Transcript OSTEOPROSIS

OSTEOPOROSIS
Dr. K K Sawlani
Department of Medicine
KGMU, Lucknow
30.07.14
OSTEOPOROSIS
• A disease characterized by low bone mass
(reduced bone density) and micro-architectural
deterioration of bone tissue, leading to enhanced
bone fragility and a consequent increase in
fracture risk.
• Most common bone disease
• Affects million of people worldwide
Development of osteoporotic bone
Rizzoli R ed In Atlas of Postmenopausal Osteoporosis (1st edition) Science Press, 2004
OSTEOPOROSIS
• Fractures related to osteoporosis affect around 30 % of
women and 12 % of men in developed countries.
• Major public health problem
• Osteoporotic fractures can affect any bone
• The most common sites are
– Spine (vertebral fracture)
– Forearm (Colles fracture)
– Hip
Vertebral Fracture
Hip Fracture
Wrist Fracture (Colles fracture)
OSTEOPOROSIS
• Hip fractures are the most serious
• Immediate mortality is about 12 %
• Continued increase in mortality of about 20 %
when compared with age matched controls.
• Account for the majority of health care cost
associated with osteoporosis.
OSTEOPOROSIS
• The prevalence increases with age reflecting
that bone density decreases with age
especially in women
• Accompanied by increased risk of fractures
– Fall in bone density
– Increased risk of falling
Pathopysiology
• Occurs because of defect in attaining peak
bone mass and/or because of accelerated
bone loss.
• In normal individuals bone mass increases to
reach a peak between the age of 20 and 40
years but falls thereafter.
Age-related changes in bone mass
Attainment of peak bone mass
Consolidation
Age-related bone loss
Bone mass
Menopause
Men
Fracture threshold
Women
0
10
Compston JE. Clin Endocrinol 1990; 33: 653–682.
20
30
Age (years)
40
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60
Pathopysiology
• Peak bone mass and bone loss are regulated
by both genetic and environmental factors.
• Polymorphisms have been identified in several
genes that contribute to pathogenesis.
• Many of these are in the RANK and Wnt
signaling pathways which play critical role in
regulating bone turnover.
Major risk factors
• Non modifiable
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Age
Race
Female gender
Early menopause
Slender build
Positive family history
• Modifiable
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Low calcium intake
Low vitamin D intake
Estrogen deficiency
Sedentary lifestyle
Cigarette smoking
Alcohol excess (> 2 drinks/day)
Caffeine excess (> 2 servings / day)
Post menopausal osteoporosis
• Most common cause
• Accelerated phase of bone loss after menopause due to estrogen
deficiency.
• Causes uncoupling of bone resorption and bone formation
• Amount of bone reduced by osteoclasts exceeds the rate of new
bone formation by osteoblasts
• Early menopause ( before the age of 45 years ) is important risk
factor
Male osteoporosis
• Less common in men
• Secondary cause can be identified in 50% of cases
• The most common causes are
– Hypogonadism
– Corticosteroid use
– Alcoholism
• Testosterone deficiency results in increase in bone turnover and
uncoupling of bone resorption and bone formation.
• Genetic factors important in the cases with no identifiable cause.
Corticosteroid induced osteoporosis
• Risk increases with prednisolone use 5-7.5 mg daily for more than 3
months.
• Reduced bone formation due to
– Inhibitory effect on osteoblast function
– Osteoblast and osteocyte apoptosis
• Also reduce serum calcium
– Inhibit intestinal calcium absorption
– Renal leak of calcium
• Secondary hyperparathyroidism with increased bone resorption
• Hypogonadism may also occur with high doses.
Secondary causes of osteoporosis
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Endocrine disease
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Hypogonadism
Hyperthyroidism
Hyperparathyroidism
Cushing,s disease
Inflammatory disease
– Inflammotory bowel disease
– Ankylosing spondylitis
– RA
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Gastrointestinal
– Malabsorption
– Chronic liver disease
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Lung disease
– COPD
– Cystic fibrosis
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Drugs
Miscellaneous
Secondary causes of osteoporosis
• Drugs
– Corticosteroids
– Thyroxine over-replacement
– Anticonvulsants
– GnRH agonists
– Thiazolidinediones- pioglitazone
– Alcohol intake
– Heparin
Secondary causes of osteoporosis
• Miscellaneous
– Myeloma
– HIV infection
– Systemic masotcytosis
– Renal failure
– BMI < 18
– Anorexia nervosa
– Heavy smokers
Clinical Features
• Asymptomatic until a fracture occurs
• Incidental osteopenia on X-ray performed for other
reasons.
• Spine fracture
– Acute back pain ( 1/3 cases)
– gradual loss of height , kyphosis and chronic pain
• Peripheral fracture
– Local pain, tenderness and deformity
– Often with an episode of minimal trauma
Investigations
• Measurement of bone mineral density (BMD) by
dual energy X-ray absorptiometry (DEXA).
• BMD can also be measured by computed
tomography (CT) and ultrasound.
• Central (spine and hip) are best predictors of
fracture risk.
• Peripheral( radius, heel and hands) are less
expensive and widely available.
Investigations
• T-Score: The number of SDs the patient value is below
or above the mean value for young normal subjects.
– Good predictor of fracture risk
• Z-score: The number of SDs the patient value is below
or above the mean value for age matched normal
controls.
– Whether or not the BMD is appropriate for age.
• Absolute BMD: expressed in g/cm2
– Used to calculate changes in BMD during follow up.
Diagnosis
• Any patient who sustains a fragility fracture.
• On the basis of BMD T-score
≥ -1 = normal
Between -1 and -2.5 = Osteopenia
≤ -2.5 = Osteoporisis
Changes in BMD with age (T-score values)
Souce- Davidsons textbook of Medicine 22nd edition
Diagnosis
• History: early menopause, smoking, excessive
alcohol intake, corticosteroid therapy
• Examination: Signs of endocrine disease,
neoplasia, and inflammatory diseases
• A history of fall should be taken
• Unstable gait and unsteadiness
Diagnosis - Investigations
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Renal function
Alkaline phosphatase
Serum calcium, Vit D 25 (OH)
Parathyroid (PTH)
Thyroid function tests
Immunoglobulins and ESR
Celiac disease antibody testing
Testosterone (men)
24 hour urine calcium, sodium and creatinine.
Management
• The aim of treatment is to reduce the risk of
fractures
– Non-pharmacological
– Pharmacological
Non Pharmacological Treatment
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Smoking cessation
Moderation of alcohol intake
Adequate dietary calcium intake
Exercise
Vitamin D
Fall prevention
Good nutrition
Pharmacological Treatment
• Several drugs have been shown to reduce the risk
of osteoporotic fractures.
• Effect on vertebral and non-vertebral fracture is
variable.
• Considered with
– BMD T-score < 2.5
– BMD T-score < 1.5 in corticosteroid induced
– Vertebral Fractures ,unless resulted from significant
trauma
DXA Results
T Score
Classification
> minus 1.0
Normal
< minus 1.0 > minus 2.5
< minus 2.5
Osteopenia
Osteoporosis
Action
Lifestyle measures.
Lifestyle measures.
Consider specific treatment
where there is ongoing
risk, e.g. steroids, and in
those who have had a
minimal trauma fracture.
Lifestyle measures.
Prevent falls.
Treatment may be
indicated.
CURRENT THERAPIES
• Anti-resorptive
• Anabolic
• Calcium, Vitamin D, lifestyle modification
– Adjunct to other treatments
– 1000-1200 mg/day of calcium
– 800-1200 U/day of vitamin D
Treatment Options in Osteoporosis
Antiresorptive drugs
• Bisphosphonates
Etidronate
Alendronate
Risedronate
Ibandronate
Zoledronate
• Denosumab (monoclonal antibody against RANK-L)
• SERMs
Raloxifene
• Calcitonin
• HRT (estrogen)
Anabolic drugs
Teriparatide(PTH 1-34)
Dual Action Bone Agents (DABAs)
Strontium ranelate
Bisphosphonates
• Inhibit bone resorption by binding to hydroxyapatite
crystals on bone surface
• Osteoclasts reabsorb bone-drug released within cellinhibt key signaling pathways.
• Increase in Spine BMD of 5-8% and Hip BMD 2-4%.
• Should be taken on an empty stomach with plain
water.
• No food should be eaten 30-45 minutes after
administration
Adverse effects of biphosphonates
• Common
– Upper GI intolerance (oral)
– Acute phase response(intravenous)
• Less Common
– Atrial fibrillation (IV zoledronic acid)
– Renal impairment (IV zoledronic acid)
– Atypical subtrochanteric fractures
• Rare
– Uveitis
– Osteonecrosis of the jaw
INDICATIONS FOR ANABOLISM
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Pre-existing osteoporotic fractures
Very low BMD
Very high fracture risk
Unsatisfactory response to antiresorptive
therapy
• Intolerant to anti-resorptive therapy
TERIPARATIDE
• Daily SC injection 20 mcg
• Maximum 18-24 months
• May be followed by anti-resorptive therapy
• PTH is expensive and is reserved for severe
osteoporosis, who fail to response to other therapies.
• No advantage of combined anabolic and
anti-resorptive therapy
Selective estrogen receptor modulator (SERM)
Raloxifene
• 60 mg daily orally
• Partial agonist of estrogen receptor in bone & liver
• Antagonist in breast & endometrium
• SE: muscle cramps, hot flushes, increased risk of VTE.
• Bazedoxifene is a related SREM
HRT
• Cyclical HRT wirh estrogen and progestogen
• Prevents post menopausal bone loss and reduces risk of
fractures in post menopausal women
• Primarily indicated for prevention of osteoporosis in
women with early menopause
• Women in early fifties with troublesome menopausal
symptoms.
• Increased risk of breast cancer and cardiovascular disease
Duration of therapy
• Oral biphosphonates
long term (5 YRS)
• HRT, raloxifene
continuously
• Denosumab
continuously
• Strontium ranelate
not established
• Teriparatide
2 yrs fb
antiresorptive Tt
Response to drug treatment
• Repeat BMD measurements after 2-3 yrs.
• Spine BMD best for monitoring
• Biochemical markers ( N-telopeptide) respond
more quickly; can be used to assess
adherence.
Surgery
• Reduce and stabilize osteoporotic fractures
Painful vertebral compression fractures
• Vertebroplasty ( Injection of MMA)
• Kyphoplasty ( balloon inflation – MMA)
Response to Drugs
Fracture risk reduction
• 30-40% # risk reduction with antiresorptives
• 60% # risk reduction with teriparatide
BMD
• 2-3% BMD increase with anti-resorptives
• 4-6% BMD increase with teriparatide
Osteoporosis MCQ
1. Most common cause of osteoporosis
a.
b.
c.
d.
Hypogonadism
Malabsorption
Post menopausal
Hyperparathyroidism
Osteoporosis MCQ
2. Most common bone disease is
a. Osteomalacia
b. Osteoporosis
c. Secondaries bone
d. Osteopetrosis
Osteoporosis MCQ
3. Which of the following drug is most common
cause of drug induced osteoporosis
a. Thyroxine over-relacement
b. Corticosteroids
c. Pioglitazone
d. Anticonvulsants
Osteoporosis MCQ
4. Osteopenia is defined as T- Score of
a. < -1
b. < -1 to < -2.5
c. < -2.5
d. None of the above
Osteoporosis MCQ
5. Risk of fracture in osteoporosis is best
predicted by
a. T-score
b. Z-score
c. Absolute BMD
d. Serum calcium levels
Osteoporosis MCQ
6. Risk factors for osteoporosis are all except
a. BMI > 30
b. Smoking
c. Low calcium intake
d. Immobilization
Osteoporosis MCQ
7. Following are all anti-resroptive drugs except
a. Biphophonates
b. Raloxifene
c. Estrogen
d. Teriparatide (PTH analogue)
Osteoporosis MCQ
8. Which of the following is drug of choice for
severe osteoporosis (T-score 0f < -3.5 )
a.
b.
c.
d.
Teriparatide
Biphosphonates
Calcitonin
Strontium
Osteoporosis MCQ
9. Osteonecrosis of the jaw is seen with the
use of
a.
b.
c.
d.
Calcitonin
PTH analogues
Biphosphonates
Raloxifene
Osteoporosis MCQ
10. The response to drug therapy is assessed by
repeating BMD measurements after
a.
b.
c.
d.
3 months
6months
1 year
2 year