The effect of denosumab and alendronate on trabecular plate and rod microstructure at the distal tibia and radius:​ a post-hoc HR-pQCT study

Hu, Yizhong Jenny; Chines, Arkadi; Shi, Yifei; Seeman, Ego; Guo, X. Edward

Affiliations

¹Bone Bioengineering Laboratory, Department of Biomedical Engineering, Columbia University, New York, NY, USA

²Amgen Inc., Thousand Oaks, CA, USA

³Departments of Endocrinology and Medicine, Austin Health, University of Melbourne, Melbourne, Australia

⁴Mary MacKillop Institute of Healthy Aging, Australian Catholic University, Melbourne, Australia

Abstract and keywords

Background: Age-related trabecular microstructural deterioration and conversion from plate-like trabeculae to rod-like trabeculae occur because of unbalanced rapid remodeling. As denosumab achieves greater remodeling suppression and lower cortical porosity than alendronate, we hypothesized that denosumab might also preserve trabecular plate microstructure, bone stiffness and strength more effectively than alendronate.

Methods: In this post hoc analysis of a phase 2 study, postmenopausal women randomized to placebo (P, n = 74), denosumab (D, n = 72), or alendronate (A, n = 68). HR-pQCT scans of the distal radius and tibia were performed at baseline and Month-12 (M12). Trabecular compartment was subjected to Individual Trabecula Segmentation while finite element analysis was performed to estimate stiffness and strength. Percent change from baseline at M12 of each parameter was compared between patient groups.

Results: At the distal tibia, in the placebo group, plate surface area (pTb.S, −1.3%) decreased while rod bone volume fraction (rBV/TV, +4.5%) and number (rTb.N, +2.1%) increased. These changes were prevented by denosumab but persisted despite alendronate therapy (pTb.S: −1.7%; rBV/TV: +6.9%; rTb.N: +3.0%). Both treatments improved whole bone stiffness (D: +3.1%; A: +1.8%) and failure load (D: +3.0%; A: +2.2%); improvements using denosumab was significant compared to placebo (stiffness: p = 0.004; failure load: p = 0.003). At the distal radius, denosumab increased total trabecular bone volume fraction (BV/TV, +3.4%) and whole bone failure load (+4.0%), significantly different from placebo (BV/TV: p = 0.044; failure load: p = 0.046). Significantly different effects of either drug on plate and rod microstructure were not detected.

Conclusions: Denosumab preserved trabecular plate microstructure. Alendronate did not. However, estimated strength did not differ between denosumab and alendronate treated groups.

Keywords: Osteoporosis; Antiresorptives; Bone QCT/microCT; Matrix mineralization; Microstructure; Individual trabecula segmentation

Links

DOI: 10.1016/j.bone.2021.116187

PubMed: 34530172

WoS: 000703972800005

History

Received: 2021-03-26

Revised: 2021-09-2

Accepted: 2021-09-9

Online: 2021-09-14

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2022	Haider IT, Sawatsky A, Zhu Y, Page R, Kostenuik PJ, Boyd SK, Edwards WB. Denosumab treatment is associated with decreased cortical porosity and increased bone density and strength at the proximal humerus of ovariectomized cynomolgus monkeys. Bone. November 2022;164:116517.