Date: Tuesday, November 12, 2019
Session Title: Osteoporosis & Metabolic Bone Disease – Basic & Clinical Science Poster
Session Type: Poster Session (Tuesday)
Session Time: 9:00AM-11:00AM
Background/Purpose: Denosumab (DMAb) is a potent antiresorptive agent, but findings in non-human primates suggest that modeling-based bone formation (MBBF) may persist despite DMAb treatment (Ominsky JBMR 2015). This study assessed whether MBBF in the femoral neck (FN) is preserved in the context of inhibited remodeling-based bone formation (RBBF) in subjects receiving DMAb (NCT02576652).
Methods: This open-label study enrolled ambulatory postmenopausal women and men with osteoporosis (OP) who had received ≥2 doses of DMAb (60 mg subcutaneously Q6M) per standard of care and were planning to undergo elective total hip replacement (THR) due to osteoarthritis of the hip. Transverse sections of the FN were obtained after THR surgery and analyzed histomorphometrically. The primary endpoint was the subject incidence of MBBF, based on fluorochrome labeling and the presence of smooth cement lines, in cancellous, endocortical, and periosteal surfaces of the FN. Secondary and exploratory analyses used histomorphometric parameters to characterize rates of MBBF and RBBF in the 3 envelopes in enrolled subjects and historical controls. Controls were from the placebo group of a prior study and were not treated with DMAb. All analyses were descriptive.
Results: Four of the 6 subjects enrolled were included in the analyses (all women, mean age 73.5 y, mean duration of DMAb use 1.8 y); one subject withdrew consent due to an allergic reaction to the tetracycline label, and one subject did not undergo THR. The 17 historical controls had a mean age of 68.3 y; 71% were women, and 47% had received OP treatment that did not include DMAb. All subjects in both groups exhibited MBBF in periosteal bone surfaces; in cancellous and endocortical surfaces, all DMAb-treated subjects and 88% and 82% of historical controls, respectively, showed evidence of MBBF (Table). Compared with historical controls, DMAb-treated subjects showed 792% and 242% higher values of MBBF in the cancellous and endocortical surfaces, respectively, while RBBF values were 79% and 82% lower. In the periosteal surface, MBBF and RBBF rates were similar between subjects and controls.
Conclusion: These results demonstrate the occurrence of MBBF in the adult human FN and suggest that DMAb preserves MBBF while inhibiting RBBF, consistent with previous findings. This effect may contribute to the continued increases in bone mineral density demonstrated with up to 10 y of DMAb treatment (Bone Lancet Diabetes Endocrinol 2017).
To cite this abstract in AMA style:Dempster D, Butler P, Bostrom M, Nieves J, Zhou H, Chen L, Pannacciulli N, Wagman R, Cosman F. Modeling-Based Bone Formation Persists in the Femoral Neck Despite Remodeling Inhibition in Subjects Treated with Denosumab [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/modeling-based-bone-formation-persists-in-the-femoral-neck-despite-remodeling-inhibition-in-subjects-treated-with-denosumab/. Accessed March 20, 2023.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/modeling-based-bone-formation-persists-in-the-femoral-neck-despite-remodeling-inhibition-in-subjects-treated-with-denosumab/