1. Bone death in osteoarthritis
2ο Τριεθνές Συνέδριο στην Οστεοπόρωση και
Οστεοαρθρίτιδα & 9ο Συνέδριο Μεταβολικών
Νοσημάτων των Οστών,
30/6-2/7/2011,
Ουρανούπολη -Χαλκιδική

2. Osteoarthritis (OA)
Disease of complex etiology
Results in loss of normal function
(Joint Failure)
Breakdown of articular cartilage

3. The established picture of O.A
The balance of two opposed but interpenetrating
processes: structural breakdown and reparative
or reactive changes

4. Morphological features of OA
Hunter brothers (200 years ago)
Robert Adams (1857)
“The cartilaginous incrustations which invest
the articular extremities …. the place of
cartilage is supplied by an ivory-like enamel…
as a billiard ball… the denuded surfaces are
partially worn away… around the articular
surface... bony vegetations arise.”

5. Morphological features of OA
The result of biologic and mechanical events ….
destabilize the normal joint coupling…
degradation – synthesis…
articular cartilage chondrocytes
extracellular matrix
subchondral bone
synovium
ligaments, tendons, muscles

6. Subchondral bone
Subchondral trabecular fragmentation
Localized bone death
Cyst formation
Collapse of the articular surface
Abundant new bone formation
(sclerosis – osteophytosis – remodelling)

8. Bone death in OA
Extensively studied
Not fully delineated
Vertical sections of femoral head
Clean – cut transection across lamellar systems
Empty osteocyte lacunae
Superficial osteonecrosis (usually)
More deeply (6%)
Meachim and Brooke, 1984
Migram, 1983
Ilardi and Sokoloff, 1984

10. Possible explanations
Loss of the protective effect of articular
cartilage
Cytotoxic chemical reaction by
synovial fluid seeping into the
uncovered bone

11. Bone death in OA
Bone remodelling
Reduplication of the tide
mark
Vascular incursion into the
articular cartilage
Thinning of cartilage
Eburnation

12. Osteoarthritic Femoral Heads
Histochemical stain to demonstrate LDH (Lactate Dehydrogenase)
activity in osteocytes
25 cases - 16 with dead osteocytes without LDH activity
Central regions of many trabeculae separated with cement lines from
viable bone
Bone collapse
A cause rather than a result of OA
Wong et al, 1987

14. Secondary osteonecrosis: 38.2% in osteoarthritis
1007 femoral heads with OA
Two types
Shallow flat lesions (axis 3 - 10mm, depth 2-3
mm)
Deep wedge-shaped large lesions (20mm, 10mm)
Shallow necrosis is the result of eburnation
Wedge-shaped - real osteonecrosis
Yamamoto et al, 2000

15. Bone marrow oedema is seen in osteoarthritis
Bone pain
Related to pathophysiology of OA?
Hypothesis
Bone narrow oedema
Reduction in perfusion in subchondral bone
Focal and segmental bone
necrosis Cartilage breakdown
Aaron et al, 2007

16. Osteocytes
“The forgotten bone cells”
They do serve an important role
bone function
bone maintenance
Major orchestrators of bone remodelling

17. Osteocytes entombed in bone matrix
Form an extensive cell communication network
Detect microdamage
Mechanical strains
Transmit signals
Leading to repair
Compensatory bone augmentation
Plotkin et al, 2005

18. Mechanistic basis
The evidence linking
Mechanical stimulation
Activation of the signalling pathway
Osteocyte survival or death
Provides the basis for
Skeletal health or disease
Plotkin et al, 2005

19. Vascular pathology and OA
Mounting evidence
Vascular pathology plays a role in
initiation and progression of osteoarthritis
Subchondral bone
Reduced blood flow
Reduced interstitial fluid flow
Venous occlusion and stasis
Development of microemboli
D.M. Findlay, 2007

20. Bone is highly vascular
The blood supply serves
the marrow
the calcified tissue
Intimate relationship between vasculature and bone
turnover
Rhinelander, 1979
Subchondral regions highly vascularised
High nutrient requirements
Compromised blood flow
Deleterious effects on bone and cartilage

21. Subchondral ischaemia
Cascade of events
Compromised nutrient
Reduced gas exchange
Apoptosis of osteocytes
Osteoclastic resorption of dead bone
Reduced nutrients and oxygen to cartilage
Reduced bony support of cartilage

22. Communication between bone and cartilage
Microchannels penetrate the subchondral
mineralization zone
By perfusion 50% of glucose, oxygen, water
of cartilage requirements
Imhof et al, 1997
Interruption of contact between
subchondral bone and cartilage
Degeneration of cartilage
Malinin et al, 2000

23. Subchondral bone remodelling
Osteocyte death provokes increased bone turnover
to repair damaged and necrotic bone
leading to
Bone collapse and unsupported cartilage
Subchondral sclerosis - reduced shock absorption

24. SUBCHONDRAL BONE SCLEROSIS
c- DNA microarray analysis to compare
(a) Normal controls (b) OA individuals
Both samples had in common 4000 genes
BUT
41 genes were different
3 genes lower in OA (Tyrosine – Kinase 1 – FLT 1)
Genes related to angiogenesis and bone remodelling
Hopwood et al,2005 - 2007

25. Venous stasis
Patients with OA have impaired venous
drainage
Leading to… increased vascular resistance…
reduced supply of nutrients and oxygen…
death of osteocyte < 4 hours

26. Conclusions
Inchaemia in subchondral bone may produce
osteocyte death, bone resoption and articular
damage in OA
Disruption of blood flow in subchondral bone
may reduce nutrient diffusion to articular cartilage
in OA
Bone death may represent a cause rather than a
result of OA

27. Destructive OA
Rapid progression to severe bone destruction
Old women
Osteoporotic
Intraoperatively
Capsule distended – villus synovium
Loose bodies
Crystalls “BRISTOL HIP”

29. Destructive OA 6 cases
Secontary OA 6 cases
(hip dysplasia)
Immunostained microvessels and osteoclasts
counted
Bone surface hypervascular
Osteoclasts increased
RDOA associated with hypervascularity
Yamakawa, et al 2005

30. Synovial fluid of RDOA shows high levels of bone
resorbing activity.
Little or no bone resorbing activity in non
destructive OA.
Stimulated by hydroxyapatite crystals.
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