Osteoporosis
Rajesh Kataria, D.O.
Southern Ohio Rheumatology
Disclosures
Speaker’s Bureau
Novartis
Warner Chilcott
Objectives
State the indications for bone mineral
density testing
Understand and describe the utility of
the FRAX tool
List the medications that have proven
reduction on nonvertebral fractures
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
Bone Health
Bone Remodeling (Turnover)
Cells in Bone Tissue
Bone Remodeling Cycle
Bone Remodeling Cycle (cont)
Role of Modulators in Bone Remodeling
Unbalanced Remodeling in Menopause Leads to Osteoporosis
Biochemical Markers of Bone Remodeling
Osteoporosis: A Common Problem in
the General Population
•
In the United States, 10 million individuals
are estimated to have osteoporosis
•
•
8 million are women
34 million more are estimated to have low
bone mass (osteopenia)
•
They have an increased risk for developing
osteoporosis
Estimated Annual Incidence of Osteoporosis-Related Fractures in Women and Men
Annual Incidence of Osteoporotic Fractures Higher Than Other Epidemic
Diseases
Osteoporosis
•
Fractures
•
•
1 in 2 females over age 50 will fracture
1 in 4 males over age 50 will fracture
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)
Osteoporosis
•
Cost
•
•
•
Each hip fracture costs $40,000 (2001)
Fractures cost $13 billion per year (2005)
Expected costs to exceed $60 billion by
2030
Prior Fracture as a Predictor of Fracture Risk
Risk Factors for Osteoporotic Fractures
Vertebral Fractures Have Significant Consequences for Patients, Including Dorsal
Kyphosis
Hip and Other Non-Vertebral Fractures Have Significant Consequences
Most Hip Fracture Patients Receive No Pharmacologic Treatment for
Osteoporosis
Clinical Presentation of Osteoporosis
DXA
• “Gold-standard” for BMD (Bone Mineral
Density) measurement
• Measures “central” or “axial” skeletal sites:
spine and hip
• May measure other sites: total body and
forearm
• Widely available (about 10,000 DXA
machines in USA)
27
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.
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
60
50
–1.0 to –2.5
 BMD distribution
Fracture rate
No. of women
with fractures
450
≤ –2.5
400
350
40
300
250
30
200
20
150
100
10
0
50
>1.0
0.5 to 0.0
1.0 to 0.5
–0.5 to –1.0 –1.5 to –2.0 –2.5* to –3.0
0.0 to –0.5
<–3.5
–1.0 to –1.5 –2.0 to –2.5 –3.0 to –3.5
BMD T-Scores†
*The World Health Organization defines osteoporosis as a T-score ≤ –2.5
†Peripheral devices used to measure T-score
Adapted with permission from Siris ES et al. Arch Intern Med. 2004;164:1108-1112.
0
No. of Women With Fractures
Fracture per 1000 Person-Years
NORA: Relationship of BMD with Risk of
Fracture in Postmenopausal Women
Most Women Who Had a Fracture in the NORA Study Would Not Receive Treatment
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
Women discontinuing estrogen should be considered for
bone density testing according to the indications listed above
Densitometric Vertebral Fracture Assessment
(VFA)
Who Should Be Treated?
Who Should Be Treated? (cont)
Using the FRAX® Tool to Help Determine Fracture Risk in Treatment-Naïve
Patients With Low Bone Mass
Osteoporosis Treatment: Goals and Strategies
Calcium and Vitamin D Supplementation
Calcium Purchase Habits in Households With Patients on Bisphosphonates
Bisphosphonate and Supplement Intake Habits Survey
Pharmacotherapy
Pharmacotherapy (cont)
Osteoporosis
•
Calcitonin (Miaclacin, Fortical)
•
•
•
Daily nasal spray
Reduction in vertebral fractures
Short-term analgesic effect
Osteoporosis
•
Raloxifene (Evista)
•
•
•
•
Selective estrogen receptor modulator
(SERM)
Reduction in vertebral fractures
Cholesterol reduction
Increased VTE, hot flushes, leg cramps
Osteoporosis
•
Teriparatide (Forteo)
•
•
•
•
Anabolic agent (new bone formation)
Daily SQ injection
Reduction in vertebral and non-vertebral
fractures
Increased leg cramps
Osteoporosis
•
Denosumab (Prolia)
•
•
•
•
•
Antibody to RANKL (osteoclast
differentiating factor)
q6 month SQ injection
Reduction in vertebral and non-vertebral
fractures
Increased eczema, cellulitis* & flatulence
Hypocalcemia in CKD
Proven Reduction on Vertebral
Fracture
Alendronate (Fosamax)
Calcitonin (Miacalcin, Fortical)
Denosumab (Prolia)
Ibandronate (Boniva)
Raloxifene (Evista)
Risedronate (Actonel, Atelvia)
Teriparatide (Forteo)
Zoledronic acid (Reclast)
Proven Reduction on Nonvertebral
Fracture
Alendronate (Fosamax)
Denosumab (Prolia)
Risedronate (Actonel, Atelvia)
Teriparatide (Forteo)
Zoledronic acid (Reclast)
Osteonecrosis of the Jaws (ONJ)
•
•
Bone exposure in the mandible, maxilla,
or both
Simulates dental abscesses,
“toothaches”, denture sore spots or
osteomyelitis
Osteonecrosis of the Jaws (ONJ)
•
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
•
Risk is < 1/100,000
AAOMS, ADA & ASBMR
Recommendations
• Route dental exams & promotion of
good oral hygiene
• Dental exam is not necessary prior
to bisphosphonate therapy
• No alteration or delay in planned
surgery is necessary
• Discuss benefits/risks of treatment
Safety Topics in the Media
•
Atrial Fibrillation
•
No cause and effect relationship
Safety Topics in the Media
•
Atypical subtrochanteric femur fracture
•
•
FDA (3/10): data have not shown a clear
connection with bisphosphonate use
Similar number of these fractures in those
not on bisphosphonates
Safety Topics in the Media
Typical femur fracture
Atypical femur fracture
Associated with fall (95%)
No fall
No prodrome
Prodromal thigh pain
30-50% reduction with effective
bisphosphonate
Often associated with
bisphosphonate/steroid use
Located at or above trochanter
Below intertrochanteric line
General unilateral
Uni or bilateral
No cortical thickness change
Increased femoral cortical
thickness
Generally spiral
Transverse with medial spike
Safety Topics in the Media
•
Esophageal Cancer
•
•
•
2 large studies in the UK with conflicting
results
FDA has not concluded that taking an oral
bisphosphonate increases the risk of
esophageal cancer
Would avoid bisphosphonates in patients
with Barrett’s esophagus
Drug Holiday: FDA
“ In light of all the risk-benefit challenges with the
bisphosphonate class, these data suggest that
bisphosphonate therapy could be safely discontinued
from an efficacy standpoint. However, additional longterm data would be needed to further define an
appropriate duration of drug cessation and to
determine if interim monitoring is appropriate on an
individual basis.”
“There are no substantial data available to inform decision
regarding the initiation or duration of a drug holiday.”
FDA Advisory Committee (9/9/11)