ABO and Rh blood group phenotypes in DXA-defined osteoporosis: an age- and sex-adjusted case–control study

Osteoporosis is a multifactorial skeletal disorder influenced by demographic, metabolic, environmental, and genetic factors. ABO blood group phenotypes have been associated with inflammatory, endothelial, and thrombotic pathways that may theoretically interact with bone remodeling, but evidence regarding osteoporosis remains limited and inconsistent. To investigate whether ABO and Rh blood group phenotypes are independently associated with DXA-defined osteoporosis using a strictly normal-BMD control group and age- and sex-adjusted analyses. This single-center retrospective case–control study evaluated hospital records from January 1, 2013, to June 1, 2022. The osteoporosis group comprised 857 unique patients diagnosed with osteoporosis by DXA and subsequently treated pharmacologically. From a separate source population of 2,747 individuals recorded as having normal BMD, 1,097 controls were purposively selected to obtain a mean age close to that of the osteoporosis group. DXA classification was based on the lowest recorded T-score from the lumbar spine (L1–L4) and femoral neck. ABO/Rh phenotype, age, and sex were analyzed using crude and age- and sex-adjusted estimates and age-stratified sensitivity analyses. The osteoporosis and control groups had mean ages of 72.13 ± 10.63 and 70.97 ± 12.13 years, respectively (p = 0.025), and women constituted 84.13% and 83.77% of the groups (p = 0.831). ABO distributions did not differ between osteoporosis cases and controls (p = 0.958), nor did Rh distributions (p = 0.727). With blood group O as the reference, adjusted ORs were 1.00 (95% CI 0.81–1.23) for A, 0.94 (0.73–1.22) for B, and 0.94 (0.65–1.38) for AB. Rh-positive status was not independently associated with osteoporosis (aOR 1.04, 95% CI 0.78–1.39). Findings remained consistent across age-stratified analyses. ABO and Rh blood group phenotypes were not independently associated with osteoporosis in this hospital-based cohort. These findings do not support moderate-to-large phenotype-level associations with osteoporosis, although smaller effects, particularly for less frequent phenotypes, cannot be excluded.