Prevention and Treatment of Osteoporosis 4/27/2017 Prevention and Treatment of Osteoporosis Jane A. Cauley, DrPH University of Pittsburgh

Osteoporotic Bone Loss 4/27/2017 Osteoporotic Bone Loss A skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture. Bone Strength: Bone Density: Grams of mineral per area or volume (70% bone strength) Bone Quality: Architecture Turnover Damage accumulation Mineralization Normal Bone NIH. Consensus Conference Statement. 2000;17(1):1-36. WHO. Available at: http://www.who.int/hrp/progress/40/prog40.pdf. 1996. These figures illustrate the changes in bone architecture at the microscopic level that are characteristic of osteoporosis. Normal trabecular bone, as shown on the left, appears as a dense network of thick trabeculae with small spaces. Osteoporotic trabecular bone, on the right, shows clear loss of bone, with large spaces and perforation of the trabecular network (see arrows). These perforations lead to weakened bone, and ultimately to fractures. This bone loss and architectural damage is relatively rapid in the perimenopausal phase of PMO and has been reported to be rapid in patients initiating chronic glucocorticoid therapy. Osteoporosis

World Health Organization (WHO) Osteoporosis Guidelines 4/27/2017 World Health Organization (WHO) Osteoporosis Guidelines WHO, Guidelines for Preclinical Evaluation and Clinical Trials in Osteoporosis, 1998. Speaker’s Notes It should be noted that these guidelines are based on data from postmenopausal Caucasian women; they may not be applicable to other races or ethnic groups. Patients with osteopenia may still be at risk for fracture. There are patients with osteopenia who have fractures already. Many physicians are confused about this phenomenon. For example, a patient having a T-score –2.2 is at significant risk for fracture even though osteopenic. T-Score

Densitometric Diagnosis of Osteoporosis 4/27/2017 Densitometric Diagnosis of Osteoporosis Age, Gender and Race Differences Adjust Bone Differences to a STANDARD T-score Z-score Comparison to young normals What is desirable Assess fx risk Comparison to age, gender, race, peers What is expected Assess BMD unusually low

Both t-scores and z-scores Expressed as Standard Deviation (SD) Scores 4/27/2017 Both t-scores and z-scores Expressed as Standard Deviation (SD) Scores Calculation Example t-score = Patient BMD – BMD of Young Normals 1 SD of Young Normals Example PT BMD = 0.8 g/cm Mean Young Normals = 1.0 SD= 0.10 t-score = 0.8-1.0 = -2.0 0.10

4/27/2017 Who has osteoporosis?

Number of Women age 50+ with Osteoporosis and Low Bone Mass: 2002 – 2020 4/27/2017 # in Millions America’s Bone Health: The State of Osteoporosis and Low Bone Mass in our Nation. NOF 2002

Prevalence of Osteoporosis (Hip BMD) by Age for Caucasian Women 4/27/2017 Prevalence of Osteoporosis (Hip BMD) by Age for Caucasian Women 100% 80% 52% 60% Prevalence 34% 40% 20% Looker AC, et al. J Bone Miner Res. 1997;12(11):1761-1768. 20% 4% 0% 50-59 60-69 70-79 80+ Age (Years)

Frequency of Hip Fractures worldwide as a ratio of rates observed to those expected for white women in USA 4/27/2017 Cummings and Melton Lancet 2002; 359: 1761

Projected Burden of Osteoporotic Hip Fracture Worldwide 4/27/2017 3,250,000 1,000,000 800,000 600,000 400,000 200,000 Cooper et al. Osteo Int 1992; 2:285-89. North America Europe Latin America Asia 1990 = 1.66 million 2050 = 6.26 million

Prevalence of Vertebral Fractures by Age 4/27/2017 Prevalence of Vertebral Fractures by Age Cummings and Melton Lancet 2002; 359: 1761 Age

Annual incidence of common diseases 4/27/2017 OSTEOPOROTIC FRACTURES ARE MORE COMMON IN WOMEN THAN HEART ATTACK, STROKE, AND BREAST CANCER COMBINED1-3 2,000,000 * 1,500,000 1,500,000 250,000 hip Annual incidence of common diseases 250,000 forearm 1,000,000 250,000 other sites ** 513,000 † 1. Riggs, B.L., and Melton, L.J. III, Bone 17(5)(Suppl.):505S-511S, 1995 2. Heart and Stroke Facts: 1996 Statistical Supplement, American Heart Association 3. Cancer Facts & Figures—1996, American Cancer Society This slide demonstrates that the incidence of osteoporotic fracture in women is far greater than the incidence of heart attack, stroke and breast cancer combined. This information couples nicely with the information on the previous slide to further emphasize that osteoporosis should be considered a major health concern among postmenopausal women in the United States. The point is not to suggest that osteoporosis is more important than the other diseases, but rather that it should be managed as routinely as are the other diseases. 500,000 228,000 ‡ 750,000 vertebral 184,300 Osteoporotic Heart Attack Stroke Breast Cancer Fractures * annual incidence all ages ** annual estimate women 29+ † annual estimate women 30+ ‡ 1996 new cases, women all ages

Lifetime Fracture Risk in 50 Year Old Caucasian Men&Women 4/27/2017 Lifetime Fracture Risk in 50 Year Old Caucasian Men&Women Women (%) Men (%) Hip 17.5 6.0 Spine 15.6 5.0 Wrist 16.0 2.5 Any of above 39.7% 13.1% Black Women : 6%; Black men 3% Melton LJ et al. JBMR 1992; 7: 1005-10

Five Year Fracture Risk in white women at various ages and t-scores 4/27/2017 Cummings SR et al JAMA 2002;288: 1889

Five Year Fracture Risk in white women at various ages and t-scores 4/27/2017 Cummings SR et al JAMA 2002;288: 1889

Five Year Fracture Risk in white women at various ages and t-scores 4/27/2017 Five Year Fracture Risk in white women at various ages and t-scores Cummings SR et al JAMA 2002;288: 1889

Lifetime Risk Of Hip Fracture for White women by Age and T-score

What are the consequences of osteoporosis? Mortality Morbidity Economic

One Year Mortality After a Hip Fracture+ 4/27/2017 One Year Mortality After a Hip Fracture+ % Mortality (972 Patients; 19% Male) Keene GS et al. Br Med J 1993;307:1248-50. Age at fracture

4/27/2017 Increased Mortality associated with Radiographic Vertebral Fractures Study of Osteoporotic Fractures (SOF) 50 40 30 Mortality (1000 Person-Years) 20 10 1 2 3 4 ³5 Number of Vertebral Fractures N=9575 Kado DM, et al.Arch Intern Med.1999;159:1215-20. p for trend <.001

Morbidity: Recovery to Pre-fracture Status One Year After Hip Fracture 60.0% 48.5% 51.5% 40.0% Walking Physical ADL’s Recovered Not Recovered Magaziner et al. J Geront 1990; 45: M101-7

SOF Incident Vertebral Fractures Are Associated with Back Pain and Disability 4/27/2017 Back Disability Back Pain * 60% 55% 60% * 50% 50% 44% * * 38% 40% 36% 40% % With Back Disability % With Back Disability 30% 30% 22% 20% 17% 20% Nevitt et al. Annals Int Med;7:4. * p<0.01 vs No new deformity, adj age, BMI, strength, smoking, HRT, other fxs, dx osteoporosis 10% 10% 0% 0% No 1 2 or No 1 2 or More More

Economic Burden of Osteoporotic Fractures in the US 4/27/2017 Economic Burden of Osteoporotic Fractures in the US Osteoporotic fractures account for: ~$20 billion in direct medical costs 547,000 hospital admissions 4.6 million hospital bed days ~2.5 million physician visits >180,000 nursing home admissions Projected direct costs of osteoporosis by 2040: ~$50 billion Cummings and Melton Lancet 2002; 359: 1761

OVERVIEW OF RISK FACTORS

Pathogenesis of Osteoporotic Fractures 4/27/2017 Pathogenesis of Osteoporotic Fractures Other Risk Factors Aging Menopause Genetics Decreased Bone Mass Low Peak Bone Mass Genetics Low Bone Density Figure reprinted from National Osteoporosis Foundation, Physician’s Guide to Prevention and Treatment of Osteoporosis. Modified from Riggs BL, Melton LJ: Etiology, Diagnosis and Management. New York: Raven Press; 1988. Poor Bone Quality Propensity to Fall Fractures

PREVALENT VERTEBRAL FRACTURE INCREASES RISK OF SUBSEQUENT FRACTURE 4/27/2017 PREVALENT VERTEBRAL FRACTURE INCREASES RISK OF SUBSEQUENT FRACTURE Study Follow-Up R.R. of Subsequent Fracture (Years) Vertebral Hip Hawaii1 4.7 5-12 Mayo2 14 1.8 SOF3 8.3 3.2-10.6 1.7 MORE4 3.0 4.5 Risedronate studies5 1.0 2.6-7.3 1. Ross PD, et al. Ann Intern Med. 1991;114:919-923. 2. Kotowicz MA, et al. J Bone Miner Res. 1994;9:599-605. 3. Black DM, et al. J Bone Miner Res. 1999;14:821-828. 4. Ettinger B, et al. JAMA. 1999;282:637-645. 5. Lindsay R, et al. JAMA. 2001;285:320-323.

BONE DENSITY PREDICTS FRACTURE RISK (META-ANALYSIS) 11 prospective cohort studies 90,000 person-years observation >2,000 fractures Age-adjusted relative risk for 1 SD decrease in BMD Hip Vertebral Site Fracture Fracture Distal radius 1.8 1.7 Proximal radius 2.1 2.2 Calcaneus 2.0 2.4 Spine 1.6 2.3 Femoral neck 2.6 1.8 Marshall D et al, BMJ 1996;312:1254