Albuminuria and rapid loss of GFR and risk of new hip and pelvic fractures

Clin J Am Soc Nephrol. 2013 Feb;8(2):233-40. doi: 10.2215/CJN.06640712. Epub 2012 Nov 26.


Background and objectives: The microvascular circulation plays an important role in bone health. This study examines whether albuminuria, a marker of renal microvascular disease, is associated with incident hip and pelvic fractures.

Design, setting, participants, & measurements: This study reanalyzed data from the Ongoing Telmisartan Alone and in combination with Ramipril Global End Point Trial/Telmisartan Randomized Assessment Study in Angiotensin-Converting Enzyme Intolerant Subjects with Cardiovascular Disease trials, which examined the impact of renin angiotensin system blockade on cardiovascular outcomes (n=28,601). Albuminuria was defined as an albumin-to-creatinine ratio≥30 mg/g (n=4597). Cox proportional hazards models were used to determine the association of albuminuria with fracture risk adjusted for known risk factors for fractures, estimated GFR, and rapid decline in estimated GFR (≥5%/yr).

Results: There were 276 hip and pelvic fractures during a mean of 4.6 years of follow-up. Participants with baseline albuminuria had a significantly increased risk of fracture compared with participants without albuminuria (unadjusted hazard ratio=1.62 [1.22, 2.15], P<0.001; adjusted hazard ratio=1.36 [1.01, 1.84], P=0.05). A dose-dependent relationship was observed, with macroalbuminuria having a large fracture risk (unadjusted hazard ratio=2.01 [1.21, 3.35], P=0.007; adjusted hazard ratio=1.71 [1.007, 2.91], P=0.05) and microalbuminuria associating with borderline or no statistical significance (unadjusted hazard ratio=1.52 [1.10, 2.09], P=0.01; adjusted hazard ratio=1.28 [0.92, 1.78], P=0.15). Estimated GFR was not a predictor of fracture in any model, but rapid loss of estimated GFR over the first 2 years of follow-up predicted subsequent fracture (adjusted hazard ratio=1.47 [1.05, 2.04], P=0.02).

Conclusions: Albuminuria, especially macroalbuminuria, and rapid decline of estimated GFR predict hip and pelvic fractures. These findings support a theoretical model of a relationship between underlying causes of microalbuminuria and bone disease.

Trial registration: NCT00153101.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albuminuria / complications*
  • Albuminuria / physiopathology*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Benzimidazoles / therapeutic use
  • Benzoates / therapeutic use
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / drug therapy
  • Fractures, Bone / epidemiology
  • Fractures, Bone / etiology*
  • Glomerular Filtration Rate*
  • Hip Fractures / epidemiology
  • Hip Fractures / etiology*
  • Humans
  • Pelvic Bones / injuries*
  • Prospective Studies
  • Ramipril / therapeutic use
  • Risk Factors
  • Telmisartan
  • Time Factors


  • Angiotensin-Converting Enzyme Inhibitors
  • Benzimidazoles
  • Benzoates
  • Ramipril
  • Telmisartan

Associated data