Reproduction Differentially Affects Trabecular Bone Depending on Its Mechanical Versus Metabolic Role.

During pregnancy and lactation, the maternal skeleton provides calcium for fetal/infant growth, resulting in substantial bone loss, which partially recovers after weaning. However, the amount of bone that is lost and the extent of post-weaning recovery are highly variable among different skeletal sites, and, despite persistent alterations in bone structure at some locations, reproductive history does not increase postmenopausal fracture risk. To explain this phenomenon, we hypothesized that the degree of reproductive bone loss/recovery at trabecular sites may vary depending on the extent to which the trabecular compartment is involved in the bone's load-bearing function. Using a rat model, we quantified the proportion of the load carried by the trabeculae, as well as the extent of reproductive bone loss and recovery, at two distinct skeletal sites: the tibia and lumbar vertebra. Both sites underwent significant bone loss during pregnancy and lactation, which was partially recovered post-weaning. However, the extent of the deterioration and the resumption of trabecular load-bearing capacity after weaning varied substantially. Tibial trabecular bone, which bore a low proportion of the total applied load, underwent dramatic and irreversible microstructural deterioration during reproduction. Meanwhile, vertebral trabecular bone bore a greater fraction of the load, underwent minimal deterioration in microarchitecture, and resumed its full load-bearing capacity after weaning. Because pregnancy and lactation are physiological processes, the distinctive responses to these natural events among different skeletal sites may help to elucidate the extent of the trabecular bone's structural versus metabolic functions.

Intermittent Parathyroid Hormone After Prolonged Alendronate Treatment Induces Substantial New Bone Formation and Increases Bone Tissue Heterogeneity in Ovariectomized Rats.

Postmenopausal osteoporosis is often treated with bisphosphonates (eg, alendronate, [ALN]), but oversuppression of bone turnover by long-term bisphosphonate treatment may decrease bone tissue heterogeneity. Thus, alternate treatment strategies after long-term bisphosphonates are of great clinical interest. The objective of the current study was to determine the effect of intermittent parathyroid hormone (PTH) following 12 weeks of ALN (a bisphosphonate) treatment in 6-month-old, ovariectomized (OVX) rats on bone microarchitecture, bone remodeling dynamics, and bone mechanical properties at multiple length scales. By using in vivo µCT and 3D in vivo dynamic bone histomorphometry techniques, we demonstrated the efficacy of PTH following ALN therapy for stimulating new bone formation, and increasing trabecular thickness and bone volume fraction. In healthy bone, resorption and formation are coupled and balanced to sustain bone mass. OVX results in resorption outpacing formation, and subsequent bone loss and reduction in bone tissue modulus and tissue heterogeneity. We showed that ALN treatment effectively reduced bone resorption activity and regained the balance with bone formation, preventing additional bone loss. However, ALN treatment also resulted in significant reductions in the heterogeneity of bone tissue mineral density and tissue modulus. On the other hand, PTH treatment was able to shift the bone remodeling balance in favor of formation, with or without a prior treatment with ALN. Moreover, by altering the tissue mineralization, PTH alleviated the reduction in heterogeneity of tissue material properties induced by prolonged ALN treatment. Furthermore, switching to PTH treatment from ALN improved bone's postyield mechanical properties at both the whole bone and apparent level compared to ALN alone. The current findings suggest that intermittent PTH treatment should be considered as a viable treatment option for patients with prior treatment with bisphosphonates. © 2017 American Society for Bone and Mineral Research.