Interaction effects of testosterone and platelet-to-lymphocyte ratio on osteoporosis in U.S. adults: Insights from the NHANES 2011 to 2016 cohort

Testosterone (TST) deficiency and systemic inflammation may both contribute to osteoporosis, yet their joint effects remain underexplored. The platelet-to-lymphocyte ratio (PLR), a readily measurable marker of inflammation, may interact with TST to influence osteoporosis risk. To assess the independent and interactive associations between serum TST and PLR with osteoporosis in U.S. adults using National Health and Nutrition Examination Survey 2011 to 2016 data. We analyzed adults aged ≥20 years with complete data on bone mineral density, TST, and PLR. Osteoporosis was defined per World Health Organization criteria based on dual-energy X-ray absorptiometry bone mineral density. Low TST in men was defined as <300 ng/dL; PLR quartiles were derived from survey data, and cutoff points identified using restricted cubic spline analysis. Weighted logistic regression, restricted cubic spline modeling, and multiplicative interaction analysis were performed. Sensitivity analysis was conducted in participants ≥50 years. Weighted mean age was 39.5 years; 33.2% were male. Osteoporosis prevalence was 5.9%. Higher PLR showed a nonlinear positive association with osteoporosis risk ( P for nonlinearity < .05), characterized by a steep increase in risk above the upper quartile. Lower TST was associated with increased odds of osteoporosis in men. A significant multiplicative interaction between low TST and high PLR was observed ( P -interaction < .05). Results were consistent in adults ≥50 years. In U.S. adults, elevated PLR and lower TST were independently associated with greater odds of osteoporosis, with evidence of synergistic interaction. Prospective studies are warranted to validate these findings.