Transcript Case Presentation - Scioto County Medical Society

Osteoporosis
Rajesh Kataria, D.O.
Osteoporosis
“…is 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: Diagnosis, Prophylaxis, and Treatment
of Osteoporosis, Am J Med 1993;94:646-650. WHO Study Group 1994.
Definition of Osteoporosis
What Is Bone Strength?
The Bone Quality Framework
Osteoporosis
• Osteoporosis is common - 44 million Americans have
osteoporosis or low bone mineral density (BMD)
• Osteoporosis is serious - Osteoporotic fractures
cause increased morbidity and mortality
• Osteoporosis is easy to diagnose - Bone density
testing can detect osteoporosis before the first
fracture occurs
• Good treatments are available- Fracture risk can be
reduced by about 50%
Osteoporosis
•
Prevalence
•
10 million with osteoporosis
•
•
8 million females
34 million with osteopenia
Osteoporosis
•
Fractures
•
1 in 2 females and 1 in 4 males over age 50
will fracture
• Approximately 1.5 million fractures annually
in U.S.
– 700,000 vertebral fractures
– 300,000 hip fractures
– 250,000 radial fractures
Osteoporosis
•
Fractures
•
•
•
•
Increased mortality seen after hip and
vertebral fractures
20% mortality in first year after hip fracture
25% require long-term nursing home care
after hip fracture
80,000 male hip fractures annually (2x
mortality with age matched females)
Prior Fracture as a Predictor of Fracture Risk
Osteoporosis
•
Cost
•
•
•
Each hip fracture costs $40,000 (2001)
Fractures cost $18 billion per year (2002)
Expected costs to exceed $60 billion by
2030
Major Risk Factors for Fracture
Osteoporosis
•
Risk Factors
•
•
•
•
•
•
Estrogen deficiency (menopause,
amenorrhea, anorexia nervosa)
Vitamin D deficiency
Medications (chemotherapy,
anticonvulsants)
Testosterone deficiency
Inactive lifestyle
Caucasian or Asian race
DXA
• “Gold-standard” for BMD measurement
• Measures “central” or “axial” skeletal sites:
spine and hip
• May measure other sites: total body and
forearm
• Extensive epidemiologic data
• Validated in many clinical trials
• Widely available (about 10,000 DXA
machines in USA)
14
Diagnostic Classification
Classification
T-score
Normal
-1 or greater
Osteopenia
Between -1 and -2.5
Osteoporosis
-2.5 or less
-2.5 or less and fragility
Severe Osteoporosis
fracture
WHO Study Group. 1994.
Diagnosis Caveats
• T-score -2.5 or less does not always mean
osteoporosis
– Example: osteomalacia
• Clinical diagnosis of osteoporosis may be
made with T-score greater than -2.5
– Example: atraumatic vertebral fracture with Tscore equals -1.9
• Low T-score does not identify the cause
– Medical evaluation should be considered
– Example: celiac disease with malabsorption
Fracture Risk Doubles
With Every SD Decrease in BMD
35
30
Relative
Risk
for
Fracture
25
20
15
10
5
0
-5.0
-4.0
-3.0
-2.0
-1.0
Bone Density (T-score)
0.0
1.0
Indications For Bone Mineral
Density (BMD) Testing
•
•
•
•
•
•
•
•
•
Women aged 65 and older
Postmenopausal women under age 65 with risk factors
Men aged 70 and older
Adults with a fragility fracture
Adults with a disease or condition associated with low
bone mass or bone loss
Adults taking medications associated with low bone mass
or bone loss
Anyone being considered for pharmacologic therapy
Anyone being treated, to monitor treatment effect
Anyone not receiving therapy in whom evidence of bone
loss would lead to treatment
Women discontinuing estrogen should be considered for
bone density testing according to the indications listed above
Vertebral fractures are often
unrecognized
Only about 25% of vertebral fractures
are clinically apparent
Vertebral Fractures Are Often Not
Recognized
But Are Important To Diagnose
Because They:
• Predict future fractures
• Are associated with increased mortality and
•
morbidity
Can be prevented with appropriate therapy
Densitometric Vertebral Fracture Assessment
(VFA)
VFA: DXA Imaging of the Spine For
Detection of Vertebral Fractures
GE: DVA or LVA
Normal
Fracture
Hologic: IVA or RVA
Normal
Fracture
Indications for Vertebral Fracture Analysis
(VFA)
• When BMD measurement is indicated, performance of
VFA should be considered in clinical situations that
may be associated with vertebral fractures. Examples
include:
 Documented height loss of greater than 2 cm (0.75 in) or
historical height loss greater than 4 cm (1.5 in) since
young adult
 History of fracture after age 50
 Commitment to long-term oral or parenteral
glucocorticoid therapy
 History and/or findings suggestive of vertebral fracture
not documented by prior radiologic study
Comparison of X-ray and VFA
X-ray
VFA
Radiation dose
800μSv
2-8 μSv
Access
Separate visit
Point of service
Cost
Higher ($92*)
Lower ($40*)
Resolution
Higher
Lower
Visualization
Superior above T7
May be superior in LS
Obliquity
Common in LS
Less parallax effect
Automated
morphometry
No
Yes
*Medicare reimbursement
Who Should Be Treated?
Osteoporosis Treatment:
Goals and Strategies
Average Daily Intake of Calcium in Women in the General Population Who Had
Low Bone Mass
Calcium Purchase Habits in Households With Patients on Bisphosphonates
Pharmacotherapy for Osteoporosis
Pharmacotherapy for Osteoporosis (Continued)
Osteoporosis
•
Calcitonin
•
•
•
•
•
Binds to osteoclast
Daily nasal spray
Reduction in vertebral fractures
Short-term analgesic effect
Tachyphylaxis
Osteoporosis
•
Raloxifene
•
•
•
•
•
Selective estrogen receptor modulator
(SERM)
Anti-resorptive effects on bone
Reduction in vertebral fractures
Cholesterol reduction
Increased VTE, hot flushes, leg cramps
Osteoporosis
•
Teriparatide
•
•
•
•
•
Recombinant human PTH (1-34)
Anabolic agent (stimulates osteoblasts)
Daily SQ injection
Reduction in vertebral and non-vertebral
fractures
Osteosarcoma in rats
Teriparatide: Effect on a Composite Endpoint of Nonvertebral Fractures at 21
Months†‡
Osteoporosis
•
Bisphosphonate formulations
•
Alendronate
•
•
•
Ibandronate
•
•
•
5 mg,10mg,35 mg,70 mg tablets (daily or weekly)
70 mg/75 ml oral solution (weekly)
2.5 mg, 150 mg tablets (daily or monthly)
3 mg/3 ml intravenous injection (quarterly)
Risedronate
•
5mg, 35 mg tablets (daily or weekly)
Osteoporosis
Anti-fracture Efficacy of
Bisphosphonates: A Review of the
Evidence
Osteoporosis
Anti-fracture Results with
Alendronate
FIT I:
FIT II:
Fracture Intervention Trial – Patients with
Vertebral Fracture at Baseline
Fracture Intervention Trial – Patients with
Low Bone Mass But Without a Baseline
Radiographic Vertebral Fracture
Osteoporosis
Anti-fracture Results with
Risedronate
VERT-NA: Vertebral Efficacy with Risedronate Therapy
- North America
VERT-MN: Vertebral Efficacy with Risedronate Therapy
- Multinational
Osteoporosis
Anti-fracture Results with
Ibandronate
BONE: Oral IBandronate Osteoporosis
Vertebral Fracture Trial in North America
and Europe
Proven Reduction on Vertebral
Fracture
Alendronate
Calcitonin
Ibandronate
Raloxifene
Risedronate
Teriparatide
Proven Reduction on Nonvertebral
Fracture
Alendronate
Risedronate
Teriparatide
Utility of BMD Measures
Osteoporosis
Osteoporosis is defined as a skeletal disorder
characterized by compromised Bone Strength
predisposing to an increased risk of fracture.
Bone
Quality
Bone
Strength
1.
2.
3.
4.
and
Architecture
Turnover
Damage Accumulation
Mineralization
Bone
Density
BMD
NIH Consensus Conference: Osteoporosis Prevention, Diagnosis, and Therapy
JAMA 2001;285:785-795
Osteoporosis
Rajesh Kataria, D.O.
Osteonecrosis of the Jaws (ONJ)
Bisphosphonate-associated
osteonecrosis (BON)
•
368 reported cases (5/06)
•
94% with intravenous bisphosphonate use
•
•
(multiple myeloma or bone mets)
15 cases in patients taking bisphosphonates for
osteoporosis
•
20 million users for osteoporosis
Osteonecrosis of the Jaws (ONJ)
Bisphosphonate-associated
osteonecrosis (BON)
•
•
•
Mandible affected more than 2x maxilla
Sores often painful though 1/3 are painless
Usually follows an invasive dental
procedure (tooth extraction)
•
•
Also seen with periosteal denture trauma
Can be seen as soon as 4 months after
therapy (mean 9 to 14 months)
Osteonecrosis of the right mandible after tooth extraction in a patient taking
zoledronic acid for metastatic breast cancer
Woo, S.-B. et. al. Ann Intern Med 2006;144:753-761
Osteonecrosis of the palatal torus in a patient with osteoporosis taking
alendronate
Woo, S.-B. et. al. Ann Intern Med 2006;144:753-761
Primary Diagnoses and Types of Bisphosphonates in Reported Cases of
Osteonecrosis of the Jaws
Woo, S.-B. et. al. Ann Intern Med 2006;144:753-761
Management Recommendations
Woo, S.-B. et. al. Ann Intern Med 2006;144:753-761