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https://wslhd.intersearch.com.au/wslhdjspui/handle/1/9660
Title: | Temporal patterns of osteoclast formation and activity following withdrawal of RANKL inhibition |
Authors: | Kim, Albert S.;Taylor, V. E.;Castro-Martinez, A.;Dhakal, S.;Zamerli, A.;Mohanty, S.;Xiao, Y.;Simic, M. K.;Wen, J.;Chai, R.;Croucher, P. I.;Center, J. R.;Girgis, Christian M.;McDonald, M. M. |
WSLHD Author: | Kim, Albert S.;Girgis, Christian M. |
Issue Date: | 2024 |
Citation: | Journal of Bone & Mineral Research 39(4):484-497, 2024 |
Abstract: | Rebound bone loss following denosumab discontinuation is an important clinical challenge. Current treatment strategies to prevent this fail to suppress the rise and overshoot in osteoclast-mediated bone resorption. In this study, we use a murine model of denosumab treatment and discontinuation to show the temporal changes in osteoclast formation and activity during RANKL inhibition and withdrawal. We show that the cellular processes that drive the formation of osteoclasts and subsequent bone resorption following withdrawal of RANKL inhibition precede the rebound bone loss. Furthermore, a rise in serum TRAP and RANKL levels is detected before markers of bone turnover used in current clinical practice. These mechanistic advances may provide insight into a more defined window of opportunity to intervene with sequential therapy following denosumab discontinuation. |
URI: | https://wslhd.intersearch.com.au/wslhdjspui/handle/1/9660 |
DOI: | https://dx.doi.org/10.1093/jbmr/zjae023 |
Journal: | Journal of Bone & Mineral Research |
Type: | Journal Article |
Study or Trial: | Research Support, Non-U.S. Gov't |
Department: | Diabetes and Endocrinology |
Facility: | Westmead |
Keywords: | Animals Osteoclasts RANK Ligand Denosumab Mice Bone Resorption Time Factors Tartrate-Resistant Acid Phosphatase Mice, Inbred C57BL Biomarkers |
Appears in Collections: | Westmead Hospital 2019 - 2024 |
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