Lack of Evidence that Soluble Urate Directly Influences Bone Remodelling: A Laboratory and Clinical Study.

Show simple item record Dalbeth, Nicola en Pool, Bregtina en Chhana, Ashika en Lin, Jianming en Tay, Mei Lin en Tan, Paul en Callon, Karen en Naot, Dorit en Horne, Anne en Drake, Jill en Gamble, Gregory en Reid, Ian en Grey, Andrew en Stamp, Lisa K en Cornish, Jillian en 2018-11-15T02:20:35Z en 2018-01 en
dc.identifier.issn 0171-967X en
dc.identifier.uri en
dc.description.abstract INTRODUCTION:Numerous observational studies have reported that serum urate concentration positively correlates with bone density and reduced risk of fractures. The aim of this study was to examine whether soluble urate directly influences bone remodelling. METHODS:In laboratory studies, the in vitro effects of soluble urate were examined in osteoclast, osteoblast and osteocyte assays at a range of urate concentrations consistent with those typically observed in humans (up to 0.70 mmol/L). The clinical relevance of the in vitro assay findings was assessed using serial procollagen-1 N-terminal propeptide (P1NP) and Month 12 bone density data from a randomised controlled trial of allopurinol dose escalation in people with gout. RESULTS:Addition of urate in the RAW264.7 cell osteoclastogenesis assay led to small increases in osteoclast formation (ANOVA p = 0.018), but no significant difference in bone resorption. No significant effects on osteoclast number or activity were observed in primary cell osteoclastogenesis or resorption assays. Addition of urate did not alter viability or function in MC3T3-E1 pre-osteoblast, primary human osteoblast, or MLO-Y4 osteocyte assays. In the clinical trial analysis, reducing serum urate over a 12 month period by allopurinol dose escalation did not lead to significant changes in P1NP or differences in bone mineral density. CONCLUSION:Addition of soluble urate at physiological concentrations does not influence bone remodelling in vitro. These data, together with clinical trial data showing no effect of urate-lowering on P1NP or bone density, do not support a direct role for urate in influencing bone remodelling. en
dc.format.medium Print-Electronic en
dc.language eng en
dc.relation.ispartofseries Calcified tissue international en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri en
dc.subject Bone and Bones en
dc.subject Osteoclasts en
dc.subject Osteocytes en
dc.subject Humans en
dc.subject Bone Resorption en
dc.subject Uric Acid en
dc.subject Bone Remodeling en
dc.subject Cell Differentiation en
dc.subject Osteogenesis en
dc.title Lack of Evidence that Soluble Urate Directly Influences Bone Remodelling: A Laboratory and Clinical Study. en
dc.type Journal Article en
dc.identifier.doi 10.1007/s00223-017-0328-6 en
pubs.issue 1 en
pubs.begin-page 73 en
pubs.volume 102 en
dc.rights.holder Copyright: The author en
dc.identifier.pmid 29018897 en
pubs.end-page 84 en
pubs.publication-status Published en
dc.rights.accessrights en
pubs.subtype Research Support, Non-U.S. Gov't en
pubs.subtype Journal Article en
pubs.elements-id 692488 en Academic Services en Examinations en Medical and Health Sciences en Medical Sciences en Anatomy and Medical Imaging en School of Medicine en Medicine Department en Science en Science Research en Maurice Wilkins Centre (2010-2014) en
dc.identifier.eissn 1432-0827 en
pubs.record-created-at-source-date 2017-10-12 en
pubs.dimensions-id 29018897 en

Files in this item

There are no files associated with this item.

Find Full text

This item appears in the following Collection(s)

Show simple item record


Search ResearchSpace