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OSTEOPOROSIS Dr. K K Sawlani Department of Medicine KGMU, Lucknow 30.07.14.
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Transcript of OSTEOPOROSIS Dr. K K Sawlani Department of Medicine KGMU, Lucknow 30.07.14.
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OSTEOPOROSIS
Dr. K K SawlaniDepartment of Medicine
KGMU, Lucknow30.07.14
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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
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Development of osteoporotic bone
Rizzoli R ed In Atlas of Postmenopausal Osteoporosis (1st edition) Science Press, 2004
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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
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Vertebral Fracture
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Hip Fracture
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Wrist Fracture (Colles fracture)
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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.
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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
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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.
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0 10 20 30 40 50 60
Bone
mas
s
Age (years)
Attainment of peak bone mass Consolidation
Age-related bone loss
Men
Women
Menopause
Fracture threshold
Age-related changes in bone mass
Compston JE. Clin Endocrinol 1990; 33: 653–682.
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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.
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Major risk factors• Non modifiable
– Age – Race– Female gender– Early menopause– Slender build– Positive family history
• Modifiable– Low calcium intake– Low vitamin D intake– Estrogen deficiency– Sedentary lifestyle– Cigarette smoking– Alcohol excess (> 2 drinks/day)– Caffeine excess (> 2 servings / day)
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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
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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.
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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.
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Secondary causes of osteoporosis• Endocrine disease
– Hypogonadism– Hyperthyroidism– Hyperparathyroidism– Cushing,s disease
• Inflammatory disease– Inflammotory bowel disease– Ankylosing spondylitis– RA
• Gastrointestinal– Malabsorption– Chronic liver disease
• Lung disease– COPD– Cystic fibrosis
• Drugs• Miscellaneous
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Secondary causes of osteoporosis
• Drugs– Corticosteroids– Thyroxine over-replacement– Anticonvulsants– GnRH agonists– Thiazolidinediones- pioglitazone– Alcohol intake – Heparin
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Secondary causes of osteoporosis
• Miscellaneous– Myeloma– HIV infection– Systemic masotcytosis– Renal failure– BMI < 18– Anorexia nervosa– Heavy smokers
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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
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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.
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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.
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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
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Changes in BMD with age (T-score values)
Souce- Davidsons textbook of Medicine 22nd edition
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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
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Diagnosis - Investigations• 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.
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Management
• The aim of treatment is to reduce the risk of fractures
– Non-pharmacological– Pharmacological
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Non Pharmacological Treatment
• Smoking cessation• Moderation of alcohol intake• Adequate dietary calcium intake• Exercise• Vitamin D• Fall prevention• Good nutrition
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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
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DXA Results
T Score Classification Action
> minus 1.0 Normal Lifestyle measures.
< minus 1.0 > minus 2.5 Osteopenia
Lifestyle measures. Consider specific treatment
where there is ongoing risk, e.g. steroids, and in those who have had a minimal trauma fracture.
< minus 2.5 Osteoporosis Lifestyle measures.Prevent falls.Treatment may be
indicated.
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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
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Treatment Options in OsteoporosisAntiresorptive drugs
• BisphosphonatesEtidronateAlendronateRisedronateIbandronateZoledronate
• Denosumab (monoclonal antibody against RANK-L)• SERMs
Raloxifene• Calcitonin• HRT (estrogen)
Anabolic drugsTeriparatide(PTH 1-34)
Dual Action Bone Agents (DABAs)Strontium ranelate
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Bisphosphonates
• Inhibit bone resorption by binding to hydroxyapatite crystals on bone surface
• Osteoclasts reabsorb bone-drug released within cell-inhibt 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
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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
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INDICATIONS FOR ANABOLISM
• Pre-existing osteoporotic fractures• Very low BMD• Very high fracture risk• Unsatisfactory response to antiresorptive
therapy• Intolerant to anti-resorptive therapy
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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
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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
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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
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Duration of therapy
• Oral biphosphonates long term (5 YRS)
• HRT, raloxifene continuously
• Denosumab continuously
• Strontium ranelate not established
• Teriparatide 2 yrs fb antiresorptive Tt
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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.
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Surgery
• Reduce and stabilize osteoporotic fractures
Painful vertebral compression fractures• Vertebroplasty ( Injection of MMA)• Kyphoplasty ( balloon inflation – MMA)
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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
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Osteoporosis MCQ
1. Most common cause of osteoporosis
a. Hypogonadismb. Malabsorptionc. Post menopausald. Hyperparathyroidism
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Osteoporosis MCQ
2. Most common bone disease is
a. Osteomalaciab. Osteoporosisc. Secondaries boned. Osteopetrosis
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Osteoporosis MCQ
3. Which of the following drug is most common cause of drug induced osteoporosis
a. Thyroxine over-relacementb. Corticosteroidsc. Pioglitazoned. Anticonvulsants
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Osteoporosis MCQ
4. Osteopenia is defined as T- Score of
a. < -1b. < -1 to < -2.5c. < -2.5
d. None of the above
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Osteoporosis MCQ
5. Risk of fracture in osteoporosis is best predicted by
a. T-scoreb. Z-scorec. Absolute BMDd. Serum calcium levels
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Osteoporosis MCQ
6. Risk factors for osteoporosis are all except
a. BMI > 30b. Smokingc. Low calcium intake
d. Immobilization
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Osteoporosis MCQ
7. Following are all anti-resroptive drugs except
a. Biphophonatesb. Raloxifenec. Estrogend. Teriparatide (PTH analogue)
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Osteoporosis MCQ
8. Which of the following is drug of choice for severe osteoporosis (T-score 0f < -3.5 )
a. Teriparatideb. Biphosphonatesc. Calcitonind. Strontium
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Osteoporosis MCQ
9. Osteonecrosis of the jaw is seen with the use of
a. Calcitoninb. PTH analoguesc. Biphosphonatesd. Raloxifene
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Osteoporosis MCQ
10. The response to drug therapy is assessed by repeating BMD measurements after
a. 3 monthsb. 6monthsc. 1 yeard. 2 year