Abstract：
OBJECTIVE: Previous evidence suggests that bisphosphonates (BPs) may lower the risk of recurrent fractures and enhance functional recovery in patients with fractures. However, there has been controversy regarding the optimal timing of treatment initiation for patients with fragility fractures. We conducted a meta-analysis to evaluate the available evidence on the use of BPs during the perioperative period and compared it to both non-perioperative periods and non-usage.
METHODS: Electronic searches were performed using PubMed, EMBASE, Web of Science and the Cochrane Library published before February 2023, without any language restrictions. The primary outcomes included fracture healing rate, healing time, and new fractures. We also examined a wide range of secondary outcomes. Random effects meta-analysis was used.
RESULTS: A total of 19 clinical trials involving 2543 patients were included in this meta-analysis. When comparing patients with non-perioperative BPs use in 4-6 weeks and approximately 10-12 weeks post-surgically, the overall risk ratios (RRs) of perioperative BPs use for healing rate were 1.06 (95% CI: 0.81, 1.38, p=0.69) and 1.02 (95% CI: 0.94, 1.11, p=0.65), respectively, suggesting no difference in healing rate between perioperative and non-perioperative BP initiation. For healing time, the overall mean difference between perioperative and non-perioperative periods was -0.19 week (95% CI: -1.03, 0.64, p=0.65) at approximately 10-12 weeks, indicating no significant impact of perioperative BP initiation on healing time. In terms of new fractures, the overall RR with BP use was 0.35 (95% CI: 0.17-0.73, p=0.005), when compared to patients without BPs use. This suggests a protective impact of BP use against new fractures compared to patients without BP use. Perioperative BP use was associated with a markedly higher likelihood of having adverse experiences, including fever (RR: 23.78, 95% CI: 8.29, 68.21, p< 0.001), arthralgia (RR: 10.20, 95% CI: 2.41, 43.16, p=0.002), and myalgia (RR: 9.42, 95% CI: 2.54, 34.87, p< 0.001), compared with non-BPs use.
CONCLUSIONS: Treatment with BP during the perioperative period does not affect the healing process and has positive effects on therapy for patients with fragility fractures. These compelling findings underscore the potential efficacy of BP use during the perioperative period as a viable treatment option for patients with fragility fractures.
METHODS: Electronic searches were performed using PubMed, EMBASE, Web of Science and the Cochrane Library published before February 2023, without any language restrictions. The primary outcomes included fracture healing rate, healing time, and new fractures. We also examined a wide range of secondary outcomes. Random effects meta-analysis was used.
RESULTS: A total of 19 clinical trials involving 2543 patients were included in this meta-analysis. When comparing patients with non-perioperative BPs use in 4-6 weeks and approximately 10-12 weeks post-surgically, the overall risk ratios (RRs) of perioperative BPs use for healing rate were 1.06 (95% CI: 0.81, 1.38, p=0.69) and 1.02 (95% CI: 0.94, 1.11, p=0.65), respectively, suggesting no difference in healing rate between perioperative and non-perioperative BP initiation. For healing time, the overall mean difference between perioperative and non-perioperative periods was -0.19 week (95% CI: -1.03, 0.64, p=0.65) at approximately 10-12 weeks, indicating no significant impact of perioperative BP initiation on healing time. In terms of new fractures, the overall RR with BP use was 0.35 (95% CI: 0.17-0.73, p=0.005), when compared to patients without BPs use. This suggests a protective impact of BP use against new fractures compared to patients without BP use. Perioperative BP use was associated with a markedly higher likelihood of having adverse experiences, including fever (RR: 23.78, 95% CI: 8.29, 68.21, p< 0.001), arthralgia (RR: 10.20, 95% CI: 2.41, 43.16, p=0.002), and myalgia (RR: 9.42, 95% CI: 2.54, 34.87, p< 0.001), compared with non-BPs use.
CONCLUSIONS: Treatment with BP during the perioperative period does not affect the healing process and has positive effects on therapy for patients with fragility fractures. These compelling findings underscore the potential efficacy of BP use during the perioperative period as a viable treatment option for patients with fragility fractures.
摘要：
目的：先前的证据表明，双膦酸盐（BPs）可以降低骨折患者复发的风险，并促进功能恢复。然而,对于脆性骨折患者的最佳治疗开始时机一直存在争议.我们进行了一项荟萃分析，以评估围手术期使用BP的可用证据，并将其与非围手术期和未使用进行比较。
方法：使用PubMed进行电子搜索，EMBASE,WebofScience和Cochrane图书馆在2023年2月之前出版，没有任何语言限制。主要结果包括骨折愈合率，愈合时间,和新的骨折。我们还检查了广泛的次要结果。采用随机效应荟萃分析。
结果：本荟萃分析共纳入19项临床试验，涉及2543例患者。当比较手术后4-6周和大约10-12周使用非围手术期BPs的患者时，围手术期BPs用于治愈率的总风险比（RR）为1.06（95％CI：0.81，1.38，p=0.69）和1.02（95％CI：0.94，1.11，p=0.65），分别,提示围手术期和非围手术期血压开始之间的治愈率没有差异。为了治愈的时间，围手术期与非围手术期之间的总体平均差异在约10-12周时为-0.19周（95％CI：-1.03，0.64，p=0.65），提示围手术期开始BP对愈合时间无显著影响。就新骨折而言，使用BP的总RR为0.35(95%CI：0.17-0.73，p=0.005)，与不使用BP的患者相比。这表明与不使用BP的患者相比，使用BP对新骨折具有保护性影响。围手术期使用BP与不良经历的可能性明显较高相关，包括发热（RR：23.78，95%CI：8.29，68.21，p<0.001），关节痛（RR：10.20，95%CI：2.41，43.16，p=0.002），和肌痛（RR：9.42，95%CI：2.54，34.87，p<0.001），与非BP使用相比。
结论：围手术期BP治疗不影响骨折愈合过程，对脆性骨折患者的治疗有积极作用。这些令人信服的发现强调了围手术期使用BP作为脆性骨折患者可行的治疗选择的潜在疗效。
方法：使用PubMed进行电子搜索，EMBASE,WebofScience和Cochrane图书馆在2023年2月之前出版，没有任何语言限制。主要结果包括骨折愈合率，愈合时间,和新的骨折。我们还检查了广泛的次要结果。采用随机效应荟萃分析。
结果：本荟萃分析共纳入19项临床试验，涉及2543例患者。当比较手术后4-6周和大约10-12周使用非围手术期BPs的患者时，围手术期BPs用于治愈率的总风险比（RR）为1.06（95％CI：0.81，1.38，p=0.69）和1.02（95％CI：0.94，1.11，p=0.65），分别,提示围手术期和非围手术期血压开始之间的治愈率没有差异。为了治愈的时间，围手术期与非围手术期之间的总体平均差异在约10-12周时为-0.19周（95％CI：-1.03，0.64，p=0.65），提示围手术期开始BP对愈合时间无显著影响。就新骨折而言，使用BP的总RR为0.35(95%CI：0.17-0.73，p=0.005)，与不使用BP的患者相比。这表明与不使用BP的患者相比，使用BP对新骨折具有保护性影响。围手术期使用BP与不良经历的可能性明显较高相关，包括发热（RR：23.78，95%CI：8.29，68.21，p<0.001），关节痛（RR：10.20，95%CI：2.41，43.16，p=0.002），和肌痛（RR：9.42，95%CI：2.54，34.87，p<0.001），与非BP使用相比。
结论：围手术期BP治疗不影响骨折愈合过程，对脆性骨折患者的治疗有积极作用。这些令人信服的发现强调了围手术期使用BP作为脆性骨折患者可行的治疗选择的潜在疗效。
