Vitamin D deficiency and disease conditions relevant to: Orthopaedic translation

Vitamin D, traditionally known for its role in calcium-phosphate homeostasis and bone health, is now recognised as a pleiotropic hormone with critical effects on multiple physiological processes. It exists primarily as ergocalciferol (vitamin D₂) and cholecalciferol (vitamin D₃), which are biologically inactive until undergoing a sequential hydroxylation in the liver to form 25-hydroxyvitamin D (calcidiol), and subsequently in kidney to form the active metabolite 1,25-dihydroxyvitamin D (calcitriol). By engaging the vitamin D receptor, it exerts immunomodulatory, neuroprotective, and anti-frailty functions. Deficiency in vitamin D has been implicated in a wide range of disorders, including musculoskeletal weakness, frailty, cognitive decline, autoimmune diseases, and respiratory infections. Vitamin D deficiency affects nearly half of the global population and remains a widespread public health challenge, and effective interventions such as food fortification and targeted supplementation should be prioritized in future strategies.

Vitamin D deficiency represents a modifiable risk factor with implicated effects across systemic, neurocognitive and musculoskeletal systems. Epidemiological evidence links deficiency to increased risk of infection, cognitive decline, frailty and orthopaedic morbidity. In orthopaedic and geriatric populations, maintaining sufficient vitamin D supplementation may reduce fracture and fall risk as well as postoperative complications and infections. These factors are also influenced by vitamin D deficiency-related effects on neurocognition. Vitamin D status may also be relevant in the management of infectious diseases, including respiratory illnesses and COVID-19. This review also discusses mechanistic and practical rationales for clinical translation. Potential interventions include vitamin D co-supplementation, dietary fortification and optimised sun exposure. However, limitations in existing randomised trials underscore the need for consistency in dosing, appropriate formulation, targeted population, as well as baseline deficiency progression status. These insights can guide clinicians, public health policy makers and researchers in developing evidence-based protocols and interventions to reduce vitamin D deficiency-related morbidity.