Fractures: Epidemiology and Risk Factors. Osteoporosis in Men (more this afternoon) 1/5 men over age 50 will suffer osteoporotic fracture 7/16/2009

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1 Fractures: Epidemiology and Risk Factors Mary L. Bouxsein, PhD Department of Orthopaedic Surgery Beth Israel Deaconess Medical Center Harvard Medical School, Boston, MA Outline Fracture incidence and impact of fractures Major determinants of fracture incidence Gender Age Race Geography Clinical risk factors for fracture Some special issues in fracture risk Epidemiology of Osteoporotic Fractures 1.5 million fractures in US annually 44 million individuals in US at risk for fracture Treatable hypertension: 3-5 million High cholesterol: 4 million At age 5, a woman s lifetime risk of fracture exceeds combined risk of breast, ovarian & uterine cancer 1/3 women will have a fracture At age 5, a man s lifetime risk of fracture exceeds risk of prostate cancer 1/5 men will have a fracture Surgeon General s Report on Bone Health, 14 October 24 Osteoporosis in, International Osteoporosis Foundation, Oct 24 Osteoporosis in (more this afternoon) 1/5 men over age 5 will suffer osteoporotic fracture 3% of hip fractures worldwide are in men Mortality rates due to fracture higher in men than women Treatment rates following fracture are abysmal 1

2 Common sites of fracture Spine Hip Two classifications of vertebral fractures Radiographic Morphometric or radiologist s subjective assessment Can be defined by lateral DXA imaging Clinically-recognized Significant back pain Aka Clinical vertebral fracture About 1/3 of x-ray defined Wrist 5 year fracture risk Incidence of First Fracture: Role of Age and Sex 2% 15% 1% Hip Vertebrae 5% Wrist > 85 > 85 Age Group, yr Cooper C et al. J Bone Miner Res 1992 Hip Vertebrae Wrist Incidence of first osteoporotic fracture: role of age and sex Incidence (rate/1) Age (years) Hip Forearm Vertebra Any of these 2

3 Overall incidence of fractures Impact of Hip Fractures Annual incidence (rate/1) Johansen et al, % excess mortality in 1st yr Mortality rates higher in men than women Lifetime risk of death similar to breast cancer 5% unable to walk independently 25 to 5% remain in long-term care facility Age (years) Depression, chronic pain, disability Direct costs: > $1 billion / yr Cost of hip fracture > $8, per person Deaths in Sweden Total % AMI Lung cancer Prostate cancer Breast cancer Hip fracture Transport accident Impact of Vertebral Fractures 2% excess mortality in 5 yrs after fracture Deformity & height loss Acute & chronic pain Pulmonary dysfunction Diminished quality of life: loss of self-esteem, distorted body image, dependence on narcotic analgesics, sleep disorder, depression, loss of independence 3

4 Prospects for the Future... Elderly represent fastest growing segment of population By 22, one-half of US citizens older than 5 will be at risk for fractures from osteoporosis World Population: 199 and 225 Age range (years) Number (,) Worldwide Distribution of Hip Fractures in : 199 to 25 Outline Hip Fractures, x Fracture incidence and impact of fractures Major determinants of fracture incidence Gender Age Race Geography N. Am, Europe Mid East, Asia, Latin Am, Africa 4

5 Lifetime risks of clinical fractures 5 year old white women (U.S.) Lifetime risk* Hip fracture 17% Wrist fracture 16% Vertebral fracture 16% Any fracture > 5% Breast cancer 15% *Refs: Melton; Black; Kanis Lifetime risks of fracture: Impact of gender Lifetime Risk at Age 5* Fracture (%) (%) Hip 6 17 Wrist 3 16 Clinical Vert Fx 5 16 Any 16% > 5% * Among Caucasians Race and rate of hip fractures (age adjusted to U.S.) Race Female Male Caucasian (US) Blacks US Hispanics (US) Asian Japan Hong Kong California Beijing ~ 8 Rates of hip fracture vary dramatically by region and country Luz Villa, Osteoporosis, Rates per 1, person-years, age-adjustedadjusted 5

6 Geographic Variation Lifetime Risk of Hip Fracture at Age 5 yrs Less variation in prevalence of vertebral fractures by standard definitions Turkey China Hungary China (HK) Portugal Greece Spain France Finland Japan UK Canada Germany Netherlands USA Denmark Italy Australia Iceland Switzerland Norway Sweden LTR (years) Outline Fracture incidence and impact of fractures Major determinants of fracture incidence Gender Age Race Geography Clinical risk factors for fracture Some special issues in fracture risk Vertebral fractures indicate a very high risk of future fracture 4x risk of more vert fxs 2x risk of other fractures (vanstaa, Osteop Int 22) with clinical diagnosis of vertebral fracture have 5-15% 5 yr hip fracture risk! 6

7 Existing Vertebral Fracture Predictive of Future Vertebral Fracture Independent of BMD Previous Vert Frx No Vert Frx Ross Low BMD Mid BMD High BMD Risk of New Vertebral Fractures (% / yr) Absolute fracture risk (%) Effect of prevalent radiographic vertebral fracture on non-vertebral fracture risk No vert fx >1 vert fx Femoral neck T-score Siris et al, Osteop Int 27 Previous non-vertebral fracture predicts future fracture History of fracture: fold greater risk of fracture True for any fracture type (ankle, finger) even traumatic fractures especially strong for men Mostly independent of BMD vanstaa, Osteop Int 22;13:624-9 Meta-analysis: analysis: Klotzbuecher, JBMR 2;15:721; Kanis Osteop Int 24 Family history of hip fracture is a strong risk factor for hip fracture 2-fold increased risk of hip fracture Regardless of hip BMD My mother had a spine fracture or osteoporosis : no increased risk. 7

8 Guess our risk of hip fracture Higher weight is protective. Lower weight is strong predictor of hip fracture and of low BMD Corticosteroids (more later, J. Graf) 6-1% loss of spine BMD in 6-12 months of 1 mg predisolone / day Strong (r=-.6) correlation between cumulative dose and deficit in spine BMD Clinical guidelines recommend bisphosphonate therapy to prevent bone loss Van Staa, Osteop Int 22 Smokers have a 1.4 to 2-fold increased risk of hip fracture. Independent of BMD. Due to poor health, weaker muscles & impaired balance Smoking Diabetics have increased risk of certain types of fractures (more later, A. Schwartz) Foot Humerus Hip RR=1.9 RR= RR=2.7 * Adjusted for age, BMI, BMD Schwartz JCEM 21 8

9 Highest risk groups Nursing homes: 4 to 6% hip fracture per year Post-stroke Over 7 years: 3-5% annual hip fracture risk for women and ~2% per year for men Alcohol and risk of hip fracture 2 drinks/day: no increased risk > 2 / day 3-4% increased risk 6-1/day in men: ~ 5 X risk Greater risk with beer than wine! (?) Hoidrup Am J Epidemiol 1999;149:993 Other Clinical Risk Factors for Osteoporosis Inactivity / bed rest Medications that are bad for the bone Thyroid meds, TZD s, aromatase inhibitors, and more.. Early menopause Surprising Non-Risk Factors Hair color/skin pigment Common wisdom: Blonds/light skin higher risk Truth: Blondes & brunettes & redheads seem to have same risk Dementia Recent falls or other neuromuscular problems Poor vision North-South gradient of risk Common wisdom: Fracture risk increases as you go north Truth: Lower hip fracture in north U.S. 9

10 Age and BMD Are Independent Risk Factors for Hip Fracture (more later, D. Black) BMD and Risk Factors Operate Independently: A Tale of Two Age (yrs) > 5-fold increase in fracture probability from age 5 to 8 Risk factor Hillary C. Laura B. Age 7 7 BMD (g/cm 2 ).6.6 Hx of fracture no yes Mother s hip fx no yes 5 5 yr. hip frx risk 3% 1% Kanis et al, Hip BMD T-score (SD) Combining BMD with Clinical Risk Factors (1995) Combining Risk Factors for Osteoporosis Hip Fx Rate (per 1 woman-years) Heel BMD Lowest Third Middle Third Highest Third Cummings et al., NEJM 332(12): , 773, >=5 # Risk Factors In heart disease, risk factors (e.g. BP, lipids, smoking) play independent role Risk factor models and tools are in common clinical use In osteoporosis, growing realization that BMD doesn t tell the whole story and that other risk factors play important (and independent) role T-scores alone are problematic Develop systems for estimating risk based on multiple risk factors 1

11 WHO Risk Model (FRAX): Overview Summary: Risk Factors for Osteoporotic Fracture Based on 1 year risk of hip or any clinical fracture Combine a set of observational studies from around the world to define a set of robust risk factors Build models with and without BMD Make country-specific risk-based diagnostic and treatment thresholds based on local cost effectiveness models Strengths & limitations to be discussed by Dr. Black NON-MODIFIABLE Prior fx (after age 5) Family history of fx Advanced age Caucasian Female Dementia Poor health / frailty POTENTIALLY MODIFIABLE Low bone mass Low body wt Current cigarette smoking Estrogen deficiency Poor nutrition (low calcium) Alcoholism Impaired eyesight Recurrent falls Low physical activity Poor health / frailty Summary Fractures are common (and will become more common), and are associated with significant mordidity, mortality and costs. Fracture risk is multifactorial Strong risk factors (besides BMD) include: Older Age Gender History of fracture especially vertebral fracture Maternal history of hip fracture Low weight Methods for combining risk factors, together with BMD are now available 11