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Published in: Osteoporosis International 5/2011

01-05-2011 | Original Article

Menopausal bone changes and incident fractures in diabetic women: a cohort study

Authors: N. Khalil, K. Sutton-Tyrrell, E. S. Strotmeyer, G. A. Greendale, M. Vuga, F. Selzer, C. J. Crandall, J. A. Cauley

Published in: Osteoporosis International | Issue 5/2011

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Abstract

Summary

The purpose of this study was to evaluate the rate of bone loss and incident fractures in women with diabetes mellitus (DM) across menopause. During menopause, DM women experienced bone mineral density (BMD) loss that was faster at hip and slower at spine and had a higher risk of fractures, perhaps because of their earlier menopause. The increasing DM epidemic will contribute to higher fracture burden.

Introduction

Women with DM have a higher risk of fractures independent of age, body mass index (BMI), and BMD. Our objective is to evaluate if women with DM experience greater bone loss and more fractures across menopause.

Methods

Two thousand one hundred seventy one women, aged 42 to 52 years at baseline (1996), enrolled in the Study of Women's Health Across the Nation (SWAN), a prospective study, with 8 years of annual follow up. One thousand three hundred forty six (62%) completed annual visit 7 (2004). Women with baseline fasting blood glucose level of ≥126 mg/dl and those being treated for diabetes were designated as DM. Annual assessment of menopausal stage, BMD, and urinary N-telopeptide (NTx) were carried out. Rate of change in BMD across menopause and annual self-report data for risk of incident fractures by DM status were determined.

Results

Despite higher baseline BMD at hip (p = <0.001), and lumbar spine (p = <0.001), rate of decline in BMD was faster at hip (β = −0.45 vs. −0.11 gm/cm2/year, p = <0.001) for DM women, compared to non-DM. However, lumbar spine bone loss was slower in women with DM as compared to non-DM women (β = 0.04 vs. −0.25 gm/cm2/year, p = 0.004). DM women experienced menopause 3 years earlier than non-DM women (p = 0.002), and age adjusted incident fractures were two fold higher in women with DM compared to non-DM (RR = 2.20, 95% CI: 1.26–3.85, p = <0.006).

Conclusions

BMD loss is greater in hip and slower at spine in DM women during menopausal transition. Women with DM have a higher risk of fractures, perhaps because of their earlier menopause.
Literature
1.
go back to reference Burge R, Dawson-Hughes B, Solomon DH, Wong JB, King A, Tosteson A (2007) Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. J Bone Miner Res 22:465–475PubMedCrossRef Burge R, Dawson-Hughes B, Solomon DH, Wong JB, King A, Tosteson A (2007) Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. J Bone Miner Res 22:465–475PubMedCrossRef
2.
go back to reference CDC Centers for Disease Control and Prevention. National diabetes Fact sheet; general information and national estimates on diabetes in the United States (2007) Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and prevention, 2008, Accessed on Dec,11,2009 CDC Centers for Disease Control and Prevention. National diabetes Fact sheet; general information and national estimates on diabetes in the United States (2007) Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and prevention, 2008, Accessed on Dec,11,2009
3.
go back to reference Wild S, Roglic G, Green A, Sicree R, King H (2004) Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diab Care 27:1047–1053CrossRef Wild S, Roglic G, Green A, Sicree R, King H (2004) Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diab Care 27:1047–1053CrossRef
4.
go back to reference Ahlborg HG, Johnell O, Nilsson BE, Jeppsson S, Rannevik G, Karlsson MK (2001) Bone loss in relation to menopause: a prospective study during 16 years. Bone 28:327–331PubMedCrossRef Ahlborg HG, Johnell O, Nilsson BE, Jeppsson S, Rannevik G, Karlsson MK (2001) Bone loss in relation to menopause: a prospective study during 16 years. Bone 28:327–331PubMedCrossRef
5.
go back to reference Ravn P, Hetland ML, Overgaard K, Christiansen C (1994) Premenopausal and postmenopausal changes in bone mineral density of the proximal femur measured by dual-energy X-ray absorptiometry. J Bone Miner Res 9:1975–1980PubMedCrossRef Ravn P, Hetland ML, Overgaard K, Christiansen C (1994) Premenopausal and postmenopausal changes in bone mineral density of the proximal femur measured by dual-energy X-ray absorptiometry. J Bone Miner Res 9:1975–1980PubMedCrossRef
6.
go back to reference Nilas L, Christiansen C (1987) Bone mass and its relationship to age and the menopause. J Clin Endocrinol Metab 65:697–702PubMedCrossRef Nilas L, Christiansen C (1987) Bone mass and its relationship to age and the menopause. J Clin Endocrinol Metab 65:697–702PubMedCrossRef
7.
8.
go back to reference Vestergaard P (2007) Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes–a meta-analysis. Osteoporos Int 18:427–444PubMedCrossRef Vestergaard P (2007) Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes–a meta-analysis. Osteoporos Int 18:427–444PubMedCrossRef
9.
go back to reference Sowers MF, Crawford S, Sternfeld B et al (2000) SWAN: A Multicenter, Multiethnic, Community-Based Cohort Study of Women and the Menopausal Transition. In: Lobo RA, Kelsey J, Marcus R (eds) Menopause: Biology and Pathobiology (Chapter 11). Academic Press, San Diego, pp 175–188 Sowers MF, Crawford S, Sternfeld B et al (2000) SWAN: A Multicenter, Multiethnic, Community-Based Cohort Study of Women and the Menopausal Transition. In: Lobo RA, Kelsey J, Marcus R (eds) Menopause: Biology and Pathobiology (Chapter 11). Academic Press, San Diego, pp 175–188
10.
go back to reference Finkelstein JS, Brockwell SE, Mehta V, Greendale GA, Sowers MR, Ettinger B, Lo JC, Johnston JM, Cauley JA, Danielson ME, Neer RM (2008) Bone mineral density changes during the menopause transition in a multiethnic cohort of women. J Clin Endocrinol Metab 93:861–868PubMedCrossRef Finkelstein JS, Brockwell SE, Mehta V, Greendale GA, Sowers MR, Ettinger B, Lo JC, Johnston JM, Cauley JA, Danielson ME, Neer RM (2008) Bone mineral density changes during the menopause transition in a multiethnic cohort of women. J Clin Endocrinol Metab 93:861–868PubMedCrossRef
11.
go back to reference Ross PD, Norimatsu H, Davis JW, Yano K, Wasnich RD, Fujiwara S, Hosoda Y, Melton LJ 3rd (1991) A comparison of hip fracture incidence among native Japanese, Japanese Americans, and American Caucasians. Am J Epidemiol 133:801–809PubMed Ross PD, Norimatsu H, Davis JW, Yano K, Wasnich RD, Fujiwara S, Hosoda Y, Melton LJ 3rd (1991) A comparison of hip fracture incidence among native Japanese, Japanese Americans, and American Caucasians. Am J Epidemiol 133:801–809PubMed
12.
go back to reference Hans D, Duboeuf F, Schott AM, Horn S, Avioli LV, Drezner MK, Meunier PJ (1997) Effects of a new positioner on the precision of hip bone mineral density measurements. J Bone Miner Res 12:1289–1294PubMedCrossRef Hans D, Duboeuf F, Schott AM, Horn S, Avioli LV, Drezner MK, Meunier PJ (1997) Effects of a new positioner on the precision of hip bone mineral density measurements. J Bone Miner Res 12:1289–1294PubMedCrossRef
13.
go back to reference Chen Z, Kooperberg C, Pettinger MB, Bassford T, Cauley JA, LaCroix AZ, Lewis CE, Kipersztok S, Borne C, Jackson RD (2004) Validity of self-report for fractures among a multiethnic cohort of postmenopausal women: results from the Women's Health Initiative observational study and clinical trials. Menopause 11:264–274PubMedCrossRef Chen Z, Kooperberg C, Pettinger MB, Bassford T, Cauley JA, LaCroix AZ, Lewis CE, Kipersztok S, Borne C, Jackson RD (2004) Validity of self-report for fractures among a multiethnic cohort of postmenopausal women: results from the Women's Health Initiative observational study and clinical trials. Menopause 11:264–274PubMedCrossRef
14.
go back to reference Nevitt MC, Cummings SR, Browner WS, Seeley DG, Cauley JA, Vogt TM, Black DM (1992) The accuracy of self-report of fractures in elderly women: evidence from a prospective study. Am J Epidemiol 135:490–499PubMed Nevitt MC, Cummings SR, Browner WS, Seeley DG, Cauley JA, Vogt TM, Black DM (1992) The accuracy of self-report of fractures in elderly women: evidence from a prospective study. Am J Epidemiol 135:490–499PubMed
15.
go back to reference Sowers MR, Jannausch M, McConnell D, Little R, Greendale GA, Finkelstein JS, Neer RM, Johnston J, Ettinger B (2006) Hormone predictors of bone mineral density changes during the menopausal transition. J Clin Endocrinol Metab 91:1261–1267PubMedCrossRef Sowers MR, Jannausch M, McConnell D, Little R, Greendale GA, Finkelstein JS, Neer RM, Johnston J, Ettinger B (2006) Hormone predictors of bone mineral density changes during the menopausal transition. J Clin Endocrinol Metab 91:1261–1267PubMedCrossRef
16.
go back to reference Luborsky JL, Meyer P, Sowers MF, Gold EB, Santoro N (2003) Premature menopause in a multi-ethnic population study of the menopause transition. Hum Reprod 18:199–206PubMedCrossRef Luborsky JL, Meyer P, Sowers MF, Gold EB, Santoro N (2003) Premature menopause in a multi-ethnic population study of the menopause transition. Hum Reprod 18:199–206PubMedCrossRef
17.
go back to reference Dorman JS, Steenkiste AR, Foley TP, Strotmeyer ES, Burke JP, Kuller LH, Kwoh CK (2001) Menopause in type 1 diabetic women: is it premature? Diabetes 50:1857–1862PubMedCrossRef Dorman JS, Steenkiste AR, Foley TP, Strotmeyer ES, Burke JP, Kuller LH, Kwoh CK (2001) Menopause in type 1 diabetic women: is it premature? Diabetes 50:1857–1862PubMedCrossRef
18.
go back to reference Strotmeyer ES, Cauley JA, Schwartz AV, Nevitt MC, Resnick HE, Zmuda JM, Bauer DC, Tylavsky FA, de Rekeneire N, Harris TB, Newman AB (2004) Diabetes is associated independently of body composition with BMD and bone volume in older white and black men and women: The Health, Aging, and Body Composition Study. J Bone Miner Res 19:1084–1091PubMedCrossRef Strotmeyer ES, Cauley JA, Schwartz AV, Nevitt MC, Resnick HE, Zmuda JM, Bauer DC, Tylavsky FA, de Rekeneire N, Harris TB, Newman AB (2004) Diabetes is associated independently of body composition with BMD and bone volume in older white and black men and women: The Health, Aging, and Body Composition Study. J Bone Miner Res 19:1084–1091PubMedCrossRef
19.
go back to reference Rishaug U, Birkeland KI, Falch JA, Vaaler S (1995) Bone mass in non-insulin-dependent diabetes mellitus. Scand J Clin Lab Invest 55:257–262PubMedCrossRef Rishaug U, Birkeland KI, Falch JA, Vaaler S (1995) Bone mass in non-insulin-dependent diabetes mellitus. Scand J Clin Lab Invest 55:257–262PubMedCrossRef
20.
go back to reference Schwartz AV, Sellmeyer DE (2007) Diabetes, fracture, and bone fragility. Curr Osteoporos Rep 5:105–111PubMedCrossRef Schwartz AV, Sellmeyer DE (2007) Diabetes, fracture, and bone fragility. Curr Osteoporos Rep 5:105–111PubMedCrossRef
21.
go back to reference Janghorbani M, Van Dam RM, Willett WC, Hu FB (2007) Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am J Epidemiol 166:495–505PubMedCrossRef Janghorbani M, Van Dam RM, Willett WC, Hu FB (2007) Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am J Epidemiol 166:495–505PubMedCrossRef
22.
go back to reference Holmberg AH, Johnell O, Nilsson PM, Nilsson J, Berglund G, Akesson K (2006) Risk factors for fragility fracture in middle age. A prospective population-based study of 33, 000 men and women. Osteoporos Int 17:1065–1077PubMedCrossRef Holmberg AH, Johnell O, Nilsson PM, Nilsson J, Berglund G, Akesson K (2006) Risk factors for fragility fracture in middle age. A prospective population-based study of 33, 000 men and women. Osteoporos Int 17:1065–1077PubMedCrossRef
23.
go back to reference Lipscombe LL, Jamal SA, Booth GL, Hawker GA (2007) The risk of hip fractures in older individuals with diabetes: a population-based study. Diab Care 30:835–841CrossRef Lipscombe LL, Jamal SA, Booth GL, Hawker GA (2007) The risk of hip fractures in older individuals with diabetes: a population-based study. Diab Care 30:835–841CrossRef
24.
go back to reference Janghorbani M, Feskanich D, Willett WC, Hu F (2006) Prospective study of diabetes and risk of hip fracture: the Nurses' Health Study. Diab Care 29:1573–1578CrossRef Janghorbani M, Feskanich D, Willett WC, Hu F (2006) Prospective study of diabetes and risk of hip fracture: the Nurses' Health Study. Diab Care 29:1573–1578CrossRef
26.
go back to reference Schwartz AV, Sellmeyer DE, Nevitt MC, Resnick HE, Margolis KL, Hillier TA, Black DM, Ensrud KE, Cummings SR (2000) Older women with diabetes have a higher rate of bone loss at the hip. J Bone Miner Res 15:S1–S188CrossRef Schwartz AV, Sellmeyer DE, Nevitt MC, Resnick HE, Margolis KL, Hillier TA, Black DM, Ensrud KE, Cummings SR (2000) Older women with diabetes have a higher rate of bone loss at the hip. J Bone Miner Res 15:S1–S188CrossRef
27.
go back to reference Schwartz AV, Sellmeyer DE, Strotmeyer ES, Tylavsky FA, Feingold KR, Resnick HE, Shorr RI, Nevitt MC, Black DM, Cauley JA, Cummings SR, Harris TB (2005) Diabetes and bone loss at the hip in older black and white adults. J Bone Miner Res 20:596–603PubMedCrossRef Schwartz AV, Sellmeyer DE, Strotmeyer ES, Tylavsky FA, Feingold KR, Resnick HE, Shorr RI, Nevitt MC, Black DM, Cauley JA, Cummings SR, Harris TB (2005) Diabetes and bone loss at the hip in older black and white adults. J Bone Miner Res 20:596–603PubMedCrossRef
28.
go back to reference Kawashima Y, Fritton JC, Yakar S, Epstein S, Schaffler MB, Jepsen KJ, LeRoith D (2009) Type 2 diabetic mice demonstrate slender long bones with increased fragility secondary to increased osteoclastogenesis. Bone 44:648–655PubMedCrossRef Kawashima Y, Fritton JC, Yakar S, Epstein S, Schaffler MB, Jepsen KJ, LeRoith D (2009) Type 2 diabetic mice demonstrate slender long bones with increased fragility secondary to increased osteoclastogenesis. Bone 44:648–655PubMedCrossRef
29.
go back to reference Verhaeghe J, Suiker AM, Einhorn TA, Geusens P, Visser WJ, Van Herck E, Van Bree R, Magitsky S, Bouillon R (1994) Brittle bones in spontaneously diabetic female rats cannot be predicted by bone mineral measurements: studies in diabetic and ovariectomized rats. J Bone Miner Res 9:1657–1667PubMedCrossRef Verhaeghe J, Suiker AM, Einhorn TA, Geusens P, Visser WJ, Van Herck E, Van Bree R, Magitsky S, Bouillon R (1994) Brittle bones in spontaneously diabetic female rats cannot be predicted by bone mineral measurements: studies in diabetic and ovariectomized rats. J Bone Miner Res 9:1657–1667PubMedCrossRef
30.
go back to reference Wang X, Shen X, Li X, Agrawal CM (2002) Age-related changes in the collagen network and toughness of bone. Bone 31:1–7PubMedCrossRef Wang X, Shen X, Li X, Agrawal CM (2002) Age-related changes in the collagen network and toughness of bone. Bone 31:1–7PubMedCrossRef
31.
go back to reference Petit MA, Paudel ML, Taylor BC, Hughes JM, Strotmeyer ES, Schwartz AV, Cauley JA, Zmuda JM, Hoffman AR, Ensrud KE (2009) Bone Mass and Strength in Older Men with Type 2 Diabetes: The Osteoporotic Fractures in Men Study. J Bone Miner Res Petit MA, Paudel ML, Taylor BC, Hughes JM, Strotmeyer ES, Schwartz AV, Cauley JA, Zmuda JM, Hoffman AR, Ensrud KE (2009) Bone Mass and Strength in Older Men with Type 2 Diabetes: The Osteoporotic Fractures in Men Study. J Bone Miner Res
32.
go back to reference Lopez-Lopez R, Huerta R, Malacara JM (1999) Age at menopause in women with type 2 diabetes mellitus. Menopause 6:174–178PubMed Lopez-Lopez R, Huerta R, Malacara JM (1999) Age at menopause in women with type 2 diabetes mellitus. Menopause 6:174–178PubMed
33.
go back to reference Kwon DJ, Kim JH, Chung KW, Kim JH, Lee JW, Kim SP, Lee HY (1996) Bone mineral density of the spine using dual energy X-ray absorptiometry in patients with non-insulin-dependent diabetes mellitus. J Obstet Gynaecol Res 22:157–162PubMed Kwon DJ, Kim JH, Chung KW, Kim JH, Lee JW, Kim SP, Lee HY (1996) Bone mineral density of the spine using dual energy X-ray absorptiometry in patients with non-insulin-dependent diabetes mellitus. J Obstet Gynaecol Res 22:157–162PubMed
34.
go back to reference Rubin MR, Silverberg SJ (2004) Vascular calcification and osteoporosis–the nature of the nexus. J Clin Endocrinol Metab 89:4243–4245PubMedCrossRef Rubin MR, Silverberg SJ (2004) Vascular calcification and osteoporosis–the nature of the nexus. J Clin Endocrinol Metab 89:4243–4245PubMedCrossRef
35.
go back to reference Raggi P, Shaw LJ, Berman DS, Callister TQ (2004) Prognostic value of coronary artery calcium screening in subjects with and without diabetes. J Am Coll Cardiol 43:1663–1669PubMedCrossRef Raggi P, Shaw LJ, Berman DS, Callister TQ (2004) Prognostic value of coronary artery calcium screening in subjects with and without diabetes. J Am Coll Cardiol 43:1663–1669PubMedCrossRef
36.
go back to reference Towler DA, Bidder M, Latifi T, Coleman T, Semenkovich CF (1998) Diet-induced diabetes activates an osteogenic gene regulatory program in the aortas of low density lipoprotein receptor-deficient mice. J Biol Chem 273:30427–30434PubMedCrossRef Towler DA, Bidder M, Latifi T, Coleman T, Semenkovich CF (1998) Diet-induced diabetes activates an osteogenic gene regulatory program in the aortas of low density lipoprotein receptor-deficient mice. J Biol Chem 273:30427–30434PubMedCrossRef
37.
go back to reference Strotmeyer ES, Cauley JA, Orchard TJ, Steenkiste AR, Dorman JS (2006) Middle-aged premenopausal women with type 1 diabetes have lower bone mineral density and calcaneal quantitative ultrasound than nondiabetic women. Diab Care 29:306–311CrossRef Strotmeyer ES, Cauley JA, Orchard TJ, Steenkiste AR, Dorman JS (2006) Middle-aged premenopausal women with type 1 diabetes have lower bone mineral density and calcaneal quantitative ultrasound than nondiabetic women. Diab Care 29:306–311CrossRef
38.
40.
go back to reference Cleghorn DB, Polley KJ, Nordin BE (1992) Fracture rates calculated from fracture histories in normal postmenopausal women. J Epidemiol Community Health 46:133–135PubMedCrossRef Cleghorn DB, Polley KJ, Nordin BE (1992) Fracture rates calculated from fracture histories in normal postmenopausal women. J Epidemiol Community Health 46:133–135PubMedCrossRef
41.
go back to reference Midthjell K, Holmen J, Bjorndal A, Lund-Larsen G (1992) Is questionnaire information valid in the study of a chronic disease such as diabetes? The Nord-Trondelag diabetes study. J Epidemiol Community Health 46:537–542PubMedCrossRef Midthjell K, Holmen J, Bjorndal A, Lund-Larsen G (1992) Is questionnaire information valid in the study of a chronic disease such as diabetes? The Nord-Trondelag diabetes study. J Epidemiol Community Health 46:537–542PubMedCrossRef
42.
go back to reference Manson JE, Rimm EB, Stampfer MJ, Colditz GA, Willett WC, Krolewski AS, Rosner B, Hennekens CH, Speizer FE (1991) Physical-activity and incidence of non-insulin-dependent diabetes-mellitus in women. Lancet 338:774–778PubMedCrossRef Manson JE, Rimm EB, Stampfer MJ, Colditz GA, Willett WC, Krolewski AS, Rosner B, Hennekens CH, Speizer FE (1991) Physical-activity and incidence of non-insulin-dependent diabetes-mellitus in women. Lancet 338:774–778PubMedCrossRef
43.
go back to reference Lo JC, Zhao X, Scuteri A, Brockwell S, Sowers MR (2006) The association of genetic polymorphisms in sex hormone biosynthesis and action with insulin sensitivity and diabetes mellitus in women at midlife. Am J Med 119:S69–S78PubMedCrossRef Lo JC, Zhao X, Scuteri A, Brockwell S, Sowers MR (2006) The association of genetic polymorphisms in sex hormone biosynthesis and action with insulin sensitivity and diabetes mellitus in women at midlife. Am J Med 119:S69–S78PubMedCrossRef
44.
go back to reference Kaye SA, Folsom AR, Sprafka JM, Prineas RJ, Wallace RB (1991) Increased incidence of diabetes mellitus in relation to abdominal adiposity in older women. J Clin Epidemiol 44:329–334PubMedCrossRef Kaye SA, Folsom AR, Sprafka JM, Prineas RJ, Wallace RB (1991) Increased incidence of diabetes mellitus in relation to abdominal adiposity in older women. J Clin Epidemiol 44:329–334PubMedCrossRef
45.
go back to reference Levin ME, Boisseau VC, Avioli LV (1976) Effects of diabetes mellitus on bone mass in juvenile and adult-onset diabetes. N Engl J Med 294:241–245PubMedCrossRef Levin ME, Boisseau VC, Avioli LV (1976) Effects of diabetes mellitus on bone mass in juvenile and adult-onset diabetes. N Engl J Med 294:241–245PubMedCrossRef
Metadata
Title
Menopausal bone changes and incident fractures in diabetic women: a cohort study
Authors
N. Khalil
K. Sutton-Tyrrell
E. S. Strotmeyer
G. A. Greendale
M. Vuga
F. Selzer
C. J. Crandall
J. A. Cauley
Publication date
01-05-2011
Publisher
Springer-Verlag
Published in
Osteoporosis International / Issue 5/2011
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-010-1357-4

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