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Twelve Months of Denosumab and/or Alendronate Is Associated With Improved Bone Fatigue Life, Microarchitecture, and Density in Ovariectomized Cynomolgus Monkeys
dc.contributor.authorHaider, Ifaz T.
dc.contributor.authorLoundagin, Lindsay L.
dc.contributor.authorSawatsky, Andrew
dc.contributor.authorKostenuik, Paul J.
dc.contributor.authorBoyd, Steven K.
dc.contributor.authorEdwards, W. Brent
dc.date.accessioned2023-04-04T17:40:44Z
dc.date.available2024-04-04 13:40:43en
dc.date.available2023-04-04T17:40:44Z
dc.date.issued2023-03
dc.identifier.citationHaider, Ifaz T.; Loundagin, Lindsay L.; Sawatsky, Andrew; Kostenuik, Paul J.; Boyd, Steven K.; Edwards, W. Brent (2023). "Twelve Months of Denosumab and/or Alendronate Is Associated With Improved Bone Fatigue Life, Microarchitecture, and Density in Ovariectomized Cynomolgus Monkeys." Journal of Bone and Mineral Research 38(3): 403-413.
dc.identifier.issn0884-0431
dc.identifier.issn1523-4681
dc.identifier.urihttps://hdl.handle.net/2027.42/176049
dc.description.abstractProlonged 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).
dc.publisherJohn Wiley & Sons, Inc.
dc.subject.otherOSTEOPOROSIS
dc.subject.otherATYPICAL FEMORAL FRACTURE
dc.subject.otherINSUFFICIENCY FRACTURE
dc.subject.otherANTIRESORPTIVE
dc.subject.otherμCT
dc.titleTwelve Months of Denosumab and/or Alendronate Is Associated With Improved Bone Fatigue Life, Microarchitecture, and Density in Ovariectomized Cynomolgus Monkeys
dc.typeArticle
dc.rights.robotsIndexNoFollow
dc.subject.hlbsecondlevelInternal Medicine and Specialities
dc.subject.hlbtoplevelHealth Sciences
dc.description.peerreviewedPeer Reviewed
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/176049/1/jbmr4758.pdf
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/176049/2/jbmr4758_am.pdf
dc.identifier.doi10.1002/jbmr.4758
dc.identifier.sourceJournal of Bone and Mineral Research
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