A randomized controlled trial of the effect of raloxifene plus cholecalciferol versus cholecalciferol alone on bone mineral density in postmenopausal women with osteopenia

Abstract

Raloxifene increases lumbar spine bone mineral density (BMD) and lowers vertebral fracture risk in patients with osteoporosis. However, few prospective clinical trials have studied its efficacy in postmenopausal women with osteopenia. This study investigated the efficacy of raloxifene in postmenopausal women with osteopenia. An investigator-initiated, randomized, open-label, prospective, single-center trial was conducted in 112 postmenopausal women with osteopenia. Osteopenia was defined based on the lowest BMD T-score in the lumbar spine, femoral neck, or total hip (−2.5 < lowest T-score < −1.0). Participants were randomly assigned to receive raloxifene 60 mg/day plus cholecalciferol 800 IU/day (RalD) or cholecalciferol 800 IU/day (VitD) for 48 weeks. At baseline, mean age (63.1 ± 6.8 years) did not differ between the two groups. However, in the RalD group, mean body mass index (BMI) and baseline T-score were lower, while 25-hydroxyvitamin D level was higher. At 48 weeks, the RalD group showed a greater increase in lumbar spine BMD (RalD vs. VitD; 2.6% vs. −0.6%, p = 0.005) and attenuated the total hip BMD loss (−0.3% vs. −2.9%, p = 0.003). The effect of raloxifene on the lumbar spine remained significant after adjustment for age, BMI, baseline BMD T-score, and other covariates (adjusted β: +3.05 vs. VitD, p = 0.015). In subgroup analysis, the difference in lumbar spine BMD between the RalD and VitD groups was robust in those with severe osteopenia group (lowest T-score ≤ −2.0). Raloxifene plus cholecalciferol significantly improved lumbar spine BMD and attenuated total hip BMD loss compared to cholecalciferol alone, with a more robust effect in severe osteopenia. Clinical trial registration: The trial was registered with ClinicalTrials.gov (NCT05386784).