title: 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.
  
  
  METHODS
  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.
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.|The Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Dihua
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.|The Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: I Alexandru
authors.initials: IA
authors.lastname: Bobulescu
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.|The Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Naim M
authors.initials: NM
authors.lastname: Maalouf
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.|The Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.|Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Beverley
authors.initials: B
authors.lastname: Adams-Huet
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.|The Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: John
authors.initials: J
authors.lastname: Poindexter
authors.affiliation: The Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Sun
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Orthopaedic Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Fuxin
authors.initials: F
authors.lastname: Wei
authors.affiliation: The Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.|Department of Orthopaedic Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.|The Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.|Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Orson W
authors.initials: OW
authors.lastname: Moe
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.|The Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Khashayar
authors.initials: K
authors.lastname: Sakhaee
mesh_terms: D000328:Adult; D000818:Animals; D015519:Bone Density; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D033461:Hyperuricemia / Q000097:blood* / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D017698:Postmenopause / Q000097:blood; D017697:Premenopause / Q000097:blood; D051381:Rats; D014527:Uric Acid / Q000097:blood*
chemical_list: D014527:Uric Acid
keywords: ANALYSIS/QUANTITATION OF BONE; BIOCHEMICAL MARKERS OF BONE TURNOVER; BONE MODELING AND REMODELING; DISEASES AND DISORDERS OF/RELATED TO BONE; DXA; HORMONE REPLACEMENT/RECEPTOR MODULATORS; OSTEOPOROSIS; THERAPEUTICS