Treatment of Male Osteoporosis: Recent Advances with Alendronate

Overall, the data from the two alendronate studies clearly document the efficacy and safety of alendronate in osteoporotic men. The positive effects of alendronate on BMD, markers and fractures are very consistent between studies. Importantly, they are also very consistent with the results of multiple clinical studies conducted in postmenopausal women with osteoporosis. Treatment with 10 mg alendronate for 2 years produced significant and clinically meaningful increases in BMD, similar to those previously observed in postmenopausal women. Data from studies including men and women confirm the similarity of response suggested by single-gender studies. Consistent with much larger studies in postmenopausal women, alendronate 10 mg/day also reduced the incidence of new vertebral fracture and, correspondingly, reduced height loss. The safety and tolerability of alendronate in men was favorable and consistent with the safety profile previously observed in postmenopausal women. Alendronate represents an important and needed therapeutic advancement in the management of osteoporosis in men.     

Vitamin D status and response to treatment in post-menopausal osteoporosis

Summary  Treatment with anti-resorptive agents over 13 months was associated with for three to fivefold lower bone mineral density changes and 1.5-fold increased risk of incidence fracture in vitamin D insufficient as compared to vitamin D repleted postmenopausal osteoporotic women. Introduction  Several drugs were registered for the treatment of osteoporosis on the basis of clinical trials in which vitamin D repletion was a pre-requisite inclusion criteria and vitamin D supplements were used as adjunctive therapy. However, in routine clinical practice these supplements are not consistently recommended. Methods  We studied 1515 women with postmenopausal osteoporosis under treatment with anti-resorbing agents (alendronate, risedronate, raloxifene) for 13.1 months with an adherence > 75%. The patients were classified as vitamin D deficient (N = 514) or vitamin D repleted (N = 1001) according to risk factors (N = 1062) or the level of 25(OH) vitamin D [25(OH)D] above or below 50 nmol/l (N = 453). Results  Vitamin D deficient and vitamin D repleted subjects differed significantly for annualized spine and hip bone mineral density (BMD) changes adjusted for all available confounding factors (type of treatment, age, global calcium intake, baseline BMD values). One hundred fifty one patients suffered from a new incident clinical fracture. The adjusted odds ratio for incident fractures in vitamin D deficient as compared to vitamin D repleted women was 1.77 (1.20 – 2.59, 95% CI; p = 0.004). Conclusions  Optimal vitamin D repletion seems to be necessary to maximize the response to anti-resorbers in terms of both BMD changes and anti-fracture efficacy.     

Treatment of Osteoporosis in Men with Fluoride Alone or in Combination with Bisphosphonates

Alendronate has been approved as a first antiresorptive drug for treatment of osteoporosis in men. Except for fluoride, in some countries so far there has been no approved anabolic substance for the treatment of male osteoporosis. From small studies in men and male patients included in studies on postmenopausal osteoporosis there is sufficient evidence that fluoride has the same osteoblast-stimulating potency in men and women. In our own study on 64 men with idiopathic osteoporosis without prevalent fractures, a low-dose intermittent fluoride regimen (15 mg fluoride ions 3 months on, 1 month off) resulted in an average gain of lumbar spine BMD of 3% per year and a lower rate of incident fractures as compared with patients treated with calcium only. A combination of fluoride with an antiresorptive drug may improve the therapeutic results in terms of pattern of biochemical marker response and gain in BMD. This was shown for postemopausal osteoporosis in several studies using fluoride and hormone replacement therapy (HRT). Encouraged by a Dutch study using etidronate/fluoride in corticoid-induced osteoporosis, we performed a pilot study in 33 men with severe established primary osteoporosis giving cyclically etidronate for 14 days followed by fluoride plus calcium/vitamin D for 76 days. This combined regimen resulted in significantly higher increases of BMD than fluoride or etidronate alone. In an ongoing trial we are studying a continuous, combined treatment of alendronate and fluoride plus calcium/vitamin D in established idiopathic osteoporosis in men. The results of a preliminary evaluation look very promising. A large study with a bisphosphonate plus fluoride, taking fractures as the primary endpoint and bone biopsies to assess safety, would be very valuable.     

46例绝经后骨质疏松症妇女骨密度及尿吡啶啉、血清Ⅰ型前胶原肽的初步分析

本文通过对60～70岁绝经后妇女20例健康对照组、28例骨质疏松组、18例骨质疏松伴骨折组骨密度及尿吡啶啉(Pyridinoline,PYD)、血清Ⅰ型前胶原肽(Carboxy\|terminalpropeptideoftypeIprocollagen,PICP)的测定,经过比较分析结果显示46例骨质疏松患者的骨密度显著低于健康对照组,18例骨质疏松伴骨折组患者的股骨颈部位的骨密度显著低于28例骨质疏松无骨折组.46例骨质疏松患者的尿PYD、血PICP均显著高于健康对照组.由此提示绝经后妇女测量骨密度尤其是股骨上端的骨密度,结合骨吸收及骨形成的生化指标尿PYD、血PICP,能更好地预测骨质疏松及提示骨折发生的危险性.     

Calcium and vitamin D intake influence bone mass,but not short-term fracture risk,in Caucasian postmenopausal women from the National Osteoporosis Risk Assessment (NORA) study

Summary The impact of calcium and vitamin D intake on bone density and one-year fracture risk was assessed in 76,507 postmenopausal Caucasian women. Adequate calcium with or without vitamin D significantly reduced the odds of osteoporosis but not the risk of fracture in these Caucasian women. Introduction Calcium and vitamin D intake may be important for bone health; however, studies have produced mixed results. Methods The impact of calcium and vitamin D intake on bone mineral density (BMD) and one-year fracture incidence was assessed in 76,507 postmenopausal Caucasian women who completed a dietary questionnaire that included childhood, adult, and current consumption of dairy products. Current vitamin D intake was calculated from milk, fish, supplements and sunlight exposure. BMD was measured at the forearm, finger or heel. Approximately 3 years later, 36,209 participants returned a questionnaire about new fractures. The impact of calcium and vitamin D on risk of osteoporosis and fracture was evaluated by logistic regression adjusted for multiple covariates. Results Higher lifetime calcium intake was associated with reduced odds of osteoporosis (peripheral BMD T-score ≤−2.5; OR = 0.80; 95% CI 0.72, 0.88), as was a higher current calcium (OR = 0.75; (0.68, 0.82)) or vitamin D intake (OR = 0.73; 95% CI 0.0.66, 0.81). Women reported 2,205 new osteoporosis-related fractures. The 3-year risk of any fracture combined or separately was not associated with intake of calcium or vitamin D. Conclusions Thus, higher calcium and vitamin D intakes significantly reduced the odds of osteoporosis but not the 3-year risk of fracture in these Caucasian women. Sources of support: This work was supported by grant AG1406701 from the National Institute on Aging. The National Osteoporosis Risk Assessment (NORA) was funded and managed by Merck & Co Inc.     

维生素D、维生素B12和同型半胱氨酸水平与绝经后女性骨密度的相关性研究

目的探索绝经后非骨质疏松症和骨质疏松症女性患者高半胱氨酸、维生素D、维生素B_(12)和骨密度(bone mineral density,BMD)之间的关系。方法选取2017年8～12月在我院就诊的138名女性作为研究对象,根据骨密度将绝经后女性分为骨质疏松组(n=58)和非骨质疏松组(n=80)。记录两组患者的体质量指数(body mass index,BMI)、年龄、腰围等一般资料,检测腰椎L_(1～4)前后位、左侧股骨近端的BMD,测定血清同型半胱氨酸、维生素B_(12)、维生素D、碱性磷酸酶、钙、磷水平。分析两组患者不同指标的差异以及高半胱氨酸、维生素D、维生素B_(12)和BMD之间的相关性。结果两组患者的年龄、BMI、腰围、同型半胱氨酸、维生素D、维生素B_(12)、腰椎L_(1～4)和左股骨颈骨密度比较差异有统计学意义(P均0.05);Rho相关性和回归分析表明,同型半胱氨酸与维生素D和B_(12)在绝经后非骨质疏松症和同型半胱氨酸与维生素B_(12)在绝经后骨质疏松症女性中呈显著负相关。结论高水平同型半胱氨酸可以通过绝经后非骨质疏松症患者维生素D水平和绝经后骨质疏松症女性维生素B_(12)水平预测。     

A comprehensive review of treatments for postmenopausal osteoporosis

 The aim of this review is to assess the efficacy of treatments for postmenopausal osteoporosis in women with low bone mass or with an existing vertebral fracture. We searched the literature for studies (randomized, double-masked, placebo-controlled and prospective) that reported on drugs registered in Europe or North America. We included 41 reports on 12 agents. To assess the consistency among the studies for each drug, we plotted the percent change in bone mineral density (BMD) for the control group against the percent change in BMD for the treated group for lumbar spine and femoral neck. We used methods of cluster analysis to determine consistency among the studies. For each agent we summarized the relative risk for vertebral fracture (patients with new fracture) and for hip fractures. The duration of the studies ranged from 1 to 4.3 years. The proportion of patients who discontinued treatment ranged from 4% to 80%. Most of the studies reported on change in BMD. Twenty-six studies (10 drugs) provided data on new vertebral fractures and 12 (6 drugs) on hip fractures. Apart from fluoride effects on spine BMD, increases in BMD with bisphosphonates were greater than those seen with the remaining treatments. Generally, for each agent the changes in BMD (relative to placebo) were consistent among the studies. The exceptions were calcitriol and calcitonin for changes in BMD of the spine and of the femoral neck. Alendronate, calcitonin, risedronate and raloxifene caused significant reductions in the risk of vertebral fractures. Alendronate, risedronate or the combination of calcium plus vitamin D had a significant effect on the risk of hip fracture. Most therapies are effective in increasing BMD; some decrease the risk of vertebral fracture. For hip fracture, alendronate and risedronate reduce the risk in women with osteoporosis, and calcium and vitamin D reduce the risk in institutionalized patients. Received: 15 October 2001 / Accepted: 18 July 2002 Acknowledgement We acknowledge the invaluable help of J. Jeger, MD, for useful discussion, D. Thompson, PhD, for statistical advice, and D. Koch for data collection. We thank Mrs M. Perez for secretarial assistance. This work was partially supported by a grant from the Merck Sharp and Dohme-Chibret Company (Glattbrugg, Switzerland).     

Effects of two intermittent alendronate regimens in the prevention or treatment of postmenopausal osteoporosis

In clinical practice, a large proportion of patients have bone mass values for which a therapeutic intervention is considered necessary, but the accepted aim might be the sole preservation or marginal increases of the actual bone mass. These goals might be achieved with lower or intermittent doses of a powerful agent for the purpose of fewer side effects and improved compliance. The aim of this study was to assess the effects of two intermittent alendronate regimens in the treatment of postmenopausal osteoporosis. One hundred twenty-four postmenopausal women (age range 52-75 years, at least 7 years since last menopause) with a bone mineral density (BMD) at either the femoral neck or lumbar spine of 2 SD below the mean values of young healthy individuals, and without a history of previous osteoporotic fracture, were randomly assigned either to calcium/vitamin D supplements, alone or associated with two different intermittent oral alendronate regimens: 20 mg once a week (weekly alendronate group) or 10 mg daily (orally) for 1 month out of 3 (cyclical alendronate group). After 1 year, in both groups given intermittent alendronate, we observed significant increases in BMD at both the spine (+2.2 +/- 2.6 and +2.5 +/- 2.9) and femoral neck (+1.6 +/- 4.8 and +1.5 +/- 2.2) for the weekly and cyclical regimens, respectively. This was associated with a significant diminution of both serum bone-specific alkaline phosphatase and urinary N-telopeptides of collagen type I excretion. In the patients in the control group BMD decreased significantly at the lumbar spine, with a slight decline of serum bone-specific alkaline phosphatase. Compliance with treatment and drug tolerability were good in both alendronate groups. In conclusion, intermittent alendronate administration at cumulative doses (and costs) three times lower than those currently recommended for osteoporosis treatment is very well accepted, and is able to significantly increase BMD at the spine and femoral neck and to decrease the markers of bone turnover. These regimens can be clinically useful in the long-term treatment of postmenopausal osteoporosis without prevalent osteoporotic fractures, particularly in women with lower compliance for continuous administration.     

Cost‐effectiveness of alendronate for the treatment of osteopenic postmenopausal women in Japan

Many postmenopausal women have osteopenia, a condition characterized by loss of bone mineral density (BMD) that is not as severe as in osteoporosis. The objective of this study was to estimate the cost‐effectiveness of alendronate to prevent fractures in osteopenic postmenopausal women without a history of fracture in Japan. An individual simulation model was developed to predict lifetime costs and quality‐adjusted life years (QALYs) of 5 years of preventive alendronate therapy versus no preventive therapy. The risk of hip and vertebral fracture associated with age and BMD was derived from epidemiologic studies in Japan. We ran the model with different combinations of age (65, 70, and 75 years), BMD (70%, 75%, and 80% of young adult mean [YAM]), and additional clinical risk factors. For 70‐year‐old women with a BMD of 70% of the YAM having one of the following risk factors: a family history of hip fracture, high alcohol intake, or current smoking, the incremental cost‐effectiveness ratio (ICER) of alendronate was $92,937, $126,251, and $129,067 per QALY, respectively. These results were sensitive to age, BMD, and number of clinical risk factors. Probabilistic sensitivity analysis for the base case showed that in the presence of one, two, and three risk factors, alendronate was cost‐effective in 0.2% to 2.6%, 13.1% to 56.1%, and 99.1% of the simulations, respectively, if society is willing to pay $50,000 per QALY. Additional analysis indicated that alendronate can be a good value in osteopenic women if the 10‐year probability for a osteoporotic hip or vertebral fracture is more than 26.2%. Our results indicate that whether to treat osteopenia with alendronate should be determined on the basis of age, BMD, and number of clinical risk factors in terms of cost‐effectiveness. © 2013 American Society for Bone and Mineral Research     

不同给药方案阿仑膦酸钠治疗绝经后妇女骨质疏松症18个月效果研究

目的阿仑膦酸钠是临床治疗绝经后妇女骨质疏松症的首选药物。本实验观察阿仑膦酸钠不同给药方案对绝经后妇女骨质疏松症的治疗效果以及不良反应的发生情况。方法本实验为开放、随机、平行对照临床研究。纳入西安两社区绝经后妇女共80名,年龄49～79岁,绝经年限3～31年。实验分为低剂量组和常规剂量组。低剂量组为每两周口服阿仑膦酸钠一次,每次70mg,疗程18个月。常规剂量组为每周口服阿仑膦酸钠一次,每次70mg,疗程18个月。两组同时每日服用钙尔奇D3600mg。实验主要观察指标为:第二腰椎到第四腰椎(L2-L4)、股骨颈、大转子、股骨干骨密度值变化,血液指标(血钙、血磷、碱性磷酸酶),肝肾功能指标(丙氨酸氨基转移酶、血肌酐),不良反应及新发骨折情况。结果 80例患者全部进入结果分析:①骨密度测定:每组患者治疗18个月后L2-L4、股骨颈、股骨大转子、股骨干的骨密度与治疗前相比均明显升高,差异有显著性意义(P﹤0.05)。低剂量组与常规剂量组相比L2-L4骨密度、股骨颈骨密度、股骨干骨密度值差异无统计学意义(P﹥0.05),表明两种给药方案相比增加骨密度效果相似。②两组患者血液指标及肝肾功能指标治疗前后均在正常范围内,显示两种用药方法均安全可靠。③不良反应主要为上腹部不适,两组不良反应差异有统计学意义(P﹤0.05),低剂量组显著低于常规剂量组。④两组患者均无新发骨折病例。结论阿仑膦酸钠治疗绝经后妇女骨质疏松症安全有效,低剂量用药方案与常规剂量用药方案相比增加骨密度效果和药物安全性相似,用药更加简单方便,不良反应更小,经济效益更高,是临床值得推荐的用药方案。     

Alendronate for the Treatment of Osteoporosis in Men

The incidence of osteoporotic fracture in males is approximately one-third of that observed in women, but information on specific therapies is almost exclusively limited to bisphosphonate alendronate. The most important study with this compound included 241 men, randomized to receive either alendronate 10 mg/day or placebo. In another study 134 men were given either 10 mg alendronate or alfacalcidiol 1 microg/day. After 24 months, the treatment with alendronate bone mineral density (BMD) significantly increased in both studies by 7-10% at the lumbar spine and by 2.5-5.2% at the femoral neck. These changes were associated with decreases in vertebral fracture rate and in stature loss, both statistically significant when the data of the two trials were meta-analysed. The BMD changes after alendronate therapy were comparable to those observed in postmenopausal osteoporosis. This was confirmed in a trial specifically designed to compare alendronate efficacy in men and postmenopausal women with either primary or secondary osteoporosis. Gender-comparative efficacy data can also be inferred from clinical trials in glucocorticoid-induced osteoporosis of alendronate, risedronate, and etidronate, carried out in both women and men. By combining the results of all these trials, bisphosphonate efficacy in terms of both BMD changes and fracture incidence appears to be moderate in premenopausal women but quite obvious and comparable in males and postmenopausal women.     

Cost effectiveness of alendronate for the treatment of male osteoporosis in Sweden

Background: One third of all the hip fractures occur in men. The risk for mortality following hip fracture is higher for men compared to women. The Fracture Intervention Trial (FIT) showed that the bisphosphonate alendronate reduces the risk of fractures and increases bone mineral density (BMD) in osteoporotic women. Similar effects of alendronate were observed in men in some other trials. There are also results demonstrating alendronate to be cost-effective in the treatment of osteoporosis in women. Objective: To investigate the cost effectiveness of alendronate for male osteoporosis in Sweden by assuming the same relative risk reduction of fractures in men as for women, based on the FIT trial. Design: A Markov model earlier used to analyze cost effectiveness of alendronate in treatment of postmenopausal osteoporosis in Sweden was adapted to fit a cohort of Swedish men. Cost effectiveness of alendronate vs. no treatment was assessed by transitioning men in the model over time between different health states. Time horizon: The patients were followed from start of intervention until 100 years of age or death. In the base-case alendronate was assumed to have a fracture-risk-reducing effect for 10 years; a treatment duration period of 5 years followed by a 5-year period where the effect declined linearly to zero. Results: Taking a societal perspective treating a 71-year-old man (mean age in the FIT) with low BMD and prior vertebral fracture (VFA) with alendronate was found to be associated with a cost of €14,843 per quality adjusted life year (QALY) gained. Conclusions: The results in this study indicate that treating osteoporotic men with alendronate was projected to be cost-effective, under the assumption of the same fracture-risk-reducing effect of alendronate for men as for women.     

Lower vitamin E serum levels are associated with osteoporosis in early postmenopausal women: a cross-sectional study

The aim of this study was to evaluate the relationship between vitamin E status and osteoporosis in early postmenopausal women. Anthropometric data, osteoporosis risk factors, vitamin E serum levels, bone mineral density (BMD) and other serum parameters which may influence bone mineral density in postmenopausal women were analyzed in a cross-sectional study. The association between osteoporosis and age, age of menopause, body mass index, osteocalcin, calcium, vitamin D, vitamin E (measured as 25 hydroxyvitamin D and as α-tocopherol:lipids ratio, respectively), bone alkaline phosphatase, smoking status, leisure physical activity and alcohol intake were modeled by a multivariate logistic regression and multi-linear regression analysis in 232 early postmenopausal women. A lower vitamin E:lipid ratio was associated with osteoporosis in multivariate logistic regression. In a multivariate linear model with BMD of the lumbar spine as a dependent variable, the vitamin E:lipid ratio was clearly related with BMD of the lumbar spine (F ratio = 6.30, p = 0.002). BMD of the lumbar spine was significantly higher in the highest tertile of the vitamin E:lipid ratio than in the lowest tertile. The mean vitamin E:lipid ratio was significantly lower in osteoporotic postmenopausal women (T score ≤?2.5) (3.0 ± 0.6 μmol/mmol) than normal (neither osteoporotic nor osteopenic) postmenopausal women (T score >?1) (3.5 ± 0.7 μmol/mmol) using multivariable-adjusted BMD. These findings highlight that vitamin E may increase BMD in healthy postmenopausal women.     

Associations of vitamin D status with bone mineral density, bone turnover, bone loss and fracture risk in healthy postmenopausal women. The OFELY study

INTRODUCTION: Vitamin D status is considered as an important determinant of bone health but supplementation trials with vitamin D(3) have yielded conflicting results. The aim of this study was to investigate the associations between serum 25-hydroxyvitamin D (25-OH D), bone turnover markers, bone mineral density (BMD), radius bone loss and incidence of fracture in postmenopausal women. METHODS: 669 postmenopausal women (mean age: 62.2 years) belonging to a population-based cohort were followed prospectively for a median of 11.2 years. At baseline, 25-OH D levels, BMD, bone turnover markers and clinical risk factors of osteoporosis were assessed. BMD loss at the radius was estimated by annual measurements of BMD and all incident fractures which occurred in 134 women were confirmed by radiographs. RESULTS: 73% and 35% of women had serum 25-OH D levels below 75 and 50 nmol/l which correspond respectively to the median and lowest optimal values recently proposed for fracture prevention. 11% of women had levels below 30 nmol/l. Serum 25-OH D correlated modestly with intact PTH (r(2)=0.023, p<0.0001), but not with bone turnover markers or BMD at the hip and radius after adjustment for age. When levels of 25-OH D were considered as a continuous variable, there was no significant association between 25-OH D levels and radius BMD loss or fracture risk. After adjustment for age, there was no significant difference in incidence of fracture, BMD, radius BMD loss, bone turnover markers, grip strength and the percentage of fallers in the previous year between women with 25-OH D levels below or above 75, 50 or 30 nmol/l. CONCLUSIONS: In a population of home-dwelling healthy postmenopausal women with few of them with severe vitamin D deficiency, vitamin D status may not be an important determinant of bone health.     

唑来膦酸盐与骨质疏松症

目的 双膦酸盐是目前抗骨质疏松治疗最常用药物.唑来膦酸盐是每年1次静脉注射用双膦酸盐,探讨唑来膦酸盐对骨质疏松的治疗作用及安全性分析.方法 PubMed上检索应用唑来膦酸盐治疗骨质疏松及其他疾病的相关文献并进行分析.结果 HORIZON-PFT 3年研究表明唑来膦酸盐与安慰剂比较,能明显降低椎体、非椎体骨折风险,增加骨密度,降低骨转换标志物水平,增加骨小梁容量.在90 d内行髋部骨折外科治疗的患者中进行的HORIZON-RFT研究发现唑来膦酸盐与安慰剂比较能够明显降低再发骨折风险,降低全因死亡率,增加髋部及股骨颈骨密度.绝经后低骨密度妇女从阿伦膦酸钠改为唑来膦酸盐3个月内平均骨转换标志物水平先下降,后逐渐增至绝经前妇女正常范围,且可维持腰椎骨密度值12个月.另一研究表明与阿伦膦酸钠比较,唑来膦酸盐能更迅速的降低骨吸收标志物,抑制骨吸收.在安全性方面唑来膦酸盐可能的副作用包括急性一过性不良反应,如发热、肌痛、流感样症状,主要为轻到中度,常发生在静脉输注后3 d内,3～7 d左右缓解.研究表明唑来膦酸盐短期内可能引起肾功能的变化,但长期对肾功能未发现明显影响.颌骨骨质疏松性坏死可能与唑来膦酸盐相关,但发生率较低,且多发生在恶性肿瘤如多发性骨髓瘤和转移癌的患者中,尚未证实颌骨骨质疏松性坏死风险增高与用于治疗骨质疏松症批准剂量的唑来膦酸盐有关.其他少见的副作用包括房颤,无症状及一过性低钙血症,尚需要大样本长期研究证实.结论 每年1次唑来膦酸盐是治疗绝经后骨质疏松新的选择.     

Characteristics of elderly patients admitted to an urban tertiary care hospital with osteoporotic fractures: correlations with risk factors, fracture type, gender and ethnicity

Osteoporosis is a major public health problem in the United States of America and around the world, largely due to the morbidity and mortality associated with osteoporotic fractures. In the past decade, large epidemiologic studies have contributed greatly to our understanding of patients who fracture. However, most studies are limited to postmenopausal white women. In this retrospective review, we analyze data from 185 men and women with acute fragility fractures who received osteoporosis consultations during admission to a single urban hospital between 2001 and 2003. Men and women differed in terms of risk factors for falls and osteoporosis but had areal bone mineral density (BMD) measurements remarkably similar, except at the total hip. Black and Hispanic subjects with fractures were significantly younger than whites yet were much more likely to have serious co-morbidities, such as diabetes mellitus and hypertension. In spite of significantly higher BMD measurements, black patients had the highest rates of vitamin D deficiency and secondary hyperparathyroidism. Patients admitted with hip fractures differed from those with non-hip fractures on a number of important variables. Based on these data, we conclude that elderly subjects admitted to an urban hospital with osteoporotic fractures are a heterogeneous group, with features that vary according to fracture type, gender and ethnicity. Future studies of patients with clinical fragility fractures should include ample numbers of men and ethnic minorities, since differences in underlying risk factors may suggest alternative strategies for fracture prevention.     

The cost-effectiveness of alendronate in the management of osteoporosis

The National Institute for Health and Clinical Excellence (NICE) in the UK has recently issued health economic appraisals for the primary and secondary prevention of osteoporotic fracture that are more restrictive than previous guidelines for the management of osteoporosis despite a marked reduction of the cost of intervention. The aim of the present study was to examine the cost-effectiveness of the bisphosphonate, alendronate for the prevention and treatment of fractures associated with osteoporosis. A second aim was to investigate reasons for any disparities in cost-effectiveness between our findings and the NICE appraisals. We compared the effects of alendronate 70 mg weekly by mouth for 5 years with no treatment in postmenopausal women with clinical risk factors for fracture and computed the incremental cost-effectiveness ratio (ICER) using a lifetime simulation model based on Markov cohort methodology. A sensitivity analysis examined other common interventions. Using a threshold of pound sterling 30,000 and pound sterling 20,000 per quality of life-year (QALY) gained to determine cost-effectiveness, alendronate was cost-effective for the primary prevention of fracture in women with osteoporosis irrespective of age as was treatment of women with a prior fragility fracture irrespective of BMD. Cost-effective scenarios were also found in women with strong risk factors for fracture with a bone mineral density value above the threshold for osteoporosis. The results were robust over reasonable assumptions in sensitivity analysis. We conclude that alendronate is a cost-effective agent for the prevention and treatment of fractures associated with osteoporosis. These findings, suitable for informing practice guidance, contrast with recent appraisals from NICE.     

Anabolic agents for treating postmenopausal osteoporosis.

The main efficacy criterion for drugs against osteoporosis is protection against fractures. Many resorption-inhibiting agents meet this criterion, including estrogens, alendronate, risedronate, raloxifene, calcitonin, and calcium-vitamin D supplements). Conversely, among anabolic agents, only parathyroid hormone (PTH) is known to reduce the fracture risk, the mechanism being increased bone matrix production by osteoblasts with no alterations in the mechanical properties of bone. Although fluoride salts induce a marked increase in bone mineral density (BMD), there is no evidence that this protects against vertebral or peripheral fractures. Growth hormone, IGF-I, statins, and strontium ranelate are under investigation. A recent controlled clinical trial in 1,637 women with osteoporosis showed that daily subcutaneous injections of PTH (1-34) (20 or 40 microg) for 21 months reduced the fracture risk. With 20 microg/day, the reductions were 65% for vertebral fractures and 57% for extravertebral fractures, 11% of patients had moderate postinjection hypercalcemia, and BMD increased by 9% at both the lumbar spine and the femoral neck. These findings open up the exciting possibility that PTH used alone or in combination with resorption-inhibiting agents may be helpful. To date, PTH is the only anabolic agent that has proved capable of reducing the risk of vertebral and extravertebral fractures in women with established postmenopausal osteoporosis.     

Anti-hip fracture efficacy of biophosphonates: a Bayesian analysis of clinical trials.

In postmenopausal women, the efficacy of bisphosphonates on hip fracture risk is not clear. This Bayesian meta-analysis quantitatively reviewed data from 12 randomized clinical trials with 18,667 patients and found that bisphosphonate treatment was associated with a reduced risk for hip fracture by 42%. INTRODUCTION: The efficacy of antiresorptive bisphosphonates therapy on reducing hip fracture is not clear, because evidence from randomized clinical trials (RCTs) is inconclusive. This study was undertaken to quantitatively assess the effect of bisphosphonates on hip fracture using literature review and meta-analysis. MATERIALS AND METHODS: Bayesian methods of meta-analysis were applied to synthesize data from 12 RCTs available between 1990 and 2004. The trials involved 18,667 postmenopausal women with low BMD or osteoporosis who have been followed or treated for between 1 and 4 years. The medications used were etidronate (two trials) alendronate (six trials), risedronate (three trials), and clodronate (one trial). The primary endpoint was the incidence of hip fracture. RESULTS: When data from all 12 studies were pooled, treatment with bisphosphonates was associated with a reduced risk for hip fracture by 42% (relative risk [RR], 0.58; 95% credible interval [CrI], 0.42-0.80). The absolute rate reduction was 52 hip fractures per 10,000 women (95% CrI, 4-110) for a period of 3-year treatment. The probability that bisphosphonates are better than placebo (in reducing hip fracture risk by at least 30%) was 0.90. CONCLUSIONS: In postmenopausal women with osteoporosis or low BMD, bisphosphonate treatment is associated with reduced risk of hip fracture.