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Relationship between serum uric Acid and bone mineral density in the general population and in rats with experimental hyperuricemia.

ABSTRACT: Higher serum uric acid concentrations have been associated with higher bone mineral density (BMD) in observational studies of older men and perimenopausal or postmenopausal women, prompting speculation of a potential protective effect of uric acid on bone. Whether this relationship is present in the general population has not been examined and there is no data to support causality. We conducted a cross-sectional analysis of a probability sample of the U.S.Demographic data, dietary intake, lifestyle risk factors and physical activity assessment data, serum biochemistry including serum uric acid, and BMD were obtained from 6759 National Health and Nutrition Examination Survey (NHANES; 2005-2010) participants over 30 years of age. In unadjusted analyses, higher serum uric acid levels were associated with higher BMD at the femoral neck, total hip, and lumbar spine in men, premenopausal women, and postmenopausal women not treated with estrogen. However, these associations were no longer statistically significant after adjustment for potential confounders, including age, body mass index (BMI), black race, alcohol consumption, estimated glomerular filtration rate (eGFR), serum alkaline phosphatase, and C-reactive protein (CRP). This is in contradistinction to some prevailing conclusions in the literature. To further examine the causal effect of higher serum uric acid on skeletal health, including biomechanical properties that are not measurable in humans, we used an established rat model of inducible mild hyperuricemia. There were no differences in BMD, bone volume density, and bone biomechanical properties between hyperuricemic rats and normouricemic control animals. Taken together, our data do not support the hypothesis that higher serum uric acid has protective effects on bone health.

SUBMITTER: Zhang D

PROVIDER: S-EPMC4439277 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Relationship between serum uric Acid and bone mineral density in the general population and in rats with experimental hyperuricemia.

Zhang Dihua D Bobulescu I Alexandru IA Maalouf Naim M NM Adams-Huet Beverley B Poindexter John J Park Sun S Wei Fuxin F Chen Christopher C Moe Orson W OW Sakhaee Khashayar K

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 20150601 6

<h4>Unlabelled</h4>Higher serum uric acid concentrations have been associated with higher bone mineral density (BMD) in observational studies of older men and perimenopausal or postmenopausal women, prompting speculation of a potential protective effect of uric acid on bone. Whether this relationship is present in the general population has not been examined and there is no data to support causality. We conducted a cross-sectional analysis of a probability sample of the U.S.<h4>Population</h4>De ...[more]

PMID: 25491196

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Project description:BackgroundThe results of previous studies on the association between serum uric acid levels and bone mineral density and the risk of osteoporosis are controversial. Fat free mass (FFM) is more strongly associated with bone mineral density (BMD) than it is with body fat mass (BFM). Skeletal muscle mass is assumed to contribute indirectly to the relationship between serum uric acid levels and BMD. Therefore, we aimed to evaluate the association between serum uric acid levels and BMD and abnormal BMD (at least osteopenia) by considering body composition in men aged ≥ 50 years.MethodsThis was a retrospective observational cross-sectional study. We used data obtained from 2,991 men aged ≥50 years who completed questionnaires, anthropometric surveys, laboratory tests, and bone mineral density scans. A subgroup analysis of 1,135 men who additionally underwent body composition data analysis using Inbody® was performed. Multiple linear regression analysis was used to explore the relationship between serum uric acid levels and BMD at three sites (L1-L4, Femur neck, Femur total). In addition, multiple logistic regression analysis was performed to determine the association of serum uric acid levels with abnormal BMD (at least osteopenia).ResultsPositive correlations between serum uric acid levels and BMD at the three sites (L1-L4, Femur neck, Femur total) were observed in unadjusted and fully adjusted models except the BMD of the femoral neck (P-value=0.054).Furthermore, FFM and skeletal muscle mass index (SMI) showed positive association with serum uric acid level and BMD at three sites, with statistical significance. An increase in serum uric acid level was associated with a lower risk of abnormal BMD after adjusting for confounders including FFM and SMI.ConclusionSerum uric acid level was positively associated with BMD at three sites and had a protective effect against abnormal BMD after adjusting for multiple confounders, including FFM and SMI, in men aged ≥ 50 years.

Project description:BackgroundChronic metabolic acidosis leads to bone mineral loss and results in lower bone mineral density (BMD), which is a risk factor for osteoporosis-related fractures. The effect of low-level metabolic acidosis on bone density in the general population is unknown.Study designCross-sectional study.Setting & participants9,724 nationally representative adults 20 years or older in NHANES (National Health and Nutrition Examination Survey) 1999-2004.FactorSerum bicarbonate level.OutcomesLumbar and total BMD, as well as low lumbar and total bone mass, defined as 1.0 SD below the sex-specific mean value of young adults.MeasurementsBMD was measured by dual-energy x-ray absorptiometry and serum bicarbonate was measured in all participants.ResultsBoth men and women with lower serum bicarbonate levels were more likely to be current smokers and had higher body mass index and estimated net endogenous acid production. There was a significant linear trend across quartiles of serum bicarbonate with lumbar BMD in the total population, as well as in sex-specific models (P=0.02 for all 3 models, P=0.1 for interaction). For total BMD, a significant association was seen with serum bicarbonate level for women but not men (P=0.02 and P=0.1, respectively; P=0.8 for interaction), and a significant association was seen for postmenopausal women but not premenopausal women (P=0.02 and P=0.2, respectively; P=0.5 for interaction). Compared with women with serum bicarbonate levels <24mEq/L, those with serum bicarbonate levels ≥27mEq/L had 0.018-g/cm(2) higher total BMD (95% CI, 0.004-0.032; P=0.01) and 31% lower odds of having low total bone mass (OR, 0.68; 95% CI, 0.46-0.99; P=0.049).LimitationsCross-sectional study using a single measurement of serum bicarbonate. Subgroup differences are not definitive.ConclusionsLower serum bicarbonate levels are associated with lower BMD in US adults. Further studies should examine whether serum bicarbonate levels should be incorporated into the diagnostic assessment and management of osteoporosis.

Dataset Information

Relationship between serum uric Acid and bone mineral density in the general population and in rats with experimental hyperuricemia.

Publications

Relationship between serum uric Acid and bone mineral density in the general population and in rats with experimental hyperuricemia.

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