Bone Turnover in Bone Biopsies of Patients with Low-Energy Cortical Fractures Receiving Bisphosphonates: A Case Series
Bone Turnover in Bone Biopsies of Patients with Low-Energy Cortical Fractures Receiving Bisphosphonates: A Case Series
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DOI：
10.1007/s00223-009-9263-5
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发表时间：
2009-07-01
影响因子：
4.2
通讯作者：
Novack, Deborah
中科院分区：
文献类型：
--
作者：
Armamento-Villareal, Reina;Napoli, Nicola;Novack, Deborah
近期有关长期使用双膦酸盐治疗的患者出现皮质骨折的报道引发了人们的担忧，即此类骨折可能与长期使用这些药物后骨转换过度抑制有关。为了评估双膦酸盐治疗后出现皮质骨折的患者的骨组织学情况，我们对在华盛顿大学骨骼健康项目中接受治疗的患者进行了回顾性分析，这些患者有低能量皮质骨折（股骨干、骨盆、肋骨、跖骨和踝关节）病史，连续使用双膦酸盐至少两年且接受了骨活检。2004年11月至2007年3月期间接受骨活检的54名患者中有15名符合标准。其中，10名患者有骨小梁重塑受抑制的表现，如缺乏四环素双标记所示。骨转换受抑制的患者与其他5名骨重塑正常的患者在骨密度、临床特征和生化特征方面没有显著差异。然而，低转换组使用双膦酸盐（主要是阿仑膦酸钠）的时间明显更长（6.5±0.6年对3.9±0.8年，P = 0.02）。因此，在长期使用双膦酸盐治疗期间出现皮质骨折的患者中，约三分之二存在骨转换受抑制的情况。由于在未骨折患者中此类组织学表现的患病率尚不清楚，骨转换受抑制对皮质骨折发生的影响无法确定。考虑到双膦酸盐的广泛使用，皮质骨折的总体风险似乎较低。然而，可能有一部分尚未确定的患者可能易患这种并发症。
Recent reports of long-term bisphosphonate-treated patients developing cortical fractures have raised concerns that such fractures may relate to excessive suppression of bone turnover after prolonged use of these drugs. To evaluate the bone histology of patients presenting with cortical fractures after bisphosphonate therapy, we conducted a retrospective analysis of patients treated at Washington University Bone Health Program presenting with a history of low-energy cortical fractures (femoral shaft, pelvis, rib, metatarsal, and ankle), who had received bisphosphonates for at least two consecutive years and had undergone bone biopsy. Fifteen of 54 patients who underwent bone biopsy between November 2004 and March 2007 met the criteria. Of these, 10 patients had findings of suppressed trabecular bone remodeling, as demonstrated by lack of double tetracycline labels. There were no significant differences in bone density, clinical features, and biochemical features between those with suppressed turnover and the other five subjects with normal remodeling. However, the low-turnover group had received bisphosphonates (primarily alendronate) for a significantly longer duration (6.5 +/- A 0.6 vs. 3.9 +/- A 0.8 years, P = 0.02). Thus, about two-thirds of patients presenting with cortical fractures while on long-term treatment with bisphosphonates had suppressed turnover. Since the prevalence of such histological findings in nonfracture patients remains unknown, the impact of suppressed bone turnover on the development of cortical fractures cannot be determined. Considering the widespread use of bisphosphonates, it appears that the overall risk of cortical fractures is low. However, there may be a subset of as yet unidentified patients who could be predisposed to this complication.