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