Download Osteoporosis - Geriatrics Care Online

OSTEOPOROSIS
OBJECTIVES
Know and understand:
• How to diagnose osteopenia and osteoporosis
• The pathogenesis of osteoporosis
• Common secondary causes of bone loss
• Prevention and treatment strategies for
osteoporosis
• How to diagnose and treat osteomalacia
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TOPICS COVERED
• Bone Remodeling and Changes in Bone Mass
• Epidemiology of Osteoporotic Fractures
• Pathogenesis of Osteoporosis
• Evaluation for Osteoporosis
• Prevention and Treatment of Osteoporosis
• Management of Vertebral Fractures
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BONE REMODELING
• Bone repairs itself by actively remodeling
 Bone resorption (osteoclasts)
 Bone formation (osteoblasts)
• The remodeling cycle may become unbalanced
 After menopause; with aging in men & women
 Bone resorption increases more than bone
formation, resulting in net bone loss
Bone loss  osteopenia, osteoporosis, fractures
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LIFETIME CHANGES IN BONE MASS
Age
Puberty to mid20s and 30s
Women
Men
Bone mass increases rapidly,
reaching peak bone mass
Mid-30s to 40s
A few years of stability,
then slow bone loss
No risk factors:
bone loss 1%/year
Mid-40s to 50s
Menopause, then rapid
bone loss  7%/year for
 7 years
With risk factors:
bone loss  6%/year
Mid-50s to late
life
Continuing bone loss of
1%–2%/year
Risk factors: low calcium intake, smoking, alcoholism, certain drugs.
Both men and women lose predominantly cancellous (vertebral) bone.
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EPIDEMIOLOGY OF
OSTEOPOROTIC FRACTURES
High prevalence
• 1.5 million osteoporotic fractures in US annually
• 250,000 hip & 500,000 vertebral fractures in US annually
Serious consequences
•  quality of life, function, independence
•  morbidity & mortality (50% of women do not recover prior
function after hip fracture; 20% excess mortality in year after
hip fracture)
Cost
•
•
In 2005, estimated to be responsible for $19 billion in costs
Experts predict that by 2025, costs will rise to $25.3 billion
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DEFINITIONS OF
BONE LOSS DISORDERS
Osteopenia
• Low bone mass
• T-score < –1 but  –2.5
Osteoporosis
• BMD measurement at any site >2.5 standard
deviations below the young-adult standard, with
or without previous fracture
• T-score < –2.5
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PATHOGENESIS OF
OSTEOPOROSIS
• Estrogen deficiency
• Calcium deficiency & secondary
hyperparathyroidism
• Androgen deficiency
• Changes in bone formation
• Secondary causes and medications
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ESTROGEN DEFICIENCY
• Factors that play a role in bone loss related
to estrogen deficiency:
 Increased resorption
 Osteoclast activity
• Fracture risk is inversely related to estrogen
levels in post-menopausal women
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CALCIUM DEFICIENCY AND
SECONDARY HYPERPARATHYROIDISM
• Aging skin &  sunlight exposure  conversion of 7dehydrocholesterol to cholecalciferol (vitamin D3) by
ultraviolet light  vitamin D deficiency
• Vitamin D insufficiency   absorption of calcium
• Older adults tend to ingest inadequate amounts of
calcium and vitamin D
• PTH  in order to maintain serum levels of calcium
• When chronically elevated, PTH is a potent stimulator
of bone resorption
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ANDROGEN DEFICIENCY
• Men with estrogen deficiency or resistance
have  bone mass and failure of epiphyseal
closure
• Severe male hypogonadism can cause
osteoporosis
• The effect of moderate decreases in
testosterone levels in aging men on rate of
bone loss is uncertain
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CHANGES IN BONE FORMATION
With aging and menopause:
• Osteoblast activity decreases
• Bone resorption increases
• Growth factors (eg, transforming growth
factor B and insulin-like growth factor 1)
may be impaired, resulting in decreased
osteoblast function
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RISK FACTORS FOR OSTEOPOROSIS
• Age (postmenopausal in
women, >70 yr in men)
• Glucocorticoids
• Female sex
• Previous fragility fracture
as adult
• Low body weight (BMI
<20)
• Androgen-deprivation
therapy
• 10% decline in weight
(from usual adult body
weight)
• Current smoking
• Physical inactivity
• Low dietary calcium
• Spinal cord injury
• Alcoholism
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MODIFICATIONS TO REDUCE THE
RISK OF OSTEOPOROSIS (1 of 2)
Exercise: Encourage regular, weightbearing
exercise at least 5 times per week for 30
minutes
Nutrition: Encourage adequate intake of
calcium (1,200–1,500 mg/d in divided doses)
and vitamin D3 (800–1000 IU/d)
Smoking cessation
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MODIFICATIONS TO REDUCE THE
RISK OF OSTEOPOROSIS (2 of 2)
Medications that can increase risk of
osteoporosis—use with caution:
• Glucocorticoids
• Methotrexate
• Anticonvulsants
• GnRH agonists used
for prostate cancer
• Cyclosporine
• Long-term heparin
• Excess thyroid
hormone
replacement
• Aromatase inhibitors
(eg, anastrozole,
letrozole, exemestane)
used for breast cancer
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SECONDARY CAUSES
OF BONE LOSS
Women
• Primary hyperparathyroidism
• Glucocorticoid use
Men
• Hypogonadism
• Malabsorption syndrome including gastrectomy
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EVALUATION
• Measure Vitamin D level
• Measure bone density
• Assess for secondary causes of bone
loss
• Use of biochemical markers in clinical
practice is controversial
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BMD MEASUREMENT
Best predictor of fracture
• Relative risk of fracture is 10 greater in women in
the lowest quartile than in those in highest quartile
Dual-energy x-ray absorptiometry (DEXA)
• Preferred method of measurement
• Can measure hip, anterior-posterior spine, lateral
spine, and wrist
• Cost = $200 to $300; covered by Medicare and
Medicaid if indications for use are met
Lateral vertebral assessment
• Technology available for diagnosis of vertebral
fractures as part of DEXA
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INDICATIONS FOR BMD TESTING
(1 of 2)
Disease
Hyperparathyroidism
Recommended Laboratory Tests
Calcium, PTH level
Hyperthyroidism
TSH, thyroxine levels
Hypogonadism (men
only)
Bioavailable testosterone or total
testosterone, free testosterone with
sex hormone-binding globulin
Multiple myeloma
CBC, serum protein electrophoresis,
urine electrophoresis
Gold font = recommended routinely
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INDICATIONS FOR BMD TESTING
(2 of 2)
Disease
Osteomalacia
Recommended Laboratory Tests
Bone-specific alkaline phosphatase,
25(OH)D level
Paget’s disease
Bone-specific alkaline phosphatase,
urine NTx
Electrolytes, 24-h urinary free
cortisol
Cushing’s disease
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LATERAL VERTEBRAL
ASSESSMENT
• Vertebral fractures are highly associated with
future fracture risk and morbidity
• Can be present in patients with T-scores
> ‒2.5
• Used as an adjunct to BMD testing
Slide 21
BIOCHEMICAL MARKERS OF
BONE TURNOVER
• May be early indicator of treatment efficacy
• Bone resorption markers
 Cross-linked C-telopeptides of type I collagen
(serum CTX)
 Cross-linked N-telopeptides of type I collagen
(NTx – urine or serum)
• Bone formation marker
 Bone alkaline phosphatase
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LIMITATIONS ON THE USE OF
BIOCHEMICAL MARKERS
• Clinical use is controversial because of
substantial overlap of values in women with
high and low bone density or rate of bone loss
• Few studies have compared the response of
a particular marker and bone density with
goals of therapy
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WHOM TO TREAT
• Older men and women with osteoporosis
diagnosed by DEXA or with history of fragility
fracture
• FRAX is an algorithm that uses clinical and
BMD information to model the 10-year
fracture probability in men and women
(http://www.shef.ac.uk/FRAX/index.htm)
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PREVENTING AND TREATING
OSTEOPOROSIS
• Exercise
• Calcium and vitamin D
• Bisphosphonates
• Selective estrogen receptor modulators
• Calcitonin
• Estrogen replacement
• Investigational agents
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EXERCISE
• Marked decrease in physical activity or
immobilization  decline in bone mass
• Walking, a weight-bearing exercise, can be
recommended for all adults
• Start slowly and gradually increase the number
of days and time spent walking each day
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CALCIUM & VITAMIN D
RECOMMENDED REQUIREMENT
• 1200 mg/day of calcium: men 65 years and older
& postmenopausal women
• 800-1000 IU/day of vitamin D
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BISPHOSPHONATES
Rationale: Approved for osteoporosis prevention in postmenopausal women and treatment in men and women
•  bone density of spine & hip (alendronate and
risedronate)
•  vertebral fracture rate (ibandronate)
• Optimal duration of treatment unclear
Side effects: GI (abdominal pain, dyspepsia, esophagitis,
nausea, vomiting, diarrhea); musculoskeletal pain;
osteonecrosis of the jaw (rare in patients being treated for
osteoporosis); atypical fractures; there have been cases of
atrial fibrillation after doses of zoledronate
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BISPHOSPHONATES COMPARED (1 of 2)
Medication
Dosage
Special
Considerations
Observed Beneficial
Treatment Outcomesa
Bisphosphonates should not be used if CrCl <30 mL/min
Alendronate
70 mg/wk;
35 mg/wk
for
prevention
Adherence to
dosing
instructions
required; used in
men and women
to prevent
glucocorticoidinduced
osteoporosis
Vertebral fracture: absolute risk reduction
(ARR)=7.1%, number needed to treat
(NNT)=14 over 3 yr
Hip fracture: ARR=1.1%, NNT=91 over 3 yr
Risedronate
35 mg/wk
or 150
mg/moh
Adherence to
dosing
instructions
required
Vertebral fracture: ARR=5%, NNT=20 over 3
yr
Nonvertebral fracture: ARR=4%, NNT=25
over 3 yr
aPatient
populations were not comparable, so direct comparisons of ARR and NNT may not be valid
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BISPHOSPHONATES COMPARED (2 of 2)
Medication
Dosage
Special
Considerations
Observed Beneficial
Treatment Outcomesa
Bisphosphonates should not be used if CrCl <30 mL/min
Ibandronate
150 mg/mo
or 3 mg IV
every 3 mo
Adherence to
dosing
instructions
required
Vertebral fracture: ARR=4.9%, NNT=20 over
3 yr
Zoledronic
acid
5 mg/year
IV
Adherence to
dosing
instructions
required
Morphometric vertebral fracture:
ARR=7.6%, NNT=13 over 3 yr
Clinical vertebral fracture: ARR=2.1%,
NNT=48 over 3 yr
All nonvertebral fractures: ARR=2.7%,
NNT=37 over 3 yr
Hip fracture: ARR=1.1%, NNT=91 over 3 yr
aPatient
populations were not comparable, so direct comparisons of ARR and NNT may not be valid
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INSTRUCTIONS FOR TAKING
BISPHOPHONATES
• Take first thing in the morning before eating or drinking
anything else
• Take with at least 8 oz of plain tap water
• Take while upright in a chair or standing, and remain
upright for 30 minutes after ingestion
• With alendronate and risedronate, do not eat or drink
anything for 30 minutes after ingestion (60 minutes for
ibandronate)
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SELECTIVE ESTROGEN RECEPTOR
MODULATORS (SERMs)
• Act as estrogen agonists in bone and heart
• Act as estrogen antagonists in breast and
uterine tissue
• Potential for preventing osteoporosis or
cardiovascular disease without the increased
risk of breast or uterine cancer
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SERMs: RALOXIFENE
• Approved for osteoporosis prevention & treatment in
postmenopausal women
• Dose: 60 mg/d
• In comparison with placebo:
  vertebral fractures
  breast cancer (relative risk 0.24)
  bone turnover & maintains BMD
• Side effects: Flu-like symptoms, hot flushes, leg
cramps, peripheral edema
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CALCITONIN
Rationale
• Hormonal inhibitor of bone resorption
• In comparison with placebo:
  vertebral fractures and  spine bone density
 No  in hip or nonvertebral fractures
• Possible analgesic effect in women with painful
vertebral compression fractures
Dosing
• Subcutaneous injection (50–100 IU 3–5 times/week
• Nasal spray 200 IU/day, alternate nostrils (fewer
reported side effects, greater patient acceptance, may
be less effective)
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ESTROGEN REPLACEMENT
• Prevents bone loss at hip & spine when initiated
within 10 years of menopause
• An option for osteoporosis prevention but not
recommended as first-line choice
• Women’s Health Initiative showed  risk of hip
fracture, vertebral fracture, and colon cancer but ↑
risk of breast cancer, heart disease, stroke, and
venous thromboembolism
• USPSTF Guidelines advise against routine use of
estrogen plus progesterone for the prevention of
chronic conditions in postmenopausal women
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PARATHYROID HORMONE
• Increases bone formation and resorption
• Reduces vertebral and nonvertebral fractures in
postmenopausal women
• Increases BMD at all sites
• Typically reserved for those with severe osteoporosis
and fracture history
• Teriparatide dose 20 mcg/d SC for patients who
cannot tolerate other treatment
• FDA-approved for only 2 years of use
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DENOSUMAB
• Human monoclonal antibody that inhibits
RANKL (receptor activator for nuclear factor
κB ligand)
• ↓ bone turnover and ↑ BMD
• Approved in US for postmenopausal women
at high risk of fractures
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STRONTIUM RANELATE
• Anabolic agent that ↑ bone formation and ↓ bone
resorption
• Not approved in US
• Many patients are taking other forms of strontium
bought OTC
• No data available
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VERTEBRAL FRACTURES
• Asymptomatic (the majority)
 Diagnosed by spinal radiographs
  kyphosis or  height
 Chronic back pain due to spinal changes
that occur with vertebral compression
• Symptomatic
 Pain usually lasts 2 to 4 weeks
 Can be debilitating
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MANAGING VERTEBRAL FRACTURES
(1 of 2)
• Medications
 NSAIDs and calcitonin
 Narcotics commonly required for pain control
• Physical therapy
 Important for both acute and chronic pain
 Postural exercises
 Alternative modalities for  pain
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MANAGING VERTEBRAL FRACTURES
(2 of 2)
• Education, support groups
• Vertebroplasty and kyphoplasty
 Surgical options for treatment of painful
compression fractures
 Complications can occur (eg, emboli, infection)
 Limited randomized, controlled trials
Slide 41
SUMMARY (1 of 2)
• Osteoporosis is prevalent among older adults
and is associated with high personal and
financial costs as well as mortality
• Osteopenia and osteoporosis can be diagnosed
by measuring BMD using dual-energy x-ray
absorptiometry
• Evaluation of patients with osteoporosis should
include assessment for secondary causes of
bone loss
Slide 42
SUMMARY (2 of 2)
• Osteoporosis prevention and treatment
combines risk reduction, exercise, calcium and
vitamin D supplementation, hormones, and
other pharmacotherapies
• Pain of osteoporotic vertebral fractures can be
treated with NSAIDs, calcitonin, and narcotics,
as well as physical therapy with surgical options
of vertebroplasty and kyphoplasty
Slide 43
CASE 1 (1 of 3)
• A 69-year-old man comes to the office to
establish care.
• His wife is being treated for osteoporosis.
• She wants to know whether her husband should
also undergo a screening assessment.
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CASE 1 (2 of 3)
Which of the following is the strongest risk factor
for osteoporosis in men?
A. Androgen deprivation therapy
B. Low dietary intake of vitamin D
C. Respiratory disease
D. Thyroid replacement therapy
E. Type 2 diabetes mellitus
Slide 45
CASE 1 (3 of 3)
Which of the following is the strongest risk factor
for osteoporosis in men?
A. Androgen deprivation therapy
B. Low dietary intake of vitamin D
C. Respiratory disease
D. Thyroid replacement therapy
E. Type 2 diabetes mellitus
Slide 46
CASE 2 (1 of 3)
• A 75-year-old woman with established osteoporosis
wishes to discuss advertisements she has seen for
ibandronate and risedronate.
• She currently takes alendronate and wonders
whether she would benefit more from a different
agent.
• She has not had a fracture.
Slide 47
CASE 2 (2 of 3)
Which of the following is the best agent for
preventing fracture?
A. Alendronate
B. Ibandronate
C. Pamidronate
D. Risedronate
E. Data are not available to answer her question
Slide 48
CASE 2 (3 of 3)
Which of the following is the best agent for
preventing fracture?
A. Alendronate
B. Ibandronate
C. Pamidronate
D. Risedronate
E. Data are not available to answer her question
Slide 49
CASE 3 (1 of 3)
• An 80-year-old woman comes to the office for
follow-up because a recent evaluation identified
significant osteoporosis.
• She agrees to begin oral bisphosphonate therapy.
Slide 50
CASE 3 (2 of 3)
What is the most common adverse effect of
oral bisphosphonate therapy?
A. Atrial fibrillation
B. GI effects
C. Osteogenic sarcoma
D. Osteonecrosis of the jaw
E. Thromboembolic disease
Slide 51
CASE 3 (3 of 3)
What is the most common adverse effect of
oral bisphosphonate therapy?
A. Atrial fibrillation
B. GI effects
C. Osteogenic sarcoma
D. Osteonecrosis of the jaw
E. Thromboembolic disease
Slide 52
ACKNOWLEDGMENTS
Editor:
Annette Medina-Walpole, MD
GRS7 Chapter Author:
Pamela Taxel, MD
Leen Bakkali, MD
GRS7 Question Writer:
C. Bree Johnston, MD, MPH
Pharmacotherapy Editor:
Judith L. Beizer, PharmD
Medical Writers:
Beverly A. Caley
Faith Reidenbach
Managing Editor:
Andrea N. Sherman, MS
Copyright © 2010 American Geriatrics Society
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