Stevenson M, Davis S, Lloyd-Jones M, Beverley C
School of Health and Related Research (ScHARR), University of Sheffield, UK.
Health Technol Assess. 2007 Feb;11(4):1-134. doi: 10.3310/hta11040.
To estimate the clinical effectiveness and cost-effectiveness of strontium ranelate for the prevention of osteoporotic fractures in postmenopausal women, at different levels of absolute fracture risk. This considers secondary prevention in women who have sustained a previous fracture and primary prevention in those women without a previous fracture, as women with osteoporosis are asymptomatic until a fracture is sustained.
Major electronic bibliographic databases were searched in September 2004 and updated in March 2005.
A systematic review was carried out to determine clinical effectiveness using the major electronic bibliographic databases and handsearching reference lists of relevant articles and sponsor submissions. Data from selected studies were assessed and included in the meta-analyses, if appropriate. The model used to calculate cost-effectiveness ratios was an updated version of Sheffield Health Economic Model for Osteoporosis that was populated with absolute risk of fractures using an algorithm being developed for the World Health Organization and supplied in confidence to the authors. The model calculated the number of fractures that occur and provided as output data the costs associated with osteoporotic fractures, and the quality adjusted life-years (QALYs) accrued by a cohort of 100 osteoporotic women, with each fracture being detrimental to health and incurring a cost. When the costs of the intervention were included, the incremental cost compared with no treatment was calculated and divided by the gain in QALYs to calculate cost-effectiveness measures. Treatment with strontium ranelate was calculated against a no-treatment option to evaluate whether it could be given cost-effectively. An incremental analysis against alendronate was also conducted to estimate the cost-effectiveness of strontium ranelate relative to a current standard treatment. The cost-effectiveness of strategies for identifying and treating women without a prior fracture used the risk of fracture as an input to the cost-effectiveness model.
Three trials were identified. Pooled data from two studies indicate that strontium ranelate therapy is associated with a reduction in the risk of vertebral fracture [relative risk (RR) compared with placebo 0.60, 95% confidence interval (CI) 0.53 to 0.69, p < 0.001] and non-vertebral fracture (RR 0.84, 95% CI 0.73 to 0.97, p = 0.01). In general, strontium ranelate therapy did not seem to be associated with an increased risk of adverse events. However, the risk of one rare but serious adverse event, venous thromboembolism (including pulmonary embolism), was found to be significantly higher in patients receiving strontium ranelate compared with placebo (RR 1.42, 95% CI 1.02 to 1.98, p = 0.036). Some nervous system disorders, including mental impairment, disturbed consciousness, memory loss and seizures, were also more common in patients randomised to strontium ranelate. Strontium ranelate provided gains in QALYs compared with no treatment in women with sufficient calcium and vitamin D intakes. The size of the QALY gain for each intervention was strongly related to the absolute risk of fracture. From the algorithm used, it is seen that strontium ranelate can be used cost-effectively in women at relatively high risk of osteoporotic fracture. However, the results of the probabilistic sensitivity analysis, using efficacy data from randomised controlled trials, suggest that it is not as cost-effective as alendronate, a comparator intervention from the bisphosphonate class. The use of strontium ranelate in women without a prior fracture will be dependent on identification algorithms being produced in conjunction with the National Institute for Health and Clinical Excellence Osteoporosis Guidelines Development Group.
Strontium ranelate was shown to be clinically effective in the prevention of osteoporotic fractures. Scenarios have been found where strontium ranelate can be used cost-effectively, however given the probabilistic sensitivity analyses conducted, this intervention appears to be less cost-effective than the bisphosphonate alendronate. The evidence base for the efficacy of fracture prevention for strontium ranelate needs to be strengthened, particularly for hip fractures, where there is currently a non-significant reduction. If it were believed that the efficacy of strontium ranelate is dependent on either age or absolute risk, this would need to be proven. The evidence base on the T-score by age of the general female population needs to be strengthened, particularly in women over the age of 80 years. The prevalence of risk factors associated with fracture rates, over and above that provided by bone mineral density, also needs to be significantly strengthened to ensure that the estimated number of women that could be cost-effectively treated is accurate.
评估雷奈酸锶在不同绝对骨折风险水平下，预防绝经后女性骨质疏松性骨折的临床有效性和成本效益。这考虑了既往有骨折女性的二级预防，以及既往无骨折女性的一级预防，因为骨质疏松女性在发生骨折之前通常没有症状。
2004年9月检索了主要电子文献数据库，并于2005年3月更新。
进行系统综述，以使用主要电子文献数据库、手工检索相关文章的参考文献列表以及申办方提交的资料来确定临床有效性。对所选研究的数据进行评估，并在适当情况下纳入荟萃分析。用于计算成本效益比的模型是谢菲尔德骨质疏松症健康经济模型的更新版本，该模型使用为世界卫生组织开发的一种算法，根据骨折的绝对风险进行填充，并以保密方式提供给作者。该模型计算发生骨折的数量，并将骨质疏松性骨折相关成本以及100名骨质疏松女性队列积累的质量调整生命年（QALY）作为输出数据，每次骨折都会对健康产生不利影响并产生成本。当纳入干预措施的成本时，计算与不治疗相比的增量成本，并除以QALY的增加量以计算成本效益指标。将雷奈酸锶治疗与不治疗方案进行比较，以评估其是否具有成本效益。还针对阿仑膦酸钠进行了增量分析，以估计雷奈酸锶相对于当前标准治疗的成本效益。识别和治疗既往无骨折女性的策略的成本效益，将骨折风险作为成本效益模型的输入。
确定了三项试验。两项研究的汇总数据表明，雷奈酸锶治疗与椎体骨折风险降低相关[与安慰剂相比相对风险（RR）为0.60，95%置信区间（CI）为0.53至0.69，p<0.001]，与非椎体骨折风险降低相关（RR为0.84，95%CI为0.73至0.97，p=0.01）。总体而言，雷奈酸锶治疗似乎与不良事件风险增加无关。然而，发现接受雷奈酸锶治疗的患者发生一种罕见但严重的不良事件，即静脉血栓栓塞（包括肺栓塞）的风险显著高于安慰剂组（RR为1.42，95%CI为1.02至1.98，p=0.036）。一些神经系统疾病，包括精神障碍、意识障碍、记忆力减退和癫痫发作，在随机接受雷奈酸锶治疗的患者中也更常见。与钙和维生素D摄入量充足的未治疗女性相比，雷奈酸锶可使QALY增加。每种干预措施的QALY增加幅度与骨折的绝对风险密切相关。从所使用的算法可以看出，雷奈酸锶可用于具有相对较高骨质疏松性骨折风险的女性，具有成本效益。然而，使用随机对照试验的疗效数据进行的概率敏感性分析结果表明，它不如双膦酸盐类的对照干预措施阿仑膦酸钠具有成本效益。在既往无骨折的女性中使用雷奈酸锶将取决于与国家卫生与临床优化研究所骨质疏松症指南制定小组联合制定的识别算法。
雷奈酸锶在预防骨质疏松性骨折方面显示出临床有效性。已发现雷奈酸锶在某些情况下具有成本效益，然而，鉴于所进行的概率敏感性分析，该干预措施似乎不如双膦酸盐类的阿仑膦酸钠具有成本效益。雷奈酸锶预防骨折疗效的证据基础需要加强，特别是对于髋部骨折，目前其降低风险的效果不显著。如果认为雷奈酸锶的疗效取决于年龄或绝对风险，则需要对此进行证实。普通女性人群按年龄划分的T评分的证据基础需要加强，特别是在80岁以上的女性中。与骨折率相关的风险因素（除骨密度外）的患病率也需要显著加强，以确保能够准确估计可进行成本效益治疗的女性数量。
