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Elevated Urate Levels Do Not Alter Bone Turnover Markers: Randomized Controlled Trial of Inosine Supplementation in Postmenopausal Women
Author(s) -
Dalbeth Nicola,
Horne Anne,
Mihov Borislav,
Stewart Angela,
Gamble Gregory D.,
Merriman Tony R.,
Stamp Lisa K.,
Reid Ian R.
Publication year - 2021
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.41691
Subject(s) - medicine , bone remodeling , placebo , n terminal telopeptide , osteoporosis , bone mineral , endocrinology , hyperuricemia , uric acid , gout , randomized controlled trial , inosine , osteocalcin , alkaline phosphatase , chemistry , pathology , biochemistry , alternative medicine , adenosine , enzyme
Objective Observational studies have consistently demonstrated that serum urate level positively correlates with bone mineral density (BMD). We undertook this study to determine whether moderate hyperuricemia induced by inosine supplements influences bone turnover markers in postmenopausal women over a 6‐month period. Methods One hundred twenty postmenopausal women were recruited for a 6‐month randomized, double‐blind, placebo‐controlled trial. Key exclusion criteria were osteoporosis, previous fragility fracture, bisphosphonate therapy, gout, kidney stones, and a urine pH level of ≤5.0. Participants were randomized in a 1:1 ratio to receive placebo or inosine. The coprimary end points were change in levels of N‐propeptide of type I procollagen (PINP) and change in levels of β‐C‐telopeptide of type I collagen (β‐CTX). Change in BMD, as measured by dual x‐ray absorptiometry, was an exploratory end point. Results Administration of inosine led to a significant increase in serum urate concentration over the study period ( P < 0.0001 for all follow‐up time points). At week 26, the mean change in serum urate concentration was +0.13 mmoles/liter (+2.2 mg/dl) in the inosine group and 0.00 mmoles/liter (0 mg/dl) in the placebo group. There was no difference in PINP or β‐CTX levels between groups over the 6 months. There were no significant changes in bone density between groups over the 6 months. Adverse events and serious adverse events were similar between the 2 groups. Conclusion This clinical trial shows that although inosine supplementation leads to sustained increases in serum urate levels over a 6‐month period, it does not alter markers of bone turnover in postmenopausal women. These findings do not support the concept that urate has direct biologic effects on bone turnover.