Longitudinal effects of Parathyroid Hormone treatment on morphological, densitometric and mechanical properties of mouse tibia

The use of Parathyroid Hormone (PTH) as bone anabolic is limited due to cost-benefit assessments. Preclinical studies evaluating the effects of PTH on bone have reported variable and often contradictory results. Here, we have applied a new approach using a combination of in-vivo longitudinal microCT, image processing techniques and finite element models to monitor early local changes in the whole tibia (divided in 40 compartments) and mechanical properties of female C57BL/6J mice treated with PTH 1-34, compared to controls. Compared with standard 3D bone morphometric analysis, our new approach allowed detection of much smaller and localised changes in bone mineral content (BMC) at very early time points (1 week vs 3 weeks with standard methods) and showed that changes do not occur uniformly over time and across the anatomical space. Indeed, in the PTH treated mice, significant changes in BMC were observed in the medial and posterior sectors of the proximal tibia, a week after treatment, and in the medial sector of the tibia midshaft region a week later (p < 0.05). By the third week, two thirds of the regions showed significantly higher values of BMC (p < 0.05). The effect of PTH on bone regional volume is similar to that on BMC, but there is almost no effect of PTH on bone tissue mineral density. The differences in estimated mechanical properties became significant after three weeks of treatment (p < 0.05). These results provide the first evidence of an early and localised PTH effect on murine bone, and show that our novel partitioning approach, compared to the standard evaluation protocol, allows a more precise quantification of bone changes following treatment, which would facilitate preclinical testing of novel mono- and/or combination therapies throughout the bone.