Maternal bone adaptation to mechanical loading during pregnancy, lactation, and post-weaning recovery

Abstract

The maternal skeleton undergoes dramatic bone loss during pregnancy and lactation, and substantial bone recovery post-weaning. The structural adaptations of maternal bone during reproduction and lactation exert a better protection of the mechanical integrity at the critical load-bearing sites, suggesting the importance of physiological load-bearing in regulating reproduction-induced skeletal alterations. Although it is suggested that physical exercise during pregnancy and breastfeeding improves women's physical and psychological well-being, its effects on maternal bone health remain unclear. Therefore, the objective of this study was to investigate the maternal bone adaptations to external mechanical loading during pregnancy, lactation, and post-weaning recovery. By utilizing an in vivo dynamic tibial loading protocol in a rat model, we demonstrated improved maternal cortical bone structure in response to dynamic loading at tibial midshaft, regardless of reproductive status. Notably, despite the minimal loading responses detected in the trabecular bone in virgins, rat bone during lactation experienced enhanced mechano-responsiveness in both trabecular and cortical bone compartments when compared to rats at other reproductive stages or age-matched virgins. Furthermore, our study showed that the lactation-induced elevation in osteocyte peri-lacunar/canalicular remodeling (PLR) activities led to enlarged osteocyte lacunae. This may result in alterations in interstitial fluid flow-mediated mechanical stimulation on osteocytes and an elevation in solute transport through the lacunar-canalicular system (LCS) during high-frequency dynamic loading, thus enhancing mechano-responsiveness of maternal bone during lactation. Taken together, findings from this study provide important insights into the relationship between reproduction- and lactation-induced skeletal changes and external mechanical loading, emphasizing the importance of weight-bearing exercise on maternal bone health during reproduction and postpartum.

Keywords: Bone mechano-responsiveness; Lactation; Maternal bone adaptation; Osteocyte mechanosensing; Peri-lacunar/canalicular remodeling (PLR); Reproduction.

Figure 1.

Schematics of study design.

Figure 2.

(A) Representative 3D renderings of trabecular bone at the proximal tibia in Virgin, Pregnancy, Lactation, and Post-Weaning rats. % changes in (B) BV/TV, (C) Tb.Th, (D) Tb.N, (E) Tb.Sp, and (F) Conn.D, as well as (G) change in SMI in loaded and non-loaded tibiae in rats with different reproductive status. p<0.05: # indicates significant changes over the 2-week time period (week 0 vs. week 2); * indicates significant differences between loaded and non-loaded tibiae.

Figure 3.

% changes in (A) Ct.Area, (B) pMOI, and (C) Ct.Th at tibial midshaft in loaded and non-loaded tibiae in rats with different reproductive status. Comparisons of loading-induced differences in % change between loaded and non-loaded tibiae in (D) Ct.Area, (E) pMOI, and (F) Ct.Th at tibial midshaft in rats with different reproductive status. p<0.05: # indicates significant changes over the 2-week time period (week 0 vs. week 2); * indicates significant differences between loaded and non-loaded tibiae.

Figure 4.

(A) Representative histology images of tibial midshaft. Comparisons of (B) MS/BS, (C) MAR, and (D) BFR/BS at periosteal cortical bone of tibial midshaft between loaded and non-loaded tibiae in rats with different reproductive status. Comparisons of loading-induced fold changes in periosteal (E) MS/BS, (F) MAR, and (G) BFR/BS at tibial midshaft in rats with different reproductive status. p<0.05: * indicates significant differences between loaded and non-loaded tibiae; + indicates significant differences in loading-induced fold change among groups.

Figure 5.

(A) Representative images of lacunar-canalicular network by Ploton silver staining. Comparisons of (B) lacunar perimeter, (C) lacunar area, (D) canalicular number per lacunar surface, and (E) canalicular number per lacuna at the tibial cortex in rats with different reproductive status. * indicates significant differences among groups (p<0.05).

Figure 6.

Representative images of (A) MMP13 and (C) CtsK immunostaining. Comparisons of (B) % MMP13-postive and (D) CtsK-postive osteocytes at the tibial cortex in rats with different reproductive status. * indicates significant differences among groups (p<0.05).