Endocrine Abstracts

Introduction: Denosumab reduces bone resorption, increases BMD, and reduces fracture risk. Denosumab discontinuation (DD) induces an increase of B-crosslaps above baseline values for two years, and a decrease of BMD values. This rebound effect is associated with spontaneous clinical vertebral fractures (SCVF) in close to 15% of patients considering a follow-up of 2 years without taking another osteoporosis treatment. Prescribing a bisphosphonate or SERMs at DD would prevent the rebound effect and the risk of SCVF.

Case report: A breast cancer was diagnosed in this 60-year-old woman. BMD T-scores were −2.9 DS at the lumbar spine and −1.9 DS at the total hip. The 10-year probability of major osteoporotic fractures assessed by FRAX® was 13%. Letrozole and denosumab were given for 5 years. At the end of the treatment, lumbar spine and total hip BMD increase significantly (+18% and +8%, respectively). Vertebral morphometry confirmed the absence of fractures. Raloxifene 60 mg daily was startet 7 months after DD. B-crosslaps were measured at 33 ng/l (normal range: 25-573 ng/l). Four months later, she experienced spontaneous low back pain. MRI revealed D11 and L5 fractures. B-crosslaps were measured at 2070 ng/l.

Discussion: Raloxifene has not been effective, neither in reducing the high bone turnover, nor in preventing SCVF. In addition, follow-up of B-crosslaps was too much apart. To minimize the high bone turnover at DD, it seems preferable to prescribe a potent bisphosphonate, alendronate or zoledronate. However, frequent measurements of bone turnover should make it possible: 1) to detect the beginning of the rebound effect; 2) to evaluate the effectiveness of the given antiresorptive treatment; and, if necessary, 3) to replace it or to adjust its dosage. However, the threshold value that determines the need for an intervention is unknown. Furthermore, a significant decrease in the high bone turnover after DD is not a guarantee to prevent bone loss and to avoid the risk of SCVF.

Conclusion: Studies are urgently needed to assess the efficacy of bisphosphonates and their optimal doses in such situations.