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

Slide 2
 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

Slide 3
 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

Slide 4
 LIFETIME CHANGES IN BONE MASS

Age Women Men

Puberty to mid- Bone mass increases rapidly,
20s and 30s reaching peak bone mass
Mid-30s to 40s A few years of stability, No risk factors:
then slow bone loss bone loss 1%/year
Mid-40s to 50s Menopause, then rapid
bone loss 7%/year for With risk factors:
7 years bone loss 6%/year
Mid-50s to late Continuing bone loss of
life 1%2%/year

Risk factors: low calcium intake, smoking, alcoholism, certain drugs.

Both men and women lose predominantly cancellous (vertebral) bone.

Slide 5
 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
Slide 6
 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

Slide 7
 PATHOGENESIS OF
OSTEOPOROSIS
Estrogen deficiency

Calcium deficiency & secondary

hyperparathyroidism

Androgen deficiency

Changes in bone formation

Secondary causes and medications

Slide 8
 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

Slide 9
 CALCIUM DEFICIENCY AND
SECONDARY HYPERPARATHYROIDISM
Aging skin & sunlight exposure conversion of 7-
dehydrocholesterol 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
Slide 10
 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

Slide 11
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

Slide 12
RISK FACTORS FOR OSTEOPOROSIS
Age (postmenopausal in Glucocorticoids
women, >70 yr in men)
Previous fragility fracture
Female sex as adult
Low body weight (BMI Androgen-deprivation
<20) therapy
10% decline in weight Current smoking
(from usual adult body
Low dietary calcium
weight)
Spinal cord injury
Physical inactivity
Alcoholism

Slide 13
 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 (1,2001,500 mg/d in divided doses)
and vitamin D3 (8001000 IU/d)
Smoking cessation

Slide 14
 MODIFICATIONS TO REDUCE THE
RISK OF OSTEOPOROSIS (2 of 2)
Medications that can increase risk of
osteoporosisuse with caution:
Glucocorticoids Methotrexate
Anticonvulsants GnRH agonists used
Cyclosporine for prostate cancer
Long-term heparin Aromatase inhibitors
(eg, anastrozole,
Excess thyroid
letrozole, exemestane)
hormone
used for breast cancer
replacement

Slide 15
 SECONDARY CAUSES
OF BONE LOSS
Women
Primary hyperparathyroidism
Glucocorticoid use

Men
Hypogonadism
Malabsorption syndrome including gastrectomy

Slide 16
 EVALUATION

Measure Vitamin D level

Measure bone density

Assess for secondary causes of bone

loss

Use of biochemical markers in clinical

practice is controversial

Slide 17
 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
Slide 18
 INDICATIONS FOR BMD TESTING
(1 of 2)

Disease Recommended Laboratory Tests

Hyperparathyroidism Calcium, PTH level
Hyperthyroidism TSH, thyroxine levels
Hypogonadism (men Bioavailable testosterone or total
only) testosterone, free testosterone with
sex hormone-binding globulin
Multiple myeloma CBC, serum protein electrophoresis,
urine electrophoresis
Gold font = recommended routinely

Slide 19
 INDICATIONS FOR BMD TESTING
(2 of 2)

Disease Recommended Laboratory Tests

Osteomalacia Bone-specific alkaline phosphatase,
25(OH)D level
Pagets disease Bone-specific alkaline phosphatase,
urine NTx
Cushings disease Electrolytes, 24-h urinary free
cortisol

Slide 20
 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
Slide 22
 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

Slide 23
 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)

Slide 24
PREVENTING AND TREATING
OSTEOPOROSIS
Exercise
Calcium and vitamin D
Bisphosphonates
Selective estrogen receptor modulators
Calcitonin
Estrogen replacement
Investigational agents
Slide 25
 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

Slide 26
 CALCIUM & VITAMIN D
RECOMMENDED REQUIREMENT
1200 mg/day of calcium: men 65 years and older
& postmenopausal women

800-1000 IU/day of vitamin D

Slide 27
 BISPHOSPHONATES
Rationale: Approved for osteoporosis prevention in post-
menopausal 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
Slide 28
 BISPHOSPHONATES COMPARED (1 of 2)
Special Observed Beneficial
Medication Dosage Considerations Treatment Outcomesa
Bisphosphonates should not be used if CrCl <30 mL/min
Alendronate 70 mg/wk; Adherence to Vertebral fracture: absolute risk reduction
35 mg/wk dosing (ARR)=7.1%, number needed to treat
for instructions (NNT)=14 over 3 yr
prevention required; used in Hip fracture: ARR=1.1%, NNT=91 over 3 yr
men and women
to prevent
glucocorticoid-
induced
osteoporosis
Risedronate 35 mg/wk Adherence to Vertebral fracture: ARR=5%, NNT=20 over 3
or 150 dosing yr
mg/moh instructions Nonvertebral fracture: ARR=4%, NNT=25
required over 3 yr

aPatient populations were not comparable, so direct comparisons of ARR and NNT may not be valid

Slide 29
 BISPHOSPHONATES COMPARED (2 of 2)
Special Observed Beneficial
Medication Dosage Considerations Treatment Outcomesa
Bisphosphonates should not be used if CrCl <30 mL/min
Ibandronate 150 mg/mo Adherence to Vertebral fracture: ARR=4.9%, NNT=20 over
or 3 mg IV dosing 3 yr
every 3 mo instructions
required
Zoledronic 5 mg/year Adherence to Morphometric vertebral fracture:
acid IV dosing ARR=7.6%, NNT=13 over 3 yr
instructions Clinical vertebral fracture: ARR=2.1%,
required 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

Slide 30
 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)

Slide 31
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

Slide 32
 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

Slide 33
 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 (50100 IU 35 times/week
Nasal spray 200 IU/day, alternate nostrils (fewer
reported side effects, greater patient acceptance, may
be less effective)

Slide 34
 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

Womens 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
Slide 35
 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

Slide 36
 DENOSUMAB

Human monoclonal antibody that inhibits

RANKL (receptor activator for nuclear factor
B ligand)

bone turnover and BMD

Approved in US for postmenopausal women

at high risk of fractures

Slide 37
 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

Slide 38
 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

Slide 39
 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

Slide 40
 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.

Slide 44
 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

Slide 53