Top

Osteoporosis International

Published in:

01-06-2021 | Insulins | Original Article

Sex-specific associations of serum insulin-like growth factor-1 with bone density and risk of fractures in Chinese patients with type 2 diabetes

Authors: F. Lv, X. Cai, R. Zhang, L. Zhou, X. Zhou, X. Han, L. Ji

Published in: Osteoporosis International | Issue 6/2021

Abstract

Summary

We evaluated the associations of serum insulin-like growth factor-1 (IGF-1) with bone mineral density (BMD) and risk of fractures in Chinese patients with type 2 diabetes (T2D). We found positive associations between IGF-I and BMD and negative associations between IGF-I and all three modified 10-year probabilities of MOFs and HFs in men, but not in women.

Introduction

The objective was to investigate the associations of serum insulin-like growth factor-1 (IGF-1) with bone mineral density (BMD) and risk of fractures in Chinese patients with type 2 diabetes (T2D) in each gender.

Methods

This was a cross-sectional, retrospective study that included men over 50 years and postmenopausal women with T2D without medical conditions or medications known to significantly affect BMD or serum IGF-I levels. Data of IGF-1, bone metabolism markers, lumbar spine (LS), femoral neck (FN), and total hip (TH) BMD were obtained; 10-year probability of major osteoporotic fractures (MOFs) and hip fractures (HFs) was calculated and modified with rheumatoid arthritis, femoral neck T-score, and age. Correlations of IGF-1 levels with bone metabolism and risk of fractures were statistically analyzed in men and women, respectively.

Results

A total of 391 patients, including 226 men and 165 women, were included. The age, serum fasting C-peptide, glycosylated hemoglobin (HbA1c), bone formation marker, and all three modified 10-year probabilities of MOFs and HFs were higher in women than those in men (all p < 0.05). The levels of 25 hydroxyvitamin D (25OHD), IGF-1, and BMD were lower in women than those in men (all p < 0.05). In men, IGF-1 was positively correlated with FN and TH BMD (FN BMD: r = 0.267, p < 0.001; TH BMD: r = 0.235, p < 0.001) and negatively correlated with all three modified 10-year probabilities of MOFs (RA-modified MOFs: r = - 0.289, p < 0.001; age-modified MOFs: r = - 0.237, p < 0.001; FN T-score−modified MOFs: r = - 0.280, p < 0.001) and HFs (RA-modified HFs: r = - 0.291, p < 0.001; age-modified HFs: r = - 0.271, p < 0.001; FN T-score−modified HFs: r = - 0.270, p < 0.001), while no significant correlations were found between serum IGF-I and BMD and three modified 10-year probability in women.

Conclusions

According to this study, we found sex differences in the associations of serum IGF-1 with BMD and risk of fractures in Chinese patients with T2D. These results suggested that increasing serum IGF-1 might be a clinical target for protecting fractures in T2D, especially in men.

Chiodini I, Catalano A, Gennari L, Gaudio A (2020) Osteoporosis and fragility fractures in type 2 diabetes. J Diabetes Res 2020:9342696. https://doi.org/10.1155/2020/9342696CrossRefPubMedPubMedCentral

Ferrari SL, Abrahamsen B, Napoli N, Akesson K, Chandran M, Eastell R, El-Hajj Fuleihan G, Josse R, Kendler DL, Kraenzlin M, Suzuki A, Pierroz DD, Schwartz AV, Leslie WD, Bone and Diabetes Working Group of IOF (2018) Diagnosis and management of bone fragility in diabetes: an emerging challenge. Osteoporos Int 29:2585–2596. https://doi.org/10.1007/s00198-018-4650-2CrossRefPubMedPubMedCentral

Schwartz AV, Vittinghoff E, Bauer DC, Hillier TA, Strotmeyer ES, Ensrud KE, Donaldson MG, Cauley JA, Harris TB, Koster A, Womack CR, Palermo L, Black DM Study of Osteoporotic Fractures (SOF) Research Group; Osteoporotic Fractures in Men (MrOS) Research Group; Health, Aging, and Body Composition (Health ABC) Research Group(2011) Association of BMD and FRAX score with risk of fracture in older adults with type 2 diabetes. JAMA 305:2184–2192. https://doi.org/10.1001/jama.2011.715CrossRefPubMedPubMedCentral

Schacter GI, Leslie WD (2017) DXA-based measurements in diabetes: can they predict fracture risk? Calcif Tissue Int 100:150–164. https://doi.org/10.1007/s00223-016-0191-xCrossRefPubMed

Leslie WD, Johansson H, McCloskey EV, Harvey NC, Kanis JA, Hans D (2018) Comparison of methods for improving fracture risk assessment in diabetes: the Manitoba BMD Registry. J Bone Miner Res 33:1923–1930. https://doi.org/10.1002/jbmr.3538CrossRefPubMedPubMedCentral

Geusens PP, Boonen S (2002) Osteoporosis and the growth hormone-insulin-like growth factor axis. Horm Res 58(Suppl 3):49–55. https://doi.org/10.1159/000066483CrossRefPubMed

Giustina A, Mazziotti G, Canalis E (2008) Growth hormone, insulin-like growth factors, and the skeleton. Endocr Rev 29:535–559. https://doi.org/10.1210/er.2007-0036CrossRefPubMedPubMedCentral

Kanazawa I, Yamaguchi T, Yamamoto M, Yamauchi M, Yano S, Sugimoto T (2007) Serum insulin-like growth factor-I level is associated with the presence of vertebral fractures in postmenopausal women with type 2 diabetes mellitus. Osteoporos Int 18:1675–1681. https://doi.org/10.1007/s00198-007-0430-0CrossRefPubMed

Kanazawa I, Yamaguchi T, Sugimoto T (2011) Serum insulin-like growth factor-I is a marker for assessing the severity of vertebral fractures in postmenopausal women with type 2 diabetes mellitus. Osteoporos Int 22:1191–1198. https://doi.org/10.1007/s00198-010-1310-6CrossRefPubMed

10.

Ardawi MS, Akhbar DH, Alshaikh A, Ahmed MM, Qari MH, Rouzi AA, Ali AY, Abdulrafee AA, Saeda MY (2013) Increased serum sclerostin and decreased serum IGF-1 are associated with vertebral fractures among postmenopausal women with type-2 diabetes. Bone 56:355–362. https://doi.org/10.1016/j.bone.2013.06.029CrossRefPubMed

11.

Miyake H, Kanazawa I, Sugimoto T (2017) Decreased serum insulin-like growth factor-I is a risk factor for non-vertebral fractures in diabetic postmenopausal women. Intern Med 56:269–273. https://doi.org/10.2169/internalmedicine.56.7416CrossRefPubMedPubMedCentral

12.

Kanazawa I, Notsu M, Miyake H, Tanaka K, Sugimoto T (2018) Assessment using serum insulin-like growth factor-I and bone mineral density is useful for detecting prevalent vertebral fractures in patients with type 2 diabetes mellitus. Osteoporos Int 29:2527–2535. https://doi.org/10.1007/s00198-018-4638-yCrossRefPubMed

13.

Dawson-Hughes B, Tosteson AN, Melton LJ 3rd, Baim S, Favus MJ, Khosla S, Lindsay RL, National Osteoporosis Foundation Guide Committee (2008) Implications of absolute fracture risk assessment for osteoporosis practice guidelines in the USA. Osteoporos Int 19:449–458. https://doi.org/10.1007/s00198-008-0559-5CrossRefPubMed

14.

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 166:495–505. https://doi.org/10.1093/aje/kwm106CrossRefPubMed

15.

Li M, Lv F, Zhang Z, Deng W, Li Y, Deng Z, Jiang Y, Wang O, Xing X, Xu L, Xia W (2016) Establishment of a normal reference value of parathyroid hormone in a large healthy Chinese population and evaluation of its relation to bone turnover and bone mineral density. Osteoporos Int 27:1907–1916. https://doi.org/10.1007/s00198-015-3475-5CrossRefPubMed

16.

Jiajue R, Qi X, Jiang Y, Wang Q, Wang W, Pei Y, Wang X, Huang W, Zheng X, Ning Z, Wang O, Li M, Xing X, Yu W, Xu L, Xia W (2019) Incident fracture risk in type 2 diabetic postmenopausal women in Mainland China: Peking Vertebral Fracture Study. Calcif Tissue Int 105:466–475. https://doi.org/10.1007/s00223-019-00598-xCrossRefPubMed

17.

Liu S, Chen R, Ding N, Wang Q, Huang M, Liu H, Xie Z, Ou Y, Sheng Z (2020) Setting the new FRAX reference threshold without bone mineral density in Chinese postmenopausal women. J Endocrinol Invest. https://doi.org/10.1007/s40618-020-01315-4

18.

Cui L, He T, Jiang Y, Li M, Wang O, Jiajue R, Chi Y, Xu Q, Xing X, Xia W (2019) Predicting the intervention threshold for initiating osteoporosis treatment among postmenopausal women in China: a cost-effectiveness analysis based on real-world data. Osteoporos Int 31:307–316. https://doi.org/10.1007/s00198-019-05173-6CrossRefPubMedPubMedCentral

19.

Mohsin S, Kaimala S, Sunny JJ, Adeghate E, Brown EM (2019) Type 2 Diabetes mellitus increases the risk to hip fracture in postmenopausal osteoporosis by deteriorating the trabecular bone microarchitecture and bone mass. J Diabetes Res 2019:3876957–3876910. https://doi.org/10.1155/2019/3876957CrossRefPubMedPubMedCentral

20.

van Varsseveld NC, Sohl E, Drent ML, Lips P (2015) Gender-specific associations of serum insulin-like growth factor-1 with bone health and fractures in older persons. J Clin Endocrinol Metab 100:4272–4281. https://doi.org/10.1210/jc.2015-2549CrossRefPubMed

21.

Langlois JA, Rosen CJ, Visser M, Hannan MT, Harris T, Wilson PW, Kiel DP (1998) Association between insulin-like growth factor I and bone mineral density in older women and men: the Framingham Heart Study. J Clin Endocrinol Metab 83:4257–4262. https://doi.org/10.1210/jcem.83.12.5308CrossRefPubMed

22.

Muñoz-Torres M, Mezquita-Raya P, Lopez-Rodriguez F, Torres-Vela E, de Dios LJ, Escobar-Jimenez F (2001) The contribution of IGF-I to skeletal integrity in postmenopausal women. Clin Endocrinol (Oxf) 55:759–766. https://doi.org/10.1046/j.1365-2265.2001.01390.xCrossRef

23.

Garnero P, Sornay-Rendu E, Delmas PD (2000) Low serum IGF-1 and occurrence of osteoporotic fractures in postmenopausal women. Lancet 355:898–899. https://doi.org/10.1016/s0140-6736(99)05463-xCrossRefPubMed

24.

Pye SR, Almusalam B, Boonen S, Vanderschueren D, Borghs H, Gielen E, Adams JE, Ward KA, Bartfai G, Casanueva FF, Finn JD, Forti G, Giwercman A, Han TS, Huhtaniemi IT, Kula K, Labrie F, Lean ME, Pendleton N, Punab M, Silman AJ, Wu FC, O'Neill TW, EMAS Study Group (2011) Influence of insulin-like growth factor binding protein (IGFBP)-1 and IGFBP-3 on bone health: results from the European Male Ageing Study. Calcif Tissue Int 88:503–510. https://doi.org/10.1007/s00223-011-9484-2CrossRefPubMedPubMedCentral

25.

Ohlsson C, Mellström D, Carlzon D, Orwoll E, Ljunggren O, Karlsson MK, Vandenput L (2011) Older men with low serum IGF-1 have an increased risk of incident fractures: the MrOS Sweden study. J Bone Miner Res 26:865–872. https://doi.org/10.1002/jbmr.281CrossRefPubMed

26.

Center JR, Nguyen TV, Sambrook PN, Eisman JA (1999) Hormonal and biochemical parameters in the determination of osteoporosis in elderly men. J Clin Endocrinol Metab 84:3626–3635. https://doi.org/10.1210/jcem.84.10.6051CrossRefPubMed

27.

Yeap BB, Alfonso H, Chubb SAP, Center JR, Beilin J, Hankey GJ, Almeida OP, Golledge J, Norman PE, Flicker L (2020) U-shaped association of plasma testosterone, and no association of plasma estradiol, with incidence of fractures in men. J Clin Endocrinol Metab 105:dgaa115. https://doi.org/10.1210/clinem/dgaa115CrossRefPubMed

28.

ES LB, Nielson CM, Marshall LM, Lapidus JA, Barrett-Connor E, Ensrud KE, Hoffman AR, Laughlin G, Ohlsson C, Orwoll ES, Osteoporotic Fractures in Men Study Group (2009) The effects of serum testosterone, estradiol, and sex hormone binding globulin levels on fracture risk in older men. J Clin Endocrinol Metab 94:3337–3346. https://doi.org/10.1210/jc.2009-0206CrossRef

29.

Hsu B, Cumming RG, Seibel MJ, Naganathan V, Blyth FM, Bleicher K, Dave A, Le Couteur DG, Waite LM, Handelsman DJ (2015) Reproductive hormones and longitudinal change in bone mineral density and incident fracture risk in older men: the Concord Health and Aging in Men Project. J Bone Miner Res 30:1701–1708. https://doi.org/10.1002/jbmr.2493CrossRefPubMed

Title: Sex-specific associations of serum insulin-like growth factor-1 with bone density and risk of fractures in Chinese patients with type 2 diabetes
Authors: F. Lv
X. Cai
R. Zhang
L. Zhou
X. Zhou
X. Han
L. Ji
Publication date: 01-06-2021
Publisher: Springer London
Keywords: Insulins
Insulins
Type 2 Diabetes
Published in: Osteoporosis International / Issue 6/2021
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-020-05790-6

At a glance: The STEP trials

Springer Medicine

Sex-specific associations of serum insulin-like growth factor-1 with bone density and risk of fractures in Chinese patients with type 2 diabetes

Abstract

Summary

Introduction

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Summary

Introduction

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 6/2021

Zoledronic acid reduces the rate of clinical fractures after surgical repair of a hip fracture regardless of the Pretreatment bone mineral density

Association between body mass index and the risk of falls: a nationwide population-based study

Long-term direct and indirect economic burden associated with osteoporotic fracture in US postmenopausal women

Multiple vertebral compression fractures in a human immunodeficiency virus-positive patient with glucocorticoid-induced Cushing syndrome treated with percutaneous vertebroplasty: a case report

Situational risk factors for fall-related vertebral fractures in older men and women

The diabetes-fracture association in women with type 1 and type 2 diabetes is partially mediated by falls: a 15-year longitudinal study