Fracture risk assessment Norwich, John A Kanis SCOOP Launch, November 07

Consensus Development Conference, 1993 Common sites of fracture 03ca011 03 Osteoporosis Definition a systemic skeletal disease characterised by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture Consensus Development Conference, 1993 Common sites of fracture Spine Hip Wrist

Diagnostic thresholds for women 99ca160 ex94ca117 from 91ca129 Diagnostic thresholds for women Percent of population 0.6 15 50 85 >99 Osteoporosis Low bone Normal mass -4 -3 -2 -1 1 2 3 4 Bone mineral density (SD units or T-score)

Indications for the diagnostic use of BMD - Presence of strong risk factors oestrogen deficiency corticosteroid therapy (>7.5 mg >1 year) maternal history of hip fracture low BMI (<19 kg/m ) - Radiographic osteopenia - Previous fragility fracture - Height loss/ thoracic kyphosis (after radiography)

Case finding strategies IOF NOF

Osteoporotic fracture and BMD 05ca085 Osteoporotic fracture and BMD Fractures/1,000 person-years Number of fractures 50 Fracture rate Women with fractures 400 40 300 30 200 20 100 10 1.0 0.5 0.0 -0.5 -1.0 -1.5 -2.0 -2.5 -3.0 -3.5 Siris. Surgeon General’s Workshop on Osteoporosis and Bone Health, December 2002

Ten year probability of hip fracture in Sweden 00ca104 Ten year probability of hip fracture in Sweden -3 -2 -1 1 10 20 Fracture probability (%) 50 60 70 80 Age (years) Women T-score (SD)

Assessment of osteoporosis at primary health care level 04ca148rev Assessment of osteoporosis at primary health care level Objectives - to optimise sensitivity for fracture risk prediction - case finding or screening strategy - men and women - cost-effective setting - international validity - suitable for primary care

Risk factors Validated in multiple populations 03ca175 Risk factors Validated in multiple populations Data for age, sex and type of fracture Readily assessable by primary care practitioners Be intuitive rather than counterintuitive to medical care. Contribute to a risk that is amenable to the therapeutic manipulation intended

Cohorts studied EVOS / EPOS Hiroshima CaMoS Rochester Sheffield Rotterdam Kuopio Gothenburg I Gothenberg II EPIDOS Dubbo OFELY n = 59,232 person-years = 249,898 % female = 74 Any fracture = 5,444 osteoporotic fractures = 3,495 hip fractures = 957

Femoral neck BMD and hip fracture prediction 04ca138 Femoral neck BMD and hip fracture prediction RR/SD 5 Men and women 4 3 2 1 50 55 60 65 70 75 80 85 Age (years)

Prior fracture and hip fracture risk 05ca186 Prior fracture and hip fracture risk 2 4 6 50 55 60 65 70 75 80 85 Age (years) RR

Osteoporotic fracture 07ca080 BMI and fracture risk RR (20 v 25 kg/m2) 3.0 Without BMD With BMD 2.0 1.0 0.0 Osteoporotic fracture Hip fracture

Risk factors for hip fracture in men and women 04ca248 Risk factors for hip fracture in men and women RR Prior fracture FH (hip) Smoking current Alcohol >2u Steroids ever RA 3.0 2.0 1.0 0.0 Without BMD With BMD

10-year probability of hip fracture in Malmo 99ca094 10-year probability of hip fracture in Malmo Probability (%) 20 women 15 10 5 men 50 60 70 80 90 Age (years)

Ten year probability of hip fracture - Swedish women 01ca048 Ten year probability of hip fracture - Swedish women 10 year risk (%) 70 60 50 40 30 6.0 5.0 20 4.0 3.0 RR 10 2.0 1.0 50 55 60 65 70 75 80 85 Age (years)

FRAX 06ca106 Patient 65 -2.5 65 165 24 23.9 8.0

Clinical risk factors and fracture probability 10 year hip fracture probability (%) Mrs X Age = 65 y Height =161cm Weight = 61kg BMI = 23.5 kg/m2 6 4 2 FH None Smoking Alcohol Steroids Prior Fx 2o osteoporosis

Probability of osteoporotic fracture* at age 65 05ca106 Probability of osteoporotic fracture* at age 65 Men Women 10-year probability (%) None Prior fracture +Glucocorticoids +Family history 70 60 50 40 30 20 10 -1 -2 -3 -1 -2 -3 T-score US Caucasian, no CRF, BMI=24 *Hip, spine, humerus, forearm

Case finding strategies

Stratification of hip fracture risk Woman aged 65, BMI=24 No Yes Rheumatoid arthritis No Yes No Yes Glucocorticoids No Yes No Yes No Yes No Yes Prior fracture 10-year hip fracture probability (%) 1.5 3.7 3.1 7.5 2.6 6.4 5.4 12.9

Gradient of risk for hip fracture prediction 07ca027 Gradient of risk for hip fracture prediction RR/SD 6 CRFs BMD CRFs+BMD 5 4 3 2 1 50 60 70 80 90 50 60 70 80 90 50 60 70 80 90 Age (years)

Gradient of risk and fracture prediction 07ca030 Gradient of risk and fracture prediction 2 4 6 8 10 -4 -3 -2 -1 1 3 Risk ratio (vs. general population) GR=2.6 GR=1.6 Z-score % 50.0 100.0 97.7 99.9 84.1 15.9 2.3 0.1 0.0 4.9 3.5 Mean RR 5.0 0.5 % Population 1.63 2.57 2.6 1.6 GR

Ten year probability of hip fracture compared with Sweden 01ca025 Ten year probability of hip fracture compared with Sweden Relative probability Very high High Moderate Low risk 1.2 Sweden 1.0 Denmark China (TW) 0.8 Switzerland Australia Netherlands Finland Greece 0.6 Argentina Hungary Japan France 0.4 China 0.2 Korea Norway Iceland USA Canada UK Italy Spain Chile Singapore Germany Kuwait Portugal China (HK) Venezuela Turkey

00ca008 End

Identification of reversible risk Risk amenable to intervention Low BMD Previous fracture Use of glucocorticoids Presence of risk factor does adversely affect therapeutic response Age Body mass index Family history of fracture Smoking and alcohol Markers of bone turnover Uncertain effects Neuromuscular incompetence Liability to falling