Our data clearly demonstrate existence of a physiological-pathological continuum: obesity-VDD-IL-34 and both OP and KOA, with structural equation modeling confirming that FM/WT predicts VDD status, VDD is directly associated with elevated IL-34 levels, and IL-34 levels in turn are a possible cause of KOA and OP.
Key Findings
Results
Individuals with vitamin D deficiency had a significantly higher prevalence of osteoporosis and knee osteoarthritis compared with those with vitamin D sufficiency.
Cross-sectional study of 1075 adults classified into VDD (n = 304) and VDS (n = 771) groups.
Data on osteoporosis (OP) and knee osteoarthritis (KOA) were collected and compared between groups.
Regression analyses confirmed that VDD was independently linked to higher prevalence of both musculoskeletal conditions.
Results
Fat mass-to-weight ratio (FM/WT) was a significant predictor of vitamin D deficiency status.
Structural equation modeling confirmed FM/WT as a significant predictor of VDD status (β = 0.305, 95% CI: 0.231–0.367).
Body composition was assessed using bioelectrical impedance analysis.
FM/WT was independently associated with VDD in regression analyses.
Results
Vitamin D deficiency was directly associated with elevated IL-34 plasma levels.
Structural equation modeling quantified the association between VDD and IL-34 levels (β = 0.353, 95% CI: 0.308–0.398).
Plasma levels of IL-34 were measured alongside IL-9 and MCP-1.
The association between VDD and IL-34 was independent of other measured variables.
Results
Elevated IL-34 levels were identified as a possible cause of knee osteoarthritis.
Structural equation modeling showed IL-34 levels were associated with KOA (β = 0.573, 95% CI: 0.460–0.687).
This was the strongest of the IL-34-to-musculoskeletal disease associations identified in the model.
IL-34 was positioned as a mediating variable between VDD and KOA in the pathological continuum.
Results
Elevated IL-34 levels were identified as a possible cause of osteoporosis.
Structural equation modeling showed IL-34 levels were associated with OP (β = 0.433, 95% CI: 0.329–0.536).
IL-34 was positioned as a mediating variable between VDD and OP in the pathological continuum.
The association was weaker than the IL-34 to KOA association (β = 0.433 vs. β = 0.573).
Conclusions
The study identified a physiological-pathological continuum linking obesity, vitamin D deficiency, IL-34, and musculoskeletal disorders.
The continuum was described as: obesity-VDD-IL-34 and both OP and KOA.
Structural equation modeling was used to confirm and quantify these sequential associations.
IL-34 was proposed as a novel mediator linking VDD with both osteoporosis and knee osteoarthritis.
The study measured plasma levels of IL-9, IL-34, and MCP-1 to assess systemic inflammation.
Tarabeih N, Sleiman A, Kalinkovich A, Ashkenazi S, Shalata A, Livshits G. (2025). IL-34 as a Novel Mediator Linking Vitamin D Deficiency with Osteoporosis and Knee Osteoarthritis.. International journal of molecular sciences. https://doi.org/10.3390/ijms262211090