Significant bone loss after stopping long-term denosumab treatment: a post FREEDOM study.

Area of Science:

• Endocrinology
• Gerontology
• Orthopedics

Background:

• Denosumab (DMAb) is a RANKL inhibitor that does not incorporate into bone matrix.
• Discontinuation of DMAb is known to reverse treatment effects, leading to rapid bone loss.

Purpose of the Study:

• To assess bone mineral density (BMD) changes one year after DMAb discontinuation in postmenopausal women.
• To evaluate the incidence of fragility fractures following DMAb cessation.

Main Methods:

• Follow-up study of 38 elderly women from the FREEDOM study extension who received 7-10 years of DMAb.
• BMD measurements at the lumbar spine (LS) and hip, along with X-rays, were compared to pre-cessation values.
• No participants received bisphosphonates after stopping DMAb.

Main Results:

• Significant BMD decreases were observed: -8.1% in LS, -6% in the femoral neck (FN), and -8.4% in the total hip (TH).
• 13.15% of patients (5/38) experienced fragility fractures, including wrist and vertebral fractures.
• Elevated bone turnover markers (CTX, osteocalcin) and low vitamin D levels were noted.

Conclusions:

• Cessation of denosumab treatment results in rapid bone loss and an increased risk of fragility fractures.
• Further studies are required to identify patients at highest risk of fracture after DMAb discontinuation and to assess the long-term benefits of bisphosphonate transition.