Structural Adaptations in the Rat Tibia Bone Induced by Pregnancy and Lactation Confer Protective Effects Against Future Estrogen Deficiency

Abstract

The female skeleton undergoes substantial structural changes during the course of reproduction. Although bone mineral density recovers postweaning, reproduction may induce permanent alterations in maternal bone microarchitecture. However, epidemiological studies suggest that a history of pregnancy and/or lactation does not increase the risk of postmenopausal osteoporosis or fracture and may even have a protective effect. Our study aimed to explain this paradox by using a rat model, combined with in vivo micro-computed tomography (μCT) imaging and bone histomorphometry, to track the changes in bone structure and cellular activities in response to estrogen deficiency following ovariectomy (OVX) in rats with and without a reproductive history. Our results demonstrated that a history of reproduction results in an altered skeletal response to estrogen-deficiency-induced bone loss later in life. Prior to OVX, rats with a reproductive history had lower trabecular bone mass, altered trabecular microarchitecture, and more robust cortical structure at the proximal tibia when compared to virgins. After OVX, these rats underwent a lower rate of trabecular bone loss than virgins, with minimal structural deterioration. As a result, by 12 weeks post-OVX, rats with a reproductive history had similar trabecular bone mass, elevated trabecular thickness, and increased robustness of cortical bone when compared to virgins, resulting in greater bone stiffness. Further evaluation suggested that reproductive-history-induced differences in post-OVX trabecular bone loss were likely due to differences in baseline trabecular microarchitecture, particularly trabecular thickness. Rats with a reproductive history had a larger population of thick trabeculae, which may be protective against post-OVX trabecular connectivity deterioration and bone loss. Taken together, these findings indicate that reproduction-associated changes in bone microarchitecture appear to reduce the rate of bone loss induced by estrogen deficiency later in life, and thereby exert a long-term protective effect on bone strength. © 2018 American Society for Bone and Mineral Research.

Association of breastfeeding and postmenopausal osteoporosis in Chinese women: a community-based retrospective study

“…Some studies suggested that the history of breastfeeding can significantly increased the risk of PMOP [13], while some studies showed that prolonged breastfeeding duration was an independent risk factor for the development of PMOP rather than breastfeeding itself [14, 15]. Conversely, some studies suggested that the history of breastfeeding may increase the bone mass density, which significantly decreased the incidence of PMOP [16], whereas other studies demonstrated a non-significant relationship between breast-feeding and PMOP [9, 17].…”

Microanatomical Record of Cortical Bone Remodeling and High Vascularity in a Fossil Giant Rat Midshaft Femur

“…Multiple more recent studies have confirmed the relationship of bone remodeling to calcium variation in lactating female rats, highlighting that it may serve a key role in restoring bone health associated with calcium loss (Bowman et al, 2002;Miller and Bowman, 2007;Ross and Sumner, 2017). This is further supported by ongoing research indicating that female bone microarchitecture (both trabecular and cortical) adapts in a protective way to the negative effects of reproduction and estrogen loss (de Bakker et al, 2018a;de Bakker et al, 2018b).…”

“…The effects of sexual dimorphism and species-specific bone histology could also affect our results. Given the large effect of rat lactation and reproduction on bone micro-architecture in the female sex (de Bakker et al, 2018b), future research investigating giant rat bone histology in fossils should aim to account for sexual dimorphism. However, our results constitute the first micro-anatomical record of remodeled cortical bone in a fossil giant rat in SEA.…”

Bone density and frame size in adult women: Effects of body size, habitual use, and life history

“…For many populations in industrialized or sedentary contexts, parity and lactation would be expected to have even less of an effect (Henderson III et al, 2000). Furthermore, animal models suggest that repeated reproductive events alter bone microstructure in ways that may prove beneficial after menopause (de Bakker et al, 2017, 2018), but thus far we are unaware of similar findings in humans.…”