Sithambaran Siva, Harrison Rachel, Gopal-Kothandapandi Sujatha, Rigby Alan, Bishop Nick
Department of Oncology and Metabolism University of Sheffield Sheffield UK.
Sheffield Children's NHS FT Sheffield UK.
JBMR Plus. 2022 Mar 1;6(3):e10592. doi: 10.1002/jbm4.10592. eCollection 2022 Mar.
Children with osteogenesis imperfecta (OI) are commonly treated with bisphosphonates. We investigated the skeletal response to mechanical stimulation in children with OI before and after bisphosphonate treatment. Twelve children with OI, naïve to bisphosphonate treatment, stood on a high-frequency (30 Hz), low-amplitude (50 to 200 μ) vibrating platform (Marodyne LivMD) for 10 minutes daily (2.5 minutes × 4 with interspersed 1-minute rest periods) for 7 days (whole body vibration [WBV] 1; day (D) 1-7), followed successively by 5 weeks' monitoring without intervention, 6 weeks' risedronate treatment, 1 week of WBV (WBV2; D85-91), and 1 week without intervention (D92-98). Procollagen type I N-terminal propeptide (P1NP), bone-specific alkaline phosphatase (BSALP), and carboxy-terminal telopeptide of type I collagen cross-link (CTX) were measured at baseline and intervals bracketing periods of vibration and risedronate treatment. Both P1NP and CTX rose to D8 (18.4%, 13.8%, < 0.05, respectively), plateaued, then rose again at D43 (19.8%, 19.2%, respectively, < 0.05 versus baseline). At D85 (after risedronate) both P1NP and CTX had fallen to pre-WBV1 levels. A significantly smaller increase in P1NP was found after WBV2 (D85-91) at D92 (3.5%, 9.2%, respectively) and D99 versus after WBV1 (both < 0.05). BSALP changed little after WBV1, fell during risedronate, and rose toward baseline after WBV2. We thus showed that WBV increased bone formation and resorption; that increase was attenuated after risedronate. The early increase in P1NP and CTX (D8) after WBV1 suggests increased osteoid formation within existing remodeling units but not increased mineralization. Later increases in P1NP/CTX (D42) suggest increased remodeling cycle initiation after WBV. Risedronate suppressed both biomarkers. The lower increase in P1NP/CTX after WBV2 suggests limited capacity to increase osteoid formation from existing "early stage" osteoblasts and a possible "hangover" effect of risedronate on remodeling activation. These results provide insights into both the response to WBV, ie, mechanical stimulation, and the effect of antiresorptive therapy in children with OI. © 2021 The Authors. published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.
成骨不全症（OI）患儿通常接受双膦酸盐治疗。我们研究了双膦酸盐治疗前后OI患儿对机械刺激的骨骼反应。12名未接受过双膦酸盐治疗的OI患儿每天站在高频（30Hz）、低振幅（50至200μ）的振动平台（Marodyne LivMD）上10分钟（2.5分钟×4次，中间穿插1分钟休息时间），共7天（全身振动[WBV]1；第1 - 7天），随后依次进行5周无干预监测、6周利塞膦酸盐治疗、1周WBV（WBV2；第85 - 91天）和1周无干预（第92 - 98天）。在基线以及振动和利塞膦酸盐治疗期间的各个间隔时间测量I型前胶原N端前肽（P1NP）、骨特异性碱性磷酸酶（BSALP）和I型胶原交联羧基末端肽（CTX）。P1NP和CTX在第8天均升高（分别为18.4%、13.8%，P均<0.05），趋于平稳，然后在第43天再次升高（分别为19.8%、19.2%，与基线相比P均<0.05）。在第85天（利塞膦酸盐治疗后），P1NP和CTX均降至WBV1前水平。在第92天（第85 - 91天WBV2后）和第99天，P1NP的升高幅度明显小于WBV1后（均P<0.05）。WBV1后BSALP变化不大，在利塞膦酸盐治疗期间下降，WBV2后向基线水平升高。因此，我们表明WBV增加了骨形成和骨吸收；利塞膦酸盐治疗后这种增加减弱。WBV1后P1NP和CTX早期升高（第8天）表明现有重塑单元内类骨质形成增加，但矿化未增加。P1NP/CTX后期升高（第42天）表明WBV后重塑周期启动增加。利塞膦酸盐抑制了这两种生物标志物。WBV2后P1NP/CTX升高幅度较低表明从现有“早期”成骨细胞增加类骨质形成的能力有限，以及利塞膦酸盐对重塑激活可能存在“宿醉”效应。这些结果为OI患儿对WBV即机械刺激的反应以及抗吸收治疗的效果提供了见解。© 2021作者。由Wiley Periodicals LLC代表美国骨与矿物质研究学会出版。
