Denosumab treatment of osteoporotic women arrests cortical bone remodeling events at the reversal-resorption phase but does not affect ongoing bone formation

Denosumab is an anti-resorptive therapy that effectively reduces fracture risk and increases BMD in women with postmenopausal osteoporosis. In this study, we focused on the less well-investigated cortical remodeling process and its transition from erosion to formation after denosumab treatment, using a histomorphometric classification of intracortical pores. Cortical bone is more prominent in non-vertebral bones, where denosumab is less effective in fracture reduction. In iliac crest biopsies from the FREEDOM-study, where postmenopausal osteoporotic women were treated with placebo (<i>n</i> = 43) or denosumab (<i>n</i> = 43) for 2-3 yr, the cortical microstructure and remodeling stage and type of intracortical pores were analyzed. Cortical thickness was unaffected in the denosumab group vs placebo (<i>P</i> = .9). Mean pore diameter was significantly decreased in the denosumab group vs placebo (<i>P</i> < .002) with no change in the number of pores per tissue area (<i>P</i> = .83). However, the cortical porosity was not decreased in the denosumab vs placebo group (<i>P</i> < .077). When stratifying the pores according to their remodeling stage, the eroded pores had an increased contribution to the total pore area in the denosumab vs placebo group (<i>P</i> = .001). Eroded-formative and formative pores had a decreased contribution to the total pore area (<i>P</i> < .001). The contribution of quiescent pores was unchanged. The increased contribution of eroded pores and the concomitant reduced contribution of eroded-formative and formative pores indicate that the transition from erosion to formation is largely limited, while pores with ongoing bone formation at the time of initiation of denosumab treatment are refilled.