Bone Bioengineering Laboratory, 351 Engineering Terrace, Department of Biomedical Engineering, Columbia University, 1210 Amsterdam Avenue, New York, NY 10027, USA.
Bone. 2021 Dec;153:116171. doi: 10.1016/j.bone.2021.116171. Epub 2021 Sep 4.
Intermittent injections of parathyroid hormone (PTH) and mechanical loading are both known to effect a net increase in bone mass. Fundamentally, bone metabolism can be divided into modeling (uncoupled formation or resorption) and remodeling (subsequent formation biologically coupled to resorption in space and time). Methods to delineate the bone response between these regimes are scant but have garnered recent attention and acceptance, and will be critical tools to properly assess short- and long-term efficacy of osteoporosis treatments. To this end, we employ a time-lapse micro-computed tomography strategy to quantify and localize modeling and remodeling volumes over 4 weeks of concurrent PTH treatment and mechanical loading. Modeled and remodeled volumes are probed for differences with respect to treatment, loading, and interactions thereof in trabecular and cortical bone compartments, which were further separated by plate/rod microarchitecture and periosteal/endosteal surfaces, respectively. Loading effects are further considered independently with regard to localized strain environments. Our findings indicate that in trabecular bone, PTH and loading stimulate anabolic modeling additively, and remodeling synergistically. PTH tends to lead to bone accumulation indiscriminate of trabecular microarchitecture, whereas loading tends to more strongly affect plates than rods. The cortical surfaces responded uniquely to PTH and loading, with synergistic effects on the periosteal surface for anabolic modeling, and on the endosteal surface for catabolic modeling. The increase in catabolic modeling due to loading, which is enhanced by PTH, is concentrated to areas of the endosteal surface under low strain and to our knowledge has not previously been reported. Taken together, the effects of PTH, loading, and their interactions, are shown to be dependent on the specific bone compartment and metabolic regime; this may explain some discrepancies in previously-reported findings.
间歇注射甲状旁腺激素 (PTH) 和机械加载都已知可导致骨量净增加。从根本上讲，骨代谢可分为建模（去耦形成或吸收）和重塑（随后的形成在空间和时间上与吸收生物学偶联）。但用于描绘这些状态之间的骨反应的方法很少，但最近受到了关注和认可，并且将成为正确评估骨质疏松症治疗的短期和长期疗效的关键工具。为此，我们采用延时微 CT 策略，在 4 周的 PTH 治疗和机械加载过程中，定量和定位建模和重塑体积。针对治疗、加载及其相互作用，研究了在小梁和皮质骨区中建模和重塑体积的差异，分别通过板/杆微观结构和骨外膜/骨内膜表面进一步分离。进一步分别考虑了加载效果相对于局部应变环境的影响。我们的研究结果表明，在小梁骨中，PTH 和加载以累加的方式刺激合成代谢建模，并协同刺激重塑。PTH 倾向于导致不分小梁微观结构的骨积累，而加载则更倾向于强烈影响板而不是杆。皮质表面对 PTH 和加载有独特的反应，对合成代谢建模的骨外膜表面和对分解代谢建模的骨内膜表面具有协同作用。由于加载导致的分解代谢建模增加，这是由 PTH 增强的，集中在骨内膜表面应变较低的区域，据我们所知，这以前没有报道过。综上所述，PTH、加载及其相互作用的影响取决于特定的骨区室和代谢状态；这可能解释了以前报道的发现中的一些差异。
