease the risk of fracture. Nonpharmacologic interventions include calcium and vitamin D supplementation, weight-bearing exercise, muscle strengthening, and fall prevention. Pharmacologic options include: the bisphosphonates, estrogen therapy, raloxifene, salmon calcitonin, and the anabolic agent teriparatide. Although bone mineral density is used clinically to diagnose osteoporosis, it is of limited value when evaluating pharmacologic treatment; the primary indicator of treatment efficacy is fracture risk reduction. The bisphosphonates are the preferred therapy for osteoporosis. Studies have demonstrated that in postmenopausal women, both risedronate and alendronate are associated with reductions in vertebral and nonvertebral fracture risk. The newest approved bisphosphonate, ibandronate, reduces vertebral fracture risk. Studies also support a reduction in fracture risk when alendronate and risedronate are used in men with osteoporosis and patients with corticosteroid-induced osteoporosis. When used appropriately, the bisphosphonates are well tolerated. Estrogen and raloxifene decrease fracture risk in postmenopausal women with osteoporosis but are associated with thromboembolic events. Use of estrogen therapy is also limited by concerns about the safety of this type of therapy. Although the anabolic agent teriparatide is associated with reductions in vertebral and nonvertebral fractures, its use has been limited by the necessity of subcutaneous administration and its cost relative to other agents. Regardless of which treatment regimen is selected, health care providers need to emphasize the importance of compliance and adherence to improve persistence with therapy, and subsequent fracture reduction efficacy.     

An approach to postmenopausal osteoporosis treatment: a case study review

PURPOSE: To review and discuss the clinical evaluation and therapeutic options for a postmenopausal woman with osteoporosis. DATA SOURCES: Review of scientific literature, practice guidelines, and a case study. CONCLUSIONS: To prevent and treat postmenopausal osteoporosis, women should be encouraged to perform weight-bearing exercise, to not smoke, and to optimize calcium and vitamin D intake through diet and supplements. Drug regimens are effective and well tolerated in postmenopausal women with osteoporosis. IMPLICATIONS FOR PRACTICE: Drugs currently approved by the U.S. Food and Drug Administration for the treatment of postmenopausal osteoporosis include the bisphosphonates risedronate and alendronate; the selective estrogen receptor modulator, raloxifene; and intranasal calcitonin-salmon spray. Bisphosphonates have demonstrated the most impressive fracture risk reduction in prospective clinical trials of women with postmenopausal osteoporosis. Risedronate has consistently demonstrated significant reductions in vertebral fracture risk at 1 year and in vertebral and nonvertebral fracture risk at 3 years. Alendronate has demonstrated significant reductions in vertebral and nonvertebral fracture risk after 3 years.     

Lasofoxifene in osteoporosis and its place in therapy

Selective estrogen-receptor modulators (SERMs), which have estrogen-like effects on bone and “antiestrogen effects” on other tissues, have been in development for osteoporosis prevention and treatment in postmenopausal women as a safer alternative to long-term estrogen. We conducted a literature review of the skeletal and extraskeletal effects of lasofoxifene, a new generation SERM approved by the European Commission for osteoporosis treatment. Published data on the effects of lasofoxifene are based on 23 clinical pharmacology studies with over 10,000 participants from 17 phase 2 and 3 randomized controlled trials (RCTs). In RCTs, lasofoxifene decreases bone turnover markers (BTMs), increases bone mineral density (BMD) at the spine and hip, and decreases the incidence of vertebral and nonvertebral nonhip fractures compared with placebo. Compared with raloxifene, lasofoxifene gave greater decreases in BTMs, and greater increases in lumbar spine BMD. Lasofoxifene also decreased the risk of breast cancer, major coronary heart disease events, and stroke, but—similar to raloxifene—there was an increased risk of venous thromboembolism. In one trial, endometrial hypertrophy and uterine polyps were more common with lasofoxifene than with placebo, but endometrial cancer and hyperplasia were not. Lasofoxifene is probably most appropriate for use among women in their early or middle menopausal years (age 55-65) who have, or are at risk of developing, osteoporosis and in particular vertebral fractures. At the time of publication, lasofoxifene is not approved for use by the US Food and Drug Administration, and as such is not used in North America.     

The impact of estrogen replacement therapy and raloxifene on osteoporosis, cardiovascular disease, and gynecologic cancers

OBJECTIVE: To compare the clinical utility of estrogen replacement therapy (ERT) and raloxifene in osteoporosis and cardiovascular disease in postmenopausal women and to evaluate the contrasting adverse effects of these therapies. DATA SOURCES: A MEDLINE search was performed for January 1980 through September 1998 using the key terms raloxifene, estrogen, CVD, lipoproteins, and osteoporosis. STUDY SELECTION AND DATA EXTRACTION: All clinical studies assessing ERT and raloxifene in cardiovascular disease or osteoporosis were evaluated. DATA SYNTHESIS: ERT remains the standard for prevention and treatment of osteoporosis in women. Its use increases total bone mineral density (BMD) up to 12.1% and reduces hip fracture risk by 66-73%. It reduces low-density lipoprotein (LDL) cholesterol by 15-19% and increases high-density lipoprotein (HDL) cholesterol by 6-18%. Raloxifene, an alternative to ERT in the prevention of osteoporosis, increases total BMD by 2.2%. It reduces LDL by 6.2-14.1% and increases HDL by 1.5-5.7%. Preliminary data suggest that raloxifene has contrasting effects on gynecologic cancers compared with the increased risk posed by ERT. CONCLUSIONS: Clinical trials have illustrated greater effects on BMD with ERT than with raloxifene. Studies of significant duration assessing raloxifene and its fracture risk effects are lacking. ERT appears to have greater beneficial cardiovascular risk factor effects than raloxifene. Prospective, primary prevention studies evaluating overall cardiovascular risk reduction do not exist for either intervention. Raloxifene, while more costly, is an alternative that may have a lower associated risk of breast cancer compared with ERT.     

阿仑膦酸盐预防和治疗男性骨质疏松症疗效的系统评价

目的评价阿仑膦酸盐预防和治疗男性骨质疏松症的效果和可能的不良反应。方法电子检索:MEDLINE(1990-2005)、EMBASE(1990-2005)、 Cochrane图书馆临床对照试验资料库(2005年第3期)、Current Controlled Trials、The National Research Register、中国生物医学义献数据库 (1990-2005)和中文科技期刊全文数据库(1990-2005)、中文学术期刊全文数据库(1990-2005),并手工检索相关领域其他杂志。检索时间截止至2005年11月。所有检索均不受语种限制。纳入以有骨质疏松症高危风险或患骨质疏松症男性为研究对象、比较阿仑膦酸盐与其它疗法疗效的随机对照试验,评价纳入研究的质量,并用RevMan 4．28软件进行Meta分析。结果共纳入7个随机对照试验,包括817例患者。Meta分析结果显示,阿仑膦酸盐 钙剂对提高骨质疏松症高危男性患者腰椎骨密度的作用优于单用钙剂[SMD 0．59,95％CI(0．15,1．03),P=0．009];对于降低骨折风险,阿仑膦酸盐 钙剂与单用钙剂相似;对于降低脊柱骨折的风险,2年以上疗程的阿仑膦酸盐治疗优于α-骨化醇,但是对于非脊椎骨折,两者疗效相似;阿仑膦酸盐提高骨密度的效果优于α-骨化醇、钙剂;在预防骨质疏松症、提高骨密度方面,阿仑膦酸盐不如降钙素、α-骨化醇、甲状旁腺激素;阿仑膦酸盐联合甲状旁腺激素优于单独使用阿仑膦酸盐;阿仑膦酸盐联合甲状旁腺激素与单独使用甲状旁腺激素比较,两者对提高骨密度的疗效相似。结论阿仑膦酸盐预防和治疗男性骨质疏松症的疗效优于钙剂;对于提高骨密度,阿仑膦酸盐不如降钙素、α-骨化醇;长期使用阿仑膦酸盐比α-骨化醇更能减少脊柱骨折的风险。阿仑膦酸盐联合甲状旁腺激素与单用甲状旁腺激素比较,两者在治疗男性骨质疏松症方面的效果相似。今后尚需开展更多高质量特别是多中心研究以增加证据的强度。     

Efficacy of raloxifene for treatment of menopause: a systematic review

PURPOSE: To critically appraise recent randomized controlled trials (RCT) of raloxifene and its effects on the long-term consequences of menopause. DATA SOURCES: All RCTs of greater than six months duration in post-menopausal women found in MEDLINE through July 2000. CONCLUSIONS: Raloxifene lowered lipids, but estrogen had a more beneficial effect on HDL and fibrinolytic markers. Raloxifene had a more beneficial effect on triglycerides, inflammatory and thrombogenic markers. Compared to placebo, raloxifene reduced vertebral fractures but had a similar although lesser effect on bone mineral density and markers of bone turnover than estrogen. Estrogen receptor positive breast cancer was reduced by 90% with no increase in the incidence of endometrial cancer with raloxifene. The most serious side effect of raloxifene was an increased incidence of deep vein thromboses and pulmonary emboli. IMPLICATIONS: Raloxifene has been shown to be beneficial using cardiovascular and osteoporosis end-points in studies of short duration. More RCTs of longer duration with comparisons to other traditional treatments are needed before raloxifene becomes the treatment of choice.     

Comparing therapies for postmenopausal osteoporosis prevention and treatment

OBJECTIVE: To review the literature concerning the efficacy of calcium, hormone replacement therapy (HRT), bisphosphonates, selective estrogen receptor modulators, and calcitonin in the prevention and treatment of postmenopausal osteoporosis. DATA SOURCES: Articles were identified through searches of the MEDLINE (1966-July 2002), EMBASE (1980-July 2002), and International Pharmaceutical Abstracts (1970-July 2002) databases using the key words osteoporosis, postmenopausal, fracture, calcium, vitamin D, hormone replacement therapy, bisphosphonates, alendronate, risedronate, raloxifene, and calcitonin. Additional references were located through review of the bibliographies of the articles cited. Searches were not limited by time restriction, language, or human subject. STUDY SELECTION AND DATA EXTRACTION: Experimental and observational studies of the use of calcium and antiresorptive therapies for the prevention and treatment of postmenopausal osteoporosis were selected. Articles evaluating bone mineral density (BMD) or fracture efficacy were included in this review. DATA SYNTHESIS: HRT, bisphosphonates, raloxifene, and calcitonin have demonstrated stabilization of and improvement in BMD. Randomized clinical trials have shown fracture risk reduction with bisphosphonates, raloxifene, HRT, calcium, and calcitonin. The largest risk reductions have been reported with use of bisphosphonates in several trials. CONCLUSIONS: Several therapeutic options with well-documented improvements in BMD and reductions in fracture risk are available to women for the prevention and treatment of postmenopausal osteoporosis.     

Hip fracture prevention. Drug therapies and lifestyle modifications that can reduce risk

The annual number of hip fractures sustained worldwide is expected to increase dramatically as the population ages. Adequate calcium and vitamin D intake and exercise are fundamental to any program for bone loss prevention or osteoporosis treatment. Fall prevention programs, weight-bearing and resistance exercise, hip protector use, and calcium and vitamin D supplementation can reduce hip fracture risk. Among the available antiosteoporosis agents, the bisphosphonates risedronate and alendronate have produced the greatest reductions in hip fracture risk in postmenopausal women. Nasal calcitonin and raloxifene have not demonstrated significant reductions in nonvertebral or hip fracture risk. The role of parathyroid hormone (1-34) in the treatment of hip fractures remains uncertain until more experience is gained about its use and studies with sufficient statistical power are performed. Data indicate that bisphosphonates consistently reduce hip fracture risk in patients with osteoporosis, especially those with an existing vertebral fracture. In addition to pharmacologic intervention, adequate nonpharmacologic preventive strategies should be included to ensure maximal reduction in risk of hip fracture.     

Application of anti-resorptive drugs for the treatment of osteoporosis

The applications of anti-resorptive drugs for the treatment of osteoporosis were reviewed. The aging, low bone mineral density, increased bone turnover, and prevalent fracture were risk factors for new fracture. Bisphosphonates (alendronate and risedronate) and raloxifene showed a significant reduction in relative risk for vertebral fractures. On the other hand, alendronate and risedronate were the only two therapies that had a significant pooled treatment effects on nonvertebral fracture reduction. Hip fractures in Japan increase in the age of 70 years and over. This etiology indicates that bisphosphonate might be suitable for the patients who were 70 years of age and over. There was no significant difference between alendronate and risedronate in the efficacy of the decrease of bone resorption marker.     

Diagnosis and management of osteoporosis in postmenopausal women: clinical guidelines. International Committee for Osteoporosis Clinical Guidelines.

The authors, all physicians involved in clinical research on bone and practicing clinicians, propose practical guidelines for identifying persons with osteoporosis or those at high risk of developing the disease and for managing patients who may benefit from therapy. These guidelines are based on an analysis of peer-reviewed articles published before November 1998. A flowchart of women who might benefit from treatment is provided, including clinical presentation (recent fracture of the spine, hip, or other bone or no fracture; risk factors for osteoporosis); relevant investigations (bone mineral density measurement and laboratory tests required for the differential diagnosis); and therapeutic management (general measures such as calcium and vitamin D supplementation and specific pharmacologic interventions such as estrogen, bisphosphonates, intranasal calcitonin, raloxifene, fluoride salts, and other compounds that have been assessed in randomized clinical trials). The strongest evidence for antifracture efficacy (reduction of vertebral and nonvertebral fracture risk) was observed with alendronate.     

Testing an Intervention for Preventing Osteoporosis in Postmenopausal Breast Cancer Survivors

Purpose: To test a 12-month multicomponent intervention for preventing or treating osteoporosis in 21 postmenopausal women who had completed treatment (except Tamoxifen) for breast cancer, and for whom hormone replacement therapy (HRT) was contraindicated.
Design: Pilot intervention study.
Methods: The intervention consisted of home-based strength and weight training exercises, 5 or 10 mg alendronate per day, 1500 mg calcium per day, 400 IU vitamin D per day, education on osteoporosis, and facilitative strategies to promote adherence to the intervention. Outcome measures were: adherence to the intervention, dynamic balance, muscle strength, and bone mineral density (BMD) of the hip, spine, and forearm.
Findings and Conclusions: Adherence to calcium, vitamin D, and alendronate therapy was above 95%, and adherence to strength training exercises was above 85%. Over the 12 months, the 21 participants had significant improvements in dynamic balance, muscle strength for hip flexion, hip extension, and knee flexion, and BMD of the spine and hip. Participants had a significant decrease in BMD of the forearm. Three of the 21 women who had measurable bone loss at baseline had normal BMD after 12 months of the intervention.     

Role of raloxifene in breast cancer prevention in postmenopausal women: clinical evidence and potential mechanisms of action

BACKGROUND: Raloxifene is a selective estrogen-receptor modulator (SERM) indicated for the prevention and treatment of osteoporosis in postmenopausal women. In the Multiple Outcomes of Raloxifene Evaluation (MORE) study, an osteoporosis treatment trial, raloxifene therapy was associated with a reduced incidence of invasive, estrogen receptor (ER)-positive breast cancer compared with placebo (relative risk, 0.16; 95% CI, 0.09-0.30). OBJECTIVE: This review summarizes available preclinical and clinical data pertaining to a potential role for raloxifene in the prevention of breast cancer, and examines the mechanisms of action by which raloxifene may exert an effect. METHODS: Relevant articles were identified through a search of MEDLINE for English-language studies published between 1966 and January 2003. Search terms included raloxifene, keoxifene, tamoxifen, SERM, estrogen, estrogen receptor, breast, mammary, growth factors, and apoptosis. The reference lists of identified articles were reviewed for additional publications. RESULTS: Both preclinical and clinical data suggest a role for raloxifene in the prevention of breast cancer. Like tamoxifen, raloxifene acts as an estrogen antagonist in breast tissue through competitive binding to the ER. Raloxifene may also inhibit breast tissue proliferation through mechanisms independent of the ER. CONCLUSIONS: Given raloxifene's mechanism of action and the preclinical evidence for its role in breast cancer prevention, a clinically favorable effect seems feasible. Results of ongoing clinical studies will provide evidence to support or refute the clinical findings of MORE and thus raloxifene's role in the breast cancer prevention.     

Treatment of Postmenopausal Osteoporosis

Osteoporosis is a skeletal disease characterized by low bone mass and microarchitectural deterioration with a resulting increase in bone fragility and hence susceptibility to fracture. Calcium and vitamin D are the most commonly used therapies for osteoporosis, although their efficacy in osteoporotic fracture prevention remains uncertain. Biphosphonates are the most frequently prescribed medication for treatment of osteoporosis and are often considered as first-line therapy for the treatment of osteoporosis. Currently, hormone replacement therapy is only approved by the Food and Drug Administration (FDA) for short-term treatment of severe postmenopausal symptoms with the lowest dose used for the shortest time. In view of its lack of effect on the prevention of nonvertebral fractures, the use of raloxifene should be limited to women with spinal osteoporosis. Most experts agree that it is preferable to treat osteoporosis with a more potent agent than calcitonin and manage the pain separately. Currently, the FDA recommends the use of parathyroid hormone for treatment of osteoporosis for a maximum of 2 years because of the concern of development of osteosarcoma. Drs. Gupta and Aronow have no real or apparent conflicts of interest relating to the subject under discussion.     

Osteoporosis in men and women

Osteoporosis is a cause of significant morbidity and mortality in postmenopausal women as well as men. In both men and women, increasing age and low bone mineral density (BMD) are the 2 most important independent risk factors for an initial vertebral or nonvertebral fracture. Although the prevalence of osteoporosis is greater in women, mortality after fracture is higher among men. In both men and women, the incidence of vertebral fracture increases with age, although the increase is more marked in women than in men. The diagnostic criteria for postmenopausal osteoporosis in women are well established; however, there is ongoing debate about the appropriate T-scores and BMD thresholds to diagnose osteoporosis in men. Alendronate and risedronate are considered first-line therapy for the treatment of both postmenopausal osteoporosis and male osteoporosis. The efficacy and safety of these agents have been evaluated extensively in randomized clinical trials. Studies suggest that these agents are similarly efficacious in men and women. The anabolic agent teriparatide may also be used to treat men with osteoporosis at high risk for fracture. Studies suggest that treatment with an anabolic agent like teriparatide should be followed by an antiresorptive agent.     

Risedronate for the prevention of fractures in postmenopausal osteoporosis

OBJECTIVE: To evaluate current scientific literature regarding the efficacy of risedronate in the prevention of vertebral and nonvertebral fractures in women with postmenopausal osteoporosis. DATA SOURCES: Primary research articles were identified by MEDLINE search (1966-May 2001) and through secondary sources. Key search terms were risedronate, postmenopausal osteoporosis, and fractures. DATA SYNTHESIS: Osteoporosis results in a reduction of bone mineral density, increased bone fragility, and increased risk of fractures. The goal of osteoporosis therapy is not only to increase bone mass, but also to reduce the rate of fractures. Risedronate is the newest bisphosphonate to be approved for the prevention and treatment of osteoporosis. An evaluation of clinical trials using risedronate in the treatment of postmenopausal osteoporosis was performed to determine its efficacy at decreasing fracture rates. CONCLUSIONS: Risedronate is an effective and safe option for the treatment of postmenopausal osteoporosis. Risedronate significantly decreases the risk of vertebral and nonvertebral fractures in women who have had > or =1 fractures in the past. More studies are warranted to evaluate the efficacy of risedronate in women without preexisting vertebral fractures.     

Differences in Adherence to Osteoporosis Regimens: A 2-Year Analysis of a Population Treated Under Specific Guidelines

Background

Patients’ adherence to antiosteoporotic drug therapy is essential to prevent fracture and complications of osteoporosis over the long term. The guidance given in treating osteoporosis can potentially enhance adherence.

Objective

This study was conducted to compare adherence to osteoporosis regimens by patients treated under specific guidelines in a medical center.

Methods

This study used a database pertaining to the use of antiosteoporotic medication, including alendronate, raloxifene, and calcitonin, between 2001 and 2007. We selected patients who were being treated following the therapeutic recommendations of the National Osteoporosis Foundation or the guideline for glucocorticoid-induced osteoporosis recommended by the American College of Rheumatology. Adherence was determined by compliance and the persistence ratio (PR). Compliance was estimated by using the medication possession rate, and PR was determined by the percentage of patients with no medication refill gap for a period of ≥30 days.

Results

A total of 2975 patients met the inclusion criteria. The patients were grouped according to treatment regimen: alendronate, n = 1745; raloxifene, n = 711; and calcitonin, n = 519. The good compliance rate (GCR; medication possession rate ≥80%) for alendronate, raloxifene, and calcitonin was 61.9%, 54.6%, and 36.4% at year 1 (P < 0.001), respectively. The GCR of alendronate was significantly higher than that for either raloxifene (P = 0.001) or calcitonin (P < 0.001). The GCR of the alendronate, raloxifene, and calcitonin groups at year 3 was 47.9%, 43.7%, and 36.4% of the included patients (P < 0.001). The PR of the alendronate, raloxifene, and calcitonin groups at year 1 was 57.1%, 50.2%, and 32.9% (P < 0.001) and 41.8%, 40.1%, and 23.5% (P < 0.001) at year 2.

Conclusions

Alendronate had a better adherence profile than raloxifene and calcitonin at the end of year 1 and a better adherence profile than calcitonin at the end of year 2.     

Large clinical trials for osteoporosis

The prevention and treatment of osteoporosis are now a necessary goal because of the aging of the population and the social and economic costs of fracture complications. The publication of guidelines by registration agencies during the last 10 years has provided precise rules for evaluating new drugs designed for the prevention and treatment of postmenopausal osteoporosis. The benefit of combination treatment with calcium and vitamin D in osteoporotic patients has clearly been proven, especially among the oldest patients, but results of prospective studies designed for the prevention of fracture risk are conflicting. In the Fracture Intervention Trial (FIT), treatment with alendronate 10 mg/day reduces the risk of vertebral fracture by 48% and increases bone mineral density (BMD) in patients with vertebral fractures. In the Vertebral Efficacy with Risedronate Therapy Multi-National (VERT-MN) and VERT-NA (North America) studies, treatment with risedronate 5 mg/day reduces the risk of vertebral fracture by 49% and 41%, respectively. Risedronate 5 mg daly for 3 years leads to an increase in BMD. The Prevent Recurrence Of Osteoporotic Fractures (PROOF) study has shown a significant decrease in the risk of vertebral fracture in patients treated with calcitonin 200 IU. However, numerous criticisms of the methodology of this study design have been identified. Selective estrogen receptor modulators could act as agonists or antagonists of estrogens, depending on the target tissue. In the Multiple Outcomes of Raloxifene Evaluation (MORE) study, treatment with raloxifene reduces the risk of vertebral fracture by 50% in patients without prevalent vertebral fracture and by 30% in patients with prevalent vertebral fracture. PTH treatment leads to an increase in BMD and reduces the risk of vertebral fracture by 65%. Strontium ranelate has a novel mechanism of action (stimulation of bone synthesis and decrease in bone resorption), and administration of 2 g daily has a proven positive effect, leading to an increase in bone mass among women with osteoporosis. This effect was especially evident in the Spinal Osteoporosis Therapeutic Intervention phase III (SOTI) study, in which a significant decrease in the incidence of vertebral fracture of 41% over 3 years has been shown. Thus, effective therapeutic strategies now enable improved treatment of postmenopausal osteoporosis. However, this condition is still poorly diagnosed and not all patients are correctly treated. Preventing the occurrence of the first fracture should remain the prime concern.     

Estrogen, SERM

Osteoporosis is uncommon before menopause and dramatically increases in prevalence thereafter. That is why estrogens provide protection against osteoporosis. Studies of women receiving estrogen replacement have demonstrated improvements in bone mineral density (BMD) as well as endothelial function. Recent randomized trials, however, have produced equivocal results and raised questions about whether combined hormonal replacement therapy (HRT) prevents later cardiovascular events. Investigations of alternatives to HRT have suggested that selective estrogen receptor modulators (SERMs) may confer cardiovascular and osteoporosis protection. Raloxifene is a second-generation SERM used for the prevention and treatment of postmenopausal osteoporosis. Raloxifene decreases the incidence of vertebral fractures by 30-50% in postmenopausal women with osteoporosis. We also studied its effect on postmenopausal elderly women with osteoporosis.