Osteoporosis International

, Volume 24, Issue 12, pp 2993–3000 | Cite as

Albuminuria is associated with hip fracture risk in older adults: the cardiovascular health study

  • J. I. Barzilay
  • P. Bůžková
  • Z. Chen
  • I. H. de Boer
  • L. Carbone
  • N. N. Rassouli
  • H. A. Fink
  • J. A. Robbins
Original Article



The microcirculation plays an important role in bone health. Here, we examine whether albuminuria, a marker of renal microvascular disease, is associated with the risk of hip fracture in older adults (age, 78 years). We find a small independent association in women but not in men.


The microvascular circulation plays an important role in bone physiology. Two studies of middle-aged adults have found that albuminuria (>30 mg albumin/g creatinine), a disorder of the renal microvasculature, is associated with fracture risk. Here, we examine whether albuminuria is related to hip fracture risk and reduced hip bone mineral density (BMD) in older adults with a mean age of 78 years.


From the Cardiovascular Health Study (41 % male), 3,110 adults with albuminuria testing were followed up for incident hip fracture for up to 9.5 years. BMD was performed in a subset of 1,208 participants.


There were 313 hip fractures during follow-up (7.7 % of men; 11.7 % of women). The incidence rate for men, with and without albuminuria, was 1.43 and 0.93/100 person-years of follow-up (p = 0.02); for women, 1.84 and 1.33 (p = 0.04). After adjustment for osteoporosis-related factors, frailty and falling, a doubling of albuminuria was significantly associated with hip fracture risk in women (hazard ratio, 1.12, 95 % CI, 1.001–1.25), but not in men. In the subcohort with BMD measurement, increased urine albumin levels were significantly associated with decreased total hip BMD in men (−0.009 g calcium/cm2 (−0.017, −0.001); p = 0.04), but not in women.


In older women, albuminuria is associated with a small, but statistically significant, increased risk of hip fracture independent of other explanatory factors. No such risk appears to be present in men, although their total hip BMD is lower in association with albuminuria.


Albuminuria BMD DEXA Elderly Hip fracture 



The research reported in this article was supported by contract numbers N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, and N01-HC-45133, grant number U01 HL080295 from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke. A full list of principal CHS investigators and institutions can be found at

Conflicts of interest



  1. 1.
    Parfitt AM (2000) The mechanism of coupling: a role for the vasculature. Bone 26:319–23PubMedCrossRefGoogle Scholar
  2. 2.
    Garg AX, Kiberd BA, Clark WF, Haynes RB, Clase CM (2002) Albuminuria and renal insufficiency prevalence guides population screening. Results from NHANES III. Kidney Int 61:2165–2175PubMedCrossRefGoogle Scholar
  3. 3.
    Barzilay JI, Peterson D, Cushman M, Heckbert SR, Cao JJ, Blaum C, Tracy RP, Klein R, Herrington DM (2004) The relationship of cardiovascular risk factors to microalbuminuria in older adults with or without diabetes mellitus or hypertension; the Cardiovascular Health Study. Am J Kidney Dis 44:25–34PubMedCrossRefGoogle Scholar
  4. 4.
    Redlich K, Smolen JS (2012) Inflammatory bone loss: pathogenesis and therapeutic intervention. Nat Rev Drug Discov 11:234–250PubMedCrossRefGoogle Scholar
  5. 5.
    Burkhardt R, Kettner G, Böhm W, Schmidmeier M, Schlag R, Frisch B, Mallmann B, Eisenmenger W, Gilg T (1987) Changes in trabecular bone, hematopoiesis and bone marrow vessels in aplastic anemia, primary osteoporosis, and old age: a comparative histomorphometric study. Bone 8:157–164PubMedCrossRefGoogle Scholar
  6. 6.
    Griffith JF, Yeung DK, Tsang PH, Choi KC, Kwok TC, Ahuja AT, Leung KS, Leung PC (2008) Compromised bone marrow perfusion in osteoporosis. J Bone Miner Res 23:1068–1075PubMedCrossRefGoogle Scholar
  7. 7.
    Laroche M, Ludot I, Thiechart M, Arlet J, Pieraggi M, Chiron P, Moulinier L, Cantagrel A, Puget J, Utheza G, Mazieres B (1995) Study of the intraosseous vessels of the femoral head in patients with fractures of the femoral neck or osteoarthritis of the hip. Osteoporos Int 5:213–217PubMedCrossRefGoogle Scholar
  8. 8.
    Moseley KF (2012) Type 2 diabetes and bone fractures. Curr Opin Endocrinol Diabetes Obes 19:128–135PubMedCrossRefGoogle Scholar
  9. 9.
    Vestergaard P, Rejnmark L, Mosekilde L (2009) Hypertension is a risk factor for fractures. Calcif Tissue Int 84:103–111PubMedCrossRefGoogle Scholar
  10. 10.
    Jørgensen L, Jenssen T, Ahmed L, Bjornerem A, Joakimsen R, Jacobsen BK (2007) Albuminuria and risk of nonvertebral fractures. Arch Intern Med 167:1379–1385PubMedCrossRefGoogle Scholar
  11. 11.
    Barzilay JI, Gao P, Clase K, Mente A, Mann JFE, Sleight P, Yusuf S, Teo KK, on behalf of the ONTARGET/TRANSCEND Investigators (2013) Albuminuria and rapid loss of glomerular filtration rate predict new hip and pelvic fractures: the ONTARGET/TRANSCEND studies. Clin J Am Soc Nephrol 8:233–240PubMedCrossRefGoogle Scholar
  12. 12.
    Robbins JA, Biggs ML, Cauley J (2006) Adjusted mortality after hip fracture: from the Cardiovascular Health Study. J Am Geriatr Soc 54:1885–1891PubMedCrossRefGoogle Scholar
  13. 13.
    Fried LP, Borhani NO, Enright P, Furberg CD, Gardin JM, Kronmal RA, Kuller LH, Manolio TA, Mittelmark MB, Newman A, O’Leary DH, Psaty B, Rautaharju P, Tracy RP, Weiler PG (1991) Cardiovascular Health Study: design and rationale. Ann Epidemiol 1:263–276PubMedCrossRefGoogle Scholar
  14. 14.
    Barzilay JI, Blaum C, Moore T, Xue QL, Hirsch CH, Walston JD, Fried LP (2007) Insulin resistance and inflammation as precursors of frailty: the Cardiovascular Health Study. Arch Intern Med 167:635–641PubMedCrossRefGoogle Scholar
  15. 15.
    Cushman M, Cornell ES, Howard PR, Bovill EG, Tracy RP (1995) Laboratory methods and quality assurance in the Cardiovascular Health Study. Clin Chem 41:264–270PubMedGoogle Scholar
  16. 16.
    R Development Core Team (2009) R: a language and environment for statistical computing. R Foundation for Statistical Computing: Vienna. ISBN 3-900051-07-0.
  17. 17.
    Xue QL, Beamer BA, Chaves PH, Guralnik JM, Fried LP (2010) Heterogeneity in rate of decline in grip, hip, and knee strength and the risk of all-cause mortality: the Women’s Health and Aging Study II. J Am Geriatr Soc 58:2076–2084PubMedCrossRefGoogle Scholar
  18. 18.
    Chen PJ, Lin MH, Peng LN, Liu CL, Chang CW, Lin YT, Chen LK (2012) Predicting cause-specific mortality of older men living in the Veterans home by handgrip strength and walking speed: a 3-year, prospective cohort study in Taiwan. J Am Med Dir Assoc 13:517–521PubMedCrossRefGoogle Scholar
  19. 19.
    Brown M (2008) Skeletal muscle and bone: effect of sex steroids and aging. Adv Physiol Educ 32:120–126PubMedCrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2013

Authors and Affiliations

  • J. I. Barzilay
    • 1
    • 2
    • 9
  • P. Bůžková
    • 3
  • Z. Chen
    • 4
  • I. H. de Boer
    • 5
  • L. Carbone
    • 6
  • N. N. Rassouli
    • 1
    • 2
  • H. A. Fink
    • 7
  • J. A. Robbins
    • 8
  1. 1.Division of EndocrinologyKaiser Permanente of GeorgiaAtlantaUSA
  2. 2.Division of EndocrinologyEmory University School of MedicineAtlantaUSA
  3. 3.Department of BiostatisticsUniversity of WashingtonSeattleUSA
  4. 4.Division of Epidemiology and BiostatisticsThe University of Arizona Mel and Enid Zuckerman College of Public HealthTucsonUSA
  5. 5.Division of NephrologyUniversity of WashingtonSeattleUSA
  6. 6.Division of Connective Tissue DiseasesUniversity of Tennessee Health Science Center and Department of Veterans Affairs Medical CenterMemphisUSA
  7. 7.Geriatric Research Education and Clinical CenterVeterans Affair Medical CenterMinneapolisUSA
  8. 8.Department of MedicineUniversity of CaliforniaSacramentoUSA
  9. 9.TuckerUSA

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