Epidemiology and Consequences of Fractures Ann V. Schwartz, PhD Department of Epidemiology and Biostatistics UCSF Financial Disclosures Advisory Board: Amgen Research Support: Hologic 24July12 1
Outline Fracture incidence Demographic determinants of fracture incidence Age Gender Race Geography Consequences of fracture Temporal trends and the future Osteoporotic fractures: Incidence compared with other diseases U.S. women 55+ Singer A et al Mayo Clinic Proceedings, 2015 24July12 2
Common sites of fracture Spine Hip Wrist Lifetime risks of clinical fractures 50 year old white women (U.S.) Lifetime risk* Hip fracture 17% Wrist fracture 16% Vertebral fracture 16% Any fracture > 50% Breast cancer 15% *Refs: Melton; Black; Kanis 24July12 3
SA11 Prevalence of Osteoporosis in US Major determinants of fracture incidence Demographic: Age Gender Race Geography Previous fracture: discuss under Consequences of Fracture More on risk factors for fracture and fracture prediction: Talk by Dr. Harris later today. 24July12 4
Slide 7 SA11 make a graph? Schwartz, Ann, 6/30/2017
Age and gender are important determinants of fracture incidence Harvey N et al ASBMR Primer Ch 40 2013 Age is Independent of BMD as Risk Factor for Hip Fracture 20 10 Age (yrs) 80 70 60 5-fold increase in fracture probability from age 50 to 80 at same BMD 50 Kanis et al, 2004 0-3 -2-1 0 1 Hip BMD T-score (SD) 24July12 5
Lifetime risks of fracture: Impact of gender Lifetime Risk at Age 50* Fracture Men (%) Women (%) Hip 6 17 Wrist 3 16 Clinical Vert Fx 5 16 Any 16% > 50% * Among Caucasians Osteoporosis in Men 1 in 5 to 6 men over age 50 will suffer osteoporotic fracture 30% of hip fractures worldwide are in men Mortality rates after fracture higher in men than women Treatment rates following fracture are abysmal 24July12 6
Hip fracture incidence by race (California) Sullivan et al 2016 Hip fracture rates vary dramatically by region and country Cauley et al. (2014) Nat. Rev. Endocrinol. 24July12 7
Vertebral Fracture Incidence Worldwide Radiographic fractures. Age standardized. Ballane et al Osteo Intl 2017 Consequences of fracture 24July12 8
Hip fractures are associated with increased morbidity and mortality No longer able to live independently No longer able to get in/out of bath No longer able to walk independently 40% 50% 17% 30% Death within one year Among those independent prefracture Magaziner J. J. Gerontol A Biol Sci Med Sci 2000 Mortality elevated after hip fracture Women Men Haentjens et al JAMA 2010 24July12 9
Limited Activity Days Post Fracture: Postmenopausal Women in FIT Consequences of fracture Fink et al. Osteo Intl 2003 Impact of Vertebral Fractures 20% excess mortality in 5 yrs after fracture Deformity & height loss Acute & chronic pain Pulmonary dysfunction Diminished quality of life: loss of self-esteem, sleep disorder, depression, loss of independence 24July12 10
Length of stay and costs for hospitalization Singer et al Mayo Clinic Proceedings 2015, High medical costs for hip and for other fractures Hip $25,519 Excess direct costs for Medicare patients with nonvertebral fractures Costs for year after fracture (1999-2006) Expressed in 2006 dollars Pike et al PharmacoEconomics 2012 24July12 11
Consequence of fracture: Increased risk of another fracture History of any fracture: 1.5-3.0 fold greater risk of fracture True for any fracture type even traumatic fractures especially strong for men Mostly independent of BMD vanstaa, Osteop Int 2002;13:624-9 Meta-analysis: Klotzbuecher, JBMR 2000;15:721; Kanis Osteop Int 2004 Vertebral fractures dramatically increase risk of future fracture 4x risk of more vert fxs 2x risk of other fractures (vanstaa, Osteop Int 2002) Women with clinical diagnosis of vertebral fracture have 5-15% 5 yr hip fracture risk! Not in FRAX 24July12 12
Existing Vertebral Fracture Predictive of Future Vertebral Fracture Independent of BMD Previous Vert Frx No Vert Frx 0.2 1.7 1.0 2.3 3.4 5.8 Low BMD Mid BMD High BMD Ross 1991 0 1 2 3 4 5 6 Risk of New Vertebral Fractures (% / yr) Effect of prevalent radiographic vertebral fracture on non-vertebral fracture risk Absolute fracture risk (%) 6 5 4 3 2 1 0 No vert fx >1 vert fx -2-3 -4 Femoral neck T-score Siris et al, Osteo Int 2007 24July12 13
Trends in Use of Osteoporosis Therapy NYT (6/2/16): Osteoporosis drugs shunned for fear of rare side effects 24July12 14
Osteoporosis medication use to 2004 Brauer et al JAMA 2009 Oral Bisphosphonate Use in the U.S. Declines after 2008 % of 55+ y.o. with 1 prescription in annual federal survey Jha et al JBMR 2015 24July12 15
U.S. Google search activity for Fosamax A = Lawsuit filed against Merck for Fosamax causing osteonecrosis of the jaw. B = Study published associating Fosamax with atrial fibrillation. C = Jury deliberations start for first Fosamax trial. D = ABC World News runs feature segment on Fosamax and atypical femoral fractures. Jha et al JBMR 2015 Treatment with osteoporosis medication during year after fracture Vertebral Hip Balasubramanian et al. J Bone Joint Surg Am 2014 24July12 16
Osteoporosis Medication Use After Hip Fracture U.S. Patients 2002-11 Solomon et al JBMR 2014 Osteoporosis Related Health Services Utilization After First Hip Fracture Women in the United States, 2008 2014 Gillespie & Morin JBMR 2017 24July12 17
Prospects for the Future Hip fracture incidence declining in U.S. Jha et al JBMR 2015 Including California Hip fracture incidence in CA Sullivan et al 2016 24July12 18
Hip Fracture Rates Declining in West, Increasing in East Age-standardized Ballane et al JBMR 2014 Prospects for the Future... Elderly represent fastest growing segment of population Thus, in spite of declining rates in US, total number of fractures expected to increase 24July12 19
World Population: 1990 and 2025 Age range (years) 80+ 1990 71-75 61-65 51-55 41-45 31-35 21-25 11-15 0-5 Men Women 80+ 71-75 61-65 51-55 41-45 31-35 21-25 11-15 0-5 2025 300 200 100 0 100 200 300 Number (000,000) Worldwide Distribution of Hip Fractures in Women: 1990 to 2050 Hip Fractures, x1000 3000 1990 2500 2025 2000 2050 1500 1000 500 0 Women Women N. Am, Europe Mid East, Asia, Latin Am, Africa 24July12 20
Summary Fractures are common Age is a strong determinant of fracture risk, especially for hip and spine Fractures are associated with significant morbidity, excess mortality and costs. Osteoporosis therapy use after hip fracture is <20% in women and <10% in men Age-adjusted fracture incidence is stable or even declining in the US, but total number of fractures will increase due to aging of population Thank you 24July12 21