Effect of parathyroid hormone on cortical bone response to in vivo external loading of the rat tibia

Abstract

Cortical bone responses following administration of parathyroid hormone (PTH) were evaluated using a four-point bending device to clarify the relationship between the effect of PTH and mechanical loading. Female Wistar rats, 36-months-old, were used. Rats were randomized into three groups (n = 10/group), namely PTH-5 (5 μg PTH/kg body weight), PTH-30 (30 μg PTH/kg body weight), and PTH-v (vehicle). PTH (human PTH (1–34)) was injected subcutaneously three times/week for 3 weeks. Loads on the right tibia were applied in vivo at 29.1 ± 0.3 N for 36 cycles at 2 Hz 3 days/week for 3 weeks using four-point bending. The administration of PTH and tibial mechanical loading were performed on the same day. After calcein double labeling, rats were killed and tibial cross-sections were prepared from the region with maximal bending at the central diaphysis. Histomorphometry was performed over the entire periosteal and endocortical surfaces of the tibiae, dividing the periosteum into lateral and medial surfaces. The in vivo average peak tibial strains (predicted) on the lateral periosteal surface were 1392.4, 1421.8 and 1384.7 μstrain in PTH-v, PTH-5 and PTH-30 groups, respectively, showing no significant difference among the three groups. Significant loading-related increases in the bone formation surface, mineral apposition rate, and bone formation rate were observed at the periosteal and endocortical surfaces. Significant differences between PTH groups were also seen. Interaction between mechanical loading and PTH was significant at both periosteal and endocortical surfaces. It is concluded that PTH has a synergistic effect on the cortical bone response to mechanical loading.