Vitamin D mitigates Inflammatory Bone Loss in Postmenopausal Osteoporosis via modulating the Gut-Immune-Bone axis
Abstract
Osteoporosis is a prevalent skeletal disorder characterized by deterioration of bone microarchitecture and loss of bone mineral density, leading to increased fracture risk and substantial health and economic burdens, particularly among older adults. Bone remodeling is orchestrated by a complex interplay of systemic and local regulators, among which vitamin D plays a central role in maintaining skeletal homeostasis. Although numerous studies have examined the effects of vitamin D on bone metabolism, outcomes have been inconsistent across populations, dosing regimens, and experimental models. To clarify the net skeletal impact of vitamin D, we investigated its effects in postmenopausal osteoporosis (PMO). Vitamin D (1,25-dihydroxyvitamin D3– active form of vitamin D) supplementation effectively prevented bone loss in ovariectomized mice, at both lower and higher concentrations. Mechanistically, vitamin D promoted osteoclast differentiation in vitro, consistent with its RANKL-dependent pro-osteoclastogenic activity, yet paradoxically conferred bone protection in vivo. This discrepancy was explained by vitamin D’s profound immunomodulatory effects, which reshaped both innate and adaptive immune responses to suppress osteoclast formation and function. Concurrently, vitamin D improved intestinal barrier integrity and restored gut microbial composition, thereby stabilizing the gut-immune-bone axis and reducing pro-resorptive inflammatory signaling. Together, these findings…
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Evidence Hub reads this as a preprint, done in animal, not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
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