Transcript Osteoporosis

o Definition of osteoporosis
o Pathopysiology.
o Causes.
o Clinical approach.
o Who should be screened.
o Treatment
o Monitoring of TTT
Osteoporosis is characterized by
 low bone mass,
 micro architectural disruption,
 and increased skeletal fragility.
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Osteoporosis results from:
hereditary (primary osteoporosis) and
environmental factors (secondary
osteoporosis.
Traditionally, osteoporosis was described
as type I (postmenopausal) or type II
(senile).
category
Bone mass
normal
A value for bone mineral density (BMD) within one
standard deviation of the young adult female
reference mean (T-score greater than or equal to -1
SD).
Low bone mass
(osteopenia)
A value for BMD more than one but less than 2.5
standard deviations below the young adult female
reference mean (T-score less than -1 and greater than
-2.5 SD).
Osteoporosis
A value for BMD 2.5 or more standard deviations
below the young adult female reference mean (Tscore less than or equal to -2.5).
Severe
(established)
osteoporosis
A value for BMD more than 2.5 standard deviations
below the young adult female reference mean in the
presence of one or more fragility fractures.
Causes
secondary
endocrin
e
GIT
Renal
rhematology
hematology
primary
genetic
other
Estrogen
deficiency
Aging
–
Hyperparathyrodism , hypogonadism ,
hyperthyrodism ,diabetes mellitus, Cushing
disease, prolactenoma , acromegaly ,
adrenal insuffieincy
–
inflammotory bowel disease, celiac
disease, malnutrition, history of gastric
bypass surgery, chronic liver disease,
anorexia nervosa, vitamin D or calcium
deficiency
- Chronic kidney disease,
idiopathic hypercalciuria
spondilities, SLE
–RA ankylosing
–Multipe myeloma,
thalassemia, leukemia, lymphoma,
hemophillia, SCAsystemic mastocytosis.
Cystic fibrosis,
osteogenesis imerfecta, homocysteinuria,,
marfan syndrome, hemochromotosis,
- Porphyria, sarcoid, immobilization,
pregnancy/lactation, (COPD), parenteral
nutrition, HIV/AIDS
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Corticosteroids - Prednisone (≥5 mg/d for ≥3
mo)
Anticonvulsants
Heparin (long-term)
Chemotherapeutic/
Hormonal/endocrine therapies –
(GnRH) agonists, (LHRH) analogs,
depomedroxyprogesterone, excessive
thyroid supplementation
Lithium
Aromatase inhibitors
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History
Osteoporosis is typically asymptomatic until a fracture
occurs. The history should focus on a thorough review
of risk factors, which include the following:
Age, sex, and race
Family history of osteoporosis, particularly maternal history of
fractures
Reproductive factors, especially regarding early menopause and
estrogen replacement therapy
Lifestyle factors associated with decreased bone density
› Smoking
› Alcohol consumption
› Low levels of physical activity
› Strenuous exercise (such as occurs in marathon runners) that
results in amenorrhea
Calcium and vitamin D intake
History of low-trauma “fragility
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Coexisting medical conditions.
Medications hx.
Risk factors for falls in older patients
› Poor balance
› Orthosttic hypotention.
› Weakness of the lower extremity muscles,
deconditioning
› Use of medications with sedative effects
› Poor vision or hearing
› Cognitive impairment
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Low body weight (body mass index <19 kg/m2)
Kyphosis.
Point tenderness over a vertebrae or other
suspected fracture site
Signs that might indicate a secondary cause of
osteoporosis)
Signs in older patients that may indicate
increased fall risk
› Difficulty with balance or gait
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Laboratory Studies
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CBC count
calcium, phosphate, creatinine, liver function tests,
electrolytes: levels of serum calcium, phosphate, and alkaline
phosphatase are usually normal in persons with primary
osteoporosis, although alkaline phosphatase levels may be
elevated for several months after a fracture.
Thyroid-stimulating hormone
25-hydroxyvitamin D [25(OH)D]
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 Bone
formation markers - Bonespecific alkaline phosphatase,
osteocalcin, type I procollagen
peptides
 Bone resorption markers - Urinary
deoxypyridinoline and cross-linked Nand C-telopeptide of type I collagen
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Other laboratory studies used to evaluate for secondary
causes include the following:
Twenty-four-hour urine calcium to assess for hypercalciuria
Intact parathyroid hormone
Testosterone level (in males)
Sedimentation rate.
Urinary free cortisol and tests for adrenal hypersecretion.
Serum and urine protein electrophoresis.
Antigliadin and antiendomysial antibodies for celiac disease.
Serum tryptase, urine N-methylhistamine for mastocytosis.
Bone marrow biopsy if a hematologic disorder is suspected.
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Dual-energy x-ray absorptiometry
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Bone density data from a DXA are
reported as T-scores and Z-scores.
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Women aged 65 years and older and men aged 70 years or
older, regardless of clinical risk factors.
Younger postmenopausal women and men aged 50-70 years
with clinical risk factors for fracture.
Women in menopausal transition with a specific risk factor
associated with increased risk for fracture (ie, low body weight,
prior low-trauma fracture, use of a high-risk medication)
Adults with fragility fractures
Adults who have a condition (eg, rheumatoid arthritis) or who
take a medication (eg, glucocorticoids, ≥5 mg/d for ≥3 mo)
associated with low bone mass or bone loss
Anyone being considered for pharmacologic therapy for
osteoporosis
Anyone being treated for osteoporosis (to monitor treatment
effect)
Anyone not receiving therapy in whom evidence of bone loss
would lead to treatment
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Validated risk factors that are independent
of BMD include the following:
Advanced age
Previous fracture
Long-term glucocorticoid therapy
Low body weight (less than 58 kg [127 lb])
Family history of hip fracture
Cigarette smoking
Excess alcohol intake
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History of hip or vertebral fracture.
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T-score -2.5 (DXA) at the femoral neck, total
hip, or spine, after appropriate evaluation
to exclude secondary causes.
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T-score between -1.0 and -2.5 at the femoral
neck, total hip, or spine, as measured by (DXA).
andOther prior fractures
 T-score between -1.0 and -2.5 at the femoral
neck, total hip, or spine and secondary causes
associated with high risk of fracture, such as
glucocorticoid use or total immobilization.
 T-score between -1 and -2.5 at the femoral neck,
total hip, or spine, and a 10-year probability of
hip fracture 3 percent or a 10-year probability of
any major osteoporosis-related fracture 20
percent based upon the US-adapted WHO
algorithm
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WHO fracture risk algorithm:
This algorithm (www.shef.ac.uk/FRAX/)
was developed to calculate the 10-year
probability of a hip fracture and the 10year probability of any major
osteoporotic fracture
This algorithm is most useful in identifying
patients with osteopenia who are most
likely to benefit from treatment.
Age
Sex
Personal history of fracture
Low body mass index
Use of oral glucocorticoid therapy
Secondary osteoporosis (ie, coexistence of
rheumatoid arthritis)
 Parental history of hip fracture
 Current smoking status
 Alcohol intake (3 or more drinks per day)
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Vitamin D
 Adults younger than 50 years should
receive 400-800 IU of vitamin D 3 daily.
 All adults older than 50 years should
receive 800-1000 IU of vitamin D 3 daily
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Exercise — Women with osteoporosis (or
seeking to prevent it) should exercise
(prudently) for at least 30 minutes three
times per week, as exercise has been
associated with improvements in or
maintenance of bone density and a
reduced risk of hip fracture in older
women.
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in a prospective cohort study of over
61,000 postmenopausal women, women
who walked four hours or more per week
had a 40 percent lower risk of hip
fracture than those who walked ≤ one
hour per week .
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Any weight-bearing exercise regimen,
including walking, is acceptable. A
meta-analysis of 18 randomized trials of
exercise and bone mineral density in
postmenopausal women reported that
aerobics, weight bearing, and resistance
exercises increases spine density, while
walking increases density at both the
spine and hip .
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smoking cigarettes accelerates bone
loss.
1. Bisphosphonates.
2. Selective estrogen receptor modulators.
3. Estrogen/progestin therapy.
4. Parathyroid hormone.
5. Calcitonin .
Bisphosphonates are structurally related to
pyrophosphate combounds that are
incorborated into the bone matrix.
Impair osteoclast function and reduce their
number by apoptosis.
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Bisphosphonates are also used in the
management of hypercalcemia, Paget
disease, and in a number of
malignancies including multiple
myeloma, breast cancer, and prostate
cancer
ALENDRONATE — is effective for both
the treatment and prevention of
osteoporosis in postmenopausal women.
 The optimal suppression of bone turnover
and increase in bone density with
minimal side effects is achieved at an
alendronate dose of approximately 10
mg/day ( Weekly administration of is as
effective as daily dosing.
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Increases BMD at spine by 8% and hip by
3.5%.
Reduces the incidence of vertebral
fractures by 47% and nonvertebral
fractures by 50% over 3 y.
Approved for treatment and prevention of
postmenopausal osteoporosis, male
osteoporosis, and steroid-induced
osteoporosis.
Increases BMD at spine by 5.4% and hip
by 1.6%.
 Reduces vertebral fractures by 41% and
nonvertebral fractures by 39% over 3 y.
 Approved for treatment and prevention
of postmenopausal osteoporosis, male
osteoporosis, and steroid-induced
osteoporosis.
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Increases BMD at spine by 5.7-6.5% and hip
by 2.4-2.8%.
 Reduces vertebral fractures by 50% with
intermittent (non-daily) dosing over 3 y. No
effects on reduction of nonvertebral
fractures.
 Approved for postmenopausal
osteoporosis.
 ibandronate (150 mg) appears to improve
BMD more than daily administration (2.5
mg).
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Most potent bisphosphonate available.
 Increases BMD at spine by 4.3-5.1% and
hip by 3.1-3.5% compared with placebo.
 Reduces the incidence of spine
fractures by 70%, hip fractures by 41%,
and non-vertebral fractures by 25% over
3 y.
 Approved for the treatment of
postmenopausal osteoporosis.
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Bisphosphonates should not be given
to patients with active upper
gastrointestinal disease.
Bisphosphonates should be
discontinued in patients who develop
any symptoms of esophagitis.
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Bisphosphonates should be taken alone on
an empty stomach first thing in the morning
with at least 240 mL (8 oz) of water. After
administration, the patient should not have
food, drink, medications, or supplements for
at least one-half hour (alendronate,
risedronate) or one hour (ibandronate).
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Hormone replacement therapy (HRT)
was once considered a first-line therapy
for the prevention and treatment of
osteoporosis in women. Data from the
Women's Health Initiative confirmed that
HRT can reduce fractures. However, HRT
was associated with an increased risk of
breast ca, MI, stroke, and VTE events..
HRT is approved for management of
menopausal symptoms and prevention
of osteoporosis.
 It is no longer recommended as a
treatment of osteoporosis in
postmenopausal women.
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(SERMs) act as weak estrogens in some
organ systems, while acting as estrogen
antagonists in others.
 Raloxifene is approved for the
prevention and treatment of
postmenopausal osteoporosis.
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Raloxifene (Evista)
 Increases BMD at spine and hip.
 Reduces the incidence of spine
fractures by 30-55% over 3 y.
Most suitable in women <70 y at
moderate risk for osteoporosis who have
infrequent vasomotor symptoms of
menopause (eg, hot flashes) and who
are at moderate-to-high risk for breast
cancer.
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Teriparatide is a biological product that
contains a portion of human parathyroid
hormone. When given intermittently, it
increases bone remodeling with the net
effect of increased bone mass and
improved skeletal microarchitecture.
(This is in contrast to continuous exposure
to parathyroid hormone, which increases
bone resorption with a net effect of
decreased trabecular bone volume).
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Teriparatide is approved in the United
States for postmenopausal osteoporosis
and primary or hypogonadal
osteoporosis in men.
Teriparatide (Forteo)
 Anabolic agent increases BMD at lumbar
spine by 9-13% and hip by 3-6%
compared with placebo.
 Reduced the risk of spine fractures by
65% and nonspinal fractures by 54% in
patients after an average of 18 mo of
therapy. Approved for postmenopausal
osteoporosis and male osteoporosis.
 20 mcg SC qd
› Calcitonin
› This agent is a peptide hormone used to
treat osteoporosis in patients in whom
bisphosphonates and estrogen are
contraindicated or not tolerated. It also has
some analgesic effects in patients with
fractures.
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› Calcitonin (Miacalcin, Calcimar, Cibacalcin)
› Increases BMD at lumbar spine by 1-1.5%.
› Reduced incidence of spine fracture by 33%
in group receiving 200 IU/d. Available in
parenteral and intranasal forms; however,
intranasal form is more convenient and
better tolerated.
DXA should be repeated every 2-3 years
if the baseline test results are normal.
 DXA should be performed every 1-2
years in patients who are undergoing
osteoporosis treatment.
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