Twelve Months of Denosumab and/or Alendronate Is Associated With Improved Bone Fatigue Life, Microarchitecture, and Density in Ovariectomized Cynomolgus Monkeys.

Autor: Haider IT; Human Performance Lab, Faculty of Kinesiology, University of Calgary, Calgary, AB, Canada.; McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada., Loundagin LL; Human Performance Lab, Faculty of Kinesiology, University of Calgary, Calgary, AB, Canada.; McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.; Department of Anatomy, Physiology and Pharmacology, University of Saskatchewan, Saskatoon, SK, Canada., Sawatsky A; Human Performance Lab, Faculty of Kinesiology, University of Calgary, Calgary, AB, Canada.; McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada., Kostenuik PJ; Phylon Pharma Services, Newbury Park, CA, USA.; School of Dentistry, University of Michigan (Adjunct), Ann Arbor, MI, USA., Boyd SK; McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada., Edwards WB; Human Performance Lab, Faculty of Kinesiology, University of Calgary, Calgary, AB, Canada.; McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.; Department of Biomedical Engineering, Schulich School of Engineering, University of Calgary, Calgary, AB, Canada.
Jazyk: angličtina
Zdroj: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research [J Bone Miner Res] 2023 Mar; Vol. 38 (3), pp. 403-413. Date of Electronic Publication: 2023 Jan 04.
DOI: 10.1002/jbmr.4758
Abstrakt: Prolonged use of antiresorptives such as the bisphosphonate alendronate (ALN) and the RANKL inhibitor denosumab (DMAb) are associated with rare cases of atypical femoral fracture (AFF). The etiology of AFF is unclear, but it has been hypothesized that potent osteoclast inhibitors may reduce bone fatigue resistance. The purpose of this study was to quantify the relationship between antiresorptive treatment and fatigue life (cycles to failure) in bone from ovariectomized cynomolgus monkeys. We analyzed humeral bone from 30 animals across five treatment groups. Animals were treated for 12 months with subcutaneous (sc) vehicle (VEH), sc DMAb (25 mg/kg/month), or intravenous (iv) ALN (50 μg/kg/month). Another group received 6 months VEH followed by 6 months DMAb (VEH-DMAb), and the final group received 6 months ALN followed by 6 months DMAb (ALN-DMAb). A total of 240 cortical beam samples were cyclically tested in four-point bending at 80, 100, 120, or 140 MPa peak stress. High-resolution imaging and density measurements were performed to evaluate bone microstructure and composition. Samples from the ALN (p = 0.014), ALN-DMAb (p = 0.008), and DMAb (p < 0.001) groups illustrated higher fatigue-life measurements than VEH. For example, at 140 MPa the VEH group demonstrated a median ± interquartile range (IQR) fatigue life of 1987 ± 10593 cycles, while animals in the ALN, ALN-DMAb, and DMAb groups survived 9850 ± 13648 (+395% versus VEH), 10493 ± 16796 (+428%), and 14495 ± 49299 (+629%) cycles, respectively. All antiresorptive treatment groups demonstrated lower porosity, smaller pore size, greater pore spacing, and lower number of canals versus VEH (p < 0.001). Antiresorptive treatment was also associated with greater apparent density, dry density, and ash density (p ≤ 0.03). We did not detect detrimental changes following antiresorptive treatments that would explain their association with AFF. In contrast, 12 months of treatment may have a protective effect against fatigue fractures. © 2022 American Society for Bone and Mineral Research (ASBMR).
(© 2022 American Society for Bone and Mineral Research (ASBMR).)
Databáze: MEDLINE
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