Mechanisms of Bone Remodeling Disorder in Hemophilia

Wang, Hanshi; Bai, Xiwen

doi:10.1055/s-0040-1718890

Cited by 14 publications

(15 citation statements)

References 111 publications

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“…The molecular mechanisms of FVIII or FIX deficiency leading to osteoporosis have been explored. Studies have shown that the RANK/RANKL/OPG signaling pathway plays a role in the development of osteoporosis in PWH [ 6 , 20 , 21 ]. Receptor activator of nuclear factor kappa-B ligand (RANKL) binds to its receptor, RANK, and promotes osteoclastogenesis, resulting in increased bone resorption [ 22 ].…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, thrombin influences bone metabolism mainly by altering the expression of cytokines [ 20 ]. Thrombin is involved in the metabolism of arachidonic acid by binding to PAR-1 on the osteoblast membrane [ 6 ]. PAR-1 stimulates the expression of cyclooxygenase-2 (COX-2) through the mitogen-activated protein kinase (MAPK) pathway [ 39 ], and upregulated COX-2 catalyzes the conversion of arachidonic acid to prostaglandin E2 (PGE2).…”

Section: Resultsmentioning

confidence: 99%

“…Patients with hemophilia A and B have similar clinical phenotypes, including spontaneous hemorrhages into joints (ankles, knees, and elbows), muscles, or soft tissues [ 5 ]. Hemophilia A and B can be divided into three phenotypes on the basis of plasma coagulation factor levels: mild (> 5–40 IU/dL), moderate (1–5 IU/dL), and severe (< 1 IU/dL) [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

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Pathogenesis and treatment of osteoporosis in patients with hemophilia

et al. 2023

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Introduction 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. Methods 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. Results 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. Conclusion This review summarizes recent progress in research on the pathogenesis of osteoporosis in PWH and provides insights into potential treatment for osteoporosis in PWH.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pathogenesis and treatment of osteoporosis in patients with hemophilia

et al. 2023

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“…The mechanism leading to reduced BMD is unclear, although it is likely multifactorial. Deficiencies in coagulation factors and reduced mobility due to haemophilic arthropathy and target joints have been suggested to contribute to reduced BMD 7 …”

Section: Introductionmentioning

confidence: 99%

“…Deficiencies in coagulation factors and reduced mobility due to haemophilic arthropathy and target joints have been suggested to contribute to reduced BMD. 7 Factor (F)VIII prophylaxis has long been the standard of care for PwHA without FVIII inhibitors. 8 However, despite improvements in trough factor level and improved bleed control, 9 subclinical joint bleeding can still lead to debilitating joint damage.…”

Section: Introductionmentioning

confidence: 99%

Effect of emicizumab prophylaxis on bone and joint health markers in people with haemophilia A without factor VIII inhibitors in the HAVEN 3 study

et al. 2022

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Introduction Emicizumab prophylaxis significantly reduces bleeding events; however, the associated impact on bone/joint health is unknown. Aim To explore the effect of emicizumab prophylaxis on bone/joint health in people with haemophilia A (PwHA) without FVIII inhibitors enrolled in HAVEN 3 (NCT02847637). Methods Haemophilia joint health scores (HJHS; v2.1) were evaluated at baseline and Weeks 49 and 97 in PwHA receiving emicizumab (n = 134), and at baseline and Weeks 49, 73 and 97 in PwHA who switched to emicizumab after 24 weeks of no prophylaxis (n = 17). Bone and joint biomarkers were measured in 117 PwHA at baseline and at Weeks 13, 25, 49 and 73. Results HJHS was lower for PwHA who were previously on FVIII prophylaxis, aged <40 years or had no target joints at baseline compared with PwHA who were receiving no prophylaxis, aged ≥40 years or with target joints. Clinically significant mean (95% confidence interval) improvements from baseline of −2.13 (−3.96, −.29) in HJHS joint‐specific domains were observed at Week 49 in PwHA with at least one target joint at study entry (n = 71); these changes were maintained through Week 97. Improvements in HJHS from baseline were also observed for PwHA aged 12–39 years. Biomarkers of bone resorption/formation, cartilage degradation/synthesis, and inflammation did not change significantly during emicizumab prophylaxis. Conclusions Clinically relevant improvements in HJHS were observed in younger PwHA and those with target joints after 48 weeks of emicizumab in HAVEN 3. Biomarkers of bone/joint health did not show significant changes during 72 weeks of emicizumab prophylaxis.

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Insights and implications of sexual dimorphism in osteoporosis

Zhang,

Xie,

Sun

et al. 2024

Bone Res

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Osteoporosis, a metabolic bone disease characterized by low bone mineral density and deterioration of bone microarchitecture, has led to a high risk of fatal osteoporotic fractures worldwide. Accumulating evidence has revealed that sexual dimorphism is a notable feature of osteoporosis, with sex-specific differences in epidemiology and pathogenesis. Specifically, females are more susceptible than males to osteoporosis, while males are more prone to disability or death from the disease. To date, sex chromosome abnormalities and steroid hormones have been proven to contribute greatly to sexual dimorphism in osteoporosis by regulating the functions of bone cells. Understanding the sex-specific differences in osteoporosis and its related complications is essential for improving treatment strategies tailored to women and men. This literature review focuses on the mechanisms underlying sexual dimorphism in osteoporosis, mainly in a population of aging patients, chronic glucocorticoid administration, and diabetes. Moreover, we highlight the implications of sexual dimorphism for developing therapeutics and preventive strategies and screening approaches tailored to women and men. Additionally, the challenges in translating bench research to bedside treatments and future directions to overcome these obstacles will be discussed.

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Mechanisms of Bone Remodeling Disorder in Hemophilia

Cited by 14 publications

References 111 publications

Pathogenesis and treatment of osteoporosis in patients with hemophilia

Pathogenesis and treatment of osteoporosis in patients with hemophilia

Effect of emicizumab prophylaxis on bone and joint health markers in people with haemophilia A without factor VIII inhibitors in the HAVEN 3 study

Insights and implications of sexual dimorphism in osteoporosis

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