Trabecular Bone Response to Mechanical and Parathyroid Hormone Stimulation: The Role of Mechanical Microenvironment

Abstract

Bone response under combined mechanical and PTH stimuli is important in osteoporosis. A rat tail animal model with computer modeling was used to examine bone response to loading and PTH. PTH enhances and sustains increased bone formation rate, which directly correlates to mechanical microenvironment, suggesting beneficial effects of combined PTH treatment and exercise in preventing osteoporosis.Introduction: Using an in vivo rat tail vertebra model combined with a specimen-specific, high-resolution microcomputed tomography (CT)-based finite element analysis (FEA) technique, trabecular bone response to combined dynamic compressive loading and parathyroid hormone (PTH) stimulation was characterized. Materials and Methods: Two hundred twenty-four male Sprague-Dawley rats were randomly divided into seven treatment groups: (1) Control, (2) vehicle ϩ 0N, (3) PTH ϩ 0N, (4) vehicle ϩ 50N, (5) PTH ϩ 50N, (6) vehicle ϩ 100N, and (7) PTH ϩ 100N, with three treatment durations (1, 2, or 4 weeks). Rat PTH(1-34) was administered daily in the PTH-stimulated groups approximately 3 h before daily mechanical stimulation with 0, 50, or 100N dynamic compressive loading. CT-based FEA was performed for each loaded vertebra after death. Bone histomorphometry was performed on trabecular bone with double fluorochrome labeling to assess bone formation. Results: Daily mechanical loading or PTH administration significantly increased bone formation rate (BFR) compared with control or V ϩ 0N with significant increases in both mineral apposition rate (MAR) and labeled bone surface (LS/BS). PTH, when combined with mechanical loading, enhanced BFR mainly through a significant increase in MAR after the first week and through a significant increase in LS/BS after 2 and 4 weeks. Synergistic effects in BFR were present when PTH was combined with mechanical loading, especially after 2 and 4 weeks, where the increase in BFR was sustained. However, when either PTH or mechanical loading was the only stimulus, the bone formation response diminished to the level of Control animals after 4 weeks. Furthermore, significant correlations were observed between the bone formation indices and trabecular bone tissue mechanical microenvironments at 1 and 2 weeks, with PTH administration enhancing and sustaining these correlations into 4 weeks. Conclusions: The synergistic effects of combined PTH and mechanical stimulation on trabecular bone formation rate suggest a potential benefit for combined PTH administration and exercise in the treatment of osteoporosis.

Osteoblasts and Osteoclasts in Regenerating Goldfish Scales Respond to Mechanical Loading: Analysis of Osteoblastic and Osteoclastic Marker mRNA Expression

“…These results, which are relevant to osteoblast differentiation and proliferation, indicate that vibration upregulated mRNA expression; these results are consistent with those showing the anabolic effect of mechanical stimulation on in vivo models using mammalian osteoblastic cells (Rubin et al, 1984, Turner et al, 1991, Chambers et al, 1993, Kim et al, 2003.…”

Effects on bone geometry, density, and microarchitecture in the distal radius but not the tibia in women with primary hyperparathyroidism: A case-control study using HR-pQCT

“…Mechanical loading is a prerequisite for normal bone formation, as well as for preservation, and studies in rodents have demonstrated a positive synergistic effect on both cortical and trabecular bone when combined mechanical loading and PTH treatment was instituted. (29)(30)(31)(32)(33) However, the PTH exposure in those studies were intermittent and not continuous, as in PHPT, but our findings indicate that mechanical loading plays a role in the action of PTH and that mechanical stimuli are important for the effects mediated by PTH. In our study we found reduced aBMD by DXA in the forearm, spine, and hip.…”

Molecular and cellular mechanisms of the anabolic effect of intermittent PTH

“…The involvement of osteocytes, the primary mechanosensory cell of bone, in the anabolic effect of intermittent PTH may explain why weight bearing and intermittent PTH exert synergistic effects on bone formation [63,[100][101][102]; and why the anabolic response is greater in tibiae, which experience high mechanical strain, than in the vertebra, which experience less strain [103]. Moreover, like PTH, mechanical loading of murine bone causes a fall in the level of sclerostin [104].…”