O'Donohue Alexandra K, Dao Aiken, Bobyn Justin D, Munns Craig F, Little David G, Schindeler Aaron
Bioengineering & Molecular Medicine Laboratory, The Children's Hospital at Westmead and the Westmead Institute for Medical Research, Sydney, New South Wales, Australia.
Children's Hospital Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
J Orthop Res. 2023 Apr;41(4):808-814. doi: 10.1002/jor.25414. Epub 2022 Jul 21.
Osteogenesis imperfecta (OI) is a genetic bone fragility disorder that features frequent fractures. Bone healing outcomes are contingent on a proper balance between bone formation and resorption, and drugs such as bone morphogenetic proteins (BMPs) and bisphosphonates (BPs) have shown to have utility in modulating fracture repair. While BPs are used for OI to increase BMD and reduce pain and fracture rates, there is little evidence for using BMPs as local agents for fracture healing (alone or with BPs). In this study, we examined wild-type and OI mice (Col1a2 ) in a murine tibial open fracture model with (i) surgery only/no treatment, (ii) local BMP-2 (10 µg), or (iii) local BMP-2 and postoperative zoledronic acid (ZA; 0.1 mg/kg total dose). Microcomputed tomography reconstructions of healing fractures indicated BMP-2 was less effective in an OI setting, however, BMP-2 +ZA led to considerable increases in bone volume (+193% WT, p < 0.001; +154% OI, p < 0.001) and polar moment of inertia (+125% WT, p < 0.01; +248% OI, p < 0.05). Tissue histology revealed a thinning of the neocortex of the callus in BMP-2 treated OI bone, but considerable retention of woven bone in the healing callus with BMP + ZA specimens. These data suggest a cautious approach may be warranted with the sole application of BMP-2 in an OI surgical setting as a bone graft substitute. However, this may be overcome by off-label BP administration.
成骨不全症（OI）是一种遗传性骨脆性疾病，其特征是频繁骨折。骨愈合结果取决于骨形成和吸收之间的适当平衡，骨形态发生蛋白（BMPs）和双膦酸盐（BPs）等药物已显示在调节骨折修复方面具有效用。虽然BPs用于OI以增加骨密度、减轻疼痛和降低骨折率，但几乎没有证据表明使用BMPs作为骨折愈合的局部药物（单独使用或与BPs联合使用）。在本研究中，我们在小鼠胫骨开放性骨折模型中检查了野生型和OI小鼠（Col1a2），分别采用（i）仅手术/不治疗、（ii）局部使用BMP-2（10μg）或（iii）局部使用BMP-2并术后使用唑来膦酸（ZA；总剂量0.1mg/kg）。对愈合骨折的微型计算机断层扫描重建显示，在OI环境中BMP-2的效果较差，然而，BMP-2+ZA导致骨体积显著增加（野生型增加193%，p<0.001；OI增加154%，p<0.001）和极惯性矩增加（野生型增加125%，p<0.01；OI增加248%，p<0.05）。组织组织学显示，在接受BMP-2治疗的OI骨中，骨痂新皮质变薄，但在BMP+ZA标本的愈合骨痂中保留了大量编织骨。这些数据表明，在OI手术环境中单独应用BMP-2作为骨移植替代物时，可能需要谨慎对待。然而，这可能通过超说明书使用BP给药来克服。
