Parathyroid Hormone

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(No Transcript)
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Resorption Markers

• Pyridinium cross-links of type I collagen
• pyridinoline (free and bound)
• deoxypyridinoline (free and bound)
• Methods HPLC, ELISA, automated immunoassay
• Telopeptides of the cross-links of type I
  collagen
• amino-terminal (NTx)
• carboxy-terminal (CTx)
• Methods ELISA

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Resorption Markers

• Most of currently available markers are urine
  tests and subject to considerable biological
  variability
• Substantial diurnal rhythm
• Results must be normalized for urine creatinine
  excretion
• Specimen collection is either a complete 24 hr
  collection or 1st or 2nd void (spot sample) after
  an overnight fast of at least 6 hours

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Formation Markers

• Serum-based assays subject to less biological
  variability than resorption markers
• Minimal diurnal variation
• Markers
• Total alkaline phosphatase
• Bone-specific alkaline phosphatase
• Osteocalcin

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Formation Markers

• Total serum alkaline phosphatase
• limited specificity and sensitivity
• inexpensive, widely available
• most useful when markedly elevated e.g. Pagets
  disease, osteomalacia, severe renal
  osteodystrophy
• not enough specificity/sensitivity for use in
  osteoporosis

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Formation Markers

• Bone-specific alkaline phosphatase (BAP)
• Immunoassays available Ostase and Alkphase-B
• Osteocalcin
• several immunoassays commercially available
• different assays detect intact and/or fragments

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Biochemical Markers Advantages

• Non-invasive
• Frequent measurements for monitoring
• Assess response to therapy
• Evaluate patient compliance
• Levels reflect turnover in entire skeleton

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Biochemical Markers of Bone Turnover

• Indicate bone formation and bone resorption
• Can indicate whether or not therapeutic
  intervention has slowed bone loss
• Cannot diagnose osteoporosis
• Can aid in risk prediction independent of BMD1

1. Sarkar S, et al. Relationship between changes
in biochemical markers of bone turnover and BMD
to predict vertebral fracture risk. J Bone Miner
Res. 2004 Mar19(3)394-401
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Clinical Utility of Bone Markers

• Project rate of bone loss
• High remodeling rate -- high rate of loss
• Low remodeling rate -- low rate of loss
• Assess response to therapy
• Reduction in levels of markers associated with
  increase in BMD
• Evaluate patient compliance

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Bone Markers and Anti-resorptive Therapy

• Biochemical markers can demonstrate a
  pharmacological effect of an anti-resorptive drug
  
• Changes in markers can be seen within 3 to 6
  months of commencing therapy
• Changes in bone density may take 2 to 3 years to
  be seen

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Biochemical Markers and Treatment Monitoring
Prediction of bone mass response to
antiresorptive therapy in osteoporosis
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When to Order a Biochemical Marker of Bone
Remodeling?

• Early menopause
• undecided about HRT
• equivocal bone mass
• high values suggest rapid bone loss and
  re-thinking of therapeutic decision
• reconsider HRT
• bisphosphonate,
• Calcitonin or SERM
• yearly follow-up of BMD

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When to Order a Biochemical Marker of Bone
Remodeling?

• Post-menopause
• help determine whether dose of estrogen is
  sufficient to retard bone loss
• very high baseline value
• higher than average initial dose may be
  appropriate
• high value after 3 to 6 months of therapy
  suggests
• problems with compliance
• need for higher dose or addition of other
  compound such as bisphophonate

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When to Order a Biochemical Marker of Bone
Remodeling?

• To check effectiveness of oral bisphosphonate
  therapy
• drugs are only effective if absorbed
• very few non-responders
• high values for markers in patients on therapy
  suggest problems with compliance

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Advantages of Biochemical Markers

• Specimen can be collected in any physicians
  office
• Patients and physicians are used to monitoring
  with laboratory (blood and urine) tests
• long-term effectiveness of therapy can be
  estimated much more quickly (3 to 6 vs 18 to 24
  months) than by serial BMD measurements
• Support in maintaining patients on long-term
  therapy (compliance)

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How Often Should Markers Be Used?

• Baseline and 3 to 6-month follow-up to
  demonstrate pharmacological effect
• Follow-up measurement every 6 months is
  recommended to motivate patients compliance to
  treatment

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Osteoporosis Prevention
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Prevention of Osteoporosis
The National Osteoporosis Foundation (NOF)
recommends 5 steps to bone health and
osteoporosis prevention
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5 Prevention Steps (NOF)

• Step 1. Balanced diet rich in calcium vitamin D

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Prevention of Osteoporosis

• Dairy products.
• Milk, cheese, yogurt.
• Calcium-rich foods.
• Broccoli, green leafy vegetables.
• Calcium-fortified foods.
• Orange juice, cereals, breakfast bars.
• Add nonfat powdered dry milk to soups, gravies,
  puddings and other foods.

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For Strong Bones Recommended Calcium Intake
Source National Academy of Sciences, 1997
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Bone Appetit
Source Office of Dietary Supplements. National
Institutes of Health
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Prevention of Osteoporosis

• Calcium Supplements
• Compounds used in supplements include calcium
  carbonate, calcium phosphate, calcium citrate
• The actual amount of calcium is the elemental
  calcium
• Absorbed best in doses of 500 mg or less

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Vitamin D

• Requirement
• 400-800 IU/day for individuals at risk of
  deficiency
• Function
• Aids in absorption of calcium
• Aids in resorption of calcium in kidneys
• Source
• Direct exposure to sunlight (10-15 minutes, 2-3
  times/week)
• Foods, e.g. dairy products, liver, egg yolks,
  saltwater fish
• Vitamin supplements

National Osteoporosis Foundation
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Prevention of Osteoporosis

• Step 2. Regular exercise
• Bone is living tissue that responds to exercise
  by becoming stronger
• Weight-bearing
• Walking, running, dancing,
  stair climbing
• Resistance
• Weight lifting

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Prevention of Osteoporosis

• Step 3. Healthy lifestyle with no smoking or
  excessive alcohol use

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Prevention of Osteoporosis

• Step 4. Talk to your doctor about bone health

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Prevention of Osteoporosis

• Step 5. Bone density testing and medications
  when appropriate

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Osteoporosis Treatments

• HRT (hormonal replacement therapy)
• Estrogen (Climara, Estrace, Estraderm,
  Estratab, Ogen, Ortho-Est, Premarin,
  Vivelle, and others)
• Estrogens and Progestins (Activella, FemHrt,
  Premphase, Prempro, and others)
• Parathyroid Hormone Teriparatide (PTH (1-34)
  (Fortéo).
• Bisphosphonates inhibits osteoclast activity
• Alendronate sodium (Fosamax)
• Risedronate sodium (Actonel)
• Ibandronate sodium (Boniva)
• Calcitonin inhibits bone resorption
• (Miacalcin)
• SERMs (selective estrogen receptor modulators)
• Raloxifene (Evista)

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Progression of Osteoporosis
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Osteoporosis
Patient at age 50...
And 25 years later
Used with permission of the National Osteoporosis
Foundation, Osteoporosis The Silent Disease,
National Osteoporosis Foundation, Partners in
Prevention Slide Presentation, 1993
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For additional information
The National Osteoporosis Foundation
http//www.nof.org NIH Osteoporosis and Related
Bone Diseases National Resource
Center http//www.niams.nih.gov/bone/ Internationa
l Osteoporosis Foundation http//www.osteofound.or
g/ Surgeon Generals Report on Bone Health
Osteoporosis http//www.surgeongeneral.gov/ Inter
national Food Information Council (IFIC)
Foundation http//ific.org/publications/reviews/b
onehealthir.cfm