Atypical fracture with long-term bisphosphonate therapy is associated with altered cortical composition and reduced fracture resistance
Atypical fracture with long-term bisphosphonate therapy is associated with altered cortical composition and reduced fracture resistance
复制标题
DOI：
10.1073/pnas.1704460114
复制
发表时间：
2017-08-15
影响因子：
11.1
通讯作者：
Donnelly, Eve
中科院分区：
文献类型：
--
作者：
Lloyd, Ashley A.;Gludovatz, Bernd;Donnelly, Eve
双膦酸盐是骨质疏松症最广泛的药物治疗处方，可将绝经后妇女的骨折风险降低高达50%。然而，在过去的十年中，这些药物与非典型股骨骨折（AFFs），罕见的骨折与横向，脆性形态。不寻常的骨折形态表明，双膦酸盐治疗可能会损害皮质骨的增韧机制。本研究的目的是比较接受双膦酸盐治疗的AFF患者与接受和未接受双膦酸盐治疗的典型骨质疏松性骨折患者的骨活检组织的成分和机械性能。在骨折修复手术（骨折组，n = 33）或全髋关节置换术（非骨折组，n = 17）期间，从绝经后妇女中获得骨折部位附近的股骨近端皮质骨活检。根据骨折形态和双磷酸盐治疗史，将患者分为5组[+ BIS非典型：n = 12，BIS持续时间：8.2（3.0）年; + BIS典型：n = 10，7.7（5.0）年; + BIS Nonfx：n = 5，6.4（3.5）年; -BIS典型：n = 11; -BIS Nonfx：n = 12]。振动光谱和纳米压痕显示，双膦酸盐治疗的女性非典型骨折的组织比双膦酸盐治疗的女性典型骨折的组织更硬，更矿化。此外，断裂力学测量结果表明，接受双磷酸盐治疗的患者的组织断裂韧性不足，与未接受双磷酸盐治疗的患者相比，骨组织边界处的裂纹起始韧性较低，裂纹偏转较小。总之，这些结果表明内在和外在增韧机制的缺陷，这有助于长期接受双膦酸盐治疗的患者的AFFS。
Bisphosphonates are the most widely prescribed pharmacologic treatment for osteoporosis and reduce fracture risk in postmenopausal women by up to 50%. However, in the past decade these drugs have been associated with atypical femoral fractures (AFFs), rare fractures with a transverse, brittle morphology. The unusual fracture morphology suggests that bisphosphonate treatment may impair toughening mechanisms in cortical bone. The objective of this study was to compare the compositional and mechanical properties of bone biopsies from bisphosphonate-treated patients with AFFs to those from patients with typical osteoporotic fractures with and without bisphosphonate treatment. Biopsies of proximal femoral cortical bone adjacent to the fracture site were obtained from postmenopausal women during fracture repair surgery (fracture groups, n = 33) or total hip arthroplasty (nonfracture groups, n = 17). Patients were allocated to five groups based on fracture morphology and history of bisphosphonate treatment [+ BIS Atypical: n = 12, BIS duration: 8.2 (3.0) y; + BIS Typical: n = 10, 7.7 (5.0) y; + BIS Nonfx: n = 5, 6.4 (3.5) y; -BIS Typical: n = 11; -BIS Nonfx: n = 12]. Vibrational spectroscopy and nanoindentation showed that tissue from bisphosphonate-treated women with atypical fractures was harder and more mineralized than that from bisphosphonatetreated women with typical osteoporotic fractures. In addition, fracture mechanics measurements showed that tissue from patients treated with bisphosphonates had deficits in fracture toughness, with lower crack-initiation toughness and less crack deflection at osteonal boundaries than that of bisphosphonate-naive patients. Together, these results suggest a deficit in intrinsic and extrinsic toughening mechanisms, which contribute to AFFs in patients treated with long-term bisphosphonates.