title: Albuminuria and rapid loss of GFR and risk of new hip and pelvic fractures.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Division of Endocrinology, Emory University School of Medicine, Atlanta, Georgia, USA. Joshua.barzilay@kp.org
authors.forename: Joshua I
authors.initials: JI
authors.lastname: Barzilay
authors.forename: Peggy
authors.initials: P
authors.lastname: Gao
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Clase
authors.forename: Andrew
authors.initials: A
authors.lastname: Mente
authors.forename: Johannes F E
authors.initials: JF
authors.lastname: Mann
authors.forename: Peter
authors.initials: P
authors.lastname: Sleight
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
authors.forename: Koon K
authors.initials: KK
authors.lastname: Teo
mesh_terms: D000419:Albuminuria / Q000150:complications* / Q000503:physiopathology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D001562:Benzimidazoles / Q000627:therapeutic use; D001565:Benzoates / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000150:complications / Q000188:drug therapy; D050723:Fractures, Bone / Q000453:epidemiology / Q000209:etiology*; D005919:Glomerular Filtration Rate; D006620:Hip Fractures / Q000453:epidemiology / Q000209:etiology*; D006801:Humans; D010384:Pelvic Bones / Q000293:injuries*; D011446:Prospective Studies; D017257:Ramipril / Q000627:therapeutic use; D012307:Risk Factors; D000077333:Telmisartan; D013997:Time Factors
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001565:Benzoates; D017257:Ramipril; D000077333:Telmisartan