Department of Endocrinology, National Health Commission Key Laboratory of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Department of Orthopedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Arch Osteoporos. 2023 Jan 4;18(1):17. doi: 10.1007/s11657-022-01203-9.
Hemophilia is a rare X-linked recessive inherited bleeding disorder caused by mutations of the genes encoding coagulation factor VIII (FVIII) or IX (FIX). Patients with hemophilia (PWH) often have a high risk of osteoporosis and fractures that is usually ignored. Herein, we review the underlying mechanisms of osteoporosis and the increased risk of fractures and their treatment in patients with FVIII or FIX deficiency.
The PubMed, Web of Science, Embase, and Cochrane Library databases were searched to identify original research articles, meta-analyses, and scientific reviews on the mechanisms or treatment of osteoporosis in PWH.
The pathogenic mechanisms of osteoporosis in PWH are multifactorial and remain unclear. The available evidence shows that FVIII and FIX deficiency may directly affect bone metabolism by interfering with the RANK/RANKL/OPG pathway. Other potential mechanisms of osteoporosis in PWH include thrombin deficiency and the unloading and immobilization of bone, which will affect osteoblast and osteoclast activity by changing the cytokine profiles. The treatment of osteoporosis in PWH includes antiresorptive, anabolic, and dual-action drugs; weight-bearing exercise; fall prevention; and prophylactic coagulation factor replacement therapy. However, clinical studies of the efficacy of anti-osteoporotic agents in osteoporosis of PWH are urgently needed.
This review summarizes recent progress in research on the pathogenesis of osteoporosis in PWH and provides insights into potential treatment for osteoporosis in PWH.
血友病是一种罕见的 X 连锁隐性遗传性出血性疾病，由编码凝血因子 VIII（FVIII）或 IX（FIX）的基因突变引起。血友病患者（PWH）通常存在骨质疏松症和骨折的高风险，而这一风险通常被忽视。在此，我们回顾了 FVIII 或 FIX 缺乏症患者骨质疏松症的发病机制、骨折风险增加及其治疗方法。
我们在 PubMed、Web of Science、Embase 和 Cochrane Library 数据库中检索了关于 PWH 骨质疏松症发病机制或治疗的原始研究文章、荟萃分析和科学综述。
PWH 骨质疏松症的发病机制是多因素的，目前仍不清楚。现有证据表明，FVIII 和 FIX 缺乏可能通过干扰 RANK/RANKL/OPG 通路直接影响骨代谢。PWH 骨质疏松症的其他潜在发病机制包括凝血酶缺乏和骨的卸载及固定，这些机制通过改变细胞因子谱影响成骨细胞和破骨细胞的活性。PWH 骨质疏松症的治疗包括抗吸收、合成代谢和双重作用药物；负重运动；预防跌倒；以及预防性凝血因子替代治疗。然而，迫切需要开展关于抗骨质疏松药物治疗 PWH 骨质疏松症疗效的临床研究。
本综述总结了 PWH 骨质疏松症发病机制研究的最新进展，并为 PWH 骨质疏松症的潜在治疗方法提供了新的思路。
