Combining PTH(1-34) and mechanical loading has increased benefit to tibia bone mechanics in ovariectomised mice

Abstract Combined treatment with PTH(1-34) and mechanical loading confers increased structural benefits to bone. However, it remains unclear how this longitudinal adaptation affects the bone mechanics. This study quantified the individual and combined longitudinal effects of PTH(1-34) and loading on micro-finite element (microFE) model estimates of tibia stiffness and strength in ovariectomised mice. C57BL/6 mice were ovariectomised at 14-weeks-old and treated either with injections of PTH(1-34), compressive tibia loading or both interventions concurrently. Right tibiae were in vivo microCT-scanned every two weeks from 14 until 24-weeks-old. MicroCT images were rigidly registered to reference tibia and the cortical organ (whole bone) and tissue-level (midshaft) morphometric properties and bone mineral content were quantified. MicroCT images were converted into voxel-based homogeneous, linear elastic microFE models to quantify bone stiffness and strength under uniaxial compression in vivo. Both stiffness and strength were higher with co-treatment than with individual therapies, consistent with increased benefits with the tibia bone mineral content and cortical area – properties strongly associated with the tibia mechanics. To our knowledge, this is the first study to longitudinally assess the mechanical effects of two bone anabolics, PTH(1-34) and tibia loading, in a mouse model of osteoporosis.