OA knee, Chondrocytes, Exercises, Bicycling, Viscosupplementation, local steroids, surgery, Chondrocyte transplantations.

1. Osteoarthritis of Knee
Vinod Naneria

2. Definition
• The name osteoarthritis comes from three
Greek words meaning bone, joint, and
inflammation.
• It is a progressive disorder of the joints
caused by gradual loss of articular cartilage
with secondary changes in the bone and
synovium.

3. Osteoarthritis – oldest
• Remains of the
dinosaur Diplodocus
show evidence of
osteoarthritis 150
million years ago.
• Earliest evidence of
human osteoarthritis
has been found in the
remains of Neanderthal
man. ( 0.6 – 0.03 M)
New man from a valley

4. Knee joint of an Elephant

5. Knee joint of a bird

6. Osteoarthritis
• 10% adult population
across the world
• About a quarter of all
consultations in general
practice.
• Symptoms of the disease
manifest much late.
• There is no known cure of
the disease.
Progress can be controlled or delayed

7. Articular cartilage - unique
•
•
•
•
No blood supply,
No lymphatic drainage,
No neural elements,
Chondrocytes are shielded from
immunological recognition.
• 60 – 80% of human cartilage is water.

8. Chondrocytes
• Chondrocytes are the
cellular manufacturing
sites of cartilage and
are responsible for the
production and
maintenance of the
surrounding matrix .
Chondrocyte

9. Collagens:
• Protein macromolecules
that contain characteristic
helical amino acid chains.
• Provide the tensile strength
and form of cartilage
• Proteoglycans are attached
to the collagen framework.

10. Proteoglycan
• It consist of a core protein, Aggrecan, to which
are covalently bound glycosaminoglycan side
chains of chondroitin and keratan sulfate.
• These charged side chains account for the
hydration and resistance to compression of
the cartilage matrix.

11. Cartilage Matrix Organization Zones
•
•
•
•
•
Superficial (gliding) – cells are horizontal,
Middle (transitional) – cells are crisscross,
Deep (radial) – cells are perpendicular,
Calcified cartilage.
Subchondral bone.

12. Articular Cartilage Matrix Organization
Zones
• Morphologic,
biochemical &
functional differences
between zones based
on depth from articular
surface.
• Superficial – shearing
• Deep - compression

14. Normal Articular Cartilage

15. Articular cartilage in Osteoarthritis

16. Pathogenesis of osteoarthritis of the knee
• Chronological age is the single most important
risk factor.
• In younger patients unfavourable
biomechanical environment at the joint is the
main cause.
• This results in mechanical demand that
exceeds the ability of a joint to repair and
maintain itself, predisposing the articular
cartilage to premature degeneration.
Chondrocyte apoptosis - telomere or mechanical overloading

17. OA is characterized by two phases
• A biosynthetic phase, during which the
Chondrocytes, attempt to repair the damaged
extracellular matrix.
• A degradative phase, in which the activity of
enzymes produced by the chondrocytes
digests the matrix, matrix synthesis is
inhibited, and the consequent erosion of the
cartilage is accelerated.

20. Sequence of events
•
•
•
•
•
Superficial layer abrasion,
Superficial layer fissuring,
Attempt at repair by chondrocytes,
Excess production of new cells and matrixes,
Deep layer cleavage.

21. Sequence of events
• Chondrocytes start secreting lysosomal
enzymes which start dissolving matrixes.
• Release of degradation products in the joint
leading to synovitis
• Loss of shock absorption property
• Subchondral bone fractures
• Healing of subchondral fractures by sclerosis,
and osteophyte formation.

22. Treatment chart
Medical
Surgical
Regenerative

23. Treatment Option - Medical
Life style
modifications
Physiotherapy
Nsaids
Braces
Supports

24. Treatment Option - invasive
Injections (Hydrocortisone – Hyaluronic acid)
Arthroscopy (debridement)
Alignment corrective surgery (HTO)
Total / partial joint replacement
Regenerative medicine ( cartilage transplantation)

25. Life style modification:
•
•
•
•
•
•
•
Sitting on ground
Squatting
Sit-ups
Climbing
Commode
High heels
Shoe modification (lateral
wedges)
• Cane/walker
• Braces

26. Life style
•
•
•
•
•
•
Walking instead of running,
Use alternative exercise program
Walking within the limit of pain.
Walk on soft earth.
Limp if required.
Overweight Patients, should lose a minimum
of five percent (5%) of body weight.
• low-impact aerobic fitness exercises.
Don’t scratch your wounds

27. Life style
•
•
•
•
•
•
Range of motion/flexibility exercises.
Swimming is good exercise.
Quadriceps strengthening (static)
Delay quadriceps against resistance or avoid it.
Use of high heel increases anterior knee pain.
Correct your shoe frequently if the heel is
getting wear from one side.

28. Role of Physiotherapist
• Specific instruction should be given for better
cooperation from physio in the interest of
patient.
–
–
–
–
–
–
–
Pain: Heat therapy, SWD, US
ROM: bicycle, CPM, free swing, Stretching
Correction of deformity,
Strengthening of Quad + Hamstrings
Static Quadriceps,
Improvement in gait & Balance,
Resistive exercises – with weights?
Choice of modalities should be left to physiotherapist

29. Exercises – 4 Ds
• Golden rules:
–
–
–
–
Do it
Do it regularly
Do it correctly
Do not over do it
Exercises for prevention of OA
knee is like brushing teeth.
It should be gentle &
continuous for rest of the life.
Free cycling for 5 – 10 minutes at
zero resistance. Can be repeated
twice a day
Free cycling for 5 – 10 minutes / 5 km are very good form of
exercise. Static cycle is better. It help in cartilage nutrition by
CPM type action. Can be repeated twice a day.
Bicycling for knee arthritis is not a weight reduction tool,
overdoing can damage the knee further.
Skipping: Soft surface – in garden or wooden
platform. Avoid high impact.
overdoing can
damage the knee
further.

30. Free cycling
• Free cycling for 5 – 10 minutes / 5 km are very
good form of exercise.
• Static cycle is better.
• It help in cartilage nutrition by CPM type
action.
• Can be repeated twice a day.
• Bicycling for knee arthritis is not a weight
reduction tool, overdoing can damage the
knee further.
ZERO - RESISTANCE

31. overdoing can damage
the knee further.
Free cycling for 5 – 10
minutes at zero resistance.
Can be repeated twice a day.

32. Skipping
• Skipping
• Soft surface – in garden or wooden platform
• Avoid high impact.

33. Treadmill
• Climbing uphill
increases loading on the
damaged cartilage and
at times precipitate
acute pain and effusion
in knee.
• It is a high impact
exercise.
• Specially precipitate PF
pain.

34. Patello-femoral pain

35. Braces
• Instability / lack of
confidence,
• Insecurity /
apprehension
• Meniscus tear
• Ligamentous laxity
• Unicompartmental
disease

36. Life style modification
• Unilateral joint unloading
braces are not
recommended for general
use. They are commonly
prescribed for unicompartmental disease of
the knee.

37. Acupuncture
• There is no recommendations for or against
the use of acupuncture as an adjunctive
therapy for pain relief in patients with
symptomatic OA of the knee.

38. Prolotherapy or proliferation therapy
• It involves injecting an nonpharmacological and non-active
irritant solution into the region of
tendons or ligaments.
• It re-initiate the inflammatory
process that deposits new additional
fibres to repair a perceived injury.
• dextrose, lidocaine, phenol,
glycerine, or cod liver oil extract. The
injection is given into joints or
tendons where they connect to bone
Not covered by Medicare in USA

39. Pain Relievers
• Patients with symptomatic OA of the knee can
receive one of the following analgesics for
pain unless there are contraindications to this
treatment:
• Acetaminophen
• NSAIDs only in acute flare for short term.
• Avoid them in cases of hypertension, CRF and
CAD.
• Oral cortisone have no role.
Tx - Malaria by Crocin
Prolonged use can cause neuropathic joint

40. Glucosamine & Chondroitin
• Chondroitin is the most abundant
glycosaminoglycan in cartilage and is
responsible for the resiliency of cartilage.
• Oral consumption of the substances may
increase the rate of formation of new cartilage
by providing more of the necessary building
blocks.
Approved by FDA as food supplements
Not recommended by AAOS for OA

41. Chondroprotactive drugs
• Recommendations for or against Glucosamine
and/or Chondroitin sulfate or hydrochloride
are inconclusive for symptomatic OA of the
knee.
• There are proteoglycons synthesised by
chondrocytes in normal cartilage, there
supplementation logically have no effect in
disease progression.
FDA – food supplements

42. Diacerein (interleukin alpha 1 blocker)
• The IL-1 mediated enhancement of collagenase
production in chondrocytes is actively inhibited by
Diacerein.
• Diacerein has a different spectrum of antiinflammatory activity to that of the classical NSAIDs
naproxen and ibuprofen. While NSAID drugs inhibit
cyclooxygenase, diacerein does not inhibit
prostaglandin synthesis.
Inflammation is a response to disease and not the cause of disease

43. Diacerein
• Inhibition of IL-1, which distinguishes it from
other drugs indicated for the treatment of
osteoarthritis
• Stimulate anabolic processes.
• Diacerein and rhein inhibit the production of
IL-1b by chondrocytes in the superficial and
deep zones of human osteoarthritic cartilage
Anti-inflammatory reduce pain in brain not at knee

44. Role of Vitamin D and calcium
• A weak quadriceps due to Vitamin D
deficiency can be a precipitating factor for
early OA.
• A weak muscle increases mechanical
overloading on the knee articular surface.
• There can be disuse quadriceps weakness due
to pain.
• Vitamin D and calcium can be supplemented.

45. Osteoporosis & Osteoarthritis
•
•
•
•
Do not coexist together.
BMI 22 & > – OA
BMI below 22 (< 19) OS
Both can have a presenting symptom of
difficulty in getting up from sitting position
(typical of OA). This is due to Vitamin D
deficiency.

46. Injections
• Visco supplementations.
• Hydrocortisone.
• Benefit of viscosupplementation in patients
with symptomatic osteoarthritis is minimal or
nonexistent.
• Increased risks for serious adverse events and
local adverse events, the administration of
these preparations should be discouraged.

47. Intra-Articular Injections
• Intra-articular corticosteroids for short-term pain
relief for patients with symptomatic OA of the
knee.
• AAOS does not recommend the routine use of
intra-articular corticosteroids, for patients with
mild to moderate symptomatic OA of the knee.
• It may give symptomatic relief for few months.
• It can precipitate early damage in young patients
due to over activity on a damaged cartilage.
Rest for 2 -3 weeks after a shot

48. Corticosteroids
• Known anti-inflammatory, but their
mechanism of action is not completely known.
• Corticosteroids inhibit the accumulation of
inflammatory cells, such as leukocytes and
neutrophils.
• They prevent phagocytosis, lysosomal enzyme
release, and the synthesis of several
inflammatory mediators.
Ideal for elderly who are sedentary and not fit for surgery

49. Hyaluronic acid
• The name derived from the Greek word hyalos
meaning vitreous, and uronic acid.
• Normally secreted in the synovium by Type B
synoviocytes.
• Act as a lubricant and shock absorber.
• It is made of approximately 12,500 disaccharide
units and have molecular weight of 5 million
daltons.
• In pathological condition, the concentration and
molecular weight of indigenous hyaluronic acid is
reduced.

50. Hyaluronic acid
• Hyaluronic acid has both viscous and elastic
properties.
• At high shear forces, hyaluronic acid exhibits
increased elastic properties and reduced
viscosity.
• The opposite is true with low shear forces.
• Therefore, hyaluronic acid acts as a shock
absorber during fast movements, and a
lubricant during slow movement.

51. Hyaluronic acid
• The use of HA as VS began in the late 1960s by
Biotrics, Inc. The material was taken from human
umbilical cord.
• The chondro-protective effects of HA has not
been clinically proven.
• The FDA classified VS as medical devices;
• AAOS does not recommend it for patients with
mild to moderate symptomatic OA of the knee.
• Can be used for the patient who are on waiting
list for TKR.

52. Arthroscopy Procedures
•
•
•
•
•
•
•
•
•
Joint debridement
Removal of mechanical obstructions,
Joint lavage
Drilling of sclerotic lesions
Abrasion chondroplasty
Autologous chondrocyte transplantation
Mosaicplasty
Cartilage transplantation
Regenerative medicine

53. Arthroscopy
• Recommendations for performing arthroscopy
with debridement or lavage in patients with a
primary diagnosis of symptomatic OA of the
knee is not conclusive.
• Arthroscopic partial meniscectomy or loose
body removal is advisable, in patients who
have primary signs and symptoms of a torn
meniscus and/or a loose body.

54. Cartilage Replacement
• Autologous transplantation – from one place
to another in same knee. (Mosiacplasy)
• Autologous – grow in lab – transplantation
(two stage – harvesting – growth in lab –
reimplantation with or without matrixes)
• Stem cell – cartilage grow in lab –
transplantation (iPP, induced mesenchymal
pleuripotant stem cells – from bone marrow,
skin, and other donar sites.

55. Abrasion and Micro-fracture surgery
• Abrasive procedures aimed at triggering
cartilage production.
• Abrasion, drilling, and micro fractures rely on
the phenomenon of spontaneous repair of the
cartilage tissue following vascular injury to the
subchondral bone, which allow inflow of
naturally circulating stem cells (progenitors) in
the blood.
Proteoglycon are resistant to neovascularization

56. Autologous chondrocyte transplantation
Mosaicplasy - Technique
• The patient’s chondrocytes are removed
arthroscopically from a non load-bearing area.
• 10,000 cells are harvested and grown in vitro
for approximately six weeks until the
population reaches 10-12 million cells.
• Then these cells are injected into the cartilage
defect of the patient.

57. Autologous chondrocyte transplantation
Mosaicplasy - Technique
• These cells are held in place by a periosteal
flap, which is sutured over the area to serve as
a watertight lid.
• The implanted chondrocytes then divide and
integrate with surrounding tissue and
potentially generate hyaline-like cartilage.

58. Technique cont……
• A second generation technique, called Carticel
II uses a "fleece matrix" implanted with
chondrocyte cells that is arthroscopically
inserted into the joint. This procedure is
known as matrix autologous chondrocyte
implantation or (MACI) and is available in
Germany, UK, and Australia

59. Mosaicplasy

60. Chondroplasty

61. Chondroplasty

62. Corrective -Surgery
• High Tibial Osteotomy
• Realignment osteotomy is an option in active
patients with symptomatic unicompartmental
OA of the knee with mal-alignment.
• It can be done as an isolated procedure or
may be combined with chondroplasty or
menisectomy.

63. High tibial osteotomy
• The fundamental goals is to unload diseased
articular surfaces and to correct angular
deformity at the tibiofemoral articulation.
• HTO is effective for managing OA with varus,
osteochondritis dissecans, osteonecrosis,
posterolateral instability, and chondral
resurfacing.

64. High Tibial Osteotomy
• Improved instrumentation and fixation plates for
medial opening / lateral closing wedge
osteotomy,
• Dynamic external fixation for medial opening
wedge osteotomy,
• Concomitantly correcting mal-alignment when
performing chondral resurfacing procedures (ie,
autologous chondrocyte transplantation,
mosaicplasty, and microfracture).

65. High tibial osteotomy
• A valgus alignment of 6° and 10° of valgus,
regardless of condylar width, baseline
tibiofemoral alignment, body weight, or
chondral defect size, demonstrated complete
unloading of the medial compartment, which
favors cartilage repair at these alignments.

66. High Tibial Osteotomy

67. High Tibial Oateotomy

68. Spontaneous correction due to stress
fracture

70. Replacement Surgery
•
•
•
•
•
Total knee replacement
Patient’s specific knee replacement
Unicondylar replacement
Patello-femoral replacement
Meniscus replacement
Metallurgy - replacing biology
Metallurgy has a date of expiry

71. Uni-condylar replacement
Patello – femoral replacement
oxidised zirconium” oxinium”

72. Our experience
• We did our first THR in 1985.
• We were amongst the first to start TKR on a
routine basis way back 1993.
• We conducted a national workshop on THR in
1987.

75. INOR TKR

77. Bilateral TKR

78. An interesting case
1995 - 2012

79. Tissue engineering
• Defined as the application of engineering
science and technology to the combined field
of cellular and molecular biology with the goal
of regulating the growth, differentiation, and
metabolic activity of cells that are either
transplanted or recruited to heal or
regenerate a joint surface

80. Regeneration: Growth of New Cartilage
• Because of the limited capacity of cartilage to heal, a
more attractive approach is to transplant cells or a
tissue with chondrogenic potential into the joint (socalled biological resurfacing).
• Bentley and Greer were apparently the first to show
that chondrocytes could be transplanted into articular
cartilage defects and improve healing compared with
that in controls.
• Chondrocytes, stem cells, an undifferentiated tissue
(such as periosteum or perichondrium) containing stem
cells or chondrocyte precursors, or any combination of
these can be used.

81. Autogenous periosteal grafts
• Osteochondral defects in the knees of rabbits
that were resurfaced with use of autogenous
periosteal grafts healed with predominantly
hyaline cartilage containing more than 90
percent type-II collagen and normal water,
proteoglycan, chondroitin, and keratan sulfate
contents.

82. Autogenous periosteal grafts
• A patch of periosteum sewn over an articular
defect in the knee. A small volume of
autogenous chondrocytes, which had been
grown in culture for two to three weeks after
having been isolated from biopsy specimens
of cartilage obtained during an earlier
arthroscopy, was injected beneath the patch.
The second stage of the procedure was
performed through an open arthrotomy.

85. Experimental
• intra-articular injection of growth factors, such as
transforming growth factor-ß1, insulin-like
growth factor-1, bone morphogenetic proteins,
fibroblast growth factor, and epidermal growth
factor.
• A single injection of transforming growth factorß1 stimulated a persistent increase in cartilage
proteoglycan synthesis and content, but multiple
injections induced substantial synovitis, synovial
hyperplasia, and formation of osteophytes .

86. Scaffolds
• The many substances that have been tested
include nonabsorbable materials, such as
carbon fiber, Dacron, and Teflon; porous metal
plugs; absorbable polymers or copolymers,
such as polyglycolic acid and polylactic acid;
fibrin and collagen.

87. Future - Dolly

88. Dolly (5 July 1996 – 14 February
2003) was a female domestic sheep,
and the first mammal to be cloned
from an adult somatic cell, using the
process of nuclear transfer.
Dolly was born on 5 July 1996 to
three mothers (one provided the
egg, another the DNA and a third
carried the cloned embryo to term).
She was created using the
technique of somatic cell nuclear
transfer, where the cell nucleus
from an adult cell is transferred into
an unfertilised oocyte (developing
egg cell) that has had its nucleus
removed. The hybrid cell is then
stimulated to divide by an electric
shock, and when it develops into a
blastocyst it is implanted in a
surrogate mother.

89. Dolly
• Normal age of sheep is around 11-12 years.
• Dolly lived for six years.
• It was speculated that Dolly's genetic age was
six years, the same age as the sheep from
which she was cloned. The basis for this idea
was the finding that Dolly's telomeres were
short, which is typically a result of the ageing
process.

90. Nobel Prize in medicine 2012
Shinya Yamanaka & Sir John B. Gurdon
Discovered that the developmental clock could be
turned back in mature cells, transforming them into
immature cells with the ability to become any tissue
in the body — pleuripotent stem cells. (iPS)

91. Illuminating
Chondrogenesis: Pictured
are murine induced
pluripotent stem cells
undergoing
chondrogenesis. In
addition to type II
collagen (red), F-actin
(magenta), and nucleus
(blue), upon
differentiation cells
express green fluorescent
protein under the control
of a chondrocyte-specific
promoter. Diekman et al.
employed cell sorting to
produce tissue-engineered
cartilage for potential use
in treating cartilage
defects or discovering new
drugs for osteoarthritis.

92. Future
• Some day we will be able to replace a part or
the whole articular cartilage by new cartilages
cells developed in lab by induced
Mesenchymal Stem cells.
• It will be something like changing a punctured
tire as and when needed.

93. Journey Continue………….

94. It is a crime to think “small”
- A.P.J. Abdul Kalam

96. DISCLAIMER
• Information contained and transmitted by this presentation is
based on personal experience and collection of cases at
Choithram Hospital & Research centre, Indore, India, during
last 34 years.
• It is intended for use only by the students of orthopaedic
surgery.
• Views and opinion expressed in this presentation are personal.
• Depending upon the x-rays and clinical presentations, viewers
can make their own opinion.
• For any confusion please contact the sole author for
clarification.
• Every body is allowed to copy or download and use the
material best suited to him. I am not responsible for any
controversies arise out of this presentation.
• For any correction or suggestion please contact
naneria@yahoo.com