Romosozumab increased bone density in postmenopausal women regardless of age

Older age did not diminish bone mineral density (BMD) response to romosozumab among postmenopausal women, according to a prospective observational study published in Bone in January 2026. Instead, baseline BMD — particularly at the total hip — was independently associated with treatment response after 12 months of therapy.

In postmenopausal women, fracture risk increases with advancing age and declining BMD. Each standard deviation decline in total hip BMD more than doubles the risk of hip fracture and increases vertebral fracture risk by more than 50%. By age 85 years, the average White woman reaches a BMD T-score of −2.5, the diagnostic threshold for osteoporosis by dual-energy x-ray absorptiometry (DXA). Although absolute fracture risk is highest among the oldest individuals, treatment decisions in this population must also consider competing mortality risks and cost-effectiveness. International approaches to managing severe osteoporosis vary, with some European countries broadly qualifying older women for anabolic therapy, while others restrict access beyond certain age thresholds.

Romosozumab is a monoclonal antibody that inhibits sclerostin. Unlike antiresorptive agents, it both stimulates bone formation and reduces bone resorption, leading to substantial gains in BMD. Observational data have suggested that factors such as higher baseline BMD, longer prior exposure to bisphosphonates or denosumab (especially ≥3 years), and lower bone turnover may be associated with reduced BMD response to romosozumab. However, it has remained unclear whether age itself independently influences treatment response, separate from baseline bone characteristics and prior therapy exposure.

To evaluate this question, investigators conducted a prospective observational study across 1 Italian and 2 Belgian centers. The study included 186 postmenopausal women treated with romosozumab in routine clinical practice. Participants had a median age of 76 years (range, 52-96). At baseline, the median lumbar spine T-score was −2.8 (IQR, −3.4 to −1.8), the mean total hip T-score was −2.4 (±0.95), and the femoral neck T-score was −2.7 (IQR, −3.2 to −2.2).

Multivariable linear and logistic regression models, with imputation of missing data, were used to determine associations between baseline variables and percentage BMD change or achievement of a ≥3% BMD increase after 12 months of treatment. The analysis specifically examined whether older age, longer duration of prior therapy, or higher baseline BMD were associated with diminished BMD response.

After 12 months of romosozumab therapy, mean BMD increased by 9.16% at the lumbar spine and 3.00% at the total hip. A ≥3% increase in BMD was observed in 80.4% of participants at the lumbar spine, 51% at the total hip, and 46% at the femoral neck.

Lower baseline BMD was independently associated with a greater BMD response at the total hip. In contrast, age was not significantly associated with the percentage change in BMD or the likelihood of achieving a ≥3% increase at any measured skeletal site. These findings suggested that older women responded to romosozumab similarly to younger postmenopausal women when baseline BMD and other factors were accounted for.

The authors concluded that baseline BMD—rather than chronological age—influenced total hip BMD response to romosozumab.

“Our data support the effectiveness of romosozumab in older postmenopausal women in routine clinical practice.”

Reference

Gielen E, Amini N, Coppens D, et al. Bone mineral density response to romosozumab in post-menopausal women: A prospective observational real-world study. Bone. 2026;202:117701. doi: 10.1016/j.bone.2025.117701