IL-34 as a Novel Mediator Linking Vitamin D Deficiency with Osteoporosis and Knee Osteoarthritis

Vitamin D deficiency (VDD) is a widespread human condition closely associated with musculoskeletal disorders, involving alterations in body composition and systemic inflammation. In this cross-sectional study, 1075 adults were classified into a VDD (n = 304) group and a VD sufficient (VDS) group (n = 771). Body composition measurements, including the fat mass-to-weight ratio (FM/WT), were assessed using bioelectrical impedance analysis. Plasma levels of IL-9, IL-34, and MCP-1 were also measured. Data on osteoporosis (OP) and knee osteoarthritis (KOA) were collected. Regression analyses indicated that FM/WT was independently associated with VDD, which in turn was linked to elevated IL-34 levels. Individuals with VDD had a significantly higher prevalence of OP and KOA compared with those with VDS. Structural equation modeling confirmed and quantified these associations, suggesting that FM/WT is a significant predictor of VDD status (β = 0.305, 95% CI: 0.231-0.367). VDD is directly associated with elevated IL-34 levels (β = 0.353, 95% CI: 0.308-0.398), while IL-34 levels, in turn, are a possible cause of KOA (β = 0.573, 95% CI: 0.460-0.687) and OP (β = 0.433, 95% CI: 0.329-0.536). Our data clearly demonstrate existence of a physiological-pathological continuum: obesity-VDD-IL-34 and both OP and KOA.