AGENDA. Risk factors for fracture in diabetes:

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2 AGENDA Risk factors for fracture in diabetes: - Who has to be screened? - How to screen?

3 BMD AND FRACTURES IN TYPE 2 DIABETES Vestergaard P, Osteoporos Int

4 USEFULNESS OF FRAX ALGORYTHM IN TYPE 2 DIABETES

5 RISK FACTORS FOR FRAGILITY FRACTURES IN DM2 PATIENTS

6 FRATTURE E DIABETE MELLITO: RUOLO DELLE COMPLICANZE Retinopatia alterata visione Polineuropatia alterato equilibrio Cardiopatia aritmia AUMENTATO RISCHIO DI CADUTA Ipovitaminosi D

7 BIAS: more complications and hypoglycemic episodes Schwartz AV, Diabetes Care 2002

8 Hamann C et al, Nat Rev Endocrinol 2012 Hamann C et al, Nat Rev Endocrinol 2012

9 LOW BMD AND ITS PREDICTORS IN TYPE 1 DIABETIC PATIENTS EVALUATED BY ARTIFICIAL NEURAL NETWORK ANALYSIS Eller Vainicher et al, Diabetes Care 2011

10 HIGH SERUM PENTOSIDINE IS ASSOCIATED WITH PREVALENT FRACTURES IN DM1 INDEPENDENT OF BMD AND GLYCAEMIC CONTROL Neumann T et al. Osteoporos Int 2014

11 CLINICAL RISK FACTORS ASSOCIATED WITH POOR BONE HEALTH IN TYPE 1 DIABETES Zhukouskaya VV et al, J Endocrinol Invest 2015

12 SKELETAL EFFECTS OF ANTIDIABETIC AGENTS Merlotti D et al. Nutr Metab Cardiovasc Dis Positive effect Negative effect

13 EFFECTS OF ORAL HYPOGLYCEMIC AGENTS ON THE RISK OF DEVELOPING FRAGILITY FRACTURES IN T2D Palermo A et al, Osteoporos Int 2015

14 WHO HAS TO BE SCREENED? Postmenopausal women Presence of diabetic complications Cardiovascular disease Long disease duration Poor glycometabolic control High insulin doses Glitazones in postemenopausal women Other common risk factors (familiar history for fractures, low BMI, smoke, low dietary calcium intake.)

15 AGENDA Risk factors for fracture in diabetes: - Who has to be screened? - How to screen?

16 BMD AND FRACTURES IN TYPE 2 DIABETES Vestergaard P, Osteoporos Int

17 IN T2D THE FRACTURE RISK IS HIGHER FOR A GIVEN T SCORE Among older adults with type 2 DM, femoral neck BMD T score and FRAX score were associated with hip and nonspine fracture risk; however, in these patients compared with participants without DM, the fracture risk was higher for a given T score and age or for a given FRAX score. Schwartz AV et al, JAMA 2011

18 HOW TO PREDICT VERTEBRAL FRACTURES IN TYPE 2 DIABETICS? n=99 AUC 0.69, p< AUC 0.63, p<0.004 The cutoff of TBS with the best compromise between sensitivity (75.8 %) and specificity (54.1 %) is set at The cutoff of FN-BMD with the best compromise between sensitivity (70.6 %) and specificity (58.5 %) is set at less than 1.0 Zhukouskaya VV et al, Osteoporos Int 2015

19 HOW TO PREDICT VERTEBRAL FRACTURES IN TYPE 2 DIABETICS? n=99 Zhukouskaya VV et al, Osteoporos Int 2015

20 BMD AND FRACTURES IN TYPE 1 DIABETES Vestergaard P, Osteoporos Int

21 T1D PATIENTS HAVE ELEVATED PREVALENCE OF ASYMPTOMATIC VFX, REGARDLESS OF BMD Zhukouskaya VV et al, Diabetes Care 2013

22 LOW BONE TURNOVER IN DM2 Gennari L et al, JCEM 2012

23 AND HOW TO SCREEN? SIOMMMS Guidelines BMD by DXA Spinal X-ray Biochemistry Erythrocytes sedimentation rate Blood count Serum elettrophoresis Serum calcium Serum Phosphorous Alkaline Phosphatase total activity Creatinine 24 hours urinary calcium

24 TAKE HOME MESSAGES Diabetic (type 1 or 2) patients have to be screened for bone damage if hypogonadal, with diabetic complications and/or cardiovascular disease, with long disease duration and/or poor glycometabolic control and/or high insulin doses, with glitazones therapy in postmenopausal women and with other common risk factors (familiar history for fractures, low BMI, smoke, low dietary calcium intake.). Diabetic patients should undergo BMD determination by DXA and vertebral fracture risk assessment by x-ray in addition to biochemical exams.

25 THANK YOU

26 DPP4-INHIBITORS AND BONE FRACTURES: A META-ANALYSIS OF RANDOMIZED CLINICAL TRIALS (Monami M et al, Diabetes Care 2011) The duration of the trials not sufficiently long to analyse the effect on fracture. Fractures were not the principal end points and were reported only as adverse events. No data could be obtained for sexes and menopausal status. Montagnani A, Diabetes, Obesity and Metabolism 2013

27 Kohan DE et al, Kidney International 2014

28 Hamann C et al, Nat Rev Endocrinol 2012

29 WNT/ -CATENIN SIGNALLING AND REDUCED BONE TURNOVER IN T2D Gaudio A et al, JCEM 2012

30 TERIPARATIDE IS EFFECTIVE IN DIABETES Schwartz, AV et al, Bone 2016

31 ANTIRESORPTIVES AND FRACTURE RISK IN TYPE 2 DIABETES Vestergaard, Calcif Tissue Int 2011