Uno strumento italiano per la valutazione. Francesca De Giorgio U.O. Medicina Interna Ospedale S. Jacopo ASL3 Pistoia

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1 Uno strumento italiano per la valutazione del rischio di frattura Francesca De Giorgio U.O. Medicina Interna Ospedale S. Jacopo ASL3 Pistoia

2 Valutazione clinica dell Osteoporosi Identificazione dei soggetti a rischio Valutazione del rischio di frattura Diagnosi di forme secondarie Quando e come trattare

3 La gestione dell Osteoporosi Valutazione del rischio di frattura Identificare i pazienti a maggior rischio utilizzando strumenti in grado di fornire una stima del rischio Avviare un trattamento di efficacia coerente con il rischio di frattura Stili di vita Farmaci Migliorare la percezione del rischio da parte di medici e pazienti

4 Relationship of bone mass and fractures as assessed by the relative risk of fracture of wrist, hip and vertebrae per 1 SD change in BMD in different regions, adjusted for age Measurement site Fracture site (relative risk) Wrist Hip Vertebrae Forearm Femoral neck Lumbar spine Eddy et al. Osteoporos Int, 1998

5 FEMORAL T-SCORE AND FIVE-YEAR RISK OF HIP FRACTURE IN WHITE WOMEN 20 T score 5-Year fracture risk (%) Relazione esponenziale tra diminuzione della BMD e aumento del rischio di frattura Age (yrs) Cummings SR et al. JAMA, 2002

6 Rischio di frattura vertebrale, radiale e BMD Incidenza di fratture (per paziente-anni) Colonna Radio Relazione esponenziale tra diminuzione della BMD e aumento del rischio di frattura 2 SD 1 SD Mean -1 SD -2 SD Densità Minerale Ossea Miller PD et al. Calcif Tissue Int, 1996

7 Definizioni OMS dell esito dell esame densitometrico NORMALE: BMD entro 1 DS rispetto alla media del picco di massa ossea (T score -1) OSTEOPENIA: BMD compreso tra -1 e -2,5 DS rispetto alla media del picco di massa ossea (T score < -1 e > -2,5) OSTEOPOROSI: BMD inferiore a -2,5 DS rispetto alla media del picco di massa ossea (T score < -2,5) OSTEOPOROSI SEVERA: BMD inferiore a -2,5 DS rispetto alla media del picco di massa ossea in presenza di una o più fratture da fragilità WHO Technical report series 843. Geneva, 1994

8 Bone Mineral Density, osteoporotic fracture rate, and number of women with fractures in postmenopausal women Osteopenia Siris ES et al. Arch Intern Med, 2004

9 Major risk factors for fracture in clinical practice Female gender Age* Asian or Caucasian race Low Bone Mineral Density High Bone turnover* Poor visual acuity* Neuromuscular disorders* Parental history of fractures* Previous fragility fractures* Comorbidities Kanis JA et al. Osteoporos Int, 2005 Premature menopause Amenorrhoea Hypogonadism in men Low body weight* Cigarette smoking* Alcohol consumption* Prolonged immobilisation Low dietary calcium intake Vitamin D deficiency Glucocorticoid use* Fall propensity* * oltre la BMD

10 World Health Organization Collaborating Centre for Metabolic Bone Diseases, University of Sheffield, UK

11 WHO: Assembly of cohorts Global literature review Individual datasets EVOS/EPOS EPIDOS Sheffield DOES Dubbo Rotterdam CaMos Rochester Hiroshima Kuopio Gothenburg Female 74% No. 59,232 p-y 249,898 Incident fractures any 5,444 osteoporotic 3,495 hip 957 Kanis JA, WHO Study Group, 2005

12 VARIABILI FRAX VARIABILI CONTINUE Età BMD (T-score) BMI VARIABILI DICOTOMICHE Familiarità Fumo Cortisonici Pregresse fratture Secondarietà Alcool Artrite reumatoide

13 Calculated FRAX Risk gradients (with BMD) Calculated FRAX Risk gradients (without BMD) Hip Fracture Multiple Fractures Hip Fracture Multiple Fractures Previous Fractures Family History Smoking Glucocorticoid therapy Rheumatoid arthritis Secondary Osteoporosis Alcohol > 3 units/day

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17 Ten-year probability of hip fracture averaged for age and gender and adjusted to the probabilities of Sweden 1,5 1 0,5 0 Kanis JA et al. J Bone Miner Res, 2002

18 Incidence of hip fractures in Italy between 2000 and Men Women Total Piscitelli P et al. Osteoporos Int, 2010

19 FRAX assumere come affidabile il FRAX con le variabili continue (età, BMD, BMI)

20 LIMITI INTRINSECI DEL FRAX I fattori di rischio dicotomici necessitano di una rivalutazione perchè: Per alcuni esiste gradiente di rischio (pregresse fratture, fumo, terapia cortisonica) Non sono previsti fattori di rischio importanti solo perché rari (es. connettiviti) Non sono previsti dati utili per la validazione (pregressa terapia, terapia in corso)

21 LIMITI POLITICI DEL FRAX Il FRAX è protetto da brevetto L algoritmo del FRAX non è stato reso noto Non è possibile fare stime su coorti di soggetti (prospettiche o retrospettive) Non è possibile registrare in un data-base i risultati Non è validabile

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24 VARIABILI FRAX VARIABILI CONTINUE Età BMD (T-score) BMI VARIABILI DICOTOMICHE Familiarità Fumo Cortisonici Pregresse fratture Secondarietà Alcool Artrite reumatoide

25 Fracture Risk by FRAX and DeFRA (Weight 65, Height 165, No risk factors) 30 DeFRA FRAX T Score = -3,5 risk % 10 years fracture T Score = -3,0 T Score = -2, Age

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27 DeFRA algorithm for the estimation of Ln (natural logarithm) of the 10 year risk (10YR) of either hip or multiple major fractures (as defined by FRAX ) as worked out from the tables published in the WHO technical report. ln 10YR hip fracture = age age Tscore Tscore Tscore ln 10 YR of multiple major fractures =( age 3 /1000) age Tscore Tscore Tscore BMI T-score= BMD T score at either the femoral neck or the total hip as assessed by Dual X ray absortiometry (DXA) Linee Guida Osteoporosi, SIOMMMS 2009

28 Frattura di femore: Rischio a 10 anni 20,00 15,00 X TM FRAX FRAXHipBMD D0CRF 10,00 5,00 0,00 0,00 5,00 10,00 15,00 20,0 DeFRA

29 Fratture Cliniche: Rischio a 10 anni 40,00 30,00 X TM FRAX FRAXOstBMD0 0CRF 20,00 10,00 0,00 0,00 10,00 20,00 DeFRA 30,00 40,0

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31 Relative risks of fracture by sex per decrease of 1 SD in QUS measures (33 events in 6471 men and 88 events in 8328 women) Men Women 1.7 ( ) BUA 1.9 ( ) SOS 1.6 ( ) 1.6 ( ) Relative Risk Khaw K et al. Lancet, 2004

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33 Serum CTX above the premenopausal range predicts hip fracture risk in elderly women hip fracture Relative hazard for h 2.07 ( ) 1.67 ( ) 1.86 ( ) Chapurlat RD et al. Bone, 2000

34 VARIABILI FRAX VARIABILI CONTINUE Età BMD (T-score) BMI VARIABILI DICOTOMICHE Familiarità Fumo Cortisonici Pregresse fratture Secondarietà Alcool Artrite reumatoide

35 DeFRA Risk gradients Hip fracture Clinical fractures Family history of hip fracture Corticosteroid use: >5 mg Prednisone equivalents Corticosteroid use: < 5mg >2.5 mg Prednisone equivalents One previous vertebral o hip fracture More than 1 previous hip or vertebral fracture Previous non traumatic non-hip non-vertebral fracture Alcool (>3 units/day) Smoking <10 cigarettes /day Smoking >10 cigarettes /day Rheumatoid and psoriatic arthritis, Ankylosing spondylitis, LES, other CTDs

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37 Smoking history and the risk of hip fracture in postmenopausal women assessed in 1328 cases and 3312 controls Baron JA et al. Arch Intern Med, 2001

38 Fracture Risk by FRAX and DeFRA according with smoking habits (T score =-3.0; weight 65; height 165) yrs Fx risk FRAX-Sm DeFRA DeFRA Sm <10 no >10 Sm

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40 Incidence of vertebral fractures in patients receiving Glucocorticoids compared to non users according to baseline BMD GCs GCs GCs Van Staa TP et al. Arthritis Rheum, 2003

41 Dose dependency of fracture risk in 244,235 oral corticosteroid users <2.5 mg predn mg predn. >7.5 mg predn. 6 5,18 Relative risk 4 2 1,55 2,59 0,99 1,77 2,27 0 Vertebral Fx Hip Fx van Staa et al. JBMR, 2000

42 Fracture Risk by FRAX and DeFRA according with Glucocorticoid therapy (T score =-3.0; weight 65; height 165) yrs Fx risk FRAX- DeFRA DeFRA GLC no <5 >5 GLC mg

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44 Second Hip Fracture in older men and women The Framingham Study (481 patients with an initial hip fracture) 24,1 % of patients % of patients First Second Berry SD et al. Arch Intern Med, 2007

45 Relative risk of incident vertebral fractures according to prevalent fractures 15 Relative risk of incid dent fractures Number of prevalent fractures 2 3 Black et al. J Bone Miner Res, 1999

46 Risk of subsequent fractures in peri/postmenopausalpostmenopausal women with prevalent vertebral fractures Vertebral Hip Wrist All (nonspine) Pooled Relative Risk Klotzbuecher et al. J Bone Min Res, 2000

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48 Risk of subsequent hip fracture in per i/postmenopausal women with prior fractures Vertebral 2.3 ( ) Hip 2.3 ( ) Wrist 1.9 ( ) Other 1.9 ( ) Pooled 1.9 ( ) Relative Risk Klotzbuecher et al. J Bone Min Res, 2000

49 Fracture Risk by FRAX and DeFRA according with prevalent fractures (T score =-3.0; weight 65; height 165) yrs Fx risk FRAX-DeFRA no Fx FRAX-Fx DeFRA other Fx DeFRA Vert/Hip Fx

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52 Relative risk of fracture in 30,262 patients with RA Median follow up : 7,6 years; N. 2,460 fractures Pelvis Clinical Vertebral Rib Humerus Tibia/Fibula Femur/hip Radius/Ulna Clinical/Osteoporotic Van Staa TP et al. Arthritis Rheum, 2006

53 Studio EVOS: prevalenza delle deformità vertebrali in rapporto all età ed al sesso 30 Maschi Femmine ± 13 SLE patients Età (anni) O Neill et al. JBMR, 1996

54 Prevalence of fractures in 159 SSC and 235 AR patients % of Ffracture es SSc RA Yuen SY et al. J Rheumatol, 2008

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56 Major risk factors for fracture in clinical practice Female gender Age* Asian or Caucasian race Low Bone Mineral Density High Bone turnover* Poor visual acuity* Neuromuscular disorders* Parental history of fractures* Previous fragility fractures* Comorbidities Premature menopause Amenorrhoea Hypogonadism in men Low body weight* Cigarette smoking* Alcohol consumption* Prolonged immobilisation Low dietary calcium intake Vitamin D deficiency Glucocorticoid use* Fall propensity* * Over and above BMD Kanis JA et al. Osteoporos Int, 2005

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58 Fall-related factors and risk of hip fracture EPIDOS prospective study (7575 women aged 75 or older) Femoral neck BMD Fall-risk status Lower quartiles Highest quartile (Hip fracture rate per 1000 person-year) Lower quartiles of risk Highest quartile of risk Dargent-Molina P et al. Lancet, 1996

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60 Probability of hip fracture in 47,868 naïve women treated with alendronate (daily, weekly and switch) 1% MPR decrease vs Hip Fx risk = CI 95% Rabenda V al. Osteoporos Int, 2008

61 % National Osteoporosis Guideline Group Royal College of Physicians and Bone and Tooth Society of Great Britain

62 DeFRA, 2010

63 Consenso e Linee Guida Il trattamento farmacologico è cost-effective in: Pregresse fratture osteoporotiche Trattamento cortisonico cronico Rischio di frattura a 10 anni > 20% Kanis JA et al. Osteoporos Int, 2004

64 It is cost-effective to treat subjects who have a 10-year hip fracture risk exceeding 3% or more

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66 Grazie

67 Uno strumento italiano per la valutazione del rischio di frattura Francesca De Giorgio U.O. Medicina 2 ASL3 Pistoia