Relationship Between Serum Uric Acid and Bone Mineral Density in the General Population and in Rats With Experimental Hyperuricemia

Zhang, Dihua; Bobulescu, I. Alexandru; Maalouf, Naim M.; Adams‐Huet, Beverley; Poindexter, John R.; Park, Sun; Wei, Fuxin; Chen, Christopher; Moe, Orson W.; Sakhaee, Khashayar

doi:10.1002/jbmr.2430

Cited by 65 publications

(68 citation statements)

References 25 publications

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“…Similar results have been published in peri-and postmenopausal women (10)(11)(12). However, recent data from NHANES do not support a positive association between serum uric acid and BMD (13).…”

Section: Introductionsupporting

confidence: 64%

“…The positive relationship between BMD and serum uric acid has been questioned by a recent study on general population from NHANES (13). Although the same crude results were obtained regarding BMD at lumbar spine, femoral neck, and total hip in men, premenopausal women and postmenopausal women on estrogen therapy; these associations were canceled after adjusting for potential confounders.…”

Section: Discussioncontrasting

confidence: 41%

“…Finally, an inverse correlation between uric acid and UA uric acid, BMI body mass index, BMD bone mineral density, OP osteoporosis, VF vertebral fracture, SOS speed of sound, BUA broadband ultrasound attenuation, QUI qualitative ultrasound index, GFR glomerular filtration rate, PTH parathyroid hormone, PINP procollagen type I N-terminal propeptide, CTX carboxy-terminal telopeptide serum 1,25 (OH)2 levels, indicating an inhibition of 1α-hydroxylase has been postulated, although with inconsistent results (29). The association between serum uric acid and BMD, BTM, or fractures has been reported in a few clinical studies (7)(8)(9)(10)(11)(12)(13). Only four of them have analyzed this relationship in men (7,8,12).…”

Section: Discussionmentioning

confidence: 93%

“…Firstly, antioxidant defenses are markedly decreased in osteoporotic bone (26). In this sense, uric acid possesses important antioxidant properties, been capable to scavenging superoxide, singlet oxygen, and hydroxyl radicals (13). These effects have consequences at the bone tissue level, since uric acid has been involved in the suppression of osteoclastogenesis and in the decrease in production of reactive oxygen species in osteoclast precursors (27).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, a relationship between ROS or low serum levels of antioxidants and male osteoporosis has been pointed out (6). Nevertheless, there are few reports analyzing the role of uric acid levels in patients with osteoporosis (7)(8)(9)(10)(11)(12)(13). Nabipour et al (7), found for the first time, that higher serum uric acid levels were related to higher bone mineral density (BMD), and lower prevalence of vertebral and nonvertebral fractures in older men.…”

Section: Introductionmentioning

confidence: 97%

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Serum uric acid is associated with quantitative ultrasound parameters in men: data from the Camargo cohort

et al. 2015

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Section: Introductionsupporting

confidence: 64%

Section: Discussioncontrasting

confidence: 41%

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

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Serum uric acid is associated with quantitative ultrasound parameters in men: data from the Camargo cohort

et al. 2015

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Gout and Risk of Fracture in Women: A Prospective Cohort Study

Paik

Kim

Feskanich

et al. 2017

Arthritis & Rheumatology

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Objective Uric acid may be linked to bone health through its anti-oxidant or pro-oxidant effects, thereby affecting bone resorption and formation, or through inhibition of vitamin D activation and higher parathyroid hormone level. Prior studies on the relation between uric acid and bone mineral density have demonstrated conflicting results. To date, there are no prospective studies examining the relation between gout, a disease characterized by hyperuricemia and inflammation, and hip or wrist fracture risk in women. Methods We conducted a prospective observational study of gout and risk of incident wrist and hip fracture in women participating in the Nurses’ Health Study (n=103,799 at baseline with 14 years of follow-up for the wrist fracture analysis and 22 years of follow-up for the hip fracture analysis). Gout history and wrist and hip fracture were assessed by biennial questionnaires. Cox proportional-hazards models were used to simultaneously adjust for potential confounders. Results There were 3,769 incident wrist fractures (1990–2004) and 2,147 incident hip fractures (1990–2012), with 107 wrist and 117 hip fractures among participants with gout. The multivariable-adjusted relative risk of wrist fracture in women with a history of gout compared with women without gout was 1.12 (95% CI 0.92 to 1.36). The multivariable-adjusted relative risk of hip fracture in women with a history of gout compared with women without gout was 1.38 (95% CI 1.14 to 1.68). Conclusion A history of gout is associated with a modestly increased risk of hip fracture but not significantly associated with risk of wrist fracture in women.

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Elevated Urate Levels Do Not Alter Bone Turnover Markers: Randomized Controlled Trial of Inosine Supplementation in Postmenopausal Women

Dalbeth

Horne

Mihov

et al. 2021

Arthritis & Rheumatology

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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.

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Relationship Between Serum Uric Acid and Bone Mineral Density in the General Population and in Rats With Experimental Hyperuricemia

Cited by 65 publications

References 25 publications

Serum uric acid is associated with quantitative ultrasound parameters in men: data from the Camargo cohort

Serum uric acid is associated with quantitative ultrasound parameters in men: data from the Camargo cohort

Gout and Risk of Fracture in Women: A Prospective Cohort Study

Elevated Urate Levels Do Not Alter Bone Turnover Markers: Randomized Controlled Trial of Inosine Supplementation in Postmenopausal Women

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