Residential altitude was not independently associated with osteoporosis among long-term Qinghai–Tibetan Plateau residents

Background The association between long-term high-altitude residence and osteoporosis remains unclear. This study investigated whether body mass index (BMI) and vitamin D status modify the association between residential altitude and dual-energy X-ray absorptiometry (DXA)-defined osteoporosis among long-term residents of the Qinghai–Tibetan Plateau. In resource-limited high-altitude settings, limited access to DXA may hinder timely osteoporosis detection, and opportunistic use of routine computed tomography (CT), together with simple host characteristics such as BMI, may support pragmatic risk stratification. Methods A single-centre, hospital-based retrospective case–control study was conducted among residents aged ≥50 years who had undergone non-contrast CT and DXA within 30 days and had lived on the Qinghai–Tibetan Plateau for ≥5 years. Osteoporosis was defined as a DXA T-score ≤ − 2.5, and individuals with osteopenia were excluded to increase phenotypic contrast. Residential altitude (1,500–4,600 m) was geocoded and analysed as a continuous variable per 100 m increment. Pre-specified interaction terms included residential altitude × BMI and residential altitude × 25-hydroxyvitamin D 25(OH)D. Additional BMI-stratified analyses used 24.0 kg/m 2 as a clinically interpretable threshold. Exploratory HU-adjusted sensitivity analyses are reported in the Supplementary materials . Results Among 377 participants (224 osteoporosis cases and 153 controls with normal bone mineral density), residential altitude was not independently associated with osteoporosis after multivariable adjustment (adjusted odds ratio aOR 1.020 per 100 m, 95% CI 0.976–1.065; p = 0.374). In the primary interaction model, there was suggestive but inconclusive evidence of BMI-related heterogeneity (altitude × BMI aOR 1.011, 95% CI 0.998–1.023; p = 0.087), whereas no interaction with 25(OH)D was observed ( p = 0.423). BMI-stratified analyses showed directionally different but imprecise altitude–osteoporosis associations. Conclusion Residential altitude was not independently associated with osteoporosis in this hospital-based case–control study of long-term plateau residents. The data suggested possible BMI-related heterogeneity, but the evidence was inconclusive and should be interpreted cautiously. These findings are hypothesis-generating and may inform future opportunistic bone health assessment in resource-limited high-altitude settings.