Osteoporosis NIH

1
Osteoporosis (NIH)

• Disease characterized by low bone mass and
  structural degeneration of bone tissue
• Leading to bone fragility and increased risk of
  fractures
• Prevalence
• 10 million estimated to have osteoporosis
• 8 million women 2 million men
• 34 million American, or 55 of people 50 years
  of age and older, have low bone mass

2
Osteoporosis

• Significant risk in people of all ethnic
  backgrounds
• Fractures
• One in two women and one in four men age 50 and
  over will have osteoporotic fracture sometime
• 1.5 million fractures annually
• 300,000 hip
• 700,000 vertebral
• 250,000 wrist
• 300,000 at other sites
• Estimated cost
• Estimated national direct expenditures (hospitals
  nursing homes) for osteoporotic and associated
  fractures was 17 BILLION in 2001 (47
  million/day)

3
Recommended calcium intakes

• Age Amount of
  calcium
• Infants
• birth-6 months
  210 mg
• 6 months-1 year 270
  mg
• Children/Young Adults
• 1-3 years
  500 mg
• 4-8 years
  800 mg
• 9-18 years
  1,300 mg
• Adult Women and Men
• 19-50 years
  1,000 mg
• 50
  1,200 mg
• Pregnant or Lactating Women
• 18 years or younger 1,300 mg
• 19-50 years
  1,000 mg Source National Academy of
  Sciences,
• 
  1997

4
Bone Composition and Architecture

• Composition of Bone Matrix
• Organic matrix (Type I collagen) - 90 -95
• Calcium-phosphate precipitates
• Mineralized phase of hydroxyapatite
  (Ca10(PO4)6(OH)2
• Ratio of calcium to phosphorus (Ca/P) 1.3-2.0
• Magnesium, sodium, potassium ions present
• Architecture
• Cortical
• Compact bone - accounts for 75-80 of total
  skeletal mass, only 33 of total bone surface
• Cancellous
• Trabecular or spongy bone - has a high
  surfacevolume ratio and accounts for 2/3s of
  bone surface, only 20-25 of skeletal mass
• Found primarily in the spine, pelvis and ends of
  long bone

5
Bone Composition and Architecture

• Multiple cell types cell interactions
• Inorganic components 65 of bones dry weight
• Organic compounds 35 of dry wt.
• 90 Type 1 collagen
• 10 noncollagenous proteins albumin,
  osteonectin, osteopontin, osteocalcin, growth
  factors, ?2-HS-glycoprotein

6
Bone Mass and Bone Rigidity Regulation

• Depends on the functions of 3 distinct cell
  populations
• Integrated activity of these bone cells at the
  same site or anatomically distinct sites
  contributes to the processes of remodeling and
  modeling, respectively.
• Osteoblasts
• Osteocytes
• Osteoclasts

7
Bone Cells

• Osteoblasts - synthesize organic
  matrix(glycosaminoglycans), deposit upon existing
  bone surface and subsequent mineralization
• Alkaline phosphatase-secreted by maturing
  osteoblasts
• Alters pH of interstitial spaces causing
  dissolved mineral components to precipitate out
  of solution around collagen fibers
• Some active osteoblasts are eventually surrounded
  by mineralized bone
• These isolated cells are termed osteocytes

8
Bone Cells

• Osteocytes - are best situated to detect
  mechanical strain in bone
• Communicate the amplitude of strain signal with
  biochemical signals via gap junctions

9
Osteoclast

• Multinucleated cell initiates the remodeling
  process
• Actively degrade bone
• Modeling is primary functional response to large
  increases in imposed loading on bone
• Secrete enzymes that dissolve mineral salts and
  transform them into soluble ions that enter blood

10
Bone Cells
11
Osteoclast Activity

• Calcitonin
• Inhibits destruction and re - absorption of
  mineral components of bone matrix
• Blood calcium levels drop, calcium remains in
  bone
• Parathyroid hormone
• Stimulates osteoclastic activity
• Raises blood calcium
• Inhibits the kidneys from removing calcium from
  blood

12
Bone Remodeling

• Bone deposits - where bone is injured or added
  bone strength is required
• Trigger for calcification of matrix ???
• One critical factor - local concentrations of
  calcium and phosphate ions
• Other factors include proteins such as
  osteonectin and osteocalcin that bind and
  concentrate calcium
• Enzyme alkaline phosphatase - either essential
  for mineralization or inhibiting calcification
  inhibitors

13
Regulation of Bone Strength and Stiffness

• Signal for need for change in skeletal strength
  is cumulative deformation of bone
• Minimum threshold exceeded modeling and
  remodeling systems are activated
• Leading to an adjustment of bone geometry and
  bone mass to reduce those deformations below
  physiological threshold

14
Medical Clinical ConcernsA Consequence of
Age-related Changes in Bone Osteoporotic Fracture

• Osteoporotic fractures occur with only mild or
  moderate impacts in bone of low strength,
  typically during a fall in older persons
• Major public health concern in most
  industrialized countries
• Nearly 1 in 3 women and 1 in 6 men surviving to
  age 90 y will experience a hip fracture and its
  debilitating consequences

15
Changes in Bone Mass with Aging

• Quantity of bone declines with age after the
  attainment of peak bone mass in young adulthood
  (20-25 years)
• Universal across races, habitual activity level,
  dietary habits
• Bone mass loss is site specific
• Large degree of biological variation in the rate
  and age at onset of loss
• Loss of bone mass without any change in bone
  quality is termed OSTEOPENIA

16
Changes in Bone Mass with Aging

• Local factors in bone such as Interleukins,
  tumor necrosis factor (TNF) and
  colony-stimulating factor occur as a result of
  estrogen reduction.
• Leads to increase in osteoclast numbers and life
  expectancy
• Leads to increase in bone marrow adiposity (can
  reach 90 of bone marrow cavity
• Reduction in trabecular and cortical bone volume

17
Changes in Bone Mass with Aging

• Cortical bone loss is attributed to bone
  resorption on the endosteal surface faster than
  periosteal growth
• As cortical bone thins, the bone at interface
  with cancellous bone becomes porous and no longer
  resembles cortical bone
• Architectural change of endosteal surface
  prevents further bone deposition thus bone loss
  in area is irreversible

18
Changes in Bone Mass with Aging
19
Relative Changes in Bone Mineral Density (BMD)

• Continued loss of cortical bone mass into the
  ninth decade at femoral neck, radius calcaneus
• Calcaneus most sensitive to changes in
  weight-bearing activity

20
Changes in Bone Cell Activities

• Maximum lifespan of bone tissue years
• Osteoblasts ---gt osteocytes 3 y or until the next
  remodeling event at that site (25 y upper limit)
• After 35 y, small net deficit of bone volume at
  endosteal surfaces of cortical bone and on
  cancellous bone

21
Bone Cell Activities

• Rate of remodeling, or turnover, slows with age
• decreased delivery regulatory factors (progenitor
  cells)
• changes in mineral or organic matrix properties
  that alter the transmission of strain
• decline in available osteoblast progenitor cells
• changes in secretion or clearance of the major
  hormones regulating bone and calcium metabolism.

22
Decline in Bone Quality with Aging

• Increased proportion of old bone in any given
  area of mineralized bone
• Hypermineralization - functional concern is
  brittleness of tissue.
• Decreased resistance to fracture
• 3 fold decrease in impact energy absorption
  between 3 and 90 y due to mineralization

23
Bone Quality

• Small apatite crystals size parallels decline in
  tensile strength of bone
• Age related decline in organic matrix
• Change in orientation of collagen fibers
• Accumulation of microcracks or fatigue damage

24
Disuse Osteopenia

• Balance between resorption and formation of bone
  is disrupted with disuse and particularly by the
  loss of weight - bearing
• Resulting bone loss develops at a rate 5 to 20
  times greater than in common metabolic disorders
• Classic bed - rest studies demonstrate
• doubling of urine calcium w/6 wk cast immobile.
• 4-10 decrease in BMD in 120 days strict bed rest
  - most severe loss in calcaneus

25
Risk Factors
26
Factors Influencing Bone Changes

• Hormonal factors
• Menopausal related withdrawal of estrogen
• rapid increase in bone destruction
• Absorption of calcium in intestine
• Calcitonin Vitamin D metabolites decline
• Increase in parathyroid hormone favors
  resorption
• Dietary deficiencies - NIH recommends 1200 mg/day
  pre-menopausal for calcium
• Decreased physical activity

27
Changes in Endocrine Regulators of Remodeling

• Parathyroid hormone-vitamin D axis changes-
  results in decline in intestinal absorption of Ca
• Decline in circulating growth hormone (GH)
  Insulin-like growth factor I (IGF-I)
• Not seen as a major factor explaining decline in
  bone mass in older adults.

28
Adaptations to Exercise Training in Bone

• Mechanism for the response to mechanical loading
• Increased modeling - macroscopic changes in bone
  size and shape
• Decreased remodeling - replaces old or
  fatigue-damaged bone with new bone
• Primarily responsible for changes in tissue
  material strength
• Loading of bone with Physical Activity can vary
  including magnitude of load, number of loading
  cycles,

29
Exercise Effects

• Brief, high-intensity periods of loading versus
  Endurance Training
• Middle-aged long-distance runners, male and
  female, have 40 more mineral content in
  cancellous bone of lumbar vertebrae than
  age-matched sedentary controls
• Nine months of resistance training in
  postmenopausal women prevents the decline in BMD
  of lumbar spine
• Menkes (1993) - middle-age men experienced a 3.8
  gain in femoral neck bone density after 4 mo of
  rigorous strength training (one remodeling cycle)

30
Exercise Effects

• Stationary cycling (non-weight-bearing exercise)
  - prevents age-related decrements in the lumbar
  spine (F, X60 y)
• Current anthropometric and lifestyle factors
  (including physical activity) accounted for less
  than 30 of the variance in BMD in 1600 Finnish
  perimenopausal women

31
Exercise Guidelines for Bone Health

• Weight-bearing exercise
• Type does not appear to be critical
• 30 - 60 minutes/day
• 2 - 3 days/week
• No correlation with VO2max
• Relationship between exercise and bone loss
  depends significantly on estrogen status and age

32
Measurement

• Bone integrity is assessed by
• Bone mass - the amount of bone
• Bone mineral content - calcium, phosphorous,
  magnesium, boron, and manganese
• Density - amount of calcium or minerals per unit
  volume of bone
• Bone geometry - internal structure of bone
• Rate of bone loss
• These measures allow one to determine status
  bone gain, maintenance, loss