McNeill Tyler J, Rooney Amanda M, Ross F Patrick, Bostrom Mathias P G, van der Meulen Marjolein C H
Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA; Medical Metrics, Inc., Houston, TX, USA.
Bone. 2025 Jul;196:117474. doi: 10.1016/j.bone.2025.117474. Epub 2025 Mar 29.
Parathyroid hormone (PTH) increases bone mass and decreases fracture risk. However, the anabolic effects of PTH are limited to a period of approximately 24 months, motivating the need to maximize bone growth during this timeframe. Concurrent mechanical loading with weight-bearing exercise is synergistic with PTH treatment. We sought to determine if priming with PTH prior to initiating mechanical loading would enhance their synergistic effects. We pre-treated 10-week-old, female C57Bl/6J mice with either PTH or saline vehicle (VEH) for six weeks. We subsequently initiated cyclic tibial compression for either two or six weeks while continuing PTH or VEH treatment. We analyzed bone morphology in cortical and cancellous compartments of the proximal tibia. To further explore the effects of PTH and loading in cancellous bone, we measured bone cell presence and changes in bone morphology via histology, immunohistochemistry, and dynamic histomorphometry. Concurrent treatment with PTH enhanced load-induced increases in bone mass in cortical bone but blunted the effects of loading in cancellous bone. PTH pre-treatment further increased load-induced changes in cortical bone mass and rescued the load effects in cancellous bone, returning values to those of VEH-treated animals. Osteoclast populations decreased with loading, independent of PTH treatment. Active osteoblast populations increased with PTH pre-treatment but did not change with loading. Bone formation rate increased with PTH pre-treatment in the 2-week group but did not differ between treatment groups after 6-weeks. Collectively, pre-treating with PTH prior to mechanical loading primed the skeletal tissue and enhanced the anabolic response of concurrent treatment and loading.
甲状旁腺激素（PTH）可增加骨量并降低骨折风险。然而，PTH的合成代谢作用仅限于约24个月的时间段，这促使人们需要在此时间段内使骨生长最大化。负重运动与机械负荷同时进行与PTH治疗具有协同作用。我们试图确定在开始机械负荷之前用PTH进行预处理是否会增强它们的协同作用。我们用PTH或生理盐水载体（VEH）对10周龄的雌性C57Bl/6J小鼠进行了为期六周的预处理。随后，我们在继续PTH或VEH治疗的同时，对小鼠进行了为期两周或六周的周期性胫骨压缩。我们分析了胫骨近端皮质骨和松质骨区域的骨形态。为了进一步探究PTH和负荷对松质骨的影响，我们通过组织学、免疫组织化学和动态组织形态计量学测量了骨细胞的存在情况以及骨形态的变化。PTH与负荷同时治疗可增强负荷诱导的皮质骨骨量增加，但减弱了负荷对松质骨的影响。PTH预处理进一步增加了负荷诱导的皮质骨骨量变化，并挽救了负荷对松质骨的影响，使数值恢复到接受VEH治疗动物的水平。破骨细胞数量随负荷减少，与PTH治疗无关。活跃成骨细胞数量在PTH预处理后增加，但不随负荷而变化。在2周组中，PTH预处理使骨形成率增加，但6周后各治疗组之间无差异。总体而言，在机械负荷之前用PTH进行预处理可使骨骼组织做好准备，并增强同时进行治疗和负荷时的合成代谢反应。
