Skip to main content
Top

07-06-2018 | Osteoporosis | Article

FRAX tool in type 2 diabetic subjects: the use of HbA1c in estimating fracture risk

Journal: Acta Diabetologica

Authors: Alessia Valentini, Maria Assunta Cianfarani, Livia De Meo, Pasquale Morabito, Daniele Romanello, Umberto Tarantino, Massimo Federici, Aldo Bertoli

Publisher: Springer Milan

Abstract

Aims

Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fractures, despite having greater bone mineral density (BMD) than non-diabetic subjects. This has led to the hypothesis that the presence of impaired bone quality among diabetics reduces bone strength. The Fracture Risk Assessment Score (FRAX) algorithm, introduced to facilitate the evaluation of fracture risk, underestimates the risk of fracture in diabetic patients. The purpose of this study is to confirm the relationship between the degree of metabolic compensation and the 10-year probability of a major fracture or a hip osteoporotic fracture observed in our previous study and to ascertain whether glycosylated hemoglobin (HbA1c) can improve the predictive value of FRAX in patients with T2DM.

Methods

Our data derive from a retrospective clinical study conducted at the “Tor Vergata” Polyclinic in Rome on 6355 subjects over 50 years of age evaluated for osteoporosis. All available clinical records were examined. HbA1c was available for 242 of these subjects and all had had a Dual-energy X-ray Absorption (DXA) scan of the lumbar spine and femoral neck. The risk of fracture was estimated using the Italian version of the FRAX algorithm.

Result

Patients with T2DM had BMD and T-scores higher than those of non-diabetic subjects, while FRAX average values were higher in the non-diabetic group. HbA1c and FRAX are inversely correlated with each other: for each incremental percentage point of HbA1c growth, the FRAX major osteoporotic fracture probability is reduced by 0.915 points and the FRAX hip osteoporotic fracture probability by 1.438 points. The introduction of a correction factor derived from HbA1c, resulted in mean FRAX values of diabetic patients equivalent to those of non-diabetic subjects.

Conclusions

We propose a correction factor derived from HbA1c that could enhance the predictive ability of fracture risk estimated by the FRAX algorithm in subjects with T2DM.
Literature
1.
Sambrook P, Cooper C (2006) Osteoporosis. Lancet 367:2010–2018CrossRef
2.
Rachner TD, Khosla S, Hofbauer LC (2011) Osteoporosis: now and the future. Lancet 377:1276–1287CrossRefPubMedPubMedCentral
3.
Cummings SR, Bates D, Black DM (2002) Clinical use of bone densitometry: scientific review. JAMA 288:1889–1897CrossRefPubMed
4.
Kanis JA, Hans D, Cooper C, Baim S, Bilezikian JP, Binkley N et al (2011) Interpretation and use of FRAX in clinical practice. Osteoporos Int 22:2395–2411CrossRefPubMed
5.
Hamann C, Kirschner S, Gunter KP, Hofbauer LC (2012) Bone, sweet bone—osteoporotic fractures in diabetes mellitus. Nat Rev Endocrinol 8(5):297–305CrossRefPubMed
6.
Napoli N, Chandran M, Pierroz DD et al (2017) Mechanisms of diabetes mellitus-induced bone fragility. Nat Rev Endocrinol 13(4):208–219CrossRefPubMed
7.
Rubin MR (2015) Bone cells and bone turnover in diabetes mellitus. Curr Osteoporos Rep 13:186–191CrossRefPubMed
8.
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 18:427–444CrossRefPubMed
9.
Oei L, Zillikens MC, Dehghan A, Buitendijk GHS, Castano-Betancourt MC, Estrada K et al (2013) High bone mineral density and fracture risk in type 2 diabetes as skeletal complication of inadequate glucose control. Diabetes Care 36:1619–1628CrossRefPubMedPubMedCentral
10.
Conte C, Epstein S, Napoli N (2018) Insulin resistance and bone: a biological partnership. Acta Diabetol 55(4):305–314CrossRefPubMed
11.
Leslie WD, Rubin MR, Schwartz AV, Kanis JA (2012) Type 2 diabetes and bone. J Bone Miner Res 27(11):2231–2237CrossRefPubMed
12.
Viguet-Carrin S et al (2006) The role of collagen in bone strenght. Osteoporos Int 17(3):319–336CrossRefPubMed
13.
Melton LJ et al (2008) A bone structural basis for fracture risk in diabetes. J Clin Endocrinol Metab 93(12):4804–4809CrossRefPubMedPubMedCentral
14.
Giangregorio LM, Leslie WD, Lix LM, Johansson H, Oden A, McCloskey E et al (2012) FRAX underestimates fracture risk in patients with diabetes. J Bone Miner Res 27(2):301–308CrossRefPubMed
15.
Leslie W, Hough S (2016) Fracture risk assessment in diabetes. In: Lecka-Czernik B, Fowlkes J (eds) Diabetic bone disease: basic and translational research and clinical applications. Springer International Publishing, Basel, pp 45–69CrossRef
16.
Schacter GI, Leslie WD (2017) DXA-based measurements in diabetes: can they predict fracture risk? Calcif Tissue Int 100:150–164CrossRefPubMed
17.
Conway BN, Long DM, Figaro MK, May ME (2016) Glycemic control and fracture risk in elderly patients with diabetes. Diabetes Res Clin Pract 115:47–53CrossRefPubMedPubMedCentral
18.
Li CI, Liu CS, Lin WY et al (2015) Glycated hemoglobin level and risk of hip fracture in older people with type 2 diabetes: a competing risk analysis of taiwan diabetes cohort study. J Bone Miner Res 30(7):1338–1346CrossRefPubMed
19.
Bertoli A, Valentini A, Cianfarani MA, Gasbarra E, Tarantino U, Federici M (2017) Low FT3: a possible marker of frailty in the elderly. Clin Interv Aging 12:335–341CrossRefPubMedPubMedCentral
21.
ADA (2017) Standards of medical care in diabetes-2017. Diabetes Care 40(Suppl 1):S1–S135
22.
Kirkman MS, Briscoe VJ, Clark N, Florez H, Haas LB, Halter JB et al (2012) Diabetes in older adults. Diabetes Care 35(12):2650–2664CrossRefPubMedPubMedCentral
23.
Hendickx G, Boudin E, Hul WV (2015) A look behind the scenes: the risk and pathogenesis of primary osteoporosis. Nat Rev Rheumatol 11(8):462–474CrossRef
24.
de Liefde II, van der Klift M, de Laet CEDH, van Daele PLA, Hofman A, Pols HAP (2005) Bone mineral density and fracture risk in type-2 diabetes mellitus: the Rotterdam Study. Osteoporos Int 16:1713–1720CrossRefPubMed
25.
Schwartz AV (2016) Epidemiology of fractures in type 2 diabetes. Bone 82: 2–8CrossRefPubMed
26.
Kanis JA, McCloskey EV, Johansson H, Oden A, Strom O, Borgstrom F (2010) Development and use of FRAX in osteoporosis. Osteoporos Int 21(Suppl 2):407–413
27.
Kanis JA, on behalf of the World Health Organization Scientific Group (2007) Assessment of osteoporosis at the primary health-care level. Technical Report. World Health Organization Collaborating Centre for Metabolic Bone Diseases, University of Sheffield, UK
28.
Carnevale V, Morano S, Fontana A, Annese MA, Fallarino M, Filardi T et al (2014) Assessment of fracture risk by the FRAX algorithm in men and women with and without type 2 diabetes mellitus: a cross-sectional study. Diabetes Metab Res Rev 30:313–322CrossRefPubMed
29.
Schwartz AV, Vittinghoff E, Bauer DC, Hillier TA, Strotmeyer ES, Ensrud KE et al (2011) Association of BMD and FRAX score with risk of fracture in older adults with type 2 diabetes. JAMA 305(21):2184–2192CrossRefPubMedPubMedCentral
30.
Yamamoto M, Yamaguchi T, Yamauchi M, Kaji H, Sugimoto T (2009) Diabetic patients have an increased risk of vertebral fractures independent of BMD or diabetic complications. J Bone Miner Res 24(4):702–709CrossRefPubMed
31.
Napoli N, Schwartz AV, Schafer AL et al (2018) Vertebral fracture risk in diabetic elderly men: the MrOS Study. J Bone Miner Res 33(1):63–69CrossRefPubMed
32.
Leslie WD, Lix LM, Prior HJ, Derksen S, Metge C, O’Neil J (2007) Biphasic fracture risk in diabetes: a population-based study. Bone 40:1595–1601CrossRefPubMed
33.
Janghorbani M, Feskanich D, Willet WC, Hu F (2006) Prospective study of diabetes and risk of hip fracture. Diabetes Care 29:1573–1578CrossRefPubMed
34.
Skyler JS (1996) Diabetic complications. The importance of glucose control. Endocrinol Metab Clin N Am 25(2):243–254CrossRef
35.
Ivers RQ, Cumming RG, Mitchell P, Peduto AJ, Blue Mountains Eye Study (2001) Diabetes and risk of fracture: the blue mountains eye study. Diabetes Care 24(7):1198–1203CrossRefPubMed
36.
Majumdar SR, Leslie WD, Lix LM et al (2016) Longer duration of diabetes strongly impacts fracture risk assessment: the Manitoba BMD cohort. J Clin Endocrinol Metab 101(11):4489–4496CrossRefPubMedPubMedCentral
37.
Schwartz AV, Vittinghoff E, Sellmeyer DE et al (2008) Diabetes-related complications, glycemic control, and falls in older adults. Diabetes Care 31 (3): 391–396CrossRefPubMed
38.
Monami M, Cresci B, Colombini A et al (2008) Bone fractures and hypoglycemic treatment in type 2 diabetic patients: a case-control study. Diabetes Care 31(2):199–203CrossRefPubMed
39.
Schwartz AV (2017) Diabetes, bone and glucose-lowering agents: clinical outcomes. Diabetologia 60(7):1170–1179CrossRefPubMed
40.
Gilbert MP, Pratley RE (2015) The impact of diabetes and diabetes medications on bone health. Endocr Rev 36(2):194–213CrossRefPubMed
41.
Johnston SS, Conner C, Aagren M, Ruiz K, Bouchard J (2012) Association between hypoglycaemic events and fall-related fractures in Medicare-covered patients with type 2 diabetes. Diabetes Obes Metab 14(7):634–643CrossRefPubMed
42.
Zhao Y, Kachroo S, Kawabata H et al (2016) Association between hypoglycemia and fall-related fractures and health care utilization in older veterans with type 2 diabetes. Endocr Pract 22(2):196–204CrossRefPubMed
43.
Goh SY, Cooper ME (2008) The role of advanced glycation end products in progression and complications of diabetes. J Clin Endocrinol Metab 93:1143–1152CrossRefPubMed
44.
Yamamoto M, Sugimoto T (2016) Advanced glycation end products, diabetes, and bone strength. Curr Osteoporos Rep 14:320–326CrossRefPubMedPubMedCentral
45.
Ahmed N (2005) Advanced glycation end products-role in pathology of diabetic complications. Diabetes Res Clin Pract 67:3–21CrossRefPubMed

Be confident that your patient care is up to date

Medicine Matters is being incorporated into Springer Medicine, our new medical education platform. 

Alongside the news coverage and expert commentary you have come to expect from Medicine Matters diabetes, Springer Medicine's complimentary membership also provides access to articles from renowned journals and a broad range of Continuing Medical Education programs. Create your free account »