Trabecular bone deterioration in a postmenopausal female suffering multiple spontaneous vertebral fractures due to a delayed denosumab injection - A post-treatment re-initiation bone biopsy-based case study

Background: Denosumab, is a potent anti-resorptive that, increases bone mineral density, and reduces fracture risk in osteoporotic patients. However, several case studies have reported multiple vertebral fractures in patients discontinuing denosumab.

Case presentation: This case report describes a 64-year-old female with postmenopausal osteoporosis treated with denosumab, who had her 11th injection delayed by 4 months. The patient suffered eight spontaneous vertebral fractures. After consent, an iliac crest bone biopsy was obtained following re-initiation of the denosumab treatment and analyzed by micro-computed tomography and histomorphometry.

Results: micro-computed tomography analysis revealed a low trabecular bone volume of 10 %, a low trabecular thickness of 97 μm, a low trabecular spacing of 546 μm, a high trabecular number of 1.8/mm, and a high structure model index of 2.2, suggesting trabecular thinning and loss of trabecular plates. Histomorphometric trabecular bone analysis revealed an eroded perimeter per bone perimeter of 33 % and an osteoid perimeter per bone perimeter of 62 %. Importantly, 88 % of the osteoid perimeter was immediately above an eroded-scalloped cement line with no sign of mineralization, and often with no clear bone-forming osteoblasts on the surface. Moreover, only 5 % of the bone perimeter was mineralizing, reflecting that only 8 % of the osteoid perimeter underwent mineralization, resulting in a mineralization lag time of 545 days. Taken together, this indicates limited bone formation and delayed mineralization.

Conclusion: We present a case report of multiple vertebral fractures after denosumab discontinuation with histomorphometric evidence that denosumab discontinuation leads to extensive trabecular bone resorption followed by a limited bone formation and delayed mineralization if the denosumab treatment is reinitiated. This highlights the importance of developing optimal discontinuation strategies for patients that are to discontinue treatment.