Abstract
AbstractBone loss in postmenopausal osteoporosis is caused by a remodeling imbalance towards increased bone resorption. Existing osteoporosis therapies are systemic and designed to recover bone mass, using the same molecular pathways that also allow bone to adapt to changing mechanical demands. Supraphysiological mechanical loading induces use a process on the tissue level called mechanoregulation, ensuring that bone is formed where needed and resorbed where unneeded. Little focus has been on combination therapy of physical and pharmaceutical therapy. Here, we report the effects of combining physical therapy in the form of mechanical loading with pharmaceutical treatment, i.e. bisphosphonates (BIS), parathyroid hormone (PTH), or sclerostin antibodies (SclAB) in ovariectomized C57Bl/6J mice. Mechanical loading synergistically potentiated trabecular bone mass under PTH or SclAB therapy but only marginally increased trabecular bone mass under BIS treatment. Bone remodeling was targeted to underlying micro-mechanical stimuli through mechanoregulation in all pharmaceutical treatments, but to different extents. BIS treatment showed higher untargeted remodeling compared to anabolic treatments, both alone and in combination with mechanical loading. Mechanical loading potentiated the mechanoregulatory response of SclAB treatment (synergistically) and PTH treatment (additively), indicating that in anabolic treatments, mechanical loading potentiates treatment efficacy by inducing more targeted bone formation and resorption. These findings suggest that incorporating physical therapy into anabolic pharmaceutical treatment regimens holds promise for enhancing therapeutic outcomes in osteoporosis management.One Sentence SummaryMechanoregulation at the tissue level induced by mechanical loading increases targeted remodeling in bisphosphonate, parathyroid hormone, or sclerostin antibody treatment.
Publisher
Cold Spring Harbor Laboratory