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These guidelines are endorsed by the following Lebanese Scientific Societies and Associations: Lebanese Society of Endocrinology Diabetes and Lipids, Lebanese Society of Rheumatology, Lebanese Society of Obstetrics and Gynecology, Lebanese Association of Orthopedics, Lebanese Society of Radiology, Lebanese Society of Internal Medicine, Lebanese Society of Family Medicine, Lebanese Society of General Practitioners. FRAX Based Lebanese Osteoporosis Guidelines 2013 Second Update for Lebanese Guidelines for Osteoporosis Assessment and Treatment These guidelines were developed by Dr. Ghada El-Hajj Fuleihan, with members of the Lebanese National Task Force for Osteoporosis and Metabolic Bone Disorders, and expert input from Drs. John Kanis, Michael McClung, Bill Leslie and Angela Cheung.

National Task Force Members Ghada El-Hajj Fuleihan Professor of Medicine Director Calcium Metabolism & Osteoporosis Program WHO CC for OP and Metabolic Bone Disorders AUBMC Founding President OSTEOS Asma Arabi Assistant Professor of Medicine Editor OSTEOS Newsletter Rafic Baddoura Head of Rheumatology Department-HDDF Associate Professor of Medicine President OSTEOS George Halaby Professor of Medicine-HDDF -Exec Com OSTEOS Imad Uthman Professor of Medicine- Head Rheumatology Dept AUBMC President of Lebanese Rheumatology Society Exec Com OSTEOS Jad Okais Assistant Professor Treasurer OSTEOS HDDF Ibrahim Salti Professor of Medicine Head of Endocrinology Division Member of National Bioethics Committee AUBMC Muheiddine Seoud Professor of Obstetrics and Gynecology- Past president LSOG Exec Com OSTEOS AUBMC Asaad Taha Clinical Associate Professor of Surgery President Leb Orthop Association AUBMC Ministry of Health Asaad Khoury Head of the Preventive Medicine Department Abdel Rahman El Hout Head of the Orthopedic Committee WHO Alissar Rady WHO Representative

Who to Test? FRAX Based Lebanese Osteoporosis Guidelines 2013 Definite indications in men and women >65 years: age as a risk factor (20% of Lebanese women >65 years and 12% of men have morphometric vertebral fractures) Presence of vertebral deformity or fragility fracture Radiologic evidence of demineralization Chronic corticosteroid therapy (>3-6 months) Aromatase Inhibitors and androgen deprivation therapy Less definite indications in PM women and Older men/ Use FRAX Risk Factors to decide on BMD-If overall FRAX risk calculated using risk factors is approaching 10% then do BMD

Who to Treat? FRAX Based Lebanese Osteoporosis Guidelines 2013 Patients with fragility fractures: Spine, or Hip, or two or more other fragility fractures All others use FRAX Calculation and adjust taking into consideration some limitations of FRAX, and additional risk factors Under 70 years 10 year FRAX risk 10% More than 70 years: moving thresholds: 15%, 21%, 27%, 31% (GRAPH helper) BMD FN T-score -2.5 alone is NOT an indication to treat in the absence of risk factors

10 years overall fracture risk % Who To Treat: Hybrid Model FRAX Based Lebanese Osteoporosis Guidelines 2013 Treat anyone with calculated 10 year overall fracture risk that fall above red line for corresponding age 35 30 25 20 15 Series1 Major fracture risk 10 5 FIXED THRESHOLD MOVING THRESHOLD 0 50 55 60 65 70 75 80 85 90 Ages years FRAX fracture probabilities were calculated using WHO Fracture Risk Assessment Tool accessed online at: http://www.shef.ac.uk/frax/tool.jsp on 14/09/13

Road Map Burdd FRAX based guidelines: US and UK FRAX-Based Lebanese Guidelines Full Presentation: Who to test When to treat Conclusion

Who to Test? Lebanese Guidelines for OP 2002 & 2007 Definite indications in PM women: >65 years: age as a risk factor (1/5 women >65 have VFx) Presence of vertebral deformity or fragility fracture Radiologic evidence of demineralization Chronic corticosteroid therapy (>3-6 months) Less definite indications in PM women: Medical conditions known to cause bone loss Other risk factors for bone loss: Low BMI, positive Family Hx of hip fractures No indications: Healthy cycling premenopausal women Men < 65 years For full details on the www questions go to http://www.osteofound.org/health_professionals/guidelines/guidelines_list.html

Who to Test? FRAX Based Lebanese Osteoporosis Guidelines 2013 Definite indications in men and women >65 years: age as a risk factor (20% of women, and 12% of men have morphometric vertebral compression fractures) Presence of vertebral deformity or fragility fracture Radiologic evidence of demineralization Chronic corticosteroid therapy (>3-6 months) Aromatase Inhibitors and androgen deprivation therapy Other i.e. Less definite indications in PM women and Older men/ Use FRAX Risk Factors to decide on BMD-If overall FRAX risk calculated using risk factors is approaching 10% then do BMD

Definite indications When to Treat? Lebanese Guidelines 2002 & 2007 Postmenopausal women with fragility fracture Postmenopausal women T -2.5 Postmenopausal women on CS and T 1.5 Less definite indications T- score between -1 and -2.5 (with/without risk factors) No indications T- score > -1 Pre-menopausal normally cycling healthy women http://www.osteofound.org/health_professionals/guidelines/guidelines_list.html El-Hajj Fuleihan G et al J Clin Densitom 2005; 8: 148-163

Denmark Sweden Switzerland US Caucasian Austria UK Canada Taiwan Malta Japan Belgium S'pore Chinese S Korea S' Indian Argentina Hungary Hong Kong Italy Germany Finland Mexico Turkey Netherlands Romania France New Zealand Poland Jordan US Black Lebanon Spain Australia Colombia China Philippines Tunisia FRAX Calculated 10 year Overall Fracture Risk 20 18 16 Female age 65 years, T-score -2.5, BMI=25 kg/m 2 14 12 10 8 6 4 2 0

Who to Treat? FRAX Based Lebanese Osteoporosis Guidelines 2013 BMD T-score -2.5, in absence of risk factors is NOT an indication to intervene For a Lebanese woman with a T-score =-2.5 this would imply that at: Age 50 years the 10 year overall FRAX is 1.9% Age 60 years the 10 year overall FRAX is 3.9% Age70 years the 10 year overall FRAX is 7.6% Age 80 years the 10 year overall FRAX is 14% Age 90 years the 10 year overall FRAX is 17% All above risks that are well below Lebanese intervention thresholds

Lebanese Guidelines 2013 T score -2.5 w/o risk factors cannot be used as a cut-off for intervention in Lebanese Both in men and women the 10 year FRAX derived overall fracture risk with a T-score -2.5, in the absence of risk factors, is vey low For a T-score of -2.5, it is < 10% up to age 70 yrs in women Up to age 90 years in men

FRAX Based Lebanese Osteoporosis Guidelines 2013 Definite indications: regardless of FRAX and BMD Patients with fragility fractures: Spine, or Hip, or two or more other fragility fractures Use FRAX Lebanon: for all others (with or without BMD) to calculate FRAX RISK Need to decide on FRAX Risk cut-off at which to intervene with pharmacologic therapy Moving threshold: i.e. NOGG UK Model? Fixed threshold: Examples Possible treatment at an overall 10 yrs fracture risk of 10-20% Canada Definite treatment: at an overall 10 yrs fracture risk > 20% USA and Canada, and a 10 year hip fracture risk of 3% (USA only) http://www.shef.ac.uk/frax/tool.jsp?country=21

Should We Use a Hybrid Model? Moving thresholds over treats in young < 70 yrs with very low risk (1.8% at age 50 years and 4.4% at 60 years), and would treat a large proportion of subjects, 30% of Lebanese women across all age groups, which is too taxing, and not affordable Fixed thresholds under treats the young and over treats at older age groups Hybrid model is best compromise Fixed threshold in younger subjects up to 70 yrs Moving NOGG like threshold above age 70 yrs

FRAX Based Lebanese Osteoporosis Guidelines 2013 Definite indications: regardless of FRAX and BMD Patients with fragility fractures: Spine, or Hip, or more than 2 other fragility fractures. Use FRAX Lebanon for all others -FRAX based risk threshold: If below 70 years: treat all with 10% overall fracture risk If above 70 years : use Tables or GRAPH http://www.shef.ac.uk/frax/tool.jsp?country=21

10 years overall fracture risk % Who To TREAT: Hybrid Model FRAX Based Lebanese Osteoporosis Guidelines 2013 Treat anyone with calculated 10 year overall fracture risk that fall above red line for corresponding age 35 30 25 20 15 Series1 Major fracture risk 10 5 FIXED THRESHOLD MOVING THRESHOLD 0 50 55 60 65 70 75 80 85 90 Ages years FRAX fracture probabilities were calculated using WHO Fracture Risk Assessment Tool accessed online at: http://www.shef.ac.uk/frax/tool.jsp on 14/09/13

Intervention Thresholds and Proportions of Women Treated Age (years) Intervention threshold (%) Proportions above threshold (%) Fixed at 10 % 10% 20 % 50 10 52 10 0.11 0.00 55 10 57 10 1.3 0.04 60 10 62 10 5.7 0.44 65 10 67 10 18.8 2.8 NOGG Model 70 10 72 12 30 30 75 15 77 17 30 30 80 21 82 23 28 28 85 27 87 28 25 25 90 30

Who to Treat? FRAX Based Lebanese Osteoporosis Guidelines 2013 Patients with fragility fractures: Spine, or Hip, or two or more other fragility fractures All others use FRAX calculation and adjust taking into consideration some limitations of FRAX, and additional risk factors Under 70 years 10 year FRAX risk 10% More than 70 years: moving thresholds: 15%, 21%, 27%, 31% (GRAPH helper) BMD FN T-score -2.5 alone is NOT an indication to treat in the absence of Risk Factors

Who to Treat? FRAX Based Lebanese Osteoporosis Guidelines 2013 Definite indications: regardless of FRAX and BMD, older men postmenopausal women with fragility fractures, Spine, Hip, or more than 2 other fragility fractures. Use FRAX Lebanon for all others FRAX derived Threshold: Below 70 years: Fixed cut-off, overall fracture risk 10% Above 70 years : moving NOGG threshold adapted to Lebanon Women Overall FRAX risk 70 years 10% 75 years 15% 80 years 21% 85 years 27% 90 years 30% BMD T-score -2.5, in absence of Risk Factors is NOT an indication to intervene: at age 50 years the 10 year overall FRAX is 1.9%, 60 years 3.9%, 70 years 7.6%, 80 years 14%, 90 years 17%, all risk estimates that are well below Lebanese intervention thresholds, detailed above