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Published in: Osteoporosis International 2/2018

Open Access 01-02-2018 | Original Article

The effect of insulin on bone mineral density among women with type 2 diabetes: a SWAN Pharmacoepidemiology study

Authors: K. Ruppert, J. Cauley, Y. Lian, J. C. Zgibor, C. Derby, D. H. Solomon

Published in: Osteoporosis International | Issue 2/2018

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Abstract

Summary

This was a longitudinal study examining the effects of insulin use on bone mineral density loss. Insulin use was found to be associated with greater bone mineral density loss at the femoral neck among women with diabetes mellitus.

Introduction

Women with diabetes mellitus (DM) have higher bone mineral density (BMD) and experience slower BMD loss but have an increased risk of fracture. The data regarding the effect of insulin treatment on BMD remains conflicted. We examined the impact of insulin initiation on BMD.

Methods

We investigated the annual changes in BMD associated with the new use of insulin among women with DM in the Study of Women’s Health Across the Nation (SWAN). Propensity score (PS) matching, which is a statistical method that helps balance the baseline characteristics of women who did and did not initiate insulin, was used. Covariates with a potential impact on bone health were included in all models. Mixed model regression was used to test the change in BMD between the two groups. Median follow-up time was 5.4 years.

Results

The cohort consisted of 110 women, mean age, 53.6 years; 49% white and 51% black. Women using insulin (n = 55) were similar on most relevant characteristics to the 55 not using insulin. Median diabetes duration for the user group was 10 vs. 5.0 years for the non-user group. There was a greater loss of BMD at the femoral neck among insulin users (− 1.1%) vs non-users (− 0.77%) (p = 0.04). There were no differences in BMD loss at the spine − 0.30% vs − 0.32% (p = 0.85) or at the total hip − 0.31% vs − 0.25 (p = 0.71), respectively.

Conclusions

Women with T2DM who initiated insulin experienced a more rapid BMD loss at the femoral neck as compared to women who did use insulin.
Literature
1.
go back to reference Fong DS, Aiello LP, Ferris FL 3rd, Klein R (2004) Diabetic retinopathy. Diabetes Care 27:2540–2553CrossRef Fong DS, Aiello LP, Ferris FL 3rd, Klein R (2004) Diabetic retinopathy. Diabetes Care 27:2540–2553CrossRef
2.
go back to reference The DCCT Research Group (1993) The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 329:977–986CrossRef The DCCT Research Group (1993) The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 329:977–986CrossRef
3.
go back to reference UK Prospective Diabetes Study Group (1998) Intensive blood glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 352:837–853CrossRef UK Prospective Diabetes Study Group (1998) Intensive blood glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 352:837–853CrossRef
4.
go back to reference Keenan HA, Costacou T, Sun JK, Doria A, Cavellerano J, Coney J, Orchard TJ, Aiello LP, King GL (2007) Clinical factors associated with resistance to microvascular complications in diabetic patients of extreme disease duration: the 50-year medalist study. Diabetes Care 30:1995–1997CrossRef Keenan HA, Costacou T, Sun JK, Doria A, Cavellerano J, Coney J, Orchard TJ, Aiello LP, King GL (2007) Clinical factors associated with resistance to microvascular complications in diabetic patients of extreme disease duration: the 50-year medalist study. Diabetes Care 30:1995–1997CrossRef
5.
go back to reference Gross JL, de Azevedo MJ, Silveiro SP, Canani LH, Caramori ML, Zelmanovitz T (2005) Diabetic nephropathy: diagnosis, prevention, and treatment. Diabetes Care 28:164–176CrossRef Gross JL, de Azevedo MJ, Silveiro SP, Canani LH, Caramori ML, Zelmanovitz T (2005) Diabetic nephropathy: diagnosis, prevention, and treatment. Diabetes Care 28:164–176CrossRef
6.
go back to reference Khalil N, Sutton-Tyrrell K, Strotmeyer ES, Greendale GA, Vuga M, Selzer F, Crandall CJ, Cauley JA (2011) Menopausal bone changes and incident fractures in diabetic women: a cohort study. Osteoporos Int 22(5):1367–1376CrossRef Khalil N, Sutton-Tyrrell K, Strotmeyer ES, Greendale GA, Vuga M, Selzer F, Crandall CJ, Cauley JA (2011) Menopausal bone changes and incident fractures in diabetic women: a cohort study. Osteoporos Int 22(5):1367–1376CrossRef
7.
go back to reference Krakauer JC, McKenna MJ, Buderer NF, Rao DS, Whitehouse FW, Parfitt AM (1995) Bone loss and bone turnover in diabetes. Diabetes 44:775–782CrossRef Krakauer JC, McKenna MJ, Buderer NF, Rao DS, Whitehouse FW, Parfitt AM (1995) Bone loss and bone turnover in diabetes. Diabetes 44:775–782CrossRef
8.
go back to reference Rosato MT, Schneider SH, Shapses SA (1998) Bone turnover and insulin-like growth factor I levels increase after improved glycemic control in non-insulin dependent diabetes mellitus. Calcif Tissue Int 63:107–111CrossRef Rosato MT, Schneider SH, Shapses SA (1998) Bone turnover and insulin-like growth factor I levels increase after improved glycemic control in non-insulin dependent diabetes mellitus. Calcif Tissue Int 63:107–111CrossRef
9.
go back to reference Akin O, Göl K, Aktürk M, Erkaya S (2003) Evaluation of bone turnover in postmenopausal patients with type 2 diabetes mellitus using biochemical markers and bone mineral density measurements. Gynecol Endocrinol 17(1):19–29CrossRef Akin O, Göl K, Aktürk M, Erkaya S (2003) Evaluation of bone turnover in postmenopausal patients with type 2 diabetes mellitus using biochemical markers and bone mineral density measurements. Gynecol Endocrinol 17(1):19–29CrossRef
10.
go back to reference Mansoor Karimifar, Morteza Aghajanpoor, Amirhossein Salari, Ahmadreza Zamani, Mansour Salesi, Peyman Motaghi (2012) Evaluation of bone loss in diabetic postmenopausal women. J Res Med Sci, Vol 17, No 11 Mansoor Karimifar, Morteza Aghajanpoor, Amirhossein Salari, Ahmadreza Zamani, Mansour Salesi, Peyman Motaghi (2012) Evaluation of bone loss in diabetic postmenopausal women. J Res Med Sci, Vol 17, No 11
11.
go back to reference Zakeri Z, Azizi Z, Mehrabifar H, Hashemi M (2011) Evaluation of bone mineral density in premenopausal women with type-2 diabetes mellitus in Zahedan, southeast Iran. JPMA 61:443 Zakeri Z, Azizi Z, Mehrabifar H, Hashemi M (2011) Evaluation of bone mineral density in premenopausal women with type-2 diabetes mellitus in Zahedan, southeast Iran. JPMA 61:443
12.
go back to reference Touminen, J. Mpolsc, P. Ronnemaa, T. (1999) Bone mineral density in patients with type 1 and type 2 diabetes. Diabetes care, Vol 22, Number 7 Touminen, J. Mpolsc, P. Ronnemaa, T. (1999) Bone mineral density in patients with type 1 and type 2 diabetes. Diabetes care, Vol 22, Number 7
13.
go back to reference Strotmeyer ES, Cauley JA (2007) Diabetes mellitus, bone mineral density, and fracture risk. Curr Opin Endocrinol Diabetes Obes. 14(6):429–435CrossRef Strotmeyer ES, Cauley JA (2007) Diabetes mellitus, bone mineral density, and fracture risk. Curr Opin Endocrinol Diabetes Obes. 14(6):429–435CrossRef
14.
go back to reference Khazai NB, Beck GR Jr, Umpierrez GE (2009) Diabetes and fractures: an overshadowed association. Curr Opin Endocrinol Diabetes Obes 16(6):435–445CrossRef Khazai NB, Beck GR Jr, Umpierrez GE (2009) Diabetes and fractures: an overshadowed association. Curr Opin Endocrinol Diabetes Obes 16(6):435–445CrossRef
15.
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 12:1289–1294CrossRef 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 12:1289–1294CrossRef
16.
go back to reference Schwartz AV, Ewing SK, Porzig AM, McCulloch CE, Resnick HE, Hillier TA, Sellmeyer DE (2013) Diabetes and change in bone mineral density at the hip, calcaneus, spine, and radius in older women. Front Endocrinol 4:62CrossRef Schwartz AV, Ewing SK, Porzig AM, McCulloch CE, Resnick HE, Hillier TA, Sellmeyer DE (2013) Diabetes and change in bone mineral density at the hip, calcaneus, spine, and radius in older women. Front Endocrinol 4:62CrossRef
17.
go back to reference de Liefde II, van der Klift M, de Laet CEDH et al (2005) Bone mineral density and fracture risk in type-2 diabetes mellitus: the Rotterdam study. Osteoporos Int 16:1713CrossRef de Liefde II, van der Klift M, de Laet CEDH et al (2005) Bone mineral density and fracture risk in type-2 diabetes mellitus: the Rotterdam study. Osteoporos Int 16:1713CrossRef
18.
go back to reference Ma L, Oei L, Jiang L, Estrada K, Chen H, Wang Z et al (2012) Association between bone mineral density and type 2 diabetes mellitus: a meta-analysis of observational studies. Eur J Epidemiol 27(5):319–332 Ma L, Oei L, Jiang L, Estrada K, Chen H, Wang Z et al (2012) Association between bone mineral density and type 2 diabetes mellitus: a meta-analysis of observational studies. Eur J Epidemiol 27(5):319–332
19.
go back to reference Vestergaard P, Rejnmark L, Mosekilde L (2007) Discrepancies in bone mineral density and fracture risk in patients with type1 and type 2 diabetes- a meta-analysis. Osteoporos Int 18:427CrossRef Vestergaard P, Rejnmark L, Mosekilde L (2007) Discrepancies in bone mineral density and fracture risk in patients with type1 and type 2 diabetes- a meta-analysis. Osteoporos Int 18:427CrossRef
20.
go back to reference Klein GL (2014) Insulin and bone: recent developments. World J Diabetes 5(1):14–16CrossRef Klein GL (2014) Insulin and bone: recent developments. World J Diabetes 5(1):14–16CrossRef
21.
go back to reference Thrailkill KM, Lumpkin CK, Bunn RC, Kemp SF, Fowlkes JL (2005) Is insulin an anabolic agent in bone? Dissecting the diabetic bone for clues. Am J Physiol Endocrinol Metab 289(5):E735–E745CrossRef Thrailkill KM, Lumpkin CK, Bunn RC, Kemp SF, Fowlkes JL (2005) Is insulin an anabolic agent in bone? Dissecting the diabetic bone for clues. Am J Physiol Endocrinol Metab 289(5):E735–E745CrossRef
22.
go back to reference McCarty MF (1995) Anabolic effects of insulin on bone suggest a role for chromium picolinate in preservation of bone density. Med Hypotheses 45(3) McCarty MF (1995) Anabolic effects of insulin on bone suggest a role for chromium picolinate in preservation of bone density. Med Hypotheses 45(3)
23.
go back to reference Ghodsi M, Larijani B, Ali Keshtkar A, Nasli-Esfahani E, Alatab S, Reza Mohajeri-Tehrani M (2016) Mechanisms involved in altered bone metabolism in diabetes: a narrative review. J Diabetes Metab Disord 15:52CrossRef Ghodsi M, Larijani B, Ali Keshtkar A, Nasli-Esfahani E, Alatab S, Reza Mohajeri-Tehrani M (2016) Mechanisms involved in altered bone metabolism in diabetes: a narrative review. J Diabetes Metab Disord 15:52CrossRef
24.
go back to reference Napoli N, Chandran M, Pierroz DD, Abrahamsen B, Schwartz AV, Ferrari SL (2017) Mechanisms of diabetes mellitus-induced bone fragility. Nat Rev Endocrinol 13:208–219CrossRef Napoli N, Chandran M, Pierroz DD, Abrahamsen B, Schwartz AV, Ferrari SL (2017) Mechanisms of diabetes mellitus-induced bone fragility. Nat Rev Endocrinol 13:208–219CrossRef
25.
go back to reference Sundararaghavan V, Mazur MM, Evans B, Liu J, Ebraheim NA (2017) Diabetes and bone health: latest evidence and clinical implications. Ther Adv Musculoskelet Dis 9(3):67–74CrossRef Sundararaghavan V, Mazur MM, Evans B, Liu J, Ebraheim NA (2017) Diabetes and bone health: latest evidence and clinical implications. Ther Adv Musculoskelet Dis 9(3):67–74CrossRef
26.
go back to reference Hamann C, Kirschner S, Gunther K, Hofbauer L (2012) Bone, sweet bone–osteoporotic fractures in diabetes mellitus. Nat Rev Endocrinol 8:297–305CrossRef Hamann C, Kirschner S, Gunther K, Hofbauer L (2012) Bone, sweet bone–osteoporotic fractures in diabetes mellitus. Nat Rev Endocrinol 8:297–305CrossRef
27.
go back to reference Barrett-Connor E, Kritz-Silverstein D (1996) Does hyperinsulinemia preserve bone? Diabetes Care 19:1388–1392CrossRef Barrett-Connor E, Kritz-Silverstein D (1996) Does hyperinsulinemia preserve bone? Diabetes Care 19:1388–1392CrossRef
28.
go back to reference Ishii S, Cauley JA, Crandall CJ et al (2012) Diabetes and femoral neck strength: findings from the hip strength across the menopausal transition study. J Clin Endocrinol Metab 97(1):190–197CrossRef Ishii S, Cauley JA, Crandall CJ et al (2012) Diabetes and femoral neck strength: findings from the hip strength across the menopausal transition study. J Clin Endocrinol Metab 97(1):190–197CrossRef
29.
go back to reference De Waard EAC, Koster A, Melai T, van Geel TA, Henry RMA, Schram MT, van den Bergh JPW (2016) The association between glucose metabolism status, diabetes severity and a history of fractures and recent falls in participants of 50 years and older—the Maastricht Study. Osteoporos Int 27(11):3207–3216CrossRef De Waard EAC, Koster A, Melai T, van Geel TA, Henry RMA, Schram MT, van den Bergh JPW (2016) The association between glucose metabolism status, diabetes severity and a history of fractures and recent falls in participants of 50 years and older—the Maastricht Study. Osteoporos Int 27(11):3207–3216CrossRef
30.
go back to reference Starup-Linde J, Gregersen S, Vestergaard P (2016) Associations with fracture in patients with diabetes: a nested case–control study. BMJ Open Starup-Linde J, Gregersen S, Vestergaard P (2016) Associations with fracture in patients with diabetes: a nested case–control study. BMJ Open
31.
go back to reference Srikanthan P, Crandall CJ, Miller-Martinez D, Seeman TE, Greendale GA, Binkley N, Karlamangla AS (2014) Insulin resistance and bone strength. Findings from the study of midlife in the United States. J Bone Miner Res Off J Am Soc Bone Miner Res 29(4):796–803CrossRef Srikanthan P, Crandall CJ, Miller-Martinez D, Seeman TE, Greendale GA, Binkley N, Karlamangla AS (2014) Insulin resistance and bone strength. Findings from the study of midlife in the United States. J Bone Miner Res Off J Am Soc Bone Miner Res 29(4):796–803CrossRef
32.
go back to reference Yan W, Li X (2013) Impact of diabetes and its treatments on skeletal diseases. Front Med 7:81CrossRef Yan W, Li X (2013) Impact of diabetes and its treatments on skeletal diseases. Front Med 7:81CrossRef
33.
go back to reference Majumdar SR, Josse RG, Lin M, Eurich DT (2016) Does sitagliptin affect the rate of osteoporotic fractures in type 2 diabetes? Population-based cohort study. J Clin Endocrinol Metab 101(5):1963–1969CrossRef Majumdar SR, Josse RG, Lin M, Eurich DT (2016) Does sitagliptin affect the rate of osteoporotic fractures in type 2 diabetes? Population-based cohort study. J Clin Endocrinol Metab 101(5):1963–1969CrossRef
34.
go back to reference Vestergaard P, Rejnmark L, Mosekilde L (2005) Relative fracture risk in patients with diabetes mellitus and the impact of insulin and oral antidiabetic medication on relative fracture risk. Diabetologia 48:1292CrossRef Vestergaard P, Rejnmark L, Mosekilde L (2005) Relative fracture risk in patients with diabetes mellitus and the impact of insulin and oral antidiabetic medication on relative fracture risk. Diabetologia 48:1292CrossRef
35.
go back to reference Kumar BS, Ravisankar A, Mohan A, Kumar DP, Katyarmal DT, Sachan A, Sarma KVS (2015) Effect of oral hypoglycaemic agents on bone metabolism in patients with type 2 diabetes mellitus and occurrence of osteoporosis. Indian J Med Res 141(4):431–437CrossRef Kumar BS, Ravisankar A, Mohan A, Kumar DP, Katyarmal DT, Sachan A, Sarma KVS (2015) Effect of oral hypoglycaemic agents on bone metabolism in patients with type 2 diabetes mellitus and occurrence of osteoporosis. Indian J Med Res 141(4):431–437CrossRef
36.
go back to reference Adami S (2009) Bone health in diabetes: considerations for clinical management. Curr Med Res Opin 25(5):1057–1072CrossRef Adami S (2009) Bone health in diabetes: considerations for clinical management. Curr Med Res Opin 25(5):1057–1072CrossRef
37.
go back to reference Dutta M, Pakhetra R, Garg M (2012) Evaluation of bone mineral density in type 2 diabetes mellitus patients before and after treatment. Med J Armed Forces India 68(1):48–52CrossRef Dutta M, Pakhetra R, Garg M (2012) Evaluation of bone mineral density in type 2 diabetes mellitus patients before and after treatment. Med J Armed Forces India 68(1):48–52CrossRef
38.
39.
go back to reference Ray WA (2003) Evaluating medication effects outside of clinical trials: new-user designs. Am J Epidemiol 158:915–920CrossRef Ray WA (2003) Evaluating medication effects outside of clinical trials: new-user designs. Am J Epidemiol 158:915–920CrossRef
40.
go back to reference Faries D, Leon A, Haro JM, Obenchain RL (2010) Analysis of Observational Health Care Data using SAS. SAS Institute Faries D, Leon A, Haro JM, Obenchain RL (2010) Analysis of Observational Health Care Data using SAS. SAS Institute
41.
go back to reference Brown H, Prescott R (2006) Applied mixed models in medicine, 2nd edn. Hoboken, NJ, John Wiley, Sons, LtdCrossRef Brown H, Prescott R (2006) Applied mixed models in medicine, 2nd edn. Hoboken, NJ, John Wiley, Sons, LtdCrossRef
42.
go back to reference Greendale GA, Sowers M et al (2012) Bone mineral density loss in relation to the final menstrual period in a multi-ethnic cohort: results from the study of women’s health across the nation (SWAN). J Bone Miner Res Off J Am Soc Bone Miner Res 27(1):111–118CrossRef Greendale GA, Sowers M et al (2012) Bone mineral density loss in relation to the final menstrual period in a multi-ethnic cohort: results from the study of women’s health across the nation (SWAN). J Bone Miner Res Off J Am Soc Bone Miner Res 27(1):111–118CrossRef
Metadata
Title
The effect of insulin on bone mineral density among women with type 2 diabetes: a SWAN Pharmacoepidemiology study
Authors
K. Ruppert
J. Cauley
Y. Lian
J. C. Zgibor
C. Derby
D. H. Solomon
Publication date
01-02-2018
Publisher
Springer London
Published in
Osteoporosis International / Issue 2/2018
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-017-4276-9

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