Site-Specific Responses to SERM Treatment in Postmenopausal Osteoporosis: No Clear Age Attenuation in a Real-World Study

Background: Selective estrogen receptor modulators (SERMs) are widely used for postmenopausal osteoporosis, yet whether treatment response attenuates with aging in routine practice remains unclear. We examined age- and site-specific responses to SERM therapy. Methods: We retrospectively analyzed postmenopausal women with primary osteoporosis treated with a SERM for 1 year (2017–2021). Participants were stratified by age (50–64, 65–74, and ≥75 years). We evaluated changes in bone mineral density (BMD) at the lumbar spine (L2–4) and femoral neck and changes in urinary NTX and serum BAP. Multivariable linear regression modeled BMD change ratios (1-year/baseline) adjusting for baseline site-specific BMD, estimated glomerular filtration rate (eGFR), and active vitamin D co-therapy (none, alfacalcidol, or eldecalcitol). The primary endpoint was the 1-year change in lumbar spine BMD; secondary endpoints included femoral neck BMD and bone turnover markers. Results: Lumbar spine BMD increased significantly across all age groups, whereas femoral neck BMD increased significantly only in women aged 50–64 years. However, BMD change ratios did not differ among age groups at either site. In adjusted models, age was not independently associated with BMD change at the lumbar spine or femoral neck. Lower baseline BMD predicted larger relative gains at both sites, and eldecalcitol co-therapy was independently associated with femoral neck BMD response. Conclusions: In real-world practice, BMD changes observed during SERM treatment were site-specific rather than clearly age-dependent. Lumbar spine BMD improved across age groups, whereas femoral neck changes were smaller and less consistent.