FRAX Based Guidelines: Is a Universal Model Appropriate?

FRAX Based Guidelines: Is a Universal Model Appropriate? Marlene Chakhtoura, MD Research Fellow Calcium Metabolism & Osteoporosis Program WHO Collaborating Center for Metabolic Bone Disorders American University of Beirut-Medical Center

FRAX Based Guidelines: Is a Universal Model Appropriate? - Marlene Chakhtoura, MD - Ghada El-Hajj Fuleihan, MD, MPH American University of Beirut Medical Center Beirut, Lebanon - Angela Cheung, MD, PhD, FRCP(C), CCD University Health Network, Toronto - Eugene McCloskey, MB, BCh, BAO, MD, FRCPI, FRCPE - John A Kanis, MD, FRCP University of Sheffield, United Kingdom - Michael McClung, MD, FACE, FACP Oregon Osteoporosis Center, Portland - William D. Leslie, MD, FRCPC MSc University of Manitoba, Canada

Nothing to declare Conflict of interest

Background FRAX, launched in February 2008, estimates the 10-year probability of a major osteoporotic fracture (hip, clinical spine, humerus or distal forearm) and hip fracture. based on 11 clinical risk factors, with bone mineral density at the femoral neck an optional input. FRAX has been calibrated for use in 52 countries worldwide, taking into account population-specific life expectancy and fracture incidence rates. http://www.shef.ac.uk/frax; version 3.8; March 19, 2014

FRAX Based Osteoporosis Guidelines To date, several countries have incorporated FRAX based risk assessment in their guidelines. 4 paradigm models have been developed* FRAX Based Intervention Threshold Models NOGG http://www.shef.ac.uk Age-specific threshold model Canada http://www.osteoporosis.ca NOF http://nof.org/ Lebanon http://www.aub.edu.lb Fixed threshold model Composite model Hybrid model *Some EU countries have adopted models based on NOGG or T-score cut-offs

Age Specific Threshold Model NOGG

Age Specific Threshold Model NOGG Patients with a prior fragility fracture should be considered for treatment. In others the 10 year probability of a major osteoporotic fracture (clinical spine, hip, forearm or humerus) should be determined using FRAX. The intervention threshold is defined as the 10-year probability of major osteoporotic fracture in a woman with a BMI of 25 kg/m² who has had a previous fracture (without additional risk factors). http://www.shef.ac.uk/nogg/

Age Specific Threshold Model NOGG Patients with a prior fragility fracture should be considered for treatment. In others the 10 year probability of a major osteoporotic fracture (clinical spine, hip, forearm or humerus) should be determined using FRAX. The intervention threshold is defined as the 10-year probability of major osteoporotic fracture in a woman with an identical age, a BMI of 25 kg/m² who has had a previous fracture (without additional risk factors). http://www.shef.ac.uk/nogg/

Fixed Model Canadian FRAX Based Guidelines Initial BMD Testing Assessment of fracture risk Low risk 10-year fracture risk < 10% Unlikely to benefit from pharmacotherapy Reassess in 5 yr Moderate risk 10-year fracture risk 10%-20% Lateral TL (T4-L4) or vertebral fracture assessment may aid in decision-making by identifying vertebral fractures Factors warranting consideration of pharmacologic therapy High risk 10-year fracture risk > 20% or prior fragility fracture of hip or spine or > 1 fragility fractures Always consider patient preference Good evidence of benefit from pharmacotherapy Papaioannou A, CMAJ 2010. 182: 17;1864-873

Composite Model NOF Treat post menopausal women and men > 50 years A hip or vertebral fracture BMD assessment FN or LS T-Score -2.5 Osteopenia if 10y risk for MOF 20% 10y risk for hip fracture 3%

Hybrid Model Lebanon Lebanese Guidelines 2002 & 2007 Definite Indications Postmenopausal women with fragility fracture Postmenopausal women T -2.5 (NHANES) Postmenopausal women on CS and T -1.5 Less Definite Indications T- score between -1 and -2.5 (with other risk factors) http://www.aub.edu.lb/fm/cmop/downloads/diagnosis-trt.pdf

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 10-year overall fracture risk Impact of T-score on Fracture Risk Prediction 20 18 16 14 12 10 8 6 4 2 0 Women age 65 years BMD T-score -2.5 BMI 25 kg/m² http://www.shef.ac.uk/frax; version 3.8; October 17, 2013

10-year risk for major osteoporotic fracture NOGG Age Specific Threshold Model Applied to Lebanon 40 35 30 25 20 15 UK Lebanon 10 5 0 50 55 60 65 70 75 80 85 90 Age http://www.shef.ac.uk/frax; version 3.8; October 17, 2013

10-year risk for major osteoporotic fracture NOGG Age Specific Threshold Model Applied to Lebanon At ages <70 years, NOGG Lebanon sets intervention threshold for MOF 3-10%. 40 35 30 25 20 15 UK Lebanon 10 5 0 50 55 60 65 70 75 80 85 90 Age http://www.shef.ac.uk/frax; version 3.8; October 17, 2013

FRAX Based Osteoporosis Guidelines Proportion above intervention thresholds Age group NOGG Fixed 20% Fixed 10% Lebanon women women Women 50-55 55-60 60-65 65-70 70-75 75-80 80-85 85-

FRAX Based Osteoporosis Guidelines Proportion above intervention thresholds Age group NOGG Fixed 20% Fixed 10% Lebanon women women Women 50-55 26.3 55-60 28.5 60-65 30.4 65-70 33.0 70-75 30.0 75-80 30.5 80-85 28.2 85-24.6

FRAX Based Osteoporosis Guidelines Proportion above intervention thresholds Age group NOGG Fixed 20% Fixed 10% Lebanon women women Women 50-55 26.3 0.00 55-60 28.5 0.04 60-65 30.4 0.44 65-70 33.0 2.8 70-75 30.0 9.8 75-80 30.5 22.5 80-85 28.2 35.8 85-24.6 42.7

FRAX Based Osteoporosis Guidelines Proportion above intervention thresholds Age group NOGG Fixed 20% Fixed 10% Lebanon women women Women 50-55 26.3 0.00 0.11 55-60 28.5 0.04 1.3 60-65 30.4 0.44 5.7 65-70 33.0 2.8 18.8 70-75 30.0 9.8 41.5 75-80 30.5 22.5 62.8 80-85 28.2 35.8 77.4 85-24.6 42.7 79.8

FRAX Based Osteoporosis Guidelines Proportion above intervention thresholds Age group NOGG Fixed 20% Fixed 10% Lebanon women women women 50-55 26.3 0.00 0.11 55-60 28.5 0.04 1.3 60-65 30.4 0.44 5.7 65-70 33.0 2.8 18.8 70-75 30.0 9.8 41.5 75-80 30.5 22.5 62.8 80-85 28.2 35.8 77.4 85-24.6 42.7 79.8

Women age (years) Hybrid Model: Lebanon Intervention threshold (%) Proportions above threshold* (%) for major osteoporotic fracture Fixed at 10% 50-55 10 0.11 55-60 10 1.3 60-65 10 5.7 65-70 10 18.8 NOGG Model 70-75 10-15 30 75-80 15-21 30 80-85 21-27 28 85-90 27-30 25 * Proportions include patients with fractures

Lebanese FRAX Based Guidelines 2013 Hybrid Model Definite Indications: regardless of FRAX and BMD Postmenopausal women and men 50 years with fragility fracture (Spine and Hip, More than one other fragility fractures) Postmenopausal women T -2.5 (NHANES) Postmenopausal women on CS and T 1.5 Less Definite Indications T- score between -1 and -2.5 (with/without risk factors) http://www.aub.edu.lb/fm/cmop/downloads/diagnosis-trt.pdf

Lebanese FRAX Based Guidelines 2013 Hybrid Model Definite indications: regardless of FRAX and BMD Postmenopausal women and men 50 years with fragility fracture (Spine and Hip, More than one other fragility fractures) http://www.aub.edu.lb/fm/cmop/downloads/diagnosis-trt.pdf

Case Scenario: FRAX Based Guidelines: Is a Universal Model Appropriate? A 75 years old lady presents for evaluation. Smoker FN T-score of -2.5 BMI 25kg/m² Country UK US Canada Lebanon 10y risk for MOF (%) 10y risk of hip fracture (%) Decision

Is a Universal Model Appropriate: Summary NOGG Model Reflects a translational approach to an intuitively attractive concept. The resulting cutoffs vary considerably between countries. They are low in countries with low fracture rates at younger ages: <10% They are high in countries with high fracture rates at older ages: 30-45% The model would imply intervening in a large proportion of young postmenopausal women, in countries with low/moderate fracture rates, such as Lebanon. NOF Model Easy to implement, age independent fixed threshold, MOF 20%, hip 3%. Results in treating a large proportion of elderly women in countries with low/ moderate fracture rates Lebanon (42% in women 85 years) New Zealand (46% in women with mean age 74 years) Bolland et al,2010 China (63% of women 65 years) Cheung et al,2013 Cost effective in US, but not necessarily in other countries. Canadian Model Grades risk into three categories allowing flexibility in decision making in the intermediate 10-20% overall MOF range

Conclusion The 4 models presented provide a platform to derive FRAX based guidelines to be tailored according to the profile and needs of each country. They provide a framework that does not supersede clinical judgment, including patient profiling and preference. No single model can address the individual limitations of each. Not all models implemented a cost utility approach. A universal model may not be appropriate since fracture risk, mortality, health priorities and resources vary between countries.

Acknowledgments Grant support from the Medical Resource Plan at the American University of Beirut and the Lebanese National Council for Scientific Research. Members of the Lebanese National Task Force for Osteoporosis: G El Hajj Fuleihan, A Arabi, N Atallah, R Baddoura, G Halaby, M Hout, J Okais, I Salti, M Seoud, A Rady, A Taha, and I Uthman. Lebanese scientific societies that endorsed the Lebanese FRAX based Osteoporosis Guidelines 2013: Lebanese Society for Osteoporosis and Metabolic Bone Disorders, OSTEOS; Lebanese Society of Endocrinology; Lebanese Society of Obstetrics and Gynecology; Lebanese Association of Orthopedic Surgeons; Lebanese Society of Radiology; Lebanese Society of Rheumatology; Lebanese Society of Family Medicine; Lebanese Society of Internal Medicine; Lebanese Society of General Practitioners. Lebanese Ministry of Health: endorsing the guidelines by ministerial decree.