Chiodini I. Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda – Dpt. of Medical Sciences and Community Health, University of Milan, Milan, Italy

DISCLOSURES

Dichiaro di aver ricevuto negli ultimi due anni compensi o finanziamenti dalle seguenti Aziende Farmaceutiche e/o Diagnostiche:

- Abiogen- Italfarmaco- Kyowa Kyrin

DIABETE E OSSO

AGENDA• Fisiopatologia del danno scheletrico nel DM• Densità minerale ossea e rischio di frattura• Diagnosi di osteoporosi nel paziente diabetico• Terapia dell’osteoporosi nel paziente diabetico o terapia del diabete

nel paziente osteoporotico?

Chiodini I. Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda – Dpt. of Medical Sciences and Community Health, University of Milan, Milan, Italy

Chiodini I. Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda – Dpt. of Medical Sciences and Community Health, University of Milan, Milan, Italy

Modified from Napoli N et al, Nat Rev Endocrinol 2017

MECHANISMS OF DIABETES MELLITUS INDUCED BONE FRAGILITY

LE TRABECOLE ORIZZONTALI SONO IMPORTANTI AI FINI DELLA RESISTENZA DELL’OSSO

La struttura 1 è 16 volte più resistente della Struttura 2

Si supponga: Volume 1 = Volume 2Materiali e dimensioni identici

Struttura 1 Struttura 2

Teoria di Eular Buckling

Chiodini I. Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda – Dpt. of Medical Sciences and Community Health, University of Milan, Milan, Italy

Modified from Napoli N et al, Nat Rev Endocrinol 2017

MECHANISMS OF DIABETES MELLITUS INDUCED BONE FRAGILITY

Cortisol secretion and sensitivity(Zhukouskaya VV et al, JCEM 2015)

PENTOSIDINE AND INCIDENT FRACTURE RISK IN TYPE 2 DIABETES

Chiodini I. Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda – Dpt. of Medical Sciences and Community Health, University of Milan, Milan, Italy

HIGH SERUM PENTOSIDINE IS ASSOCIATED WITH PREVALENT FRACTURES IN DM1 INDEPENDENT OF BMD AND GLYCAEMIC CONTROL

Neumann T et al. Osteoporos Int 2014

Chiodini I. Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda – Dpt. of Medical Sciences and Community Health, University of Milan, Milan, Italy

Chiodini I. Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda – Dpt. of Medical Sciences and Community Health, University of Milan, Milan, Italy

Modified from Napoli N et al, Nat Rev Endocrinol 2017

MECHANISMS OF DIABETES MELLITUS INDUCED BONE FRAGILITY

Cortisol secretion and sensitivity(Zhukouskaya VV et al, JCEM 2015)

LOW BONE TURNOVER IN DM2

Gennari L et al, JCEM 2012

Chiodini I. Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda – Dpt. of Medical Sciences and Community Health, University of Milan, Milan, Italy

WNT/β-CATENIN SIGNALLING AND REDUCED BONE TURNOVER IN T2D

Gaudio A et al, JCEM 2012

Chiodini I. Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda – Dpt. of Medical Sciences and Community Health, University of Milan, Milan, Italy

Krishnan V et al, JCI 2006

MSC differenziano in senso adipocitario e non osteoblasticoBarbagallo et al, J Bone Miner Metab 2010 , Keats et al, PloS ONE 2012

Aumento dello stress ossidativo (Reactive Oxygen Species, ROS)King et al, Histochem Cell Biol 2004, Grassi et al, Proc Natl Acad Sci 2007, Manolagas, Endocr Rev 2010

IPERGLICEMIA

AGEsKatayama Y, J Bone Miner Res 1996

Miyata T, J Am Soc Nephrol 1997

Glicazione del collagene(Pentosidina, AGEs)

Saito et al, Osteoporos Int 2006Sanguineti et al, Ann N Y Acad Sci 2008Schwartz et al, J Clin Endocrinol Metab 2009

MAJOR PATHOGENETIC MECHANISMS FOR SKELETAL FRAGILITY IN TYPE 2 DIABETES

Prof Luigi Gennari, University of Siena, with permission

Hofbauer et al, J Bone Miner Res 2007

Chiodini I. Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda – Dpt. of Medical Sciences and Community Health, University of Milan, Milan, Italy

PATHOGENETIC MECHANISMS FOR SKELETAL FRAGILITY IN TYPE 1 DIABETES

AGENDA• Fisiopatologia del danno scheletrico nel DM• Densità minerale ossea e rischio di frattura• Diagnosi di osteoporosi nel paziente diabetico• Terapia dell’osteoporosi nel paziente diabetico o terapia del diabete

nel paziente osteoporotico?

Chiodini I. Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda – Dpt. of Medical Sciences and Community Health, University of Milan, Milan, Italy

DIABETE E OSSO

BMD AND FRACTURES IN DIABETES

20

Vestergaard P, Osteoporos Int 2007

Chiodini I. Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda – Dpt. of Medical Sciences and Community Health, University of Milan, Milan, Italy

Zhukouskaya VV et al, Diabetes Care 2013

T1D PATIENTS HAVE ELEVATED PREVALENCE OF ASYMPTOMATIC VFX, REGARDLESS OF BMD

Chiodini I. Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda – Dpt. of Medical Sciences and Community Health, University of Milan, Milan, Italy

IN T2D THE FRACTURE RISK IS HIGHER FOR A GIVEN T SCORE

Schwartz AV et al, JAMA 2011

Among older adults with type 2 DM, femoral neck BMD T score and FRAX score were associated with hipand nonspine fracture risk; however, in these patients compared with participants without DM, thefracture risk was higher for a given T score and age or for a given FRAX score.

Chiodini I. Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda – Dpt. of Medical Sciences and Community Health, University of Milan, Milan, Italy

AGENDA• Fisiopatologia del danno scheletrico nel DM• Densità minerale ossea e rischio di frattura• Diagnosi di osteoporosi nel paziente diabetico• Terapia dell’osteoporosi nel paziente diabetico o terapia del diabete

nel paziente osteoporotico?

Chiodini I. Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda – Dpt. of Medical Sciences and Community Health, University of Milan, Milan, Italy

DIABETE E OSSO

USEFULNESS OF FRAX ALGORYTHM IN TYPE 2 DIABETES

Chiodini I. Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda – Dpt. of Medical Sciences and Community Health, University of Milan, Milan, Italy

BONE QUALITY ASSESSMENT BY TRABECULAR BONE SCORE

Chiodini I. Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda – Dpt. of Medical Sciences and Community Health, University of Milan, Milan, Italy

BONE QUALITY ASSESSMENT IN DM2 BY TRABECULAR BONE SCORE

Chiodini I. Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda – Dpt. of Medical Sciences and Community Health, University of Milan, Milan, Italy

Chiodini I. Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda – Dpt. of Medical Sciences and Community Health, University of Milan, Milan, Italy

Zhukouskaya VV et al, Osteoporos Int 2015

HOW TO PREDICT VERTEBRAL FRACTURES IN TYPE 2 DIABETICS?

n=99

RISK FACTORS FOR FRAGILITY FRACTURES IN DM2 PATIENTS

Chiodini I. Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda – Dpt. of Medical Sciences and Community Health, University of Milan, Milan, Italy

CLINICAL RISK FACTORS ASSOCIATED WITH POOR BONE HEALTH IN TYPE 1 DIABETES

Chiodini I. Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda – Dpt. of Medical Sciences and Community Health, University of Milan, Milan, Italy

Zhukouskaya VV et al, J Endocrinol Invest 2015

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….)

Chiodini I. Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda – Dpt. of Medical Sciences and Community Health, University of Milan, Milan, Italy

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

Chiodini I. Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda – Dpt. of Medical Sciences and Community Health, University of Milan, Milan, Italy

AGENDA• Fisiopatologia del danno scheletrico nel DM• Densità minerale ossea e rischio di frattura• Diagnosi di osteoporosi nel paziente diabetico• Terapia dell’osteoporosi nel paziente diabetico o terapia del diabete

nel paziente osteoporotico?

Chiodini I. Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda – Dpt. of Medical Sciences and Community Health, University of Milan, Milan, Italy

DIABETE E OSSO

ANTIRESORPTIVES AND FRACTURE RISK IN DIABETES

Chiodini I. Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda – Dpt. of Medical Sciences and Community Health, University of Milan, Milan, Italy

Vestergaard, Calcif Tissue Int 2011

EFFECTS OF ORAL HYPOGLYCEMIC AGENTS ON THE RISK OF DEVELOPING FRAGILITY FRACTURES IN T2D

Palermo A et al, Osteoporos Int 2015

Chiodini I. Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda – Dpt. of Medical Sciences and Community Health, University of Milan, Milan, Italy

INTENSIVE INSULIN THERAPY AND BONE MINERAL DENSITY IN TYPE 1 DIABETES MELLITUS: A PROSPECTIVE STUDY

Campos-Pastor et al, Osteoporos Int 2000

7 years later baseline

Patients with retinopathy

Chiodini I. Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda – Dpt. of Medical Sciences and Community Health, University of Milan, Milan, Italy

Chiodini I. Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda – Dpt. of Medical Sciences and Community Health, University of Milan, Milan, Italy

Napoli N et al, Nat Rev Endocrinol 2017

DIABETES MELLITUS INDUCED BONE FRAGILITY

THANK YOU

Chiodini I. Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda – Dpt. of Medical Sciences and Community Health, University of Milan, Milan, Italy