Association of Fetuin-A With Incident Fractures in Community-Dwelling Older Adults: The Cardiovascular Health Study

J Bone Miner Res. 2015 Aug;30(8):1394-402. doi: 10.1002/jbmr.2475. Epub 2015 May 21.

Abstract

Fetuin-A, a serum protein that regulates calcium mineralization, has been associated with bone mineral density (BMD) in several cross-sectional human studies, suggesting a possible beneficial effect on clinically important measures of bone health. Fetuin-A and incidence of subsequent fracture was assessed in 4714 men and women ≥65 years of age. Proportional hazards models were used to estimate risk of incident hip (hospital discharge ICD-9 codes) and composite fracture (hip, pelvis, humerus, or proximal forearm; hospital discharge ICD-9 codes and Medicare claims data). A total of 576 participants had an incident hip fracture (median follow-up 11.2 years) and 768 had an incident composite fracture (median follow-up 6.9 years). In unadjusted analyses, there was no association between fetuin-A (per SD increase) and risk of hip fracture (hazard ratio [HR], 0.96; 95% CI, 0.88 to 1.05) or composite fracture (HR, 0.99; 95% CI, 0.92 to 1.06). Results were not significantly changed after adjustment for potential confounding variables. Analyses modeling fetuin-A in quartiles or within a subset with available BMD measures also showed no statistically significant association with risk of hip or composite fracture. Though fetuin-A was positively associated with areal BMD in partially adjusted models (total hip: β, 0.013 g/cm(2) ; 95% CI, 0.005 to 0.021; femoral neck: β, 0.011 g/cm(2) ; 95% CI, 0.004 to 0.018; and lumbar spine: β, 0.007 g/cm(2) ; 95% CI, 0.001 to 0.028), these associations were no longer significant after further adjustment for BMI and in final multivariate models. In this large sample of community-dwelling older adults, a small positive association between fetuin-A and areal BMD appeared attributable to confounding variables and we found no evidence of an association between fetuin-A and risk of clinical fracture.

Keywords: ALPHA-2-HS-GLYCOPROTEIN; FETUINS; FRACTURES; GERIATRICS; HIP FRACTURES; RISK FACTORS.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bone Density*
  • Cross-Sectional Studies
  • Female
  • Follow-Up Studies
  • Fractures, Bone* / blood
  • Fractures, Bone* / epidemiology
  • Humans
  • Incidence
  • Male
  • Models, Biological*
  • alpha-2-HS-Glycoprotein / metabolism*

Substances

  • AHSG protein, human
  • alpha-2-HS-Glycoprotein