A Risk Assessment Tool for Identifying Osteoporosis in Older Women with Type 2 Diabetes Mellitus

Abstract

Purpose To develop a simple and clinically useful assessment tool for osteoporosis in older women with type 2 diabetes mellitus (T2DM).

Methods A total of 601 women over 60 years of age with T2DM were enrolled in this study. The levels of serum sex hormones and bone metabolism markers were compared between the osteoporosis and non-osteoporosis groups. The least absolute shrinkage and selection operator regularization (LASSO) model was applied to generate a risk assessment tool. The risk score formula was evaluated using receiver operating characteristic analysis and the relationship between the risk score and the bone mineral density (BMD) and T-value were investigated.

Results Serum sex hormone-binding globulin (SHBG), cross-linked C-telopeptide of type 1 collagen (CTX), and osteocalcin (OC) were significantly higher in the osteoporosis group. After adjustment for age and body mass index (BMI), SHBG was found to be correlated with the T-value or BMD. Then, a risk score was specifically generated with age, BMI, SHBG, and CTX using the LASSO model. The risk score was significantly negatively correlated with the T-value and BMD of the lumbar spine, femoral neck, and total hip (all P<0.05).

Conclusion A risk score using age, BMI, SHBG, and CTX performs well for identifying osteoporosis in older women with T2DM.

Key words

osteoporosis - T2DM - LASSO - sex hormones - bone turnover markers

• References

• 1 Sozen T, Ozisik L, Basaran NC. An overview and management of osteoporosis. Eur J Rheumatol 2017; 4: 46-56
• 2 Lin X, Xiong D, Peng YQ. et al. Epidemiology and management of osteoporosis in the People's Republic of China: current perspectives. Clin Interv Aging 2015; 10: 1017-1033
• 3 Si L, Winzenberg TM, Jiang Q. et al. Projection of osteoporosis-related fractures and costs in China: 2010-2050. Osteoporos Int 2015; 26: 1929-1937
• 4 Diab DL, Watts NB. Postmenopausal osteoporosis. Curr Opin Endocrinol Diabetes Obes 2013; 20: 501-509
• 5 Rathmann W, Giani G. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 2004; 27: 2568-2569
• 6 Paschou SA, Dede AD, Anagnostis PG. et al. Type 2 diabetes and osteoporosis: A guide to optimal management. J Clin Endocrinol Metab 2017; 102: 3621-3634
• 7 Schwartz AV, Vittinghoff E, Bauer DC. et al. Association of BMD and FRAX score with risk of fracture in older adults with type 2 diabetes. JAMA 2011; 305: 2184-2192
• 8 Rubin MR. Type 2 diabetes and fractures: more information is needed. Endocrine 2013; 43: 469-471
• 9 Liu Z, Gao H, Bai X. et al. Evaluation of Singh Index and Osteoporosis Self-Assessment Tool for Asians as risk assessment tools of hip fracture in patients with type 2 diabetes mellitus. J Orthop Surg Res 2017; 12: 37
• 10 Pisani P, Renna MD, Conversano F. et al. Screening and early diagnosis of osteoporosis through X-ray and ultrasound based techniques. World J Radiol 2013; 5: 398-410
• 11 Cannarella R, Barbagallo F, Condorelli RA. et al. Osteoporosis from an endocrine perspective: The role of hormonal changes in the elderly. J Clin Med 2019; 8: 1564
• 12 Naylor K, Eastell R. Bone turnover markers: Use in osteoporosis. Nat Rev Rheumatol 2012; 8: 379-389
• 13 Nguyen HT, von Schoultz B, Nguyen TV. et al. Sex hormone levels as determinants of bone mineral density and osteoporosis in Vietnamese women and men. J Bone Miner Metab 2015; 33: 658-665
• 14 HEARTS-D Diagnosis and Management of Type 2 Diabetes-WHO. 2020 https://apps.who.int/iris/handle/10665/331710
• 15 Jing Y, Wang X, Yu J. et al. Associations of serum sex hormone binding globulin with bone mineral densities and higher 10-year probability of fractures in postmenopausal women with type 2 diabetes mellitus. Ann Transl Med 2019; 7: 457
• 16 Mantovani A, Sani E, Fassio A. et al. Association between non-alcoholic fatty liver disease and bone turnover biomarkers in post-menopausal women with type 2 diabetes. Diabetes Metab 2019; 45: 347-355
• 17 Xu ZR, Wang AH, Wu XP. et al. Relationship of age-related concentrations of serum FSH and LH with bone mineral density, prevalence of osteoporosis in native Chinese women. Clin Chim Acta 2009; 400: 8-13
• 18 Strotmeyer ES, Cauley JA, Schwartz AV. et al. Nontraumatic fracture risk with diabetes mellitus and impaired fasting glucose in older white and black adults: The health, aging, and body composition study. Arch Intern Med 2005; 165: 1612-1617
• 19 Bonds DE, Larson JC, Schwartz AV. et al. Risk of fracture in women with type 2 diabetes: The Women's Health Initiative Observational Study. J Clin Endocrinol Metab 2006; 91: 3404-3410
• 20 Basurto-Acevedo L, Saucedo-Garcia R. Vazquez-Martinez et al. Relationship between bone remodeling and metabolism in the elderly. Rev Med Inst Mex Seguro Soc 2018; 56: S6-S11
• 21 O'Connor TP, Lee A, Jarvis JU. et al. Prolonged longevity in naked mole-rats: Age-related changes in metabolism, body composition and gastrointestinal function. Comp Biochem Physiol A Mol Integr Physiol 2002; 133: 835-842
• 22 van den Beld AW, Kaufman JM, Zillikens MC. et al. The physiology of endocrine systems with ageing. Lancet Diabetes Endocrinol 2018; 6: 647-658
• 23 Evans AL, Paggiosi MA, Eastell R. et al. Bone density, microstructure and strength in obese and normal weight men and women in younger and older adulthood. J Bone Miner Res 2015; 30: 920-928
• 24 Sornay-Rendu E, Boutroy S, Vilayphiou N. et al. In obese postmenopausal women, bone microarchitecture and strength are not commensurate to greater body weight: the Os des Femmes de Lyon (OFELY) study. J Bone Miner Res 2013; 28: 1679-1687
• 25 Yang S, Shen X. Association and relative importance of multiple obesity measures with bone mineral density: the National Health and Nutrition Examination Survey 2005-2006. Arch Osteoporos 2015; 10: 14
• 26 Abdel-Hakim SM, Ibrahim MY, Ibrahim HM. et al. The effect of ghrelin antagonist (D-Lys3) GHRP-6 on ovariectomy-induced obesity in adult female albino rats. Endocr Regul 2014; 48: 126-134
• 27 Li GH, Cheung CL, Au PC. et al. Positive effects of low LDL-C and statins on bone mineral density: an integrated epidemiological observation analysis and Mendelian randomization study. Int J Epidemiol 2019; 49: 1221-1235
• 28 Alay I, Kaya C, Cengiz H. et al. The relation of body mass index, menopausal symptoms, and lipid profile with bone mineral density in postmenopausal women. Taiwan J Obstet Gynecol 2020; 59: 61-66
• 29 Holmberg AH, Johnell O, Nilsson PM. et al. Risk factors for fragility fracture in middle age. A prospective population-based study of 33,000 men and women. Osteoporos Int 2006; 17: 1065-1077
• 30 Sharma S, Fraser M, Lovell F. et al. Characteristics of males over 50 years who present with a fracture: Epidemiology and underlying risk factors. J Bone Joint Surg Br 2008; 90: 72-77
• 31 Fitzpatrick LA. Estrogen therapy for postmenopausal osteoporosis. Arq Bras Endocrinol Metabol 2006; 50: 705-719
• 32 Chin KY. The relationship between follicle-stimulating hormone and bone health: Alternative explanation for bone loss beyond oestrogen?. Int J Med Sci 2018; 15: 1373-1383
• 33 Park SG, Hwang S, Kim JS. et al. The association between dehydroepiandrosterone sulfate (DHEA-S) and bone mineral density in Korean men and women. J Bone Metab 2017; 24: 31-36
• 34 Gourlay ML, Preisser JS, Hammett-Stabler CA. et al. Follicle-stimulating hormone and bioavailable estradiol are less important than weight and race in determining bone density in younger postmenopausal women. Osteoporos Int 2011; 22: 2699-2708
• 35 Legrand E, Hedde C, Gallois Y. et al. Osteoporosis in men: A potential role for the sex hormone binding globulin. Bone 2001; 29: 90-95
• 36 Kahn SM, Hryb DJ, Nakhla AM. et al. Sex hormone-binding globulin is synthesized in target cells. J Endocrinol 2002; 175: 113-120
• 37 Hlaing TT, Compston JE. Biochemical markers of bone turnover – uses and limitations. Ann Clin Biochem 2014; 51: 189-202
• 38 Biver E, Chopin F, Coiffier G. et al. Bone turnover markers for osteoporotic status assessment? A systematic review of their diagnosis value at baseline in osteoporosis. Joint Bone Spine 2012; 79: 20-25
• 39 Park SG, Jeong SU, Lee JH. et al. The changes of CTX, DPD, osteocalcin, and bone mineral density during the postmenopausal period. Ann Rehabil Med 2018; 42: 441-448
• 40 Lormeau C, Soudan B, d'Herbomez M. et al. Sex hormone-binding globulin, estradiol, and bone turnover markers in male osteoporosis. Bone 2004; 34: 933-939
• 41 Czajkowska M, Plinta R, Owczarek A. et al. Circulating sclerostin levels in relation to nutritional status, sex hormones and selected bone turnover biochemical markers levels in peri- and postmenopausal women. Ginekol Pol 2019; 90: 371-375
• 42 Koh LK, Sedrine WB, Torralba TP. et al. A simple tool to identify asian women at increased risk of osteoporosis. Osteoporos Int 2002; 12: 699-705
• 43 Subramaniam S, Chan CY, Soelaiman IN. et al. The performance of osteoporosis self-assessment tool for Asians (OSTA) in identifying the risk of osteoporosis among Malaysian population aged 40 years and above. Arch Osteoporos 2019; 14: 117