Preventing Rebound-Associated Fractures after Discontinuation of Denosumab Therapy: A Position Statement from the Health Insurance Committee of the Korean Endocrine Society.

Denosumab was approved for use in Korea in 2017, and its use has been rapidly increasing since it was classified as a reimbursable initial therapy for osteoporosis in April 2019. South Korea has a national health insurance system that enables all citizens to benefit from medical services with ease. Nonetheless, a problematic reality is that clinicians’ decision-making process in real-world practice is more directly affected by health insurance reimbursement policies than by medical guidelines. The American Association of Clinical Endocrinology (AACE) and the Endocrine Society recommend denosumab as the initial treatment for patients at high or very high risk for osteoporotic fracture [1,2]. It has demonstrated superior efficacy for osteoporosis treatment, as a single subcutaneous injection of 60 mg once every 6 months reduces the incidence of vertebral fractures by 60%, nonvertebral fractures by 20%, and hip fractures by 40% over 3 years [3]. Moreover, the Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) extended study demonstrated that denosumab continued to increase bone density for 10 years [4]. However, this elevated bone density decreases rapidly after the discontinuation of denosumab. In FREEDOM extended study, the bone mineral density (BMD) that had risen for 10 years decreased sharply during just 1 year after discontinuation. Of particular note, femoral BMD decreased to an even lower level than baseline. This is well known to be due to the rebound of bone turnover markers after discontinuation of denosumab. During this rapid bone loss period, some patients have also been reported to experience rebound-associated fractures [4,5]. Rebound-associated fractures are not encountered in all patients; however, once they occur, they lead to multiple vertebral fractures, which can result in serious problems [6]. Rebound-associated fractures can be prevented by using other anti-resorptive agents [7]. In patients who received alendronate after discontinuation of denosumab, their BMD, which had