Cancellous bone adaptation to tibial compression is not sex dependent in growing mice

Abstract

Mechanical loading can be used to increase bone mass and thus attenuate pathological bone loss. Because the skeleton's adaptive response to loading is most robust before adulthood, elucidating sex-specific responses during growth may help maximize peak bone mass. This study investigated the effect of sex on the response to controlled, in vivo mechanical loading in growing mice. Ten-week-old male and female C57Bl/6 mice underwent noninvasive compression of the left tibia. Peak loads of -11.5 N were applied, corresponding to +1,200 microepsilon at the tibial midshaft in both sexes. Cancellous bone mass, architecture, and dynamic formation in the proximal metaphysis were compared between loaded and control limbs via micro-computed tomography and histomorphometry. The strain environment of the proximal metaphysis during loading was characterized using finite element analysis. Both sexes responded to tibial compression through increased bone mass and altered architecture. Cancellous bone mass and tissue density were enhanced in loaded limbs relative to control limbs in both sexes through trabecular thickening and reduced separation. Changes in mass were due to increased cellular activity in loaded limbs compared with control limbs. Adaptation to loading increased the proportion of load transferred by the cancellous bone in the proximal metaphysis. For all cancellous measures, the response to tibial compression did not differ between male and female mice. When similar strains are engendered in males and females, the adaptive response in cancellous bone to mechanical loading does not depend on sex.

Fig. 1.

A: representative cancellous volume of interest (VOI) used for micro-computed tomography (microCT) analysis. Each cancellous VOI was defined in the proximal end of the tibia and excluded the cortical shell. The proximal end of the VOI began below the primary spongiosa and extended distally 10% of total tibial length. B: representative VOIs used for finite element (FE) analysis. Each VOI was 5% of total tibial length and was centered within the VOI used for microCT analysis (dashed box). Corticocancellous VOIs (left) included both cancellous and cortical bone, and cortical VOIs (right) included only the cortical shell.

Fig. 2.

Sagittal sections through the proximal metaphysis taken from representative microCT scans. Representative loaded (left) and control (right) tibias are shown from both females (top) and males (bottom).

Fig. 3.

Indexes of cancellous adaptation determined by microCT analysis of VOIs from the proximal metaphysis of loaded and control tibiae from female and male mice after 2 wk of loading. Loading induced significant changes in all parameters, but changes did not differ by sex (nonsignificant interaction term). Males had significantly greater bone volume fraction (BV/TV), trabecular thickness (Tb.Th), and tissue bone mineral density (tBMD) and lower trabecular separation (Tb.Sp) A: BV/TV increased +95% in females and +65% in males. BV/TV was 53% larger in males than in females. B: tBMD (mg/cc) increased +19% in females and +17% in males. tBMD was 2.9% higher in males than in females. C: Tb.Th (μm) increased +77% in females and +78% in males. Tb.Th was 9.1% larger in males than females. D: Tb.Sp (μm) decreased −19% in both males and females. Tb.Sp was 36% lower in males than females. Data are represented as means + SD. ^aSex effect, ^bloading effect, p < 0.05 by linear mixed model with repeated measures.