University of Auckland, Auckland, New Zealand.
University of Otago, Dunedin, New Zealand, and University of Alabama at Birmingham.
Arthritis Rheumatol. 2021 Sep;73(9):1758-1764. doi: 10.1002/art.41691. Epub 2021 Jul 16.
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.
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.
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.
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.
观察性研究一致表明，血清尿酸水平与骨密度（BMD）呈正相关。我们进行这项研究是为了确定在 6 个月的时间内，肌苷补充剂引起的中度高尿酸血症是否会影响绝经后妇女的骨转换标志物。
招募了 120 名绝经后妇女参加为期 6 个月的随机、双盲、安慰剂对照试验。主要排除标准为骨质疏松症、既往脆性骨折、双膦酸盐治疗、痛风、肾结石和尿 pH 值≤5.0。参与者以 1:1 的比例随机接受安慰剂或肌苷。主要终点是 I 型前胶原 N 端肽（PINP）水平的变化和 I 型胶原 β-C 端肽（β-CTX）水平的变化。双能 X 线吸收法测量的 BMD 变化是探索性终点。
在研究期间，肌苷的给药导致血清尿酸浓度显著升高（所有随访时间点均 P<0.0001）。在第 26 周，肌苷组血清尿酸浓度的平均变化为+0.13 毫摩尔/升（+2.2 毫克/分升），安慰剂组为 0.00 毫摩尔/升（0 毫克/分升）。在 6 个月内，两组之间的 PINP 或 β-CTX 水平没有差异。在 6 个月内，两组之间的骨密度没有显著变化。两组之间的不良事件和严重不良事件相似。
这项临床试验表明，尽管肌苷补充剂在 6 个月内持续增加血清尿酸水平，但它不会改变绝经后妇女的骨转换标志物。这些发现不支持尿酸对骨转换具有直接生物学作用的概念。
