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July 2017 CME (25 minutes) 7/11/2019 Financial Disclosures Financial Disclosures Epidemiology and Consequences of Fractures I have nothing to disclose Ann V. Schwartz, PhD Department of Epidemiology and Biostatistics UCSF Outline Outline

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July 2017 CME (25 minutes) 7/11/2019

Ann V. Schwartz, PhD

Department of Epidemiology and Biostatistics UCSF

Epidemiology and Consequences of Fractures Financial Disclosures Financial Disclosures

I have nothing to disclose

Outline Outline

  • Fracture incidence
  • Determinants of fracture incidence

– Age – Gender – Race – Geography – History of fracture

  • Consequences of fracture
  • Treatment trends
  • Projected increases in fracture

Fracture Incidence in Older Adults Fracture Incidence in Older Adults

  • The total number of fractures in adults

50+ estimated at 2.05 million (2005).

Burge et al JBMR 2007

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July 2017 CME (25 minutes) 7/11/2019

Incidence and Economic Burden of Osteoporosis‐Related Fractures in the United States, 2005–2025

Burge et al JBMR 2007

Common sites of fracture in older adults Common sites of fracture in older adults

Incident fracture distribution by type, 2005, U.S. ≥50

Lifetime risks of clinical fractures 50 year old white women (U.S.) 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

Singer A et al Mayo Clinic Proceedings, 2015

Osteoporotic fractures: Incidence rate compared with others

U.S. women 55+ Hospitalizations

10 20 30 40 50 60 70 80 50-59 60-69 70-79 80+

Postmenopausal Women

10 20 30 40 50 60 70 80 50-59 60-69 70-79 80+

Men

Prevalence of Osteoporosis in US: At high risk of fracture Prevalence of Osteoporosis in US: At high risk of fracture

Wright et al Osteo Int 2017

50+ 30% 50+ 16%

Osteoporosis: BMD T-score <-2.5 OR qualifying low trauma fx OR FRAX score >3% for hip fx or >20% for MOF

2005-08 NHANES

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July 2017 CME (25 minutes) 7/11/2019

Major determinants of fracture incidence Major determinants of fracture incidence

Demographic: Age Gender Race Geography Previous fracture: vertebral & non-vertebral More on risk factors for fracture and fracture prediction: Talk by Dr. Harris coming up next.

Age and gender are important determinants

  • f fracture incidence

Harvey N et al ASBMR Primer Ch 40 2013

Hip BMD T-score (SD)

  • 3
  • 2
  • 1

1 10 20

50 60 70 80

Age (yrs)

Kanis et al, 2004

Age is Independent of BMD as Risk Factor for Hip Fracture Age is Independent of BMD as Risk Factor for Hip Fracture

  • 5-fold increase

in fracture probability from age 50 to 80 at same BMD

Lifetime risks of fracture: Impact of gender Lifetime risks of fracture: Impact of gender

Fracture Men (%) Women (%) Hip 6 17 Wrist 3 16 Clinical Vert Fx 5 16 Any 16% > 50%

* Among Caucasians Lifetime Risk at Age 50*

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July 2017 CME (25 minutes) 7/11/2019

Osteoporosis in Men 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

Hip fracture incidence by race (California) 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.

Vertebral Fracture Incidence Worldwide Vertebral Fracture Incidence Worldwide

Clinical fractures. Age standardized.

Ballane et al Osteo Intl 2017

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July 2017 CME (25 minutes) 7/11/2019

History of fracture: Increased risk of another fracture History 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 Vertebral fractures dramatically increase risk of future fracture

  • 4x risk of more vert fxs
  • 2x risk of other fractures
  • Clinical diagnosis of

vertebral fracture -> 5 yr hip fracture risk of 13% in women and 7% in men!

Not in FRAX

Klotzbuecher JBMR 2000; Van Staa Osteoporos Int 2002

Existing Vertebral Fracture Predictive of Future Vertebral Fracture Independent of BMD Existing Vertebral Fracture Predictive of Future Vertebral Fracture Independent of BMD

1 2 3 4 5 6 Previous Vert Frx No Vert Frx Low BMD Mid BMD High BMD 5.8 3.4 2.3 1.7 1.0 0.2 Risk of New Vertebral Fractures (% / yr)

Ross 1991

1 2 3 4 5 6 No vert fx >1 vert fx

  • 2

Absolute fracture risk (%)

  • 3
  • 4

Femoral neck T-score

Siris et al, Osteo Int 2007

Existing Vertebral Fracture Predictive of Any Future Fracture Independent of BMD Existing Vertebral Fracture Predictive of Any Future Fracture Independent of BMD

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July 2017 CME (25 minutes) 7/11/2019

Prevalence of vertebral fracture: NHANES 2013-14 Prevalence of vertebral fracture: NHANES 2013-14

Age Vert Fracture (%) Women Men 50-59 3.3 5.2 60-69 4.6 6.3 70-79 10.6 10.3 80+ 16.3 20.7 DXA Vertebral Fracture Assessment (VFA)

Cosman et al Osteoporos Int 2017

Prevalence of vertebral fracture: NHANES 2013-14 Prevalence of vertebral fracture: NHANES 2013-14

Age Vert Fracture (%) Women Men 50-59 3.3 5.2 60-69 4.6 6.3 70-79 10.6 10.3 80+ 16.3 20.7 DXA Vertebral Fracture Assessment (VFA)

Cosman et al Osteoporos Int 2017

>90% were not aware of vertebral fracture

Consequences of fracture Consequences of fracture

Magaziner J. J. Gerontol A Biol Sci Med Sci 2000

40%

No longer able to walk independently

30%

No longer able to get in/out of bath

17%

Death within

  • ne year

50%

No longer able to live independently

Hip fractures are associated with increased morbidity and mortality

Among those independent prefracture

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July 2017 CME (25 minutes) 7/11/2019

Mortality elevated after hip fracture Mortality elevated after hip fracture

Haentjens et al JAMA 2010

Women Men

Impact of Vertebral Fractures 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

Consequences of fracture Consequences of fracture

Limited Activity Days Post Fracture: Postmenopausal Women in FIT

Fink et al. Osteo Intl 2003

High medical costs for hip and for other fractures

Pike et al PharmacoEconomics 2012

Excess direct costs for Medicare patients with nonvertebral fractures

Hip $25,519

Costs for year after fracture (1999-2006) Expressed in 2006 dollars

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July 2017 CME (25 minutes) 7/11/2019

Singer et al Mayo Clinic Proceedings 2015,

Length of stay and hospitalization costs: Fractures, MI, stroke, breast cancer

HIP MI

Trends in Use of Osteoporosis Therapy Trends in Use of Osteoporosis Therapy NYT (6/2/16): Osteoporosis drugs shunned for fear of rare side effects NYT (6/2/16): Osteoporosis drugs shunned for fear of rare side effects Osteoporosis medication use to 2004 Osteoporosis medication use to 2004

Brauer et al JAMA 2009

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July 2017 CME (25 minutes) 7/11/2019

Oral Bisphosphonate Use in the U.S. Declines after 2008 Oral Bisphosphonate Use in the U.S. Declines after 2008

Jha et al JBMR 2015

% of 55+ y.o. with ≥1 prescription in annual federal survey

U.S. Google search activity for “Fosamax” 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

Kim et al JBMR 2015

FDA safety announcements and use of

  • steoporosis medications

5/05 ONJ 10/07 A fib 3/10 AFF

Osteoporosis Medication Use After Hip Fracture Osteoporosis Medication Use After Hip Fracture

Solomon et al JBMR 2014

U.S., men & women, 50+, 2002-11

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July 2017 CME (25 minutes) 7/11/2019

Osteoporosis‐Related Health Services Utilization After First Hip Fracture Women in the United States, 2008–2014 Osteoporosis‐Related Health Services Utilization After First Hip Fracture Women in the United States, 2008–2014

Gillespie & Morin JBMR 2017

Osteoporosis Therapy after Fracture (Medicare, 2008-13) Osteoporosis Therapy after Fracture (Medicare, 2008-13)

Weaver…Harris et al J Manag Care Spec Pharm. 2017

Within 1 yr Osteoporosis Therapy after Fracture, by Sex (Medicare, 2008-13) Osteoporosis Therapy after Fracture, by Sex (Medicare, 2008-13)

Weaver…Harris et al J Manag Care Spec Pharm. 2017

Within 1 yr

Decline in DXA testing utilization… Decline in DXA testing utilization…

Leweicki et al Osteoporos Int 2018

Medicare, women, 65+

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July 2017 CME (25 minutes) 7/11/2019

Poor Compliance with Osteoporosis Therapy: 12 months after initial prescription Poor Compliance with Osteoporosis Therapy: 12 months after initial prescription

Durden et al Arch Osteoporos 2017

U.S., women, 50+ Poor Compliance with Osteoporosis Therapy: 24 months after initial prescription Poor Compliance with Osteoporosis Therapy: 24 months after initial prescription U.S., women, 50+

Durden et al Arch Osteoporos 2017

Prospects for the Future Prospects for the Future

Prospects for the Future… Hip fracture incidence declined in U.S. after 1995 Prospects for the Future… Hip fracture incidence declined in U.S. after 1995

Jha et al JBMR 2015

U.S., 55+

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July 2017 CME (25 minutes) 7/11/2019

Reasons for Decline? Reasons for Decline?

The reasons are not clear. Some hypotheses:

  • Higher average BMI
  • Decline in smoking
  • Increased use of osteoporosis

therapy

  • Others?

Hip fracture incidence in U.S. – possible plateau after 2012 Hip fracture incidence in U.S. – possible plateau after 2012

Leweicki et al Osteoporos Int 2018

U.S., women, 65+

Prospects for the Future ... Prospects for the Future ...

  • Elderly represent fastest growing segment of population
  • Thus, in spite of stable, or even declining, rates in US,

total number of fractures expected to increase

Incidence and Economic Burden of Osteoporosis‐Related Fractures in the United States, 2005–2025

Burge et al JBMR 2007

Projected Increase in Fractures by 2025 U.S., ≥50

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July 2017 CME (25 minutes) 7/11/2019

Number (000,000)

0-5

Age range (years)

11-15 21-25 31-35 41-45 51-55 61-65 71-75 80+ Men Women

1990

100 200 300 0-5 11-15 21-25 31-35 41-45 51-55 61-65 71-75 80+ 100 200 300

2025

World Population: 1990 and 2025 World Population: 1990 and 2025

Worldwide Distribution of Hip Fractures in Women: 1990 to 2050 Worldwide Distribution of Hip Fractures in Women: 1990 to 2050

Women Women

500 1000 1500 2000 2500 3000 1990 2025 2050

  • N. Am, Europe

Mid East, Asia, Latin Am, Africa Hip Fractures, x1000

Summary 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 Thank you