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

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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. population. 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.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalJournal of Bone and Mineral Research
Volume30
Issue number6
DOIs
StatePublished - Jun 1 2015

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Hyperuricemia
Uric Acid
Bone Density
Serum
Population
Nutrition Surveys
Bone and Bones
Sampling Studies
Femur Neck
Health
Glomerular Filtration Rate
Alcohol Drinking
Causality
Biochemistry
C-Reactive Protein
Observational Studies
Alkaline Phosphatase
Life Style
Hip
Estrogens

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

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

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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. population. 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.",
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",
author = "Dihua Zhang and Bobulescu, {I. Alexandru} and Maalouf, {Naim M.} and Beverley Adams-Huet and John Poindexter and Sun Park and Fuxin Wei and Christopher Chen and Moe, {Orson W.} and Khashayar Sakhaee",
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T1 - Relationship between serum uric acid and bone mineral density in the general population and in rats with experimental hyperuricemia

AU - Zhang, Dihua

AU - Bobulescu, I. Alexandru

AU - Maalouf, Naim M.

AU - Adams-Huet, Beverley

AU - Poindexter, John

AU - Park, Sun

AU - Wei, Fuxin

AU - Chen, Christopher

AU - Moe, Orson W.

AU - Sakhaee, Khashayar

PY - 2015/6/1

Y1 - 2015/6/1

N2 - 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. population. 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.

AB - 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. population. 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.

KW - ANALYSIS/QUANTITATION OF BONE

KW - BIOCHEMICAL MARKERS OF BONE TURNOVER

KW - BONE MODELING AND REMODELING

KW - DISEASES AND DISORDERS OF/RELATED TO BONE

KW - DXA

KW - HORMONE REPLACEMENT/RECEPTOR MODULATORS

KW - OSTEOPOROSIS

KW - THERAPEUTICS

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