Frontiers in Nutrition · Nov 10, 2026
Association Between Low Serum Zinc Concentration and Newly Recorded Osteoporosis With Pathological Fracture Among Adults Aged 50 Years and Older
By Ying-Jen Chang, Wei-Ting Wang, Yu-Li Pang et al.
Background: Zinc is essential for bone remodeling, yet longitudinal evidence linking circulating zinc to subsequently recorded osteoporosis-related skeletal outcomes remains limited. We examined whether low serum zinc was associated with these outcomes in adults aged ≥50 years. Methods: This retrospective multicenter cohort study used the TriNetX Global Collaborative Network. Patients with serum or plasma zinc <0.70 μg/mL were compared with those within 0.70–1.20 μg/mL. Patients who died or had a qualifying skeletal event during days 1–90 after index were excluded (landmark analysis); follow-up ran from day 91 through year 6. After propensity score matching, 32,524 patients remained in each group. Cox proportional-hazards models assessed the first recorded diagnosis of osteoporosis with current pathological fracture (M80) and exploratory secondary skeletal outcomes. A supplementary unmatched competing-risk analysis treated death as a competing event. Results: A newly recorded M80 diagnosis occurred in 310 patients (0.95%) with low zinc and 217 controls (0.67%), an absolute difference of 0.29 percentage points (hazard ratio [HR]=1.52; 95% confidence interval, 1.28–1.81). Exploratory secondary analyses showed higher hazards of the major osteoporotic-site fracture composite (HR=1.24), femoral fracture (HR=1.34), pelvic fracture (HR=1.45), and osteoporosis without current pathological fracture (HR=1.25); all-cause mortality was also higher (HR=1.43). Sensitivity analyses yielded directionally consistent primary-outcome estimates. In an exploratory alternative-exposure analysis, severe zinc deficiency was associated with a higher primary-outcome hazard (HR=2.16). The unmatched competing-risk analysis was directionally similar but provided no matched estimate. Conclusion: Low circulating zinc was associated with a higher hazard of a newly recorded M80 diagnosis and with exploratory site-based skeletal outcomes in this selected zinc-tested population. The modest absolute event-proportion difference, residual confounding, higher mortality, and diagnostic-coding limitations preclude causal, screening, or treatment inferences. Low zinc may reflect broader physiological vulnerability rather than an actionable skeletal risk factor; prospective studies are needed to clarify its clinical significance.