Adaptations in the Microarchitecture and Load Distribution of Maternal Cortical and Trabecular Bone in Response to Multiple Reproductive Cycles in Rats

Abstract

Pregnancy, lactation, and weaning result in dramatic changes in maternal calcium metabolism. In particular, the increased calcium demand during lactation causes a substantial degree of maternal bone loss. This reproductive bone loss has been suggested to be largely reversible, as multiple clinical studies have found that parity and lactation history have no adverse effect on post-menopausal fracture risk. However, the precise effects of pregnancy, lactation, and post-weaning recovery on maternal bone structure are not well understood. Our study aimed to address this question by longitudinally tracking changes in trabecular and cortical bone microarchitecture at the proximal tibia in rats throughout three cycles of pregnancy, lactation, and post-weaning using in vivo μCT. We found that the trabecular thickness underwent a reversible deterioration during pregnancy and lactation, which was fully recovered after weaning, while other parameters of trabecular microarchitecture (including trabecular number, spacing, connectivity density, and structure model index) underwent a more permanent deterioration which recovered minimally. Thus, pregnancy and lactation resulted in both transient and long-lasting alterations in trabecular microstructure. In the meantime, multiple reproductive cycles appeared to improve the robustness of cortical bone (resulting in an elevated cortical area and polar moment of inertia), as well as increase the proportion of the total load carried by the cortical bone at the proximal tibia. Taken together, changes in the cortical and trabecular compartments suggest that while rat tibial trabecular bone appears to be highly involved in maintaining calcium homeostasis during female reproduction, cortical bone adapts to increase its load-bearing capacity, allowing the overall mechanical function of the tibia to be maintained.

Osteoporosis Treatments Affect Bone Matrix Maturation in a Rat Model of Induced Cortical Remodeling

“…During lactation and reproduction, the bone adapts to shift more of the load-bearing capacity to the cortical bone (44) and the majority of the cortical bone lost is on the endocortical surface, which provides the dam with the optimal mechanical strategy. (45) Therefore, perhaps it is not surprising that the fracture toughness in the baseline and day-7 groups is comparable to values reported for unaffected female rat femurs.…”

Identification of Genes Differentially Expressed in Simvastatin‐Induced Alveolar Bone Formation

“…Placement of the ligature around the rat maxillary second molar is a standard model for inducing inflammation and bone loss (ExP) and testing pharmacotherapeutic interventions . Mature retired breeders were chosen for this study because growth of the mandible had ceased, and though multiple reproductive cycles may weaken trabecular microarchitecture, cortical bone (focus of the current study) actually becomes more robust . Within 11 days of ligature placement, a large number of proinflammatory genes associated with both rat and human periodontitis were upregulated.…”

“…(9,26) Mature retired breeders were chosen for this study because growth of the mandible had ceased, and though multiple reproductive cycles may weaken trabecular microarchitecture, cortical bone (focus of the current study) actually becomes more robust. (27) Within 11 days of ligature placement, a large number of proinflammatory genes associated with both rat and human periodontitis were upregulated. These included two cytokines most often associated with periodontitis, IL-1b and TNF.…”

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

“…This suggests that in virgin rats, the post OVX trabecular deteriorations were substantial enough to cause a reduction in stiffness in spite of no changes in cortical bone structure. On the other hand, the relatively constant whole-bone stiffness in the reproductive group post-OVX in spite of mild reductions in trabecular bone volume may be the result of long-term adaptations in cortical bone microstructure that occurred over the course of multiple reproductive cycles (19) , which may compensate for deteriorations in trabecular microarchitecture.…”

“…Although the majority of clinical studies indicate that BMD recovers within one year of weaning (14) , recent clinical evaluations of recovery of the trabecular microarchitecture have demonstrated that reproduction-induced deteriorations in trabecular microstructure persist for at least 18–43 months post-partum (15,16) . Furthermore, rodent studies have demonstrated that substantial microarchitectural impairments in the trabecular bone compartment remain long after weaning at several skeletal sites (10,17–19) . In contrast, a large number of epidemiological studies, summarized by Kovacs (14) , have evaluated the impact of pregnancy and/or lactation on long-term risk of fracture or osteoporosis, and the vast majority indicated that reproductive history has no adverse, or even a protective effect on postmenopausal risk of osteoporosis/fracture (14) .…”