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Selecting Candidates for Fracture Prevention Based on Risk Prediction

Lubna Pal, MBBS, MRCOG, MS

Assistant Professor Department of Obstetrics, Gynecology and Reproductive Sciences Yale University School of Medicine New Haven, Connecticut

Osteoporosis

“A systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture.”

Consensus Development Conference on Osteoporosis, 1993

Normal Bone Osteoporosis

Peck WA, et al.

Am J Med.

1993;94:646. Graphics courtesy of the International Osteoporosis Foundation.

Demographics of Osteoporosis

Worldwide 1

 

1 in 3 women and 1 in 5 men >50 years of age will develop osteoporosis related fracture 30% –50% of women and 15% –30% of men will experience an osteoporosis related fracture in their lifetime



75 million people in the US, Europe, and Japan are affected by osteoporosis United States 2 By 2010:

 

12 million >50 years of age will have osteoporosis 40 million will have low bone mass By 2020:

 

14 million >50 years of age will have osteoporosis 47 million will have low bone mass By 2040:



Hip fractures will increase 2-3 fold

1. International Osteoporosis Foundation. Facts and statistics about osteoporosis and its impact. Available at: http://www.iofbonehealth.org/facts-and-statistics.html. 2. National Osteoporosis Foundation. Available at: http://www.iofbonehealth.org/facts-and-statistics.html#factsheet-category-23.

Implications of Osteoporosis

  

Mortality Morbidity

– – – –

Quality of life Dependence Pain Health issues (pulmonary, gastrointestinal) Healthcare burden

–

>1.5 million Americans experience osteoporosis related fractures/year

–

Annual cost of $14 Billion

International Osteoporosis Foundation. Facts and statistics about osteoporosis and its impact. Available at: http://www.iofbonehealth.org/facts-and-statistics.html.

Burden of Diseases Estimated as Disability-Adjusted Life Years (DALYs) in 2002 in the Americas and Europe Combined Parkinsonism Ovarian cancer Prostate cancer Hip fracture Stomach cancer Rheumatoid arthritis Breast cancer Hypertension Osteoporotic fracture Colon and rectal cancer Cirrhosis of liver Lung cancer Diabetes mellitus Chronic obstructive pulmonary disease 0 1000 2000 3000 4000 5000 6000 DALYs (thousand)

DALYs = disability-adjusted life years.

WHO. WHO Scientific Group on the Assessment of Osteoporosis at Primary Health Care Level: Summary Meeting Report. Brussels, Belgium, 2004. Available at: http://www.nof.org/professionals/WHO_Osteoporosis_Summary.pdf

Bone Mineral Density (BMD) and Fracture Risk

Changes in BMD for Women Experiencing Menopause at age 50 1

100 90

Forearm Hip and Heel Spine Age-specific Incidence Rates for Fractures in Women 2 Colles' Hip Vertebrae

80 70 60 30 40 50 60 70 80 90

Age (years) Age (years)

1. Reprinted from Faulkner KG.

J Clin Densitom

. 1998;1:279, with permission from the Copyright Clearance Center.

2. Reprinted from Cooper C, et al.

Trends Endocrinol Metab

. 1992;3:224, with permission from Cell Press.

Qualitative Skeletal Deterioration with Aging

160 Age (years) 80+ 140 120 100 80 60 40 20 0 50 –54 45 –49 <45 75 –79 >1.0

0.90–0.99

0.80–0.89

0.70–0.79

Bone Mass (g/cm) 0.60–0.69

<0.60

Reprinted from Hui SL, et al.

J Clin Invest

. 1988;81:1804, with permission from The Copyright Clearance Center.

70 –74 65 –69 60 –64 55 –59

Addressing Osteoporosis in At-Risk Populations



Identify

– –

Bone mineral density Risk factors



Intervene

–

Reduction in incident fractures



BMD Screening Strategy

Limitations

– – – –

Expense Expertise Logistic constraints for patients Preferential skeletal site?



BMD is 1 measure of skeletal structure and strength 1

–

Fracture burden is highest in patients with BMD T-score of -2.5

a or less

–

Clinical history can identify fracture risk to degree comparable to BMD

a Standard deviation below young average value.

BMD = bone mineral density.

1. Kanis JA, et al.

Osteoporos Int.

2005;16:581.

Evolving Concerns

  

How good are we at identifying patients at risk for fracture?

Low bone mineral density may not always translate into enhanced fracture risk Emerging concerns regarding unanticipated adverse effects of therapies

–

Bisphosphonate use associated with osteonecrosis of jaw

–

Menopausal hormone therapy and risks for breast cancer and cardiovascular disease

–

Long-term implications of available therapies



Osteosarcoma and parathyroid hormone

Risks for Fractures

          

Age a Female gender Premature menopause Amenorrhea a Hypogonadism in men Caucasian or Asian race Previous fracture a Low bone mineral density Glucocorticoid therapy a High bone turnover a Family history of hip fracture a

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Poor visual acuity a

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Low body weight a

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Neuromuscular disorders a

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Cigarette smoking a

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Excessive alcohol consumption a

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Prolonged immobilization

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Low dietary calcium



Vitamin D deficiency

a Characteristics capture aspects of fracture risk over and above that provided by bone mineral density.

Kanis JA, et al.

Osteoporos Int.

2005;16:581.

Fracture Risk Assessment

FRAX™



Developed by World Health Organization to evaluate fracture risk of patients



Enhances ability to predict fracture risk for an individual given the bone mineral density of femoral neck (if available) plus clinical risk factors



Provides individualized ABSOLUTE RISK over a 10-year period (similar to Gail model for risk of breast cancer or Framingham model for risk of cardiovascular disease)

– –

Hip fracture Major osteoporotic fracture



Guidelines regarding WHEN to intervene are emerging

FRAX™. Available at: http://www.shef.ac.uk/FRAX/index.htm.

Clinical Risk Factors in the FRAX™ Model



Age



Sex



Bone mineral density



Prior history of fracture



Parental history of fracture



Current smoking



Current alcohol >3 units/day



Rheumatoid arthritis



Glucocorticoid use



Secondary osteoporosis

—

Hypogonadism

— —

Premature menopause (<45 y) Chronic malnutrition or malabsorption

— —

Osteogenesis imperfecta Chronic liver disease

—

Type I diabetes

—

Long-term hyperthyroidism

 Each CRF independently contributes to fracture probability  Presence of ≥1 CRF increases probability of fracture incrementally CRF = clinical risk factors.

FRAX™. Available at: http://www.shef.ac.uk/FRAX/index.htm.

Fracture Risk Reduction



Optimize an appreciation of risk factors other than low bone mineral density



Minimize over zealous treatment of those at indeterminate risk

Conclusions

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Bone mineral density alone is inadequate for identifying individuals at risk for fracture

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Low BMD may not always translate into enhanced fracture risk Fracture risk may be predicted by a patient’s clinical history almost as reliably as by BMD assessment alone



Fracture risk assessment approach comprehensively addresses the morbidity of fracture rather than skeletal density

–