Osteoarthritis

1. Osteoarthritis

2. Osteoarthritis
•Osteoarthritis is an idiopathic disease
•Characterized by degeneration of articular
cartilage
•Leads to fibrillation, fissures, gross ulceration
and finally disappearance of the full
thickness of articular cartilage

3. Factors responsible
• Ageing
• Genetics
• Hormones
• Mechanics

4. Pathologic lesions
•Primary lesion appears to occur in cartilage
•Leads to inflammation in synovium
•Changes in subchondral bone, ligaments,
capsule, synovial membrane and
periarticular muscles

5. Normal Cartilage
•Avascular, alymphatic and aneural tissue
•Smooth and resilient
•Allows shearing and compressive forces to
be dissipated uniformly across the joint

6. Structure of Normal Cartilage
•Chondrocytes are responsible for metabolism of
ECM
•They are embedded in ECM and do not touch one
another, unlike in other tissues in the body
•Chondrocytes depend on diffusion for nutrients
and therefore the thickness of cartilage is limited
•Extracellular matrix is a highly hydrated
combination of proteoglycans and non-
collagenous proteins immobilized within a type II
collagen network that is anchored to bone

7. Structure of Normal Cartilage
•Divided into four morphologically distinct zones:
•Superficial: flattened chondrocytes
•high collagen-to-proteoglycan ratio and high
water content.
•Collagen fibrils form thin sheet parallel to
articular surface giving the superficial zone an
extremely high tensile stiffness
•Restricts loss of interstitial fluid, encouraging
pressurization of fluid.

8. Structure of Normal Cartilage
•Transitional zone:
•Small spherical chondrocytes
•Higher proteoglycan and lower water content
than superficial zone
•Collagen fibrils bend to form arcades

9. Structure of Normal Cartilage
•Radial Zone:
•Occupies 90% of the column of articular cartilage
•Proteoglycan content highest in upper radial
zone
•Collagen oriented perpendicular to subchondral
bone providing anchorage to underlying calcified
matrix
•Chondrocytes are largest and most synthetically
active in this zone

10. Structure of Normal Cartilage
•Calcified zone:
•Articular cartilage is attached to the
subchondral bone via a thin layer of calcified
cartilage
•During injury and OA, the mineralization front
advances causing cartilage to thin

11. Structure of Normal Cartilage

12. Function of Normal Cartilage
•Critically dependent on composition of ECM
•Type II (IX&XI) provide 3D fibrous network
which immobilizes PG and limits the extent of
their hydration
•When cartilage compresses H2O and solutes
are expressed until repulsive forces from PGs
balance load applied

13. Function of Normal Cartilage
•On removing load, PGs rehydrate restoring
shape of cartilage
•Loading and unloading important for the
exchange of proteins in ECM and thus to
chondrocytes
•Chondrocytes continually replace matrix
macromolecules lost during normal turnover

14. OA cartilage
•The equilibrium between anabolism and
catabolism is weighted in favor of degradation
•Disruption of the integrity of the collagen
network as occurs early in OA allows
hyperhydration and reduces stiffness of
cartilage

15. Degenerative cartilage

16. Mechanisms responsible for
degradation
•Catabolism of cartilage results in release of
breakdown products into synovial fluid which
then initiates an inflammatory response by
synoviocytes
•These antigenic breakdown products include:
chondrointon sulfate, keratan sulfate, PG
fragments, type II collagen peptides and
chondrocyte membranes

17. Mechanisms responsible for
degradation
•Activated synovial macrophages then recruit
PMNs establishing a synovitis
•They also release cytokines, proteinases and
oxygen free radicals (superoxide and nitric oxide)
into adjacent and synovial fluid
•These mediators act on chondrocytes and
synoviocytes modifying synthesis of PGs,
collagen, and hyaluronan as well as promoting
release of catabolic mediators

18. Synovial changes

19. Cytokines in OA
•It is believed that cytokines and growth
factors play an important role in the
pathophysiology of OA
•Proinflammatory cytokines are believed to
play a pivotal role in the initiation and
development of the disease process
•Antiinflammatory cytokines are found in
increased levels in OA synovial fluid

20. Proinflammatory cytokines
•TNF-α and IL-1 appear to be the major
cytokines involved in OA
•Other cytokines involved in OA are: IL-6, IL-8,
leukemic inhibitory factor (LIF), IL-11, IL-17

21. TNF-α
•Formed as propeptide, converted to active form
by TACE
•Binds to TNF-α receptor (TNF-R) on cell
membranes
•TACE also cleaves receptor to form soluble
receptor (TNF-sR)
•At low concentrations TNF-sR seems to stabilize
TNF-α but at high concentrations it inhibits
activity by competitive binding

22. IL-1
•Formed as inactive precursor, IL-1β is active
form
•Binds to IL-1 receptor (IL-1R), this receptor is
increased in OA chondrocytes
•This receptor may be shed from membrane to
form IL-1sR enabling it to compete with
membrane associated receptors

23. TNF-α and IL-1
•Induce joint articular cells to produce other
cytokines such as IL-8, IL-6
•They stimulate proteases
•They stimulate PGE2 production
•Blocking IL-1 production decreases IL-6 and
IL-8 but not TNF-α
•Blocking TNF-α using antibodies decreased
production of IL-1, GM-CSF and IL-6

24. IL-6
•Increases number of inflammatory cells in
synovial tissue
•Stimulates proliferation of chondrocytes
•Induces amplification of IL-1 and thereby
increases MMP production and inhibits
proteoglycan production

25. IL-8
•Chemotactic for PMNs
•Enhances release of TNF-α, IL-1 and IL-6

26. Leukemic inhibitory factor (LIF)
•Enhances IL-1 and IL-8 expression in
chondrocytes and TNF-α and IL-1 in
synoviocytes
•Regulates the metabolism of connective
tissue, induces expression of collagenase and
stromolysin
•Stimulates cartilage proteoglycan and NO
production

27. Antiinflammatory cytokines
•3 are spontaneously made in synovium and
cartilage and increased in OA
•IL-4, IL-10, IL-13
•Likely the body’s attempt to reduce the
damage being produced by proinflammatory
cytokines, these two processes are not
balanced in OA

28. IL-4
•Decreases IL-1
•Decreases TNF-α
•Decreases MMPs
•Increases IL-Ra (competitive inhibitor of IL-1R)
•Increases TIMP (tissue inhibitor of
metalloproteinases)
•Inhibits PGE2 release

29. IL-1Ra
•Competitive inhibitor of IL-1R, not a binding
protein of IL-1 and it does not stimulate target
cells
•Blocks PGE2 synthesis
•Decreases collagenase production
•Decreases cartilage matrix production

30. IL-10, IL-13
•IL-10 decreases TNF-α by increasing TNFsR
•IL-13 inhibits many cytokines, increases
production of IL-1Ra and blocks IL-1
production

31. Osteoarthritis and Joint
Replacement
•Once bone – bone articulation develops, joint
replacement (Arthroplasty) is only viable
option.
•Most common in Knees and Hips.
•Very serious surgeries. Often takes months /
years to get back to full strength (if ever)

32. Knee Arthroplasty aka Total
Knee Replacement (TKR)

33. Possible Side Effects of Knee
Arthroplasty
•blood clots in the leg
•blood clots in the lung
•urinary infections or difficulty urinating
•difference in leg length
•stiffness
•loosening of prosthesis
•infection in knee

34. •90% + report increased ROM following surgery
•25% report loosening of prosthesis @ 10 years
–Caused by osteolysis; inflammatory
response: reabsorption of bone
•Lots of isometric exercises and walking
Knee Arthroplasty

35. Possible Side Effects of Hip
Arthroplasty
•blood clots in the leg
•blood clots in the lung (1-2% Occurrence)
•urinary infections or difficulty urinating
•difference in leg length
•stiffness
•dislocation of hip
•infection in hip

36. •Dislocation Prevention (2-3% Occurrence)
–using 2-3 pillows between your legs while sleeping
and not crossing your legs
–not bending forward 90 degrees
•Exercise
–Lots of isometric exercises will be prescribed to
strengthen muscles surrounding joint
–Lots of walking, cycling, swimming, etc.
•Avoid high impact exercises and follow guidelines
listed above regarding prevention of dislocation.
Hip Arthroplasty

37. •90 – 95% success rate @ 10 years post op.
•Average lifespan 12 – 15 years
–Less if active (IE Younger person)
•Very effective at providing complete pain relief
–Often have to keep person from “over doing it”
Hip Arthroplasty

38. Usually Occurs @ the “Surgical Neck”
of Femur
Often results in disruption of blood
flow….Avascular Necrosis *
*
Hip Fractures

39. •Usually requires surgery
–THR
–ORIF (Open Reduction, Internal Fixation)
•Uses plates, rods, & screws to fixate femoral
fracture
•Post operative Exercise
–Isometrics, ROM exercises
–SLOWLY progress to weight bearing exercises
as directed by Physician
Treatment of Hip Fracture

40. •One year post mortality is as high as 40%
(leading cause of “traumatic death” in elderly)
•Very small percentage regain previous mobility
•20% require nursing home care following
fracture
•Often results in accumulation / increase in
incidence of other health problem
–CAD, diabetes, stroke, pneumonia,etc…
Hip Fractures

41. Facts about Hip Fractures and
Osteoporosis
•44 million Americans suffer from osteoporosis
and/or low BMD
•80% are Women / 20% Men
•Women can lose up to 20 percent of their bone
mass in the five to seven years following
menopause, making them more susceptible to
osteoporosis.

42. Risk of Hip Fracture and
BMD

43. Facts about hip fractures
and Osteoporosis
•Annual cost associated with osteoporotic
fractures is $17 billion in 2001 ($47 million each
day).
•One in two women and one in four men over age
50 will have an osteoporosis-related fracture in
their lifetime.
–300,000 hip fractures; and approximately
–700,000 vertebral fractures,
–250,000 wrist fractures; and
–300,000 fractures at other sites.
•MOST ARE PREVENTABLE!!!