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CONFLITTO DI INTERESSI

Diabete e resistenza ossea: quale legame?

P. D’Amelio MD, PhDGeriatria e Malattie Metaboliche

dell’Osso – Dipartimento di Scienze Mediche – Università di Torino

61° CONGRESSO NAZIONALE SIGG“Stiamo lavorando per farti invecchiare

meglio”: simposio SIGG-SIOMMMS

Napoli, 2 Dicembre 2013

AGENDA

• Epidemiology and fracture risk

• How T2DM affects bone

• Conclusions

AGEs Bone quality Bone turnover and cellsObesity

Prevalence of T2DM

Fragility fracture incidence

8.9 milion/yr fractures in the world (1)

1,000 fractures/hr in the world (1)

1/3 of fragility fractures occur in Europe (1)

465,000 /yr nwe fractures in Italy (2)

1. Hernlund E. et al.; Arch Osteoporos 2013; 8: 136; 2. Svedbom A. et al.; Arch Osteoporos 2013; 8: 317

The number of fractures/yrs is increasing (2)

Mohsen Janghorbani et al. Am. J. Epidemiol. 2007

Diabetic patients (T2DM) have increasedrisk of fractures (1)

Strotmeyer ES et al. Arch Intern Med. 2005

Diabetic patients (T2DM) have increasedrisk of fractures (2)

Mohsen Janghorbani et al. Am. J. Epidemiol. 2007

Diabetic patients (T1DM) have increasedrisk of fractures (3)

Factors leading to fractures in diabetics

DM 1 DM2

Increased bone resorption and decreased/unaltered bone formation

Low bone turnover

Hyperglycemia Hyperglycemia

Increased propensity to falldue to acute hypoglycemia and comorbid complications (eg retinopathy, neuropathy, cerebrovascular disease)

Increased propensity to falldue to acute hypoglycemia and comorbid complications (eg retinopathy, neuropathy, cerebrovascular disease)

Low bone mass Accelerated bone loss with aging

AGENDA

• Epidemiology and fracture risk

• How T2DM affects bone

• Conclusions

AGEs Bone quality Bone turnover and cellsObesity

ROLE OF AGEs

Bone Formation is Affected by Matrix AGEs (1)

Yang X et al. Calcif Tissue Int. 2016

Bone Formation is Affected by Matrix AGEs (2)

Mechanical parameter

Control groupAGEs-treated

groupp

Elastic modulus (GPa)

12.7 ± 3.23 12.6 ± 0.823 0.93

Hardness 0.568 ± 0.171 0.587 ± 0.268 0.89

Mechanical properties of newly formed bone

Yang X et al. Calcif Tissue Int. 2016

AGENDA

• Epidemiology and fracture risk

• How T2DM affects bone

• Conclusions

AGEs Bone quality Bone turnover and cells

Burghardt AJ, et al. J Clin Endocrinol Metab. 2010

Diabetes influence bone structure …

Patsch J.M, et al. J Bone Miner Res. 2013

Diabetes influence bone structure independently by bone density

Farr J N. and Khosla S. Bone 2016

Bone material properties

AGENDA

• Epidemiology and fracture risk

• How T2DM affects bone

• Conclusions

AGEs Bone quality Bone turnover and cellsObesity

Diabetes Mellitus type II and Bone

Reduced recruitment of OB (in animals)

Reduced appositional rate (in animals)

Decreased bone formation (in humans)

Decreased bone resorption

Decreased bone turnover OC OPG

Sanguineti R, et al. Ann NY Acad Sci. 2008

AGEs affect osteoblasts formation and activity

Gennari L. et al; The Journal of Clinical Endocrinology & Metabolism 2012

Diabetes Mellitus type II and Bone Turnover

T2DM affects bone precursors cell

D’Amelio et al. manuscript in preparation

AGENDA

• Epidemiology and fracture risk

• How T2DM affects bone

• Conclusions

AGEs Bone quality Bone turnover and cellsObesity

Cohen A et al. The Journal of Clinical Endocrinology & Metabolism 2013

Obesity is associated with lowerbone volume and formation

Cohen A et al. The Journal of Clinical Endocrinology & Metabolism 2013

Obesity is associated with poor bone quality

AGENDA

• Epidemiology and fracture risk

• How T2DM affects bone

• Conclusions

AGEs Bone quality Bone turnover and cellsObesity

GRAZIE