Osteoporosis Update Fundamental Processes in Bone Physiology

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Osteoporosis Update Fundamental Processes in
Bone Physiology

• David F. Schaffner, PhD, MT(ASCP)
• Scientific Affairs Manager
• Beckman Coulter, Inc.

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Learning Objectives

• Discuss the physiological and biochemical
  elements involved in the process of bone
  remodeling
• Identify the risk factors, consequences,
  diagnosis and management of osteoporosis
• List steps for prevention of osteoporosis
• Explain the laboratory utilization of bone
  markers for assessing bone resorption and
  formation
• Define to role of Parathyroid Hormone (PTH) in
  calcium regulation
• Explain the use of Intra-operative PTH testing
  in the management of disease

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Bone Metabolism Introduction
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Bone a Dynamic Tissue

• Bone is a living tissue
• -about 10 of entire skeleton is replaced each
  year
• Bone consists of mineralized organic matrix
• -90 of the organic matrix is type I collagen
• -Calcification gives bone its hardness

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Bone a Dynamic Tissue
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Bone Function

• Mechanical
• For locomotion
• Protective
• For organs
• Metabolic
• As a reserve for minerals
• Calcium and phosphate
• 99 of calcium in the body
• 85 of phosphate

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Types of Bone

• Cortical or compact bone
• Shafts of long bones
• Outer envelope of all bones
• Cancellous or trabecular bone
• Inner parts of the bones of the axial skeleton
• E.g., vertebra

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Bone Turnover
Trabecular bone 20 of the skeletal mass 80 of
bone turnover
Cortical bone 80 of the skeletal mass 20 of
bone turnover
Cortical bone is renewed at a rate of 3 per
year.
Trabecular bone is renewed at a rate of 25 per
year.
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Bone Remodeling

• Osteoblasts
• mesenchymal lineage
• Deposition of a mineralized matrix

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Bone Remodeling

• Osteoclasts
• Hematopoietic lineage
• Attach to surface
• Secrete Hions and lysosomal enzymes (cathepsin
  K)
• Degrades all components of the bone matrix

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Bone Remodeling
Bone degradation andconstruction occurat the
same time Bone turnover impact of this process
(depends on number of remodeling
units) Remodeling balance relative result of
bone formed and bone resorbed
Healthy bone
Microfractures in old bones
Mineralisation of the osteoid, complete repair
with new bone
Osteoblastsproduceosteoid
Osteoclastsdestroy theweak bone
3months
Weak bone is resorbed,smooth surface
Bartl R Osteoporose, Stuttgart 2001, 11
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Bone Balance
Resorption and Formation are Equal
Resorption Exceeds Formation
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Osteoporosis Pathogenesis
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Definition of Osteoporosis
A systemic skeletal disease characterized by
low bone mass and microarchitectural
deterioration of bone tissue, with a consequent
increase in bone fragility and susceptibility to
fractures Consensus Development Statement.
Osteoporos Int 19971-5
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Normal Trabecular Bone
Osteoporotic Bone
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Pathogenesis of Osteoporosis

• Failure to achieve optimal peak bone mass
• - genetics, nutrition, lifestyle
• Accelerated bone loss due to increased
  resorption
• - estrogen deficiency, PTH excess
• Inadequate formation response during remodeling
• - cell aging, decreased growth factors
• Impaired mechanical function and signaling
  - decreased muscle mass and activity
  increased falls

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Bone Mass and Bone Loss
Source University of Washington Osteoporosis
and Bone Health Website (http//courses.w
ashington.edu/bonephys/ )
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Prevalence and Epidemiology

• In the US, 8 million women and 2 million men have
  osteoporosis1
• An additional 34 million Americans currently have
  low bone mass1
• In the US, approximately half of women and
  one-fourth of men aged 50 years or older will
  suffer an osteoporosis-related fracture within
  their lifetime2

1. Americas Bone Health The State of
Osteoporosis and Low Bone Mass In our Nation. NOF
2002 2. Chrischilles EA, et al. Arch Intern. Med.
1991 151 2026-32
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Osteoporosis and Risk of Fracture

• Lifetime risk of fracture for 50-year
  oldpostmenopausal white women
• 50 any kind of fracture
• 18 for hip fracture
• 1.5 million fractures annually1
• gt300,000 hip fractures
• 700,000 vertebral fractures
• 250,000 wrist fractures
• 300,000 fractures at other sites

National Osteoporosis Foundation, Osteoporosis
Int. 1998 8 S1-S88
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Hip Fracture is a Devastating Condition

• A womens risk of hip fracture is equal to her
  combined risk of breast, uterine, and ovarian
  cancer.

Cooper C, Am J Med, 1997103(2A)12S-17S.
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Osteoporosis Economic Impact

• Annual cost of osteoporotic fractures
• 18 billion in 2002 (49 million each day)
• (62.4) for inpatient care.
• (28.2) for nursing home care.
• (9.4) for outpatient services.

2002 U.S. estimates from National
Osteoporosis Foundation.
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The 2004 Surgeon Generals Report on Bone Health
and Osteoporosis.
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Risk Factors for Osteoporosis

• Environmental
• Sedentary lifestyle
• Calcium or vitamin D deficiency
• Prolonged glucocorticoid use
• Amenorrhea from intensive exercise
• Males undergoing hormonal treatment for prostatic
  cancer
• Excessive alcohol consumption
• Smoking
• High caffeine intake

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Risk Factors for Osteoporosis

• Genetic
• Caucasian or Asian descent
• Small, thin frame
• Family history
• Advancing age
• Early menopause (or surgically induced)
• Hyperthyroidism

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Diagnosing Osteoporosis
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Osteoporosis and Osteopenia

• WHO Diagnostic Categories
• BMD-Based Definition of Osteoporosis/Osteopenia
• Normal T-score or -1 SD.
• Osteopenia T-score - 1 to -2.5 SD.
• Osteoporosis T-score -2.5 or lower.
• Severe Osteoporosis T-score -2.5 or lower and
  fragility fracture(s)
• BMD bone mineral density measured at the
  hip, spine or wrist
• Normal mean of young adult women.

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OsteoporosisDiagnosis and Risk Prediction

• Diagnosis
• DEXA (dual X-ray absorptiometry)
• Ultrasound densitometry
• Risk assessment
• Either serial BMD measurements to gain an insight
  into the rate of bone loss
• Or by combining a BMD measurement and bone
  markers
• bone markers predict the speed of bone loss
• fast losers
• slow losers

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Bone Markers
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Bone Markers What are they?

• Biochemical tests that reflect osteoclast
  (resorption) and osteoblast (formation) function
  at a single point in time

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Biochemical Markers

• Resorption
• Hydroxyproline
• Pyridinoline
• Deoxypyridinoline
• Telopeptides of collagen crosslinks (C and N
  telopeptides)

• Formation
• Total alkaline phosphatase
• Bone-specific alkaline phosphatase
• Osteocalcin

When formation and resorption are coupled either
of these markers can reflect the overall bone
turnover
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Resorption Markers

• Hydroxyproline
• limited specificity
• only reliable if assayed with cumbersome, labor
  intensive HPLC method
• mainly of historical interest