Mechanical loading enhances the anabolic effects of intermittent parathyroid hormone (1-34) on trabecular and cortical bone in mice

Sugiyama, T; Saxon, L K; Zaman, G; Moustafa, A; Sunters, A; Price, J S; Lanyon, L E

Abstract

The separate and combined effects of intermittent parathyroid hormone (iPTH) (1-34) and mechanical loading were assessed at trabecular and cortical sites of mouse long bones. Female C57BL/6 mice from 13 to 19 weeks of age were given daily injections of vehicle or PTH (1-34) at low (20 mu g/kg/day), medium (40 mu g/kg/day) or high (80 [mu g/kg/day) dose. For three alternate clays per week during the last two weeks of this treatment, the tibiae and ulnae on one side were subjected to a single period of non-invasive, dynamic axial loading (40 cycles at 10 Hz with 10-second intervals between each cycle). Two levels of peak load were used; one sufficient to engender an osteogenic response, and the other insufficient to do so. The whole tibiae and ulnae were analyzed post-mortem by micro-computed tomography with a resolution of 5 pm. Treatment with iPTH (1-34) modified bone structure in a close- and time-dependent manner, which was particularly evident in the trabecular region of the proximal tibia. In the tibia, loading at a level sufficient by itself to stimulate osteogenesis produced an osteogenic response in the low-dose iPTH (1-34)-treated trabecular bone and in the proximal and middle cortical bone treated with all doses of iPTH (1-34). In the ulna, loading at a level that did not by itself stimulate osteogenesis was osteogenic at the distal site when combined with high-dose iPTH (1-34). At both levels of loading, there were synergistic effects in Cortical bone volume of the Proximal tibia and distal ulna between loading and high-dose iPTH (1-34). Images of fluorescently labelled bones confirmed that such synergism resulted from increases in both endosteal and periosteal bone formation. No woven bone was induced by iPTH (1-34) or either level of loading alone, whereas the combination of iPTH (1-34) and the "sufficient" level of loading stimulated woven bone formation on endosteal and periosteal surfaces of the proximal cortex in the tibiae. Together, these data suggest that in female C57BL/6 mice, under some but not all circumstances, mechanical loading exerts an osteogenic response with iPTH (1-34) in trabecular and cortical bone. (c) 2008 Elsevier Inc. All rights reserved.

Citation

Sugiyama, T., Saxon, L. K., Zaman, G., Moustafa, A., Sunters, A., Price, J. S., & Lanyon, L. E. Mechanical loading enhances the anabolic effects of intermittent parathyroid hormone (1-34) on trabecular and cortical bone in mice. BONE, 43(2), 238-248. https://doi.org/10.1016/j.bone.2008.04.012

• Journal Article Type: Article
• Deposit Date: Nov 11, 2014
• Journal: BONE
• Print ISSN: 8756-3282
• Publisher: Elsevier
• Volume: 43
• Issue: 2
• Pages: 238-248
• DOI: https://doi.org/10.1016/j.bone.2008.04.012
• Public URL: https://rvc-repository.worktribe.com/output/1431175