长期药物治疗和药物停药及停药期用于预防骨质疏松性骨折：系统评价。

Long-Term Drug Therapy and Drug Discontinuations and Holidays for Osteoporosis Fracture Prevention: A Systematic Review.

机构信息

University of Minnesota and Minneapolis VA Health Care System, Minneapolis, Minnesota (H.A.F., R.M., K.E.E., K.U., B.C.T., T.J.W.).

University of Minnesota, Minneapolis, Minnesota (M.L.F., C.E.R., V.A.N., M.B., C.M.O., M.B.).

出版信息

Ann Intern Med. 2019 Jul 2;171(1):37-50. doi: 10.7326/M19-0533. Epub 2019 Apr 23.

DOI:10.7326/M19-0533

PMID:31009947

Abstract

BACKGROUND

Optimal long-term osteoporosis drug treatment (ODT) is uncertain.

PURPOSE

To summarize the effects of long-term ODT and ODT discontinuation and holidays.

DATA SOURCES

Electronic bibliographic databases (January 1995 to October 2018) and systematic review bibliographies.

STUDY SELECTION

48 studies that enrolled men or postmenopausal women aged 50 years or older who were being investigated or treated for fracture prevention, compared long-term ODT (>3 years) versus control or ODT continuation versus discontinuation, reported incident fractures (for trials) or harms (for trials and observational studies), and had low or medium risk of bias (ROB).

DATA EXTRACTION

Two reviewers independently rated ROB and strength of evidence (SOE). One extracted data; another verified accuracy.

DATA SYNTHESIS

Thirty-five trials (9 unique studies) and 13 observational studies (11 unique studies) had low or medium ROB. In women with osteoporosis, 4 years of alendronate reduced clinical fractures (hazard ratio [HR], 0.64 [95% CI, 0.50 to 0.82]) and radiographic vertebral fractures (both moderate SOE), whereas 4 years of raloxifene reduced vertebral but not nonvertebral fractures. In women with osteopenia or osteoporosis, 6 years of zoledronic acid reduced clinical fractures (HR, 0.73 [CI, 0.60 to 0.90]), including nonvertebral fractures (high SOE) and clinical vertebral fractures (moderate SOE). Long-term bisphosphonates increased risk for 2 rare harms: atypical femoral fractures (low SOE) and osteonecrosis of the jaw (mostly low SOE). In women with unspecified osteoporosis status, 5 to 7 years of hormone therapy reduced clinical fractures (high SOE), including hip fractures (moderate SOE), but increased serious harms. After 3 to 5 years of treatment, bisphosphonate continuation versus discontinuation reduced radiographic vertebral fractures (zoledronic acid; low SOE) and clinical vertebral fractures (alendronate; moderate SOE) but not nonvertebral fractures (low SOE).

LIMITATION

No trials studied men, clinical fracture data were sparse, methods for estimating harms were heterogeneous, and no trials compared sequential treatments or different durations of drug holidays.

CONCLUSION

Long-term alendronate and zoledronic acid therapies reduce fracture risk in women with osteoporosis. Long-term bisphosphonate treatment may increase risk for rare adverse events, and continuing treatment beyond 3 to 5 years may reduce risk for vertebral fractures. Long-term hormone therapy reduces hip fracture risks but has serious harms.

PRIMARY FUNDING SOURCE

National Institutes of Health and Agency for Healthcare Research and Quality. (PROSPERO: CRD42018087006).

摘要

背景

骨质疏松症药物治疗的长期效果尚不确定。

目的

总结长期药物治疗和停药及停药期的效果。

数据来源

电子文献数据库（1995 年 1 月至 2018 年 10 月）和系统评价文献。

研究选择

纳入年龄 50 岁或以上、正在接受骨折预防治疗的男性或绝经后女性患者的 48 项研究，比较长期药物治疗（＞3 年）与对照组或药物治疗持续与停药，报告新发骨折（试验）或不良事件（试验和观察性研究），且偏倚风险（ROB）较低或中等。

数据提取

两名评审员独立评估 ROB 和证据强度（SOE）。一名提取数据，另一名验证准确性。

数据综合

35 项试验（9 项独特研究）和 13 项观察性研究（11 项独特研究）的 ROB 较低或中等。在骨质疏松症女性中，阿仑膦酸钠治疗 4 年可降低临床骨折（风险比 [HR]，0.64 [95%CI，0.50 至 0.82]）和影像学椎体骨折（均为中等 SOE），而雷洛昔芬治疗 4 年可降低椎体骨折但不能降低非椎体骨折。在骨量减少或骨质疏松症女性中，唑来膦酸治疗 6 年可降低临床骨折（HR，0.73 [CI，0.60 至 0.90]），包括非椎体骨折（高 SOE）和临床椎体骨折（中 SOE）。长期使用双磷酸盐会增加发生 2 种罕见不良事件的风险：非典型股骨骨折（低 SOE）和颌骨骨坏死（大多为低 SOE）。在骨质疏松症状态未明确的女性中，5 至 7 年激素治疗可降低临床骨折（高 SOE），包括髋部骨折（中 SOE），但增加严重不良事件。治疗 3 至 5 年后，继续与停止使用双磷酸盐治疗可降低影像学椎体骨折（唑来膦酸；低 SOE）和临床椎体骨折（阿仑膦酸钠；中 SOE），但不能降低非椎体骨折（低 SOE）。