OSTEOPOROSIS

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OSTEOPOROSIS

• Diagnosis and prevention

Dr.Kwanpeemai Panorchan
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Definition

• A systemic skeletal disease characterized by
  low bone mass and micro architectural
  deterioration of bone tissue lead to bone
  fragility and susceptibility to fracture

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Prevalence of osteoporosis
NHANES III. J Bone Miner Res.1997 Melton L. J. J
Bone Miner Res.1992
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Incidence of osteoporotic Fx
Riggs BL. Bone 199517(s5)
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Incidence of osteoporotic Fx
Vertebral Fracture
Forearm Fracture
Hip Fracture
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Incidence of osteoporotic Fx
The European Prospective Osteoporosis Study Group
( EPOS ) J Bone Miner Res 200217
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Impact of osteoporotic Fx
Center JR et al. Lancet 1999 353
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Impact of osteoporotic Fx

• 50 Discharged from hospital to nursing home
• 40 Regained mobility
• 25 Regained to full former status
• Increased mortality
• Increased cost of health care

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Pathogenesis
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Pathogenesis
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Pathogenesis
Peak bone mass
Microdamage
Precipitating factors
Loss of Estrogen
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Diagnosis of osteoporosis
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Diagnosis of Osteoporosis

• Physical examination
• Measurement of bone mineral content
• Dual X-ray absorptiometry (DXA)
• Ultrasonic measurement of bone
• CT scan
• Radiography

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Physical examination

• Osteoporosis
• Height loss
• Body weight
• Kyphosis
• Humped back
• Tooth loss
• Skinfold thickness
• Grip strength

• Vertebral fracture
• Arm span-height difference
• Wall-occiput distance
• Rib-pelvis distance

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Physical examination
Amanda D. Green. JAMA 2001 vol.292(23)
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Physical examination
Amanda D. Green. JAMA 2001 vol.292(23)
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Physical examination
No single maneuver is sufficient to rule in or
rule out osteoporosis or vertebral fracture
without further testing
Amanda D. Green. JAMA 2001 vol.292(23)
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Diagnosis of Osteoporosis

• Physical examination
• Measurement of bone mineral content
• Dual X-ray absorptiometry (DXA)
• Ultrasonic measurement of bone
• CT scan
• Radiography

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Dual X-ray absorptiometry

• 2-dimensional study
• BMD Amount of mineral
• Area
• Accuracy at hip gt 90
• Low radiation exposure
• Error in Osteomalacia Osteoarthritis Previ
  ous fracture

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Dual X-ray absorptiometry

• WHO criteria - Hip BMD
• Normal
• Low bone mass (Osteopenia)
• Osteoporosis
• Severe osteoporosis

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Dual X-ray absorptiometry
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Ultrasonic measurement

• Broad-band ultrasound attenuation or ultrasound
  velocity
• No radiation exposure
• Cannot be used for diagnosis
• Preferred use in assessment of fracture risk

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CT scan

• True volumetric study
• Most useful in cancellous bone assessment
• Avoid effect of degenerative disease
• Drawback High cost High radiation
  exposure Difficult quality control

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Plain radiography

• Low sensitivity
• High availability
• Subclinical vertebral fracture is a strong risk
  factor for subsequent fractures at new vertebral
  site and other sites

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Assessment of fracture risk
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Assessment of fracture risk

• DXA and quantitative ultrasound
• Clinical risk factors
• Markers of bone turnover Bone
  formation Bone resorption

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Assessment of fracture risk

• DXA Risk of fracture 1.5-3.0 for each SD
  decrease in BMD
• Low sensitivity ( comparable to BP in
  predicting stroke ) Screening is not
  recommended
• Quantitative ultrasound Risk of fracture
  1.5-2.0 for each SD decrease in BMD

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Assessment of fracture risk

• Markers of bone turnover

• Bone resorption markers
• Hydroxyproline
• Pyridinium crosslinks associated peptides

• Bone formation markers
• Alkaline phosphatase
• Bone isoenzyme AP
• Osteocalcin
• Procollagen propeptides of type I collagen

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Assessment of fracture risk

• Markers of bone turnover
• Associated with osteoporotic fracture
  independent of bone density
• 2-Fold increase in fracture risk
• ? Combined approach with BMD to increased
  sensitivity

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Assessment of fracture risk

• Clinical risk factors for fracture
• Low bone mass
• History or falls
• Impaired cognition ( plus medication adverse
  effect )
• Low physical function
• Presence of environmental hazards
• Long hip axis length
• Chronic glucocorticoid use
• Existing fracture
• Chronic use of seizure medications
• Renal, hepatic, thyroid, parathyroid,
  malabsorptive disorder, vitamin D deficiency, MM
  and local neoplasia to be ruled out

National Osteoporosis Foundation 1998
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Assessment of fracture risk

• Predictors of low bone mass
• Female
• Advanced age
• Gonadal hormone deficiency ( estrogen or
  testosterone )
• White race
• Low body weight BMI
• Family history of osteoporosis
• Low calcium intake
• Smoking / excessive alcohol intake
• Low level of physical acitivity
• Chronic glucocorticoid use
• History of fracture

National Osteoporosis Foundation 1998
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Assessment of fracture risk

• The U.S. Preventive Services Task Force
  Recommendation for BMD screening
• Women 65 years and older without risk factors
• Women at age 60 years with increased risk

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Assessment of fracture risk
Guideline for management of osteoporosis.
Osteoporos Int 19977
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Assessment of fracture risk
Gulideline for management of osteoporosis.
Osteoporos Int 19977
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Prevention Treatment
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Available treatment

• Calcium and vitamin D
• Hormone replacement therapy
• Selective estrogen receptor modulators (
  SERMs )
• Bisphosphonates
• Calcitonin
• Parathyroid hormone
• Other treatments
• Non-pharmacologic intervention

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Pathogenesis
Ca Vit D
rhPTH
Peak bone mass
Bisphosphonates Ca Calcitonin HRT SERMs
HRT
Loss of Estrogen
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Calcium

• Benefit
• Slower rate of bone loss
• Reduction of fractures in some studies
• Adjunct to other osteoporosis Rx

• Risk
• Mild GI upset
• Constipation
• ?? Kidney stone

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Calcium

• 1994 consensus on optimum calcium intake

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Calcium preparations
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Vitamin D

• Essential for intestinal absorption of calcium
• Daily recommendation 400 - 800
  IU/day Esp. Low sunlight exposure, elderly,
  low vitamin D intake
• ? Decreased risk of fracture in healthy elderly
  with normal intake BMD

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Hormone replacement therapy
27 risk reduction in nonvertebral fracture

• 33 risk reduction in vertebral fracture

Drawback Effective only in age lt 60
yr Nonsustainable effect
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SERMs - Tamoxifen
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SERMs - Raloxifene
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Bisphosphonates
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Bisphosphonates

• Benefit
• Potent inhibitor of bone resorption
• Reduce osteoclast recruitmentactivity
• Safe
• Most effective Rx

• Risk
• Low oral bioavailability (1-3)
• Food, calcium, iron, coffee, tea, orange juice
  decreased absorption
• GI discomfort
• Rarely - esophagitis
• High cost

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Calcitonin

• Peptide from Thyroid C cell
• Direct inhibition of osteoclast activity
• Less effective in cortical bone
• Salmon calcitonin nasal spray
• Dose 200 IU/day

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Parathyroid hormone

• Intermittent injection stimulate new bone
  formation CONTRAST to continuous infusion
• Teriparatide ( rhPTH1-34 ) was approved by
  US-FDA for Rx of osteoporosis
• Transient dose-related hypercalcemia
• Long term effects are not known

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Efficacy-Vertebral fracture
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Efficacy-Hip fracture
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Efficacy
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Other treatment

• Fluoride
• Vitamin K2
• Strontium ranelate
• Meunier PJ. The effect of strontium ranelate on
  the risk of vertebral fracture in women with
  postmenopausal osteoporosis. NEJM 2004350459-68
• Statins

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Available treatment

• Calcium and vitamin D
• Hormone replacement therapy
• Selective estrogen receptor modulators
  ( SERMs )
• Bisphosphonates
• Calcitonin
• Parathyroid hormone
• Other treatments
• Non-pharmacologic intervention

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Treatment decision

• Primary prevention Adequate calcium vit D
  intake HRT is no longer recommended Few
  RCTs ( FIT,MORE ) show benefit of Alendronate and
  Raloxifene
• Secondary prevention/Treatment Bisphosphonate
  ( Risedronate, Alendronate ) together with
  calcium /- vit D supplement rh-PTH (
  Teriparatide ) Salmon calcitonin Raloxife
  ne

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ExerciseOsteoporosis

• Exercise effect Adolescent - Increased peak
  bone mass Elderly - Small increase in
  BMD Fitness may prevent falling ?
• Evidence-based data Reduction of hipleg
  fractures in observational studies

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Other measures

• Treat predisposing factors
• Fall prevention Correct visual
  impairment Avoid drugs - BZs, hypnotics,
  antidepressant, drugs cause hypotension Extrinsic
  factors
• External hip protector Decrease the risk of
  hip fracture by 50 in 2 small studies

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