预防男性骨折的药物疗法。
完整摘要 · 中文译文
原理：骨折预防的药物治疗通常针对骨质疏松症，这是一种以骨量或骨质量（或两者）受损为特征的骨骼疾病。由于骨质疏松症试验的大多数受试者为女性，因此有必要对男性骨折预防的药物治疗进行评价。 目的：确定双膦酸盐、甲状旁腺激素（PTH）或甲状旁腺激素相关蛋白（PTHrP）类似物、地舒单抗和罗莫索单抗治疗在男性骨折预防中的益处和危害。 检索方法：我们检索了CENTRAL、MEDLINE、Embase和两个试验注册库（ClinicalTrials.gov和WHO ICTRP），检索时间截至2025年10月14日，对发表日期或语言无限制。 纳入标准：我们纳入随机对照试验，这些试验比较了双膦酸盐、PTH或PTHrP类似物、地舒单抗或罗莫索单抗（单独使用或联合钙或维生素D，或两者）与安慰剂、其他药物或非药物治疗在50岁及以上男性中的作用。我们的主要比较是双膦酸盐与安慰剂的比较。 结局：关键结局为髋部骨折发生率、症状性椎体骨折、其他（非髋部或椎体）骨折、残疾、发生不良事件的受试者、因不良事件退出研究的受试者以及发生严重不良事件的受试者。我们的主要时间点为试验中报告的最后时间点。 偏倚风险：我们使用Cochrane的RoB 2工具评估偏倚风险。 合成方法：我们采用随机效应模型进行荟萃分析，使用Mantel-Haenszel方法，并用DerSimonian和Laird方法估计试验间方差。我们使用GRADE评估证据确定性。 纳入研究：17项试验（4132名受试者）符合我们的纳入标准。受试者的平均年龄范围为52至73岁。12项试验使用安慰剂对照，与双膦酸盐（7项试验，2548名受试者）、PTH或PTHrP类似物（4项试验，569名受试者）、地舒单抗（1项试验，240名受试者）和罗莫索珠单抗（1项试验，244名受试者）进行比较。对于其他计划中的比较，将双膦酸盐与维生素D/维生素D类似物（2项试验，434名受试者）、降钙素（1项试验，32名受试者）、PTH或PTHrP类似物（1项试验，19名受试者）或另一种双膦酸盐（1项试验，301名受试者）进行比较，另有1项试验将双膦酸盐加钙与单独钙片进行比较（46名受试者）。 结果综合：安慰剂对照试验大多易受所报告结果的选择偏倚的影响（83%），而无安慰剂对照的大多数试验也易受随机化过程产生的偏倚（100%）和结局测量中的偏倚（80%）的影响。关于双膦酸盐类药物与安慰剂相比在最终随访（最长两年）时对髋部骨折、症状性椎体骨折或其他（非髋部非椎体）骨折发生率的影响，我们非常不确定。我们将证据确定性因偏倚风险降级一次，因不精确性（事件率极低）降级两次，并因疑似发表偏倚降级一次。其他骨折发生率的证据确定性因间接性被进一步降级，因为尚不清楚该结局中是否也包含髋部骨折。在最长两年的随访中，双膦酸盐组 2/875 名受试者（2/1000）报告髋部骨折，而安慰剂组为 2/760 名受试者（3/1000）（风险比（RR）0.73，95% 置信区间（CI）0.06 至 8.51；I² = 36%；4 项试验，1635 名受试者）；双膦酸盐组 5/1021 名受试者（4/1000）发生症状性椎体骨折，而安慰剂组为 7/855 名受试者（8/1000）（RR 0.49，95% CI 0.14 至 1.74；I² = 0%；5 项试验，1876 名受试者）；双膦酸盐组 25/1130 名受试者（16/1000）报告其他（非髋部非椎体）骨折，而安慰剂组为 19/913 名受试者（21/1000）（RR 0.78，95% CI 0.42 至 1.45；I² = 0%；6 项试验，2043 名受试者）。双膦酸盐类药物可能不会增 增加不良事件风险：1024/1374名参与者（746/1000）接受双膦酸盐，报告了不良事件，而826/1174名参与者（704/1000）接受安慰剂，报告了不良事件（RR 1.06，95% CI 0.93至1.19；I² = 75%；7项试验，2548名参与者；中等确定性证据）或严重不良事件：329/1329名参与者（272/1000）接受双膦酸盐，报告了严重不良事件，而323/1128名参与者（286/1000）接受安慰剂，报告了严重不良事件（RR 0.95，95% CI 0.84至1.08；I² = 0%；6项试验，2457名参与者；中等确定性证据）。我们因不良事件和严重不良事件的潜在偏倚将证据确定性降低一级。我们非常不确定双膦酸盐是否会导致更多因不良事件退出：双膦酸盐组41/1374名参与者（25/1000）因不良事件退出，而安慰剂组43/1174名参与者（37/1000）退出（RR 0.68，95% CI 0.39至1.18；I² = 37%；7项试验，2548名参与者；极低确定性证据）。我们因偏倚风险将证据确定性降低一级，因间接性降低一级，因不精确性降低一级。没有试验报告残疾。我们非常不确定与安慰剂相比，PTH或PTHrP类似物、地舒单抗或罗莫佐单抗对骨折结局的影响。我们非常不确定PTH/PTHrP类似物对总不良事件、因不良事件退出和严重不良事件的影响。与安慰剂相比，地舒单抗可能不会增加不良事件或严重不良事件的风险，而因不良事件退出的证据 事件非常不确定。罗莫索珠单抗可能不会增加不良事件的风险，可能不会增加严重不良事件的风险，也不会导致更多因不良事件而退出的情况。 作者结论：对于双膦酸盐与安慰剂相比，在长达两年的使用期间对男性髋部骨折、症状性椎体骨折或其他（非髋部非椎体）骨折发生率的影响，我们非常不确定。双膦酸盐可能不会增加不良事件或严重不良事件的风险，而且我们非常不确定它们是否会导致更多因不良事件退出。我们因间接性、不精确性（事件发生率低）以及报告结果选择方面的严重偏倚风险而降低了证据确定性，因为尚不清楚所有研究是否都完整报告了每一例骨折。我们发现了甲状旁腺激素（PTH）或甲状旁腺激素相关蛋白（PTHrP）类似物、地舒单抗或罗莫佐单抗与安慰剂相比的相似结果。需要更大规模、更长期的安慰剂对照研究来确定药物治疗是否有利于减少男性骨折。 资金：本Cochrane系统评价没有专项资助。 注册：方案（2021）：https://doi.org/10.1002/14651858.CD014707。
完整摘要 · 英文原文
RATIONALE: Pharmacological therapies for fracture prevention usually target osteoporosis, a skeletal disorder characterised by compromised bone mass or quality (or both). As most participants in osteoporosis trials are women, a review of pharmacological therapies for fracture prevention in men was warranted. OBJECTIVES: To determine the benefits and harms of bisphosphonates, parathyroid (PTH) or parathyroid-related protein (PTHrP) analogues, denosumab, and romosozumab therapy for the prevention of fractures in men. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trial registries (ClinicalTrials.gov and WHO ICTRP) until 14 October 2025, with no restrictions on date or language of publication. ELIGIBILITY CRITERIA: We included randomised controlled trials that compared bisphosphonates, PTH or PTHrP analogues, denosumab, or romosozumab (alone or with calcium or vitamin D, or both) with placebo, other drugs, or non-pharmacological therapies in men aged 50 years or older. Our primary comparison was bisphosphonates versus placebo. OUTCOMES: Critical outcomes were incidence of hip fractures, symptomatic vertebral fractures, other (not hip or vertebral) fractures, disability, participants with adverse events, study withdrawals due to adverse events, and participants with serious adverse events. Our primary time point was the final time point reported in the trials. RISK OF BIAS: We used Cochrane's RoB 2 tool to assess risk of bias. SYNTHESIS METHODS: We used a random-effects model for meta-analysis employing the Mantel-Haenszel approach, and the DerSimonian and Laird method to estimate between-trial variance. We assessed the certainty of evidence using GRADE. INCLUDED STUDIES: Seventeen trials (4132 participants) met our inclusion criteria. The average age of participants ranged from 52 to 73 years. Twelve trials used a placebo comparator versus bisphosphonate (7 trials, 2548 participants), PTH or PTHrP analogues (4 trials, 569 participants), denosumab (1 trial, 240 participants), and romosozumab (1 trial, 244 participants). For the other planned comparisons, a bisphosphonate was compared to vitamin D/vitamin D analogues (2 trials, 434 participants), to calcitonin (1 trial, 32 participants), to PTH or PTHrP analogues (1 trial, 19 participants), or to another bisphosphonate (1 trial, 301 participants), and one trial compared a bisphosphonate plus calcium to calcium tablets alone (46 participants). SYNTHESIS OF RESULTS: Placebo-controlled trials were largely susceptible to bias in selection of the reported result (83%), while most trials without a placebo control were also susceptible to bias arising from the randomisation process (100%) and in measurement of the outcome (80%). We are very uncertain about the effect of bisphosphonates on the incidence of hip fractures, symptomatic vertebral fractures, or other (non-hip non-vertebral) fractures compared to placebo at the final follow-up (up to two years). We downgraded the certainty of evidence once for risk of bias, twice for imprecision (very low event rates), and once for suspected publication bias. The certainty of evidence for incidence of other fractures was further downgraded for indirectness, as it was unclear if hip fractures were also included in the outcome. At up to two years, 2/875 participants (2 per 1000) in the bisphosphonate group reported hip fractures compared with 2/760 (3 per 1000) in the placebo group (risk ratio (RR) 0.73, 95% confidence interval (CI) 0.06 to 8.51; I² = 36%; 4 trials, 1635 participants); 5/1021 (4/1000) participants in the bisphosphonate group had a symptomatic vertebral fracture compared to 7/855 (8/1000) participants in the placebo group (RR 0.49, 95% CI 0.14 to 1.74; I² = 0%; 5 trials, 1876 participants); 25/1130 participants (16/1000) in the bisphosphonate group reported other (non-hip non-vertebral) fractures compared to 19/913 participants (21/1000) in the placebo group (RR 0.78, 95% CI 0.42 to 1.45; I² = 0%; 6 trials, 2043 participants). Bisphosphonates probably do not increase the risk of adverse events: 1024/1374 participants (746/1000) receiving bisphosphonates reported adverse events compared to 826/1174 participants (704/1000) receiving placebo (RR 1.06, 95% CI 0.93 to 1.19; I² = 75%; 7 trials, 2548 participants; moderate-certainty evidence) or serious adverse events: 329/1329 participants (272/1000) receiving bisphosphonate reported serious adverse events compared to 323/1128 participants (286/1000) receiving placebo (RR 0.95, 95% CI 0.84 to 1.08; I² = 0%; 6 trials, 2457 participants; moderate-certainty evidence). We downgraded the certainty of evidence once due to potential bias for adverse events and serious adverse events. We are very uncertain if bisphosphonates result in more withdrawals due to adverse events: 41/1374 participants (25/1000) in the bisphosphonate group withdrew due to adverse events compared with 43/1174 participants (37/1000) in the placebo group (RR 0.68, 95% CI 0.39 to 1.18; I² = 37%; 7 trials, 2548 participants; very low-certainty evidence). We downgraded the certainty of evidence once for risk of bias, once for indirectness, and once for imprecision. No trial reported disability. We are very uncertain about the effects of PTH or PTHrP analogues, denosumab, or romosozumab compared to placebo on fracture outcomes. We are very uncertain about the effects of PTH/PTHrP analogues on total adverse events, withdrawals due to adverse events, and serious adverse events. Denosumab may not increase the risk of adverse events or serious adverse events compared to placebo, while the evidence for withdrawals due to adverse events is very uncertain. Romosozumab probably does not increase the risk of adverse events and may not increase the risk of serious adverse events or result in more withdrawals due to adverse events. AUTHORS' CONCLUSIONS: We are very uncertain about the effects of bisphosphonates compared to placebo on the incidence of hip fractures, symptomatic vertebral fractures, or other (non-hip non-vertebral) fractures in men at up to two years of use. Bisphosphonates probably do not increase the risk of adverse events or serious adverse events, and we are very uncertain if they result in more withdrawals due to adverse events. We downgraded the certainty of evidence for indirectness, imprecision (low event rate), and serious risk of bias in selection of the reported result, as it was unclear if all studies fully reported every fracture. We found similar results for PTH or PTHrP analogues, denosumab, or romosozumab versus placebo. Larger, longer placebo-controlled studies are needed to determine whether pharmacological therapies are beneficial for reducing fractures in men. FUNDING: This Cochrane review had no dedicated funding. REGISTRATION: Protocol (2021): https://doi.org/10.1002/14651858.CD014707.