Rebound-Associated Vertebral Fractures Two Months After a Missed Dose of Denosumab

Introduction: Denosumab, an anti-resorptive medication approved for treatment of osteoporosis, increases bone mineral density and reduces fracture risk. Discontinuation of treatment is associated with bone turnover rebound and reduced bone mineral density. We report a case of a woman without prior history of fragility fractures who presented with multiple spontaneous vertebral fractures two months after a missed dose of Denosumab, which is earlier than current available literature. Clinical Case: A 54-year old female was diagnosed with osteoporosis at the age of 50 with a DXA revealing T-scores of LS -2.9 SD, LFN -0.6 SD, TH -0.5 SD. Ten-year probability of MOF evaluated by FRAX was 6%. Work-up for secondary causes of osteoporosis during the time was unremarkable. She was started on Denosumab 60 mg every 6 months from July 2016 to July 2019, receiving a total of 5 injections. She had missed her dose of Denosumab in January 2020. Two months after the missed dose, she presented to a local hospital with complaints of chest and epigastric pain. A CTA was performed as part of evaluation which was unremarkable aside from an incidental finding of thoracic compression fractures. An MRI of the spine was subsequently done which showed a recent-appearing moderate to severe wedge compression fracture and edema of the T7 and T6 vertebral bodies, and of the upper two-thirds of the T4. A biological and radiological work-up to exclude other causes of osteoporosis to explain the patient’s vertebral fractures was performed. The patient did not have renal failure, vitamin D deficiency, hyperthyroidism, primary hyperparathyroidism, Cushing’s disease, hypophosphatemia, multiple myeloma, Celiac disease, diabetes mellitus, or prior glucocorticoid treatment. During the time of treatment and discontinuation of Denosumab, the patient was on adequate supplementation of calcium and Vitamin D. The patient’s vertebral fractures were treated with kyphoplasty. To treat osteoporosis and prevent further risk of fractures, she was started on an anabolic agent Abaloparatide. Conclusion: This case demonstrates rebound vertebral fractures occurring very shortly after discontinuing Denosumab in a relatively young woman with low probability of major osteoporotic fracture. Further investigation must be done to determine pathophysiological process involved of vertebral fractures and treatment regimen after sudden discontinuation of Denosumab.