Visekruna Maja, Wilson Deborah, McKiernan Fergus Eoin
Center for Bone Disease, Marshfield Clinic, 1000 North Oak Avenue, Marshfield, Wisconsin 54449, USA.
J Clin Endocrinol Metab. 2008 Aug;93(8):2948-52. doi: 10.1210/jc.2007-2803. Epub 2008 Jun 3.
Since their introduction into clinical medicine, bisphosphonates have revolutionized clinical osteoporosis care. Ironically, in rare circumstances, long-term, combined anti-remodeling therapy may be associated with skeletal harm.
We report atypical skeletal fragility in three subjects after long-term, combined anti-remodeling therapy.
Three subjects experienced spontaneous or minimal-trauma chalk-stick type metadiaphyseal femoral fractures while on long-term bisphosphonate therapy. The fracture location, type, bilaterality, prodromal pain, and delayed healing were atypical for uncomplicated postmenopausal osteoporosis. All three subjects had concomitant circumstances (endogenous estrogen) or medications (glucocorticoids, hormone replacement therapy, and raloxifene) that likely suppressed bone remodeling beyond the effect of the bisphosphonate alone. Biochemical markers of bone turnover were very low or in the low premenopausal range. Double tetracycline-labeled bone biopsy showed very low activation frequency in one subject and limited single tetracycline label in a second consistent with severely suppressed bone turnover (SSBT). These three cases resemble previous descriptions of SSBT.
Atypical skeletal fragility may signify SSBT in the setting of long-term, combined anti-remodeling therapy. We speculate that osteoclast tolerance for pharmacological suppression may vary among individual patients and that in some cases combined anti-remodeling therapy may result in skeletal harm.
自双膦酸盐类药物引入临床医学以来，彻底改变了临床骨质疏松症的治疗方式。具有讽刺意味的是，在极少数情况下，长期联合抗骨重塑治疗可能会对骨骼造成损害。
我们报告了3例长期联合抗骨重塑治疗后出现非典型骨骼脆性的病例。
3例患者在长期接受双膦酸盐治疗期间发生了自发性或轻微创伤性的股骨干骺端粉笔样骨折。骨折的部位、类型、双侧性、前驱疼痛和愈合延迟对于单纯绝经后骨质疏松症来说都不典型。所有3例患者都有一些伴随情况（内源性雌激素）或药物（糖皮质激素、激素替代疗法和雷洛昔芬），这些因素可能单独在双膦酸盐的作用之外抑制了骨重塑。骨转换的生化标志物非常低或处于绝经前的低水平范围。双四环素标记的骨活检显示，1例患者的活化频率非常低，另1例患者的四环素标记有限，这与严重抑制骨转换（SSBT）一致。这3例病例与之前对SSBT的描述相似。
在长期联合抗骨重塑治疗的情况下，非典型骨骼脆性可能意味着SSBT。我们推测，破骨细胞对药物抑制的耐受性在个体患者中可能有所不同，并且在某些情况下，联合抗骨重塑治疗可能会对骨骼造成损害。
