Vitamin D Deficiency and Knee Osteoarthritis in Midlife Women: A Prospective Cohort Study with Annual Monitoring, Supplementation, and Menopausal Stratification

A BSTRACT Introduction: Midlife women face increased risk of knee osteoarthritis (OA), osteoporosis, and metabolic comorbidities. Vitamin D deficiency, highly prevalent in this population, may contribute to OA pathogenesis through effects on cartilage metabolism, bone remodeling, and inflammatory pathways. Addressing Vitamin D status during the menopausal transition is central to preventive care and healthy aging. Methods: In a 5-year prospective cohort study, 420 women aged 40–60 years without radiographic OA were enrolled. Serum 25(OH)D was measured annually. Deficiency was defined as <20 ng/mL, insufficiency as 20–29 ng/mL, and sufficiency as ≥30 ng/mL. Deficient participants received oral cholecalciferol (1000–2000 IU/day, adjusted annually). Primary outcome measures included radiographic OA (Kellgren–Lawrence grade ≥2) and clinical OA (ACR criteria). Cox proportional hazards models assessed risk adjusting for body mass index, menopausal status, physical activity, comorbidities, diet, and sunlight exposure. Results: At baseline, 38% were deficient. Over 5 years, 112 women developed OA. Incidence was highest in persistently deficient postmenopausal women (40%, hazard ratio [HR]: 2.30, 95% confidence interval [CI]: 1.50–3.52), intermediate in perimenopausal deficient women (28%, HR: 1.60, 95% CI: 1.02–2.52), and lowest in sufficient women (14%, reference). Correction of deficiency reduced incidence to 20% (absolute risk reduction [ARR]: 16.3%, number needed to treat [NNT]: 6.1). Annual monitoring revealed that sustained sufficiency reduced OA risk (adjusted HR: 0.6, 95% CI: 0.4–0.9, P = 0.01). Sustained sufficiency yielded ARR 22.2% and NNT 4.5. These findings highlight Vitamin D optimization as a clinically meaningful preventive strategy. Conclusion: Persistent Vitamin D deficiency is a modifiable risk factor for knee OA in midlife women, particularly postmenopausal women. Annual monitoring and supplementation reduce incidence, with ARR and NNT values demonstrating tangible clinical impact. Preventive care pathways should integrate Vitamin D screening into midlife women’s health programs to reduce musculoskeletal disease burden and enhance quality of life during the menopausal transition.