DM and Osteoporosis. Why is it important?

Transcription

1 DM and Osteoporosis Why is it important? Diabetes Osteoporosis Fractures Dr Pedro Conthe HGUGM Madrid Spain

2 Agenda: DM and Osteoporosis Observational studies Physiopathology of bone Type I and Type 2 DM How to handle this problem in clinical practice

3 Association between type 1 DM and fractures Type 1 DM M Janghorbani et al. Am J Epidemiol. 2007;166(5):

4 Association between diabetes mellitus and fractures Type 2 DM M Janghorbani et al. Am J Epidemiol. 2007;166(5):

5 Diabetes and bone: main causes risk of fractures (RR=6-12) Type 1 Type 2 type 1 risk of fractures (RR=2-4).-deficit of anabolic effects of insulin and amylin type 2.-long-term complications of the disease duration retinopathy neuropathy cataract insulin treatment Nicodemus KK, AR Diabetes Care 24:

6 Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1, diabetes type 2 and without diabetes 1 0,9 0,8 0,7 P<0.05 P< ,6 0,5 0,4 Type 1 Type 2 Controls 0,3 0,2 0,1 0 Men Women Tuominen et al, Diabetes Care, 1999

7 Krakauer et al, Diabetes, 1995 Model for the effects of diabetes on BMD at different times of life Insulina (Insulin resistance, > IGF-1) < Insulina < IGF-1

8 Serum osteocalcin in type 1 DM men premenopausal women postmenopausal women Other markers: Sclerostina FGF 23 Leptina Adiponectina Osteoquines.. Zhou M et al: Eur J Endocrinol 2009; 161:

9 Energy regulation of bone remodeling and the insulin axis osteocalcin IGF-1

10 DM is associated with a decrease in bone strength that is not reflected in the measurement of BMD

11 alterations Insulin dependent DM 1 / DM 2 > AGEs Entities specific related to DM Fractures Diabetes Bone Renal Dysfunction hyperparathyroidism hypercalciuria Alteration Vit D Treatments (Gtz) Retinopathy visual disturbances Neuropathy Orthostatic hypotonia

12 Bone Cells Formation Fractures Diabetes Bone AGEs > AGEs alteration in the composition of collagen and bone cells Rosen JC et al. Nature Clinical Practice, 2006 impairment in the secretion of cytokines and insulin-like growth factor

13 alterations Insulin dependent DM 1 / DM 2 > AGEs Entities specific related to DM Fractures Diabetes Bone Renal Dysfunction Hyper/hypo parathyroidism Vit D Alterations Hypercalciuria.. Treatments (Gtz) Retinopathy visual disturbances Neuropathy Orthostatic hypotonia

14 Renal involvement aggravates hip fracture risk Fractures Diabetes Bone Kidney Arch Intern Med 2007

15 Major targets and actions of vitamin D on Peripheral tissues Fractures Diabetes Bone vit D Palomer et al. Diabetes, Obesity and Metabolism, 2007

16 Fractures Diabetes Bone D vit Vit D Deficiency is associated to DM / Obesity/ SM / Hypert..etc Vit D directlly stimulates expression of Insulin receptors PTH level start to rise when vit D levels below 25 ng/ml Elevation of PTH leads to: Insulin Resistence / Cardiovascular mortality Vit D deficiency could be a contributor to Cv mortality Robinson JG et al: Diabetes Care. 2011

17 alterations Insulin dependent DM 1 / DM 2 > AGEs Entities specific related to DM Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered Approach Treatments (Gtz) Fractures Diabetes Bone Renal Dysfunction hyperparathyroidism hypercalciuria Alteration Vit D Neuropathy Orthostatic hypotonia Retinopathy visual disturbances conditions that lead to falls

18 Bone Is a target for glitazones Treatment Fractures Diabetes Bone Control Rosiglitazone Rzonca SO et al. Endocrinology, 2004

19 Bone homeostasis and Gtz Modified by Pei L et al. JCI, 2004

20 Conclusions take home messages 1.-The presence of osteoporosis in diabetic patients is often not considered, but the risk of fractures is higher. 2.-There are important differences between type1 / type 2: -Type 1 DM: impaired osteoblast with reduction in BMD -Type 2 DM: BMD is normal or increased but there is a maior fragility of diabetic bone of multifactorial origin (AGEs, Renal, Vit D..etc) 3.-Low Bone Turnover and increased bone fragility of multifactorial origin 4.-Besides avoiding hypoglucemia without strict A1c glycemic control and not using Gtz, with general recommendations regarding adequate dietary calcium and Vit.D intake, regular exercise, are crucial 5.- But the most important thing is to reduce the risk of falling with education advice, simple measures (when visual impariment, neuropathy..).

21 Hello 1.-Looking ahead when walking Juan Carlos I Spain Goodbye Hunting 2.-Minding the steps Angela Merkel, Germany THANKS