Densitometric gains do not uniformly translate into clinical and psychosocial recovery: a 12-month multidimensional analysis of romosozumab therapy in postmenopausal osteoporosis

BACKGROUND: Although romosozumab produces substantial increases in bone mineral density (BMD), these densitometric gains may not necessarily translate into parallel clinical and psychosocial recovery. This study aimed to determine whether improvements in BMD reflect meaningful changes in pain, quality of life, kinesiophobia, and psychological status during romosozumab therapy, and to define the multidimensional structure of treatment response. Densitometric, clinical, and psychological responses were hypothesized to follow partially independent and region-specific trajectories. METHODS: This single-center cohort study included 46 postmenopausal women with osteoporosis treated with romosozumab and followed for 12 months. BMD was assessed by dual-energy X-ray absorptiometry at the lumbar spine, femoral neck, and total femur at baseline, 6, and 12 months. Pain (VAS), kinesiophobia (TAMPA), anxiety and depression (HADS), and quality of life (QUALEFFO-41) were evaluated at the same time points. Longitudinal changes were analyzed using repeated-measures ANOVA, correlation analyses, and exploratory hierarchical cluster analysis. RESULTS: BMD increased significantly at all skeletal sites over 12 months (all p < 0.001), with the greatest gains in the lumbar spine (~ 19%), followed by the femoral neck (~ 9%) and total femur (~ 6%). All clinical and psychosocial outcomes improved significantly (all p < 0.001; partial η² = 0.625-0.934). Changes in lumbar spine BMD showed statistically significant but modest associations with quality of life and depressive symptoms (r = - 0.304 to - 0.422, p < 0.05-0.01). Similarly, changes in femoral BMD parameters were modestly associated with pain (r = - 0.341 to - 0.481, p < 0.05-0.01) and kinesiophobia (r = - 0.308 to - 0.342, p < 0.05). Exploratory hierarchical cluster analysis identified distinct clusters separating patient-reported outcomes from densitometric parameters, with prior osteoporosis treatment history emerging as a bridging variable between these domains. CONCLUSION: Densitometric gains during romosozumab therapy do not uniformly translate into patient-perceived recovery. Treatment response is multidimensional and region-specific, indicating that BMD alone is insufficient to capture therapeutic effectiveness. The region-specific pattern of these modest associations, femoral BMD changes with pain and kinesiophobia, and lumbar BMD changes with quality of life and depressive symptoms, supports the need for anatomically informed, patient-centered evaluation frameworks in osteoporosis management.