Bisphosphonates and glucocorticoid osteoporosis in men: results of a randomized controlled trial comparing zoledronic acid with risedronate

Background

We studied 265 men (mean age 56.4 years; range 18-83 years), among patients enrolled in two arms of a double-blind, 1-year study comparing the effects of zoledronic acid (ZOL) with risedronate (RIS) in patients either commencing (prednisolone 7.5 mg/day or equivalent) (prevention arm, n = 88) or continuing glucocorticoid therapy (treatment arm, n = 177).

Methods

Patients received either a single ZOL 5 mg infusion or RIS 5 mg oral daily at randomization, along with calcium (1000 mg) and vitamin D (400-1200 IU). Primary endpoint: difference in percentage change from baseline in bone mineral density (BMD) at the lumbar spine (LS) at 12 months. Secondary endpoints: percentage changes in BMD at total hip (TH) and femoral neck (FN), relative changes in bone turnover markers (β-CTx and P1NP), and overall safety.

Findings

In the treatment subpopulation, ZOL increased LS BMD by 4.7% vs. 3.3% for RIS and at TH the percentage changes were 1.8% vs. 0.2%, respectively. In the prevention subpopulation, bone loss was prevented by both treatments. At LS the percentage changes were 2.5% vs. − 0.2% for ZOL vs. RIS and at TH the percentage changes were 1.1% vs. − 0.4%, respectively. ZOL significantly increased lumbar spine BMD more than RIS at Month 12 in both the prevention population (p = 0.0024) and the treatment subpopulation (p = 0.0232) in men. In the treatment subpopulation, ZOL demonstrated a significantly greater reduction in serum β-CTx and P1NP relative to RIS at all time-points. In the prevention subpopulation, ZOL significantly reduced β-CTx? at all time-points, and P1NP at Month 3 (p = 0.0297) only. Both treatments were well tolerated in men, albeit with a higher incidence of influenza-like illness and pyrexia events post-infusion with ZOL.

Interpretation

Once-yearly ZOL preserves or increases BMD within 1 year to a greater extent than daily RIS in men receiving glucocorticoid therapy.     

Efficacy and safety of risedronate 150 mg once a month in the treatment of postmenopausal osteoporosis

INTRODUCTION: Risedronate has been shown to be effective in the treatment of postmenopausal osteoporosis when given orally in daily or weekly doses or on 2 consecutive days per month. This randomized, double-blind, multi-center study was designed to assess the efficacy and safety of a single 150 mg risedronate once-a-month oral dose compared with the 5 mg daily regimen. METHODS: Women with postmenopausal osteoporosis were randomly assigned to receive risedronate 5 mg daily (n=642) or 150 mg once a month (followed by daily placebo) (n=650) in a double-blind fashion for 2 years. Study drug was taken on an empty stomach at least 30 min before breakfast. Bone mineral density, bone turnover markers, fractures, and adverse events were evaluated. The primary efficacy endpoint was the mean percent change from baseline in lumbar spine bone mineral density after 1 year. RESULTS: 538 patients in the daily group (83.8%) and 556 patients in the once-a-month group (85.5%) completed 1 year. The mean percent change in lumbar spine bone mineral density was 3.4% (95% confidence interval, 3.03% to 3.82%) in the daily group and 3.5% (95% confidence interval, 3.15% to 3.93%) in the once-a-month group. The difference between groups was -0.1% (95% confidence interval, -0.51% to 0.27%). The once-a-month regimen was determined to be non-inferior to the daily regimen based on prospectively defined criteria. The mean percent changes in bone mineral density at sites in the hip (total proximal femur, femoral neck, femoral trochanter) were also similar in both dose groups, as were the changes in biochemical markers of bone turnover. The incidence of adverse events, adverse events leading to withdrawal, and upper gastrointestinal tract adverse events were similar in the 2 treatment groups. Both regimens were well tolerated; the percent of patients who withdrew from treatment as a result of an adverse event was 9.5% in the daily group and 8.6% in the once-a-month group. CONCLUSIONS: Risedronate 150 mg once a month is similar in efficacy and safety to daily dosing and may provide an alternative for patients who prefer once-a-month oral dosing.     

Efficacy and safety of risedronate 150-mg once a month in the treatment of postmenopausal osteoporosis: 2-year data

Summary

This study showed that risedronate 150-mg once a month provides similar efficacy and safety at 2 years compared with risedronate 5-mg daily for the treatment of postmenopausal osteoporosis. This adds to the range of risedronate dosing options and provides an alternative for patients who prefer once-a-month dosing.

Introduction

Risedronate is effective in the treatment of postmenopausal osteoporosis in oral daily, weekly, or on two consecutive days per month doses. This 2-year randomized, double-blind, multicenter study assesses the efficacy and safety of a single risedronate 150-mg once-a-month oral dose compared with the 5-mg daily regimen.

Methods

Women with postmenopausal osteoporosis were randomly assigned to receive risedronate 5-mg daily (n?=?642) or 150-mg once a month (n?=?650) for 2 years. Bone mineral density (BMD), bone turnover markers, new vertebral fractures, and adverse events were evaluated. The primary efficacy endpoint was the mean percent change from baseline in lumbar spine BMD after 1 year.

Results

Four hundred ninety-eight subjects in the daily group (77.6 %) and 513 subjects in the once-a-month group (78.9 %) completed the study. After 24 months, the mean percent change in lumbar spine BMD was 3.9 % (95 % confidence interval [CI], 3.43 to 4.42 %) and 4.2 % (95 % CI, 3.68 to 4.65 %) in the daily and once-a-month groups, respectively. The once-a-month regimen was determined to be non-inferior to the daily regimen. The mean percent changes in BMD at the hip were similar in both dose groups, as were changes in biochemical markers of bone turnover. The incidence of adverse events, adverse events leading to withdrawal, and upper gastrointestinal tract adverse events were similar in the two treatment groups.

Conclusions

After 2 years, treatment with risedronate 150-mg once a month provided similar efficacy and tolerability to daily dosing and provides an alternative for patients who prefer once-a-month oral dosing.     

利塞膦酸钠治疗糖皮质激素相关骨质疏松临床疗效及安全性研究

目的 观察利塞膦酸钠治疗糖皮质激素相关骨质疏松(GIOP)的近期疗效及安全性.方法 将59例糖皮质激素相关骨质疏松症随机分成2组,治疗组29例,对照组30例,2组均应用碳酸钙600mg/d口服,阿法骨化醇0.25μg每日2次口服.治疗组加利塞膦酸钠每日10mg口服,疗程6个月.各组用药前后分别检测骨密度、血钙磷、同时比较2组疼痛评分.结果 治疗组治疗后骨密度、疼痛评分较治疗前均明显改善(P<0.05),对照组治疗前后无明显变化(P>0.05).治疗组骨密度、疼痛评分较对照组明显改善(P<0.05).二组治疗前后血钙、磷变化均无统计学差异(P>0.05).安全性方面二组均未发现明显不良反应.结论 利塞膦酸钠是治疗糖皮质激素相关骨质疏松安全有效的药物.     

利塞膦酸钠治疗绝经后骨质疏松症的疗效及安全性

目的探讨利塞膦酸钠治疗绝经后骨质疏松症的临床疗效,并评价其安全性。方法54例绝经后骨质疏松症患者采取随机双盲、安慰剂平行对照方式进行12个月的药物研究,以双能量X线骨密度测量仪比较治疗前后0月、6月、12月腰椎及髋部骨密度(BMD)改变,同时检测骨代谢标志物血Ca、ALP、BGP及尿NTX在治疗前后的变化,并监测血尿常规、肝肾功能、心电图、X线等药物安全性指标,记录不良事件。结果腰椎(L2-4)BDM用药6月时增加(3·29±1·18)%,12月时为(4·51±1·64)%,而对照组分别为(-0·62±0·24)%和(0·48±0·18)%,股骨颈、大转子和Ward s三角区BMD改变在药物组和对照组差异无显著性;反映骨形成标记物ALP和BGP在6月和12月时,药物组显著降低,骨吸收标记物NTx在治疗6月和12月较治疗前显著降低(P<0·01)。主要不良反应为消化道反应2例(7·1%)、皮肤搔痒、皮疹2例(7·1%)和血尿1例(3·6%)。结论利塞膦酸钠能有效阻止绝经后妇女的骨丢失,以腰椎骨量增加最为显著,并且显示该药物具有良好的安全性。     

利塞膦酸盐抗男性骨质疏松性骨折的效应

目的系统评价利塞膦酸盐对男性骨质疏松的抗骨折效应。方法通过Medline数据库、EMBASE数据库、Cochrane图书馆和中国生物医学文献数据库检索1980-01至2006-12有关利塞膦酸盐与安慰剂治疗男性骨质疏松患者的随机对照试验。随访大于12个月,提供骨折发生率的文献纳入研究。分析入选文献的方法学质量,提取资料,用RevMan4.2软件进行荟萃分析。结果3篇文献符合纳入标准,包括780例男性骨质疏松患者。荟萃分析结果显示利塞膦酸盐可降低69%的椎体骨折风险(RR=0.31,95%CI:0.16,0.60)和58%的非椎体骨折风险(RR=0.42,95%CI:0.23,0.78)。结论利塞膦酸盐对男性骨质疏松症患者可提供良好的抗骨折效应。     

Prevalence of osteoporosis in Australian women: Geelong Osteoporosis Study.

To evaluate the prevalence of osteoporosis at various sites among Australian women, cross-sectional bone mineral density (BMD) data for adult females was obtained from an age-stratified population-based sample (n = 1494; 20-94 yr) drawn at random from the Barwon Statistical Division, a population characteristic of Australia. Age- and weight- (and for three sites, height) matched reference ranges for BMD at the lumbar spine, proximal femur, forearm, and total body were developed using regression techniques. The cutoff BMD level for osteoporosis at the PA spine was 0. 917g/cm(2) and 0.713 g/cm(2) at the femoral neck according to the World Health Organization (WHO) guidelines. The upper cutoff level for osteopenia was 1.128 g/cm(2) at the PA spine and 0.913g/cm(2) for the femoral neck. The proportion of Australian women categorized as having osteoporosis at the PA spine, femoral neck, or midforearm ranged from 0.9% among those aged 40-44 yr to 87.0% for those older than 79 yr. This study provides reference data representative of the Australian female population. A large proportion of elderly Australian women has osteoporosis according to the WHO guidelines.     

The cost-effectiveness of risedronate treatment in Japanese women with osteoporosis

We constructed a mathematical model for assessing the cost-effectiveness of providing BMD (bone mineral density) scans to Japanese women aged 55 years and over and treating, with risedronate, those that are shown to be osteoporotic. Fracture rates, cost data, utility values, and the increased risks of fractures associated with T-score and vertebral fracture history were taken from published literature. We estimated the cost of fractures avoided due to risedronate treatment, allowing the net changes in cost, incorporating both intervention and fracture costs to be calculated. The QALYs (quality adjusted life years) gained through treatment were calculated enabling cost per QALY ratios to be presented. Further analyses were undertaken assuming treatment was reserved for older women and/or those who had sustained a vertebral fracture in the previous 2 years. Cost per QALY values were inversely related to absolute risk of fracture. Assuming a cost per QALY value threshold of US$100,000, we concluded that providing BMD scans to women aged 70 years and over who had sustained a vertebral fracture in the previous 2 years and treating those that were osteoporotic was cost-effective. However, providing BMD scans for women without a vertebral fracture in the previous 2 years was not cost-effective, even in women aged 85 years and older.     

Treatment with once-weekly alendronate 70 mg compared with once-weekly risedronate 35 mg in women with postmenopausal osteoporosis: a randomized double-blind study.

Once-weekly alendronate 70 mg and once-weekly risedronate 35 mg are indicated for the treatment of postmenopausal osteoporosis. These two agents were compared in a 12-month head-to-head trial. Greater gains in BMD and greater reductions in markers of bone turnover were seen with alendronate compared with risedronate with similar tolerability. INTRODUCTION: The nitrogen-containing bisphosphonates, alendronate and risedronate, are available in once-weekly (OW) formulations for the treatment of postmenopausal osteoporosis. A 12-month, head-to-head study was performed to compare these agents in the treatment of postmenopausal women with low BMD. MATERIALS AND METHODS: A total of 1053 patients from 78 U.S. sites were randomized to OW alendronate 70 mg (N = 520) or risedronate 35 mg (N = 533), taken in the morning after fasting. Endpoints included BMD changes over 6 and 12 months at the hip trochanter, total hip, femoral neck, and lumbar spine (LS); percent of patients with predefined levels of change in trochanter and LS BMD at 12 months; and change in biochemical markers of bone turnover at 3, 6, and 12 months. Tolerability was evaluated by adverse experience (AE) reporting. RESULTS: Significantly greater increases in hip trochanter BMD were seen with alendronate (3.4%) than risedronate (2.1%) at 12 months (treatment difference, 1.4%; p < 0.001) as well as 6 months (treatment difference, 1.3%; p < 0.001). Significantly greater gains in BMD were seen with alendronate at all BMD sites measured (12-month difference: total hip, 1.0%; femoral neck, 0.7%; LS, 1.2%). Significant differences were seen as early as 6 months at all sites. A greater percentage of patients had > or =0% (p < 0.001) and > or =3% (p < 0.01) gain in trochanter and spine BMD at 12 months with alendronate than risedronate. Significantly greater (p < 0.001) reductions in all biochemical markers of bone turnover occurred with alendronate compared with risedronate by 3 months. No significant differences were seen between treatment groups in the incidence of upper gastrointestinal AEs or AEs causing discontinuation. CONCLUSIONS: In this 12-month, head-to-head trial of alendronate and risedronate, given in accordance with the approved OW regimens for treatment of osteoporosis in postmenopausal women, alendronate produced greater gains in BMD and greater reductions in markers of bone turnover than risedronate. The greater antiresorptive effect of alendronate was seen as early as 3 months, and the tolerability profiles were similar.     

利塞膦酸钠联合雷洛昔芬治疗绝经后骨质疏松症疗效分析

目的观察利塞膦酸钠联合雷洛昔芬治疗绝经后女性骨质疏松症的效果。方法将148例绝经后女性骨质疏松症患者随机分为治疗组和对照组,治疗组给予利塞膦酸钠联合雷洛昔芬治疗,对照组给予利塞膦酸钠治疗。在治疗前及治疗后12个月分别检测两组受试者腰椎及髋部骨密度、血清骨代谢指标、激素水平及研究期间药物不良反应和VAS评分的变化。结果药物治疗后12个月,两组腰椎(L1～4)及左侧股骨颈的骨密度明显增加,治疗组的骨密度显著高于对照组(P0. 05);血清雌激素和孕酮水平均明显下降,皮质醇水平明显上升,与治疗前相比差异有统计学意义(P0. 05),而对照组与治疗前相比差异无统计学意义(P0. 05);治疗后两组血清P1NP及β-CTX较治疗前明显下降、BAP和BGP较治疗前明显上升,比较差异有统计学意义(P0. 05),治疗组较对照组的改善更为明显(P0. 05);治疗后两组患者VAS评分较治疗前显著降低,比较差异有统计学意义(P0. 05),治疗组较对照组降低得更为明显(P0. 05);两组患者在研究期间的药物不良反应无统计学意义(P0. 05)。结论利塞膦酸钠联合雷洛昔芬治疗骨质疏松症较单独使用利塞膦酸钠治疗的效果更为显著,且不增加药物副作用。     

Risk factors for Colles' fracture in men and women: results from the European Prospective Osteoporosis Study

The aim of this study was to determine the contribution of constitutional and lifestyle variables on the subsequent risk of distal forearm (Colles') fracture in a multinational, multicenter, population-prospective study. A total of 15,745 subjects from the European Vertebral Osteoporosis Study, who had completed a baseline questionnaire on lifestyle and constitutional factors, were followed up annually using a validated questionnaire to ascertain the occurrence of new fractures. Risks are expressed as hazard ratios (with 95% confidence intervals) derived from a Cox proportional hazards regression model. The incidence of Colles' fracture was 1.7 and 7.3 per 1000 person years in men and women, respectively. In women delayed menarche, over the age of 15 years, was associated with a modest increased risk [HR 1.5 (range 1.1-2.0)]. Regular walking in that group also increased the risk [HR 1.6 (1.2-2.2)] perhaps reflecting the increased exposure to risk of falling. None of the other factors examined revealed any important influences. The results are broadly in line with the few other published prospective studies suggesting only a modest role for these factors in influencing susceptibility to fracture.     

Daily oral pamidronate in women and men with osteoporosis: a 3-year randomized placebo-controlled clinical trial with a 2-year open extension.

The efficacy and safety of oral pamidronate was examined in a double-blind, placebo-controlled trial in women and men with established osteoporosis. Seventy-eight postmenopausal women and 23 men with at least one prevalent vertebral fracture were randomized separately to 150 mg/day of pamidronate or placebo for 3 years followed by 150 mg/day of pamidronate for an additional 2 years. In addition, all patients received 400 U/day of cholecalciferol and 500 mg/day of elemental calcium. Pamidronate increased significantly bone mineral density of the lumbar spine (LS-BMD) and of the femoral neck (FN-BMD). The total increase in BMD of the spine after 5 years of treatment was 14.3%. Lateral spine radiographs were obtained at baseline and after 3 years of treatment. Fractures of previously normal vertebrae occurred in 15 of 45 patients treated with placebo (33.3%) and in 5 of 46 patients treated with pamidronate (11%). The relative risk was 0.33 (95% CI, 0.14-0.77). Treatment was well tolerated and there was no difference in gastrointestinal toxicity between pamidronate and placebo-treated patients. One hundred fifty milligrams daily of pamidronate is an effective and safe treatment of women and men with established osteoporosis.     

利塞膦酸钠不同给药方式治疗男性骨质疏松症疗效分析

【摘要】〓目的〓观察利塞膦酸钠不同给药方式在男性骨质疏松症治疗中的疗效和耐受性。方法〓共纳入72例男性骨质疏松症患者,其中38例为口服利塞膦酸钠每日5 mg;34例为每周35 mg口服,随访1年。分别测定两组患者治疗前后L1~L4椎体骨密度值和骨转化指标,并观察两组骨质疏松性骨折的发生率及服药后的不良反应。结果〓口服利塞膦酸钠治疗后,患者L1~L4椎体和股骨颈的骨密度值较治疗前上升显著,每日口服组和每周口服组间比较无统计学差异(P>0.05);两组间的骨转化指标和骨折发生率亦无统计学差异。结论〓观察口服利塞膦酸钠治疗后1年,每周口服35 mg与每日口服5 mg比较,均能有效地提高骨质量。