Effect of parathyroid hormone on the structural, densitometric and failure behaviors of mouse tibia in the spatiotemporal space

by Yongtao Lu, Jintao He, Hanxing Zhu, Yongxuan Wang

Parathyroid hormone (PTH) is an anabolic bone drug approved by the US Food and Drug Administration (FDA) to treat osteoporosis. However, previous studies using cross-sectional designs have reported variable and sometimes contradictory results. The aim of the present study was to quantify the localized effect of PTH on the structural and densitometric behaviors of mouse tibia and their links with the global mechanical behavior of bone using a novel spatiotemporal image analysis approach and a finite element analysis technique. Twelve female C57BL/6J mice were divided into two groups: the control and PTH treated groups. The entire right tibiae were imaged using an in vivo micro-computed tomography (μCT) system eight consecutive times. Next, the in vivo longitudinal tibial μCT images were rigidly registered and divided into 10 compartments across the entire tibial space. The bone volume (BV), bone mineral content (BMC), bone tissue mineral density (TMD), and tibial endosteal and periosteal areas (TEA and TPA) were quantified in each compartment. Additionally, finite element models of all the tibiae were generated to analyze the failure behavior of the tibia. It was found that both the BMC and BV started to increase in the proximal tibial region, and then the increases extended to the entire tibial region after two weeks of treatment (p < 0.05). PTH intervention significantly reduced the TEA in most tibial compartments after two weeks of treatment, and the TPA increased in most tibial regions after four weeks of treatment (p < 0.05). Tibial failure loads significantly increased after three weeks of PTH treatment (p < 0.01). The present study provided the first evidence of the localized effect of PTH on bone structural and densitometric properties, as well as their links with the global mechanical behaviors of bone, which are important pieces of information for unveiling the mechanism of PTH intervention.