Mechanical loading of mouse caudal vertebrae increases trabecular and cortical bone mass-dependence on dose and genotype

Abstract

Most in vivo studies addressing the skeletal responses of mice to mechanical loading have targeted cortical bone. To investigate trabecular bone responses also we have developed a caudal vertebral axial compression device (CVAD) that transmits mechanical loads to compress the fifth caudal vertebra via stainless steel pins inserted into the forth and sixth caudal vertebral bodies. Here, we used the CVAD in C57BL/6 (B6) and C3H/Hej (C3H) female mice (15 weeks of age) to investigate whether the effect of regular bouts of mechanical stimulation on bone modeling and bone mass was dependent on dose and genotype. A combined micro-computed tomographic and dynamic histomorphometric analysis was carried out at the end of a 4-week loading regimen (3,000 cycles, 10 Hz, 3 x week) for load amplitudes of 0N, 2N, 4N and 8N. Significant increases in trabecular bone mass of 9 and 21% for loads of 4N and 8N, respectively, were observed in B6 mice. A significant increase of 10% in trabecular bone mass occurred for a load of 8N in the C3H strain. For other loads, no significant increases were detected. Both mouse strains exhibited substantial increases in trabecular bone formation rates for all loads, B6: 111% (2N), 86% (4N), 164% (8N), C3H: 41% (2N), 38% (4N), 141% (8N). Significant decreases in osteoclast number of 146 and 93% for a load of 8N were detected in B6 and C3H mice, respectively. These findings demonstrate that the effect of loading on the structural and functional parameters of bone is dose and genotype dependent. The caudal vertebral loading model established here is proposed for further studies addressing the molecular processes involved in the skeletal responses to mechanical stimuli. Here we used the CVAD in C57BL/6 and C3H/Hej mice to investigate whether the effect of regular bouts of mechanical stimulation on bone remodeling and bone mass were dependent on dose and genotype. A combined micro-computed tomographic and dynamic histomorphometric analysis carried out at the end of a 4-week loading regimen for load amplitudes of 0N, 2N, 4N and 8N revealed that an amplitude of 8N stimulated significant increases in trabecular and cortical bone mass mainly in the C57BL/6 strain. Both biological strains exhibited substantial increases in bone formation rates and decreases in osteoblast number. These findings demonstrate that the effect of loading on the structural and functional parameters of bone is dose-and genotype dependent. The caudal vertebral loading model established here is proposed for further studies addressing the molecular processes involved in the skeletal responses to mechanical stimuli.

Bone morphology allows estimation of loading history in a murine model of bone adaptation

“…In short: fifteen-week-old female C57BL/6 mice underwent axial compressive loading of the sixth caudal vertebrae at either 8 N (loaded group; n = 8) or 0 N (control group; n = 8) for 3,000 cycles at 10 Hz three times per week for four weeks and weekly in vivo micro-computed tomography (micro-CT) scans. Loading was applied through pins inserted in adjacent vertebrae using a recently developed caudal vertebra axial compression device (CVAD) (Webster et al 2008(Webster et al , 2010. During the remaining period, mice were able to freely move their tail.…”

Experimental and finite element analysis of the mouse caudal vertebrae loading model: prediction of cortical and trabecular bone adaptation

“…Recently, we established an in vivo loading model for both cortical and trabecular bone adaptation using C57BL/6 (B6) female mice (Webster, Wasserman et al 2010). By mechanically stimulating the fifth caudal vertebra (C5), we were able to demonstrate a significant load affect in both cortical and trabecular components.…”

Longitudinal Assessment of In Vivo Bone Dynamics in a Mouse Tail Model of Postmenopausal Osteoporosis

“…To our knowledge, ovariectomy-induced bone loss has not been investigated in caudal vertebrae of mice. However, it would be very convenient if, instead of the distal femur, a caudal vertebra could be used as an osteoporosis model because this would have several advantages: (1) it is more easily accessible for high-resolution imaging, (2) the whole bone can be imaged within an acceptable scan time and dose, (3) both cortical and trabecular bone can be imaged, (4) the amount of trabecular bone is relatively high in vertebrae, and (5) it is accessible for mechanical loading [20,21].…”

“…We hypothesized that ovariectomy would induce bone loss in the caudal vertebrae of C57Bl/6 J mice since these vertebrae increase bone mass upon cyclic loading [20] and, thus, seemed responsive to interventions. Furthermore, when osteoporosis-related bone loss was evaluated in caudal vertebrae of SAMP6 mice, a senescence-accelerated mouse strain, the bone mass at 4 and 12 months of age was significantly lower than in controls [28].…”