DISCONTINUATION OF DENOSUMAB AND MULTIPLE VERTEBRAL FRACTURES: REPORT OF TWO CASES AND REVIEW OF THE LITERATURE

The duration of osteoporosis treatments depends on the drug type, anabolic or anti-catabolic, and the severity of the disease. Denosumab is a fully human monoclonal antibody that inactivates RANK-L, inhibiting the RANKL-RANK interaction. This inhibits osteoclast formation, activation, and survival. It also reduces cortical and trabecular bone resorption. Subcutaneous administration of 60 mg every 6 months for 3 years has reduced bone resorption, increased bone mineral density (BMD) and decreased vertebral, non-vertebral and hip fractures. It is indicated for the treatment of osteoporosis with high risk of fracture. Denosumab mechanism of action is reversible. After discontinuation, loss of BMD and elevation of bone turnover markers have been observed. In addition, multiple vertebral fractures after the suspension of the drug have been reported. These rebound-associated vertebral fractures are rare. A special genetic predisposition related to miRNA has been proposed. Two women with this clinical presentation are described. Fractures occurred between 7 and 10 months respectively after the last dose of denosumab. They presented with an increase in circulating C-telopeptid levels and a decrease in BMD with acute multiple vertebral fractures.