Mechanical loading and parathyroid hormone effects and synergism in bone vary by site and modeling/remodeling regime

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.