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Physiology of bone and joints

Objectives
Bone remodelling
Hormonal regulation of bone formation and growth
Changes in the mechanical properties of bone with age and
disease
Incorporation of other materials into bone
Functions of cartilage
Physiology of joints
Age related changes in joints
Major pathologies
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Functions of bone

Providing load-bearing pillars

Providing levers
Solid protection of CNS & thorax
Store of calcium
Haemopoiesis & Energy store (fat)

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Remodelling of Bone

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Active tissue with significant metabolic rate (5% of cardiac output)

Bone recycled in 1-10 years
1 yr recycling in infants
Trabecular bone fastest 2 yr adult
Compact bone slower
Via "Basic Multicellular Units" (BMU)

Bone cells
Osteogenic cells
undifferentiated,
in periosteum
formation and repair
Osteoblasts
make collagen matrix from outside
release alkaline phosphatase
High PO4 precipitates Ca
Osteoclasts
Stimulated by PHT
Decalcify bone
Large multinucleate
Osteocytes
in lacunae
surrounded by and maintain matrix
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Rebuilding bone
Teams of cells Basic Multicellular Unit
100 day life span
500 um across 50 um deep
Osteoclasts erode surface (create local H+ environment)
Acid phosphatase
-measured in serum
-blocked by pyrophosphate (and bisphosphonates)
Proteolytic enzymes to remove organic matrix
Osteoblasts replace the eroded bone
Matrix resynthesis
Alkaline phosphatase and high pH
5% of adult bone being remodelled at any one time
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Remodeling of Bone

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Bone constituents

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Organics (30% dry matter in all)

Lay down matrix of collagen type I in triple helix having
high tensile strength.
Collagen synthesis needs vitamin C
Proteoglygans & other proteins

Bone constituents

Mineral (67% weight)

Produces hydroxyapatite - 20 x 3 nm crystals of
(Ca2+)(H3O+)(PO43)(OH-) high compressive strength

Osteoblasts create locally high phosphate environment via

alkaline phosphatase PO4 esters.

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High pH to exceed Ca2+ and PO43- solubility product

cf. reinforced concrete

Bone constituents

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Also some Na+, Mg2+, citrate, fluoride increases bonding

Fluoride
stabilises hydroxyapatite crystals
stimulates bone growth?

Heavy metals in bone

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Most heavy metals form insoluble salts with PO4 like Ca

Therefore also incorporated into bone
Physiological detoxification
removed from body fluids
usually inert in bone (eg Pb)
but held in bone for many years
severe problem with radio active metals, eg strontium-90,
radium, plutonium)
Cadmium
stimulates osteoclast activity hence bone loss
renal toxicity increases Ca loss
Copper required in trace amounts to synthesise collagen matrix
deficiencies rare

Other substances deposited in bone

Technetium-99 pyrophosphate taken up into

bone

Tetracycline
during mineralisation, tooth pre-eruption
incorporated into bone and teeth (brown
staining)

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Other substances deposited in bone

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Bisphosphonates
Stable pyrophosphates
Bind to bone and released to inhibit osteoclasts when they
are active
Reduce:
osteoporosis
Pagets disease
tumour secondaries on bone

Bone mineral density

Predictor of bone strength

BMD measured by:

Ultrasound
X-ray absorption (more accurate)
Expressed as
- gram/cm2 of assessment area
- T score (referred to normal
values)
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Bone mass,

Bone mass against age

g/cm3
Peak bone

1.0

Males

mass

Females
0.5

Old age

Menopause
Puberty

0
0
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20

40
Age, years

60

80

Hormonal influences on bone

Parathyroid hormone
Ca homeostatis
Ca and PO4 removal from bone
Vitamin D
Regulating Ca intake
Long-term, stimulate bone formation
1,25-hydroxycholecalciferol
Ca and PO4 removal from bone
Increased during growth
Calcitonin
Inhibits release of Ca from bone
Several cytokines inc
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Bone morphogenic protein

IGF (insulin-like growth factor)

Growth hormone influences bone

Growth hormone - depends on age

Increases chondrocytes and bone
lengthening
Bone thickening after epiphyseal plate
closure.
Via insulin like growth factor (IGF)
GH mostly secreted at night
Also hCG

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Sex hormones influence bone

Androgens (testosterone)
Produces growth spurt in adolescence via
GH
But induces epiphyseal plate
Increase bone formation and density
Oestrogen (Oestradiol)
epiphyseal plate closure
Increase bone remodelling
(in males, from androgens)
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Estrogenic influences on bone

Osteoclast
differentiation
reduced

Inhibition of bone
resorption

Oestradi
ol
Osteoblast
proliferation

Bone formation

Both effects through different cytokines

-replicated by raloxifen (estrogen- receptor specific
agonist avoiding increased breast cancer risk)
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Cortisol influences bone

Glucocorticoid
Osteoporosis with excess (especially vertebrae)
Steroid anti-inflammatories (long term)
Cushings (excess ACTH/cortisol production)
Children - stress infections or steroid treatment delays bone
growth

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Mechanical influences on bone

Increased stress increases bone density

Dynamic loads more effective
Via collagen-hydroxyapatite piezo electric currents and nitric oxide
Shapes bones to optimally resist forces
Without load bearing, lose bone mass and strength (30% after 1 month)
weightlessness!
BMD higher in dominant arm of tennis players
Exercising post-menopausal women taller (1.7 cm) than sedentary agematched women

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Mechanical influences on bone

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Disorders of bone metabolism

Osteoporosis
Loss of matrix and mineral
Decreased bone mass
High risk of irreparable fractures
Particularly spongy bone of fore-arms (radius), vertebrae and
neck of femur why his type of bone?
higher bone turnover and resorption rate here
Progressive with age easier to arrest than reverse
Reduced sex hormones
Females 80%, high loss rate, post menopausal
Males 20%, falling testosterone, ethanol & others
Reduced exercise
Lower initial bone mass
Poor nutrition and absorption
Race - African>European=Asian (when other factors equal)
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Ethanol abuse, smoking & numerous other factors

Disorders of bone continued

Osteomalacia
Loss of mineral
Due to Ca deficiency
Collagen and other matrix proteins
retained
or unavailability of Ca (eg vitamin D)
Reversible
See case
Rickets
Unavailability of Ca during development
Permanent skeletal defects
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Disorders of bone continued

Matrix diseases
Rare genetic defects in collagen
Bone is very brittle
Sometimes osteoporosis
(Defective collagen - aortic aneurisms)
Paget's disease
Increased bone resorption, >40 yr
Increased repair but poor replacement
- bones become deformed
- weaker
Measure alkaline phosphatase (bone
specific,
an indicator of increased bone formation)
Can use bisphosphonates
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Functions of Cartilage
Providing articulating surfaces
Creating hollow structures
(trachea)
Same structural functions as
bone in fetus and babies
Provision of matrix for deposition
of

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bone during development

Properties of Cartilage

Collagen
Tight network

Loose
Radial and
attached to bone

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Proteoglycans

Cartilage
25% dry matter
Composed of:
Hydrated proteoglygans.
glucosaminoglycans (GAGs) attached to protein frame
Attract water, proteins and polysaccharides
Behaves as rigid gel
Collagen (20% of dry matter) inserted into bone and loops into cartilage
Water and salts
Chondrocytes (1-12%)
Mechanical properties
Progressively compresses as load is increased due to water squeezed out
Shape restored as load removed. (stress relaxation)
Therefore absorbs shock. Compare bone
Provides large matched pads maximising the cushioning area in joint
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Joints
Synovial fluid
lubricants
hyaluronidate stringy glucopolysaccharide
lubricin (glycoprotein adheres to cartilage surface
Clear and viscous
No fibrinogen and other clotting factors
Viscoelasticity (stringy) ensures that is stays
between articular cartilages.
Fluid layer allows lubrication
Coefficient of friction 1/10 of that of an ice skate
on ice

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Joints
Functions
Articulation
Shock absorbing (cushioning)
Synovial fluid (lubricant-hyaluronidate)
Fibrous capsule (sealed)
Held together with ligaments (&
muscles)
Bursae
Non-articular bags
Similar cushions of synovial fluid

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Diseases of joints
Osteoarthritis
Many diseases
Very common in elderly (70%)
Erosion of articular cartilages (normal process but failure to
replace)
Protrusions of bone causing pain, stiffness and noise.
Rheumatoid arthritis
Autoimmune inflammatory disease
Synovial membranes inflammation
Destruction of cartilage
Occurs in younger age group
Progressive
Also other effects
Gout
Uric acid precipitation
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Damage to joints
Sprain
Stretched or torn ligament around joint
or torn insertion
Dislocation (luxation)
Opposing bones forced out of
alignment
Cartilage damage
Avascular so little repair
Fragments can cause further damage

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The end
http://www.mededsoft.com/qub
http://www.qub.ac.uk/smrg

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