Abstract
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.
Highlights
Osteoporosis is a major bone disease that increases the risk of bone fracture and largely affects the aging members of society [1]
Regarding the intraclass correlation coefficients (ICCs), they are large for the regional bone mineral content (BMC), bone volume (BV), tibial endosteal area (TEA) and tibial periosteal area (TPA) (0.86 to 0.99) (Table 1), which means that the intersubject differences are larger than the repeated-scan differences for these measurements
The longitudinal effects of Parathyroid hormone (PTH) intervention on the bone mineral content (BMC), bone tissue mineral density (TMD), bone volume (BV), tibial endosteal area (TEA), tibial periosteal area (TPA) and tibial failure load were investigated using in vivo μCT imaging, a novel spatiotemporal image analysis, and the finite element analysis technique
Summary
Osteoporosis is a major bone disease that increases the risk of bone fracture and largely affects the aging members of society [1]. Variable and sometimes contradictory results have been reported in previous studies regarding the effects of PTH on bone [2,3,4]; the reason for these results may be that the mechanism of PTH on bone, especially in the entire spatiotemporal space of bone, is still not fully understood. Due to the intersubject variances, a large number of animals are usually needed to remove the influence of intersubject variances, which might be the main reason for the controversial results reported in the literature. Cross-sectional studies prevent longitudinal monitoring of bone changes in the spatiotemporal space, which is crucial information for providing an in-depth understanding of the PTH intervention
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