Increased bone resorption is implicated in the pathogenesis of bone loss in hemophiliacs: correlations with hemophilic arthropathy and HIV infection
Increased bone resorption is implicated in the pathogenesis of bone loss in hemophiliacs: correlations with hemophilic arthropathy and HIV infection
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DOI：
10.1007/s00277-009-0759-x
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发表时间：
2010-01-01
影响因子：
3.5
通讯作者：
Karafoulidou, Anastasia
中科院分区：
文献类型：
--
作者：
Katsarou, Olga;Terpos, Evangelos;Karafoulidou, Anastasia
骨质疏松症最近被认为是血友病的一个严重的合并症因素。然而，其发病机制仍不清楚。我们评估了90例血友病患者骨质疏松症的发病率，并调查了与临床和实验室数据的可能相关性。在90例患者中，80例（89%）患有重度血友病，35例（38.9%）为人类免疫缺陷病毒（HIV）阳性。采用世界血友病联盟临床评分和Petterson放射学评分评估血友病性关节病。采用双能X线骨密度仪测量腰椎（LS）和股骨颈（FN）的骨密度。通过测量以下指标评价骨转换：（1）骨吸收标志物[I型胶原的N-末端交联端肽（NTX）、I型胶原的C-末端交联端肽（CTX）和抗酒石酸酸性磷酸酶同种型-5b（2）骨形成标志物[骨碱性磷酸酶（bALP）和骨钙素]，和（3）破骨细胞刺激剂（核因子-κ B配体的受体活化剂、骨保护素和肿瘤坏死因子-α）。FN和LS中分别有86%和65%的患者出现骨质减少或骨质疏松症。骨质疏松症在FN（65.3% vs 41.6%; p = 0.007）和LS（17.86% vs 5.41%，p = 0.004）的HIV阳性患者中更常见。FN中骨质疏松的严重程度与患者的临床和放射学总评分相关（p = 0.001）。血友病患者表现出骨钙素活性增加（TRACP-5 b、NTX和CTX显著增加），但未伴随相当的骨形成增加（骨钙素减少和bALP临界增加）。在多变量分析中，HIV感染（p = 0.05）和总临床评分（p = 0.001）是骨质疏松症发展的独立危险因素。我们的结论是，血友病患者骨质疏松症的患病率很高，这与关节病的严重程度有关，并通过艾滋病毒感染增强。我们首次报告了高骨吸收，似乎没有通过可比的骨形成平衡。
Osteoporosis has been recently recognized as a severe comorbidity factor in hemophilia. However, its pathogenesis is still obscure. We evaluated the incidence of osteoporosis in 90 hemophilia patients and investigated possible correlations with clinical and laboratory data. Out of the 90 patients, 80 (89%) had severe hemophilia, and 35 (38.9%) were human immunodeficiency virus (HIV)-positive. Hemophilic arthropahty was assessed using World Federation of Hemophilia clinical score and Petterson radiological score. Bone mineral density of the lumbar spine (LS) and femoral neck (FN) were measured using dual-energy X-ray absortiometry. Bone turnover was evaluated by the measurement of: (1) bone resorption markers [N-terminal cross-linking telopeptide of collagen type I (NTX), C-terminal cross-linking telopeptide of collagen type I (CTX), and tartrate-resistant acid phosphatase isoform-5b (TRACP-5b)], (2) bone formation markers [bone-alkaline phosphatase (bALP) and osteocalcin], and (3) osteoclast stimulators (receptor activator of nuclear factor-kappa B ligand, osteoprotegerin, and tumor necrosis factor-alpha). Osteopenia or osteoporosis was observed in 86% and 65% of the patients in FN and LS, respectively. Osteoporosis was more common among HIV-positive patients in both FN (65.3% vs 41.6%; p = 0.007) and LS (17.86% vs 5.41%, p = 0.004). The severity of osteoporosis in FN correlated with the patients' total clinical and radiological score (p = 0.001). Hemophilia patients showed increased osteoclastic activity (significant increase of TRACP-5b, NTX, and CTX), which was not accompanied by a comparable increased bone formation (reduced osteocalcin and borderline increase of bALP). In multivariate analysis, HIV infection (p = 0.05) and total clinical score (p = 0.001) were independent risk factors for osteoporosis development. We conclude that there is a high prevalence of osteoporosis among hemophiliacs, which is related to the severity of arthropathy and is enhanced by HIV infection. We report for the first time a high bone resorption that seems not to be balanced by a comparable bone formation.