Serum fructosamine level and the risk of hip fracture in elderly women: a case-cohort study within the study of osteoporotic fractures

  • Sophie A Jamal
    Requests for reprints should be addressed to SA Jamal, MD, Osteoporosis Research Program, Women’s College Hospital, 60 Grosvenor Street, Burton Hall, Room 416, Toronto, Ontario M5S 1B6, Canada
    Department of Epidemiology and Biostatistics, University of California, San Francisco (SAJ, KS, WSB, SRC), California, USA
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  • Katie Stone
    Department of Epidemiology and Biostatistics, University of California, San Francisco (SAJ, KS, WSB, SRC), California, USA
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  • Warren S Browner
    Department of Epidemiology and Biostatistics, University of California, San Francisco (SAJ, KS, WSB, SRC), California, USA

    the General Internal Medicine Section, San Francisco Veterans Affairs Medical Center, University of California, San Francisco (WSB), California, USA
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  • Kristine E Ensrud
    the General Medicine Section, Minneapolis Veterans Affairs Medical Center University of Minnesota, Minneapolis (KEE), Minnesota, USA

    the Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis (KEE), Minnesota, USA
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  • Steven R Cummings
    Department of Epidemiology and Biostatistics, University of California, San Francisco (SAJ, KS, WSB, SRC), California, USA

    the Division of General Internal Medicine, University of California, San Francisco, California (SRC), USA
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      PURPOSE: While a high serum fructosamine level may be an indicator of undiagnosed diabetes, a low level may be indicative of poor nutrition or frailty. As malnutrition is a risk factor for osteoporosis, low serum fructosamine levels may be associated with an increased risk of osteoporotic fracture. We examined the association between serum fructosamine levels and the risk of subsequent hip and vertebral fracture.
      SUBJECTS AND METHODS: We performed a case-cohort study within the Study of Osteoporotic Fractures. Subjects were elderly, ambulatory, community-dwelling, Caucasian, women. Fructosamine levels were measured in baseline serum. Incident vertebral fractures were identified by comparing baseline spinal radiographs to those obtained an average of 3.5 years later. Hip fractures were confirmed by radiograph. We randomly selected 101 women who suffered a hip fracture, 100 women who developed a vertebral fracture, and 276 controls. We compared fructosamine levels in women with subsequent osteoporotic fractures to controls. All analyses were adjusted for age, weight, and use of estrogens.
      RESULTS: Women with fructosamine levels in the lowest decile (≤223 μmol/L) had a three-fold increase in the risk of hip fracture (95% confidence interval 1.4–6.4), compared with all other women. Adjustment for markers of frailty, including smoking, functional status, and serum albumin levels, reduced the strength of this association. No clear association was observed between serum fructosamine level and the risk of vertebral fracture.
      CONCLUSION: Low serum fructosamine levels, which likely reflect frailty or malnutrition, may be a useful clinical tool to identify women at risk for hip fracture.
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        • Baker J.R
        • O’Connor J.P
        • Metcalf P.A
        • Lawson M.R
        • Johnson R.N
        Clinical usefulness of estimation of serum fructosamine concentration as a screening test for diabetes mellitus.
        Br Med J. 1983; 287: 863-867
        • Baker J.R
        • Johnson R.N
        • Scott D.J
        Serum fructosamine concentrations in patients with type II (non-insulin-dependent) diabetes mellitus during changes in management.
        Br Med J. 1984; 288: 1484-1486
        • Cefalu W.T
        • Ettinger W.H
        • Bell-Farrow A.D
        • Rushing J.T
        Serum fructosamine as a screening test for diabetes in the elderly.
        J Am Geriatr Soc. 1993; 41: 1090-1094
        • Johnson R.N
        • Metcalf P.A
        • Baker J.R
        Clin Chim Acta. 1983; 127: 87-95
        • Woo J
        • Chan S.M
        • Mak Y.T
        • Swaminathan R
        Biochemical predictors of short term mortality in elderly residents of chronic care institutions.
        J Clin Pathol. 1989; 42: 1241-1245
        • Comtois R
        • Couturier M
        • Ammann H
        Influence of protein and albumin levels on serum fructosamine concentration in a diabetic patient with multiple myeloma.
        Clin Biochem. 1994; 27: 421-423
        • Constanti C
        • Simo J.M
        • Joven J
        Serum fructosamine concentration in patients with nephrotic syndrome and with cirrhosis of the liver.
        Ann Clin Biochem. 1992; 29: 437-442
        • Rico H
        • Relea P
        • Revilla M
        • Hernandez E.R
        • Arribas I
        • Villa L.F
        Biochemical markers of nutrition in osteoporosis.
        Calcif Tissue Int. 1993; 52: 331-333
        • Rico H
        • Relea P
        • Crespo R
        • Revilla M
        • Villa L.F
        • Arribas I
        • Usabiaga J
        Biochemical markers of nutrition in type-I and type-II osteoporosis.
        J Bone Joint Surg (Br). 1995; 77B: 148-151
        • Older M.W.J
        • Edwards D
        • Dickerson J.W.T
        A nutrient survey in elderly women with femoral neck fracture.
        Br J Surg. 1980; 67: 884-886
        • Patterson B.M
        • Cornell C.N
        • Carbone B
        • Levine B
        • Chapman D
        Protein depletion and metabolic stress in elderly patients who have a fracture of the hip.
        Bone and Joint Surg (Am). 1992; 74A: 251-260
        • Delmi M
        • Rapin C.H
        • Bengoa J.M
        • Delmas P.D
        • Vasey H
        • Bonjour J.P
        Dietary supplementation in elderly patients with fractured neck of the femur.
        Lancet. 1990; i: 1013-1016
        • Fiatarone M
        Nutrition in the geriatric patient.
        Hosp Pract. 1990; 25: 38-54
        • Huang Z
        • Himes J.H
        • McGovern P.G
        Nutrition and subsequent hip fracture risk among a national cohort of white women.
        Am J Epidemiol. 1996; 144: 124-134
      1. Assessing vertebral fractures. National Osteoporosis Foundation Working Group on Vertebral Fractures. J Bone and Miner Res. 1995;4:518–523.

        • Black D.M
        • Cummings S.R
        • Stone K
        • Hudes E
        • Palermo L
        • Steiger P
        A new approach to defining normal vertebral dimensions.
        J Bone Miner Res. 1991; 8: 883-892
        • Cummings S.R
        • Black D.M
        • Nevitt M.C
        • Browner W.S
        • Cauley J.A
        • Genant H.K
        • et al.
        Appendicular bone density and age predict hip fracture in women.
        JAMA. 1990; 263: 665-668
        • Fitti J.E
        • Kovar M.G
        The supplement on aging to the 1984 National Health Interview Survey; programs and collection procedures.
        Vital Health Stat 1. 1987; 21: 1-115
        • Prentice R
        A case-cohort design for epidemiologic cohort studies and disease prevention trials.
        Biometrika. 1986; 73: 1-11
        • Cummings S.R
        • Nevitt M.C
        • Browner W.S
        • Stone K
        • Fox K.M
        • Ensrud K.E
        • et al.
        Risk factors for hip fracture in white women.
        NEJM. 1995; 332: 767-773
        • Ensrud K.E
        • Cauley J
        • Lipschutz R
        • Cummings S.R
        Weight change and fractures in older women.
        Arch Intern Med. 1997; 157: 857-863
        • Kelsey J.L
        • Browner W.S
        • Seeley D.G
        • Nevitt M.C
        • Cummings S.R
        Risk factors for fractures of the distal forearm and proximal humerus.
        Am J Epidemiol. 1992; 135: 477-489
        • Bonjour J.-P
        • Schurch M.-A
        • Rizzoli R
        Nutritional aspects of hip fractures.
        Bone. 1996; 18: 139S-144S
        • Bastow M.D
        • Rawlings J
        • Allison S.P
        Undernutrition, hypothermia, and injury in elderly women with fractured femur.
        Lancet. 1983; i: 143-146
        • Grisso J.A
        • Kelsey J.L
        • Strom B.L
        • et al.
        Risk factors for falls as a cause of hip fracture in women.
        NEJM. 1991; 324: 1326-1331
        • Vellas B
        • Baumgartner R.N
        • Wayne S.J
        • et al.
        Relationship between malnutrition and falls in the elderly.
        Nutrition. 1992; 8: 105-108
        • Hutchinson T.A
        • Polansky S.M
        • Feinstein A.R
        Post-menopausal oestrogens protect against fractures of the hip and radius. A case-control study.
        Lancet. 1979; ii: 705-708
        • Paganini-Hill A
        • Ross R.K
        • Gerkins V.R
        • Henderson B.E
        • Arthur M
        • Mack T.M
        Menopausal estrogen therapy and hip fractures.
        Ann Intern Med. 1981; 95: 28-31
        • Heath H
        • Melton L.J
        • Chu C.-P
        Diabetes mellitus and risk of skeletal fracture.
        NEJM. 1980; 303: 567-570
        • Gallagher J.C
        • Melton L.J
        • Riggs B.L
        Examination of prevalence rates of possible risk factors in a population with a fracture of the proximal femur.
        Clin Orthop. 1980; 153: 158-165
        • Meyer H.E
        • Tverdal A
        • Falch J.A
        Risk factors for hip fracture in middle-aged Norwegian women and men.
        Am J Epidemiol. 1993; 137: 1203-1211
        • Black D.M
        • Cummings S.R
        • Karpf D.B
        • et al.
        Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures.
        Lancet. 1996; 348: 1535-1541
        • Cauley J.A
        • Seeley D.G
        • Ensrud K.E
        • Ettinger B
        • Black D.M
        • Cummings S.R
        Estrogen replacement therapy and fractures in older women.
        Ann Intern Med. 1995; 122: 9-16
        • Liberman U.A
        • Weiss S.R
        • Broll J
        • et al.
        Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis.
        NEJM. 1995; 333: 1437-1443
        • Cummings S.R
        Treatable and untreatable risk factors for hip fracture.
        Bone. 1996; 18: 165S-167S
        • Armbruster D.A
        Clin Chem. 1987; 33: 2153-2163