SUN-826 - Breaking Point: Rebound Fractures Following Denosumab Discontinuation in Primary Hyperparathyroidism

Background: Osteoporosis is characterized by reduced bone mineral density and impaired microarchitecture, leading to increased fracture risk. Denosumab is an effective antiresorptive therapy; however, discontinuation can precipitate rapid bone turnover and rebound fractures (1). The low bone turnover state following parathyroidectomy in primary hyperparathyroidism has been theorized as a strategy to reduce this risk. We report a case of rebound vertebral fracture despite biochemical surveillance and timely bisphosphonate therapy in a patient with osteoporosis secondary to primary hyperparathyroidism.

Case: An 82-year-old woman with chronic hepatitis B, MGUS, nephrolithiasis, malnutrition (BMI 16.9), primary CNS lymphoma in remission, and osteoporosis treated with denosumab presented for evaluation of hypercalcemia. She had longstanding high-normal calcium levels peaking at 11.5 mg/dL with concomitant hypophosphatemia (2.1 mg/dL), elevated intact PTH (145 pg/mL), and increased 1,25-dihydroxyvitamin D (98 pg/mL), initially attributed to dehydration, immobility, and malignancy. She was maintained on denosumab for 5 years due to gastrointestinal intolerance of bisphosphonates, along with calcium and vitamin D. Initial repeat laboratory evaluation was unremarkable; however, follow-up revealed calcium 10.9 mg/dL, iPTH 196.9 pg/mL, and 1,25-dihydroxyvitamin D 110 pg/mL. Neck ultrasound identified a right-sided thyroid lesion, and parathyroidectomy confirmed parathyroid adenoma with hyperplasia. Given patient desire to discontinue denosumab and the expected low bone turnover state following parathyroidectomy, denosumab therapy was discontinued and monthly bone turnover markers were monitored. Initial CTX and PINP were 117 pg/mL and 14 µg/L. After eight months CTX slowly increased to a peak of 320 pg/mL, prompting zoledronic acid to mitigate rebound resorption. One month later, she developed acute low back pain after severe coughing during an upper respiratory infection. Imaging revealed an acute L1 compression fracture requiring kyphoplasty, which was performed without endocrinology guidance. No adjacent post-procedural fractures occurred, and subsequent CTX a few months later was nicely suppressed at 183 pg/mL after zoledronic acid.

Conclusion: This case highlights that rebound fractures may occur despite proactive monitoring of bone turnover markers and timely bisphosphonate therapy following denosumab discontinuation. Parathyroidectomy may decrease bony resorption following denosumab discontinuation but does not fully prevent denosumab rebound fracture risk. Whether patients with hyperparathyroidism-associated osteoporosis require different thresholds or strategies to prevent denosumab rebound fractures warrants further investigation (1).

Reference:
1. Tsourdi E, Langdahl B, Cohen-Solal M, et al. Bone. 2017;105:11-17.

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