Document

Report
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
United States2
Worldwide1



1 in 3 women and 1 in 5 men
>50 years of age will
develop osteoporosisrelated fracture
By 2010:
30%–50% of women and
15%–30% of men will
experience an osteoporosisrelated fracture in their
lifetime
By 2020:
75 million people in the US,
Europe, and Japan are
affected by osteoporosis




12 million >50 years of age will
have osteoporosis
40 million will have low bone mass
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 osteoporosisrelated 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 501
Relative BMD (%)
Hip and Heel
Spine
90
80
70
60
30
40
50
60
70
Age (years)
80
Annual Fracture Incidence
Forearm
100
Age-specific Incidence Rates for
Fractures in Women2
Colles'
Hip
Vertebrae
90
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.
Fracture Risk per 1000 Person-Years
Qualitative Skeletal Deterioration
with Aging
160
Age (years)
80+
140
120
75–79
100
80
70–74
60
65–69
60–64
40
55–59
50–54
45–49
<45
20
0
>1.0
0.90–0.99
0.80–0.89
0.70–0.79
0.60–0.69
<0.60
Bone Mass (g/cm)
Reprinted from Hui SL, et al. J Clin Invest. 1988;81:1804, with permission from The Copyright Clearance Center.
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 strength1
–
Fracture burden is highest in patients with BMD T-score
of -2.5a or less
–
Clinical history can identify fracture risk to degree
comparable to BMD
aStandard
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











Agea
Female gender
Premature menopause
Amenorrheaa
Hypogonadism in men
Caucasian or Asian race
Previous fracturea
Low bone mineral density
Glucocorticoid therapya
High bone turnovera
Family history of hip fracturea
a Characteristics

Poor visual acuitya

Low body weighta

Neuromuscular disordersa

Cigarette smokinga

Excessive alcohol
consumptiona

Prolonged immobilization

Low dietary calcium

Vitamin D deficiency
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
 Secondary osteoporosis
 Sex
— Hypogonadism
 Bone mineral density
— Premature menopause (<45 y)
 Prior history of fracture
— Chronic malnutrition or
 Parental history of fracture
malabsorption
— Osteogenesis imperfecta
 Current smoking
— Chronic liver disease
 Current alcohol >3 units/day
— Type I diabetes
 Rheumatoid arthritis
— Long-term hyperthyroidism
 Glucocorticoid use
 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.
FRAX™. Available at: http://www.shef.ac.uk/FRAX/index.htm.
FRAX™. Available at: http://www.shef.ac.uk/FRAX/index.htm.
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 overzealous treatment
of those at
indeterminate risk
Conclusions




Bone mineral density alone is inadequate for
identifying individuals at risk for fracture
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
– Guidelines regarding WHEN to intervene are
emerging
Brief
Q&A

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