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

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

doi:10.1016/j.bone.2021.116187

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

Bone. 2022 Jan:154:116187. doi: 10.1016/j.bone.2021.116187. Epub 2021 Sep 14.

Authors

Yizhong Jenny Hu¹, Arkadi Chines², Yifei Shi², Ego Seeman³, X Edward Guo⁴

Affiliations

¹ Bone Bioengineering Laboratory, Department of Biomedical Engineering, Columbia University, New York, NY, USA.
² Amgen Inc., Thousand Oaks, CA, USA.
³ Departments of Endocrinology and Medicine, Austin Health, University of Melbourne, Melbourne, Australia; Mary MacKillop Institute of Healthy Aging, Australian Catholic University, Melbourne, Australia.
⁴ Bone Bioengineering Laboratory, Department of Biomedical Engineering, Columbia University, New York, NY, USA. Electronic address: ed.guo@columbia.edu.

PMID: 34530172
DOI: 10.1016/j.bone.2021.116187

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00293813.

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

Publication types

Clinical Trial, Phase II
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Alendronate* / pharmacology
Alendronate* / therapeutic use
Bone Density
Denosumab* / pharmacology
Denosumab* / therapeutic use
Female
Humans
Radius / diagnostic imaging
Tibia / diagnostic imaging

Substances

Denosumab
Alendronate

Associated data

ClinicalTrials.gov/NCT00293813