Osteoporosis

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Osteoporosis
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Osteoporosis
Summarized Presented By Yodpiti tungtrongjit
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Definition

• systemic skeletal disease characterized
  by low bone mass and microarchitectural
  deterioration of bone tissue , with a consequent
  increase in bone fragility and susceptibility to
  bone fracture

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2001 - Skeletal disorder characterized by
compromised bone strength that predisposes to
increased risk of fracture
Normal Bone
Osteoporosis
NIH consunsus development panel on Osteoporosis.
JAMA 2001
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Compromised bone strength
Increased risk fracture
Bone quality
Bone strength
Bone density

• Architecture
• Turnover
• Damage accumulation
• Mineralization

aBMD g/cc2 vBMD g/cc3
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Bone function structure

• Function
• Mechanical
• Protection
• Metabolic
• Hematopoietic

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Bone function structure

• Organic matrix
• Solid mineral phase
• Bone remodeling unit
• Osteoclast
• osteoblast

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Bone Biology
Bone
Extracellular matrix
Cell
Organic substance Nonorganic substance Water
Osteoblast Osteoclast
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Cell Type and Function
Osteoblast function Bone formation

• Extracellular matrix production
• Collagen type l
• Osteocalcin
• Osteonectin

• Mineralization
• Bone specific alkaline phosphatase (BSALP)

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Osteoclast function Bone resorption

• Extracellular matrix degradation
• Cathepsin
• Metrix metalloprotienase

• Demineralization (Acidification)
• Carbonic anhydrase

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Extracellular Matrix

• Organic substance
• 25 of extracellular matrix
• collagen (90 - collagen type I)
• Non-collagen
• Osteocalcin
• Osteonectin
• ?- carboxyglutamic acid containing proteins
  (vitamin K dependent)

• Nonorganic substance
• 70 of extracellular matrix
• Ca PO4 Hydroxyappatite form
• Mg

• Water (5)

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Bone Remodeling Cycle

• Resting(Quiescence)
• Activation phase
• Resorption phase
• Reversal phase
• Formation phase
• Production
• Maturation
• Mineralization

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Activation
Resting
Resorption
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Resorption
Reversal
Formation
Resting
Mineralization
Maturation
Production
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Factors affecting bone mass

• bone remodeling
• PTH
• Thyroxine
• Growth hormone
• Vitamin D

• bone remodeling
• Calcitronin
• Estrogen
• Glucocorticoid

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Pathophysiology

• Low Peak Bone Mass
• Increase bone resorption

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Classification

• Primary Osteoporosis
• Secondary Osteoporosis
• Female 80 Primary
• 20 Secondary
• Male 60 Primary
• 40 Secondary

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Primary Osteoporosis

• Juvenile osteoporosis
• Type I osteoporosis (postmenopausal
  osteoporosis)
• Type II osteoporosis
  (age-associated or senile)

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Secondary Osteoporosis

• Genetic
• Endocrine
• Deficiency state
• Neoplastic
• Iatrogenic
• Drugs
• Miscellaneous

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• Genetic
• Osteogenesis imperfecta Gonadal dysgenesis
  Turner syndrome Klinefelter syndrome
  Hypophosphatasia Homocystinuria
  Mucopolysaccharidosis Gaucher disease
  Sickle-cell anemia Thalassemia Hemophilia

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• Deficiency
• Scurvy Malnutrition Anorexia nervosa
  Protein deficiency Alcoholism Liver disease
• Vitamin D deficiency
• Calcium deficiency

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• Medications
• Corticosteroids
• Antiepileptics phenobarbitol phenytoin
• Cytotoxics methotrexate
  cyclosporin A
• Thyroid hormone
• Lithium
• Heparin , warfarin

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• Endocrine
• Hyperthyroidism Hyperparathyroidism Cushing
  syndrome Acromegaly Estrogen deficiency
  Hypogonadism Diabetes mellitus Pregnancy

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• Neoplastic
• Myeloma Leukemia Lymphoma Metastatic
  disease

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• Iatrogenic
• Heparin-induced Steroid-induced
  Dilantin-induced

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• Miscellaneous
• Amyloidosis Ochronosis Immobility
  Weightlessness

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Investigations for Secondary Osteoporosis
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Clinical practure guideline for the diagnosis and
management of Osteoporosis in Canada.CMAJ
200216(suppl)S1-S33
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Clinical

• Symptom / History
• Asymptomatic if no fracture
• Symptom of Fracture

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• Most common site of Osteoporosis Fx
• Vertebral Fracture
• Hip Fracture
• Colles Fracture

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• Vertebra Fx
• Pain in the mid thoracic or lumbar spine
• usually follows a fall or minor trauma
• accompanied by paravertebral muscle spasm
• exacerbated by activity
• decreased by lying supine

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• Hip Fracture
• Pain in the groin, posterior buttock, anterior
  thigh, medial thigh during weight bearing
• External rotation of the involved hip
• Diminished hip range of motion (ROM),
  particularly internal rotation and flexion

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Clinical

• Physical Examination should focus on
• Height
• Weight
• Gait
• Balance
• Kyphosis / Kyphoscoliosis
• Sign of 2nd causes of osteoporosis

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Imaging studies

• Plain radiograph
• Late detection of Osteoporosis
• Bone loss gt 30 40
• For fracture detection
• Film T-L spine
• Film hip
• Film wrist

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• Vertebral Fx deformities
• Wedge deformity
• Loss of anterior height
• End plate deformity
• Loss of middle height biconcave
• Compression deformity
• Loss of ant. Middle post. height

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BMD Measurement

• DEXA (Dual Energy X-ray Absorptiometry)
• QCT (Quantitative Computed Tomography)
• Ultrasound measures the heel
• SXA (single Energy X-ray Absorptiometry)
• PDXA (Peripheral Dual Energy X-ray
  Absorptiometry)
• RA (Radiographic Absorptiometry)
• DPA (Dual Photon Absorptiometry)
• SPA (Single Photon Absorptiometry)

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• Dual Energy X-ray Absorptiometry
• the most widely available BMD test
• Noninvasive
• Precision error spine 1 - 1.5
• femur 1.5 - 3
• Low radiation dose 5 mrem
• high degree of accuracy
• bone tissue per unit area ( g/cm2 )
• sensitive

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• Ultrasound

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• Quantitative CT scanning (QCT) volumetric
  measure of vertebral trabecular bone
  (mg/cm3)

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• QCT is the most accurate BMD test
• ultrasound is the least accurate of the tests
• DEXA is the most widely available BMD test

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Patients Recommended for BMD Measurements

• Women over age 65.
• All women under age 65 with risk factors.
• Amenorrhea ,early menopause ( 40-45),
• Bilateral oophorectomy before normal
  menopause(45-55).
• Women not receiving hormone replacement therapy
  for at least 5 years after menopause

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Patients Recommended for BMD Measurements

• Patients undergoing prolonged Rx with
  glucocorticosteroids.
• Strong family history of osteoporosis.
• Hyperparathyroidism
• Postchemotherapy (esp. breast and hematologic
  CA).
• Men with hypogonadism.
• Patients with fractures suspicious for
  osteoporosis.

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Bone markers

• Bone formation marker
• Serum osteocalcin
• Serum alkaline phosphatase

• Bone resoption marker
• Urine pyridinoline
• Deoxypyridinoline
• c terminal type I collagen peptide most
  sentivity
• n terminal
• etc

• Variation
• For research

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WHO definition
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Management

• Prevention
• Treatment
• Pharmacological intervention
• non Pharmacological intervention

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Prevention

• Primary prevention
• Diet
• exercise
• Secondary prevention
• Drug
• Prevent fall
• Tertiary prevention
• Rehabilitation program

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Pharmacological intervention

• Antiresorptive drugs
• Bisphosphanate SERMs
• Calcitonin HRT
• Bone formation agents
• Parathyroid hormone Sodium fluoride
• Supplement
• Calcium Vitamin D

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Bisphosphoate

• Inhibits bone resorption via actions on
  osteoclasts or osteoclast precursors
• Reduce bone loss and increase bone mass
  progressively
• Decrease incidence of Vertebral
  nonVertebral fracture

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Bisphosphoate

• Alendronate ( Fosamax R ) 10mg/d
  70mg/wk
• Risedronate ( Actonel R ) 5mg/d

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Bisphosphoate

• must be taken at least 30 min before first meal
• Follow with large amounts of water
• patient should sit up and walk around
• SE reflux esophagitis

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SERMs

• Raloxifene ( Celvista R )
• Estrogen receptor agonist Bone
• Inh bone resorption
• Estrogen receptor antagonist Breast
  Uterus
• no risk of CA breast or Uterus

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SERMs

• Decrease total cholesterol , LDL-C
• no effect to HDL-C
• SE hot flush , cramp

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Calcitonin

• Inh osteoclast
• Analgesic property
• Injection / Nasal inhalor
• Long term efficacy has not been clearly
  demonstrated
• Side effect
• Flushing / nausea
• Nasal irritation /crusting / ulceration

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Hormone replacement therapy

• Estrogen or Estrogen Progestin
• Inh bone resorption
• Contraindication for
• Liver Gallbladder disease
• Hx of thromboembolism / thrombophlebitis
• Suspected breast or endometrial CA

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Hormone replacement therapy

• Adverse effect
• Hypertension
• Hyperlipidemia
• Migraine
• Thrombophlebitis
• Endometriosis
• gt5 yr use increase risk for cardiac death
  ,thromboembolism , cancer

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Parathyroid hormone

• Only one bone forming agent approved for
  osteoporosis ( Nov 2002)
• Dose 20 microgram / day
• Need more studies to clarify proper dose
  administration technique

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Sodium fluoride

• Stimulate osteoblast activity
• Increase bone density
• Increase incidence of nonvertebral Fx

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Evidence-based of efficacy
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Calcium

• dietary calcium
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• Requirement / day

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Optimum Calcium Intake for Thai
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Supplement Calcium
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Calcium supplement in Thailand
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Calcium supplement in Thailand
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• Side effect constipation
• Apply with meal , follow by water

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Vitamin D

• 400-800 IU / day
• MTV 1 2 tab / day
• 1,25 (OH)2 D3

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Non-pharmacological intervention

• Lifestyle modification
• Nutrition
• Exercise / rehabilitation
• Discontinue drug induced osteoporosis
• Orthopedic intervention

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Rehabilitation Program

• Physical therapy
• control pain if a fracture has occurred
• improving strength, flexibility, posture, and
  balance to prevent falls and maximize physical
  function
• Occupational therapy
• Home modification

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Exercise

• Weight-bearing activities are essential for
  maintenance of bone mass
• strengthening of the back extensors
• Avoid back flexion

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Exercise recommendation summary
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Posture training program

• Sitting
• Standing
• Sleeping
• Lifting
• Driving

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Height loss or kyphosis
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History of low trauma fracture confirmed by X-ray
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Long term moderate to high dose of steroid
age
gt65yr
lt65yr
Y
Y
Clinical and risk factor evaluation
Y
BMD by DXA
FigureB
N
Normal
Osteoporosis
Osteopenia
Stop and reassess at 65 age
Repeat BMD 2-3yr
Treatment
HRT
F/U 1-2 yr
Consider bisphosphonate or others
Figure C
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Prednisolone be required for 3mo
Previous fracture and/or high dose prednisolone gt
6mo and age gt65y
High risk
Not high risk
BMD
Investigation
T-scoregt0
T-score 0-(-1.5)
T-scorelt-1.5
Reassure and Lifestyle advice
Lifestyle advice
Lifestyle advice and treatment
Repeat BMD 1-3yr if steroid continued
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HRT
Contraindication to HRT (DVT)
Consider bisphosphonate or others
Increased brease cancer risk
Coronary heart disease
Considrer bisphosphonate or others
HRT and reassess yearly
Considrer bisphosphonate or others
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