Osteoarthritis of Knee

Vinod Naneria

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.

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

Knee joint of an Elephant

Knee joint of a bird

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

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.

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

Chondrocyte

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.

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.

Cartilage Matrix Organization Zones

Superficial (gliding) cells are horizontal,

Middle (transitional) cells are crisscross,
Deep (radial) cells are perpendicular,
Calcified cartilage.
Subchondral bone.

Articular Cartilage Matrix Organization

Zones
Morphologic,
biochemical &
functional differences
between zones based
on depth from articular
surface.
Superficial shearing
Deep - compression

Normal Articular Cartilage

Articular cartilage in Osteoarthritis

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

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.

Sequence of events

Superficial layer abrasion,

Superficial layer fissuring,
Attempt at repair by chondrocytes,
Excess production of new cells and matrixes,
Deep layer cleavage.

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.

Treatment chart

Medical

Surgical
Regenerative

Treatment Option - Medical

Life style
modifications

Physiotherapy
Nsaids
Braces

Supports

Treatment Option - invasive

Injections (Hydrocortisone Hyaluronic acid)
Arthroscopy (debridement)
Alignment corrective surgery (HTO)
Total / partial joint replacement

Regenerative medicine ( cartilage transplantation)

Life style modification:

Sitting on ground
Squatting
Sit-ups
Climbing
Commode
High heels
Shoe modification (lateral
wedges)
Cane/walker
Braces

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.
Dont scratch your wounds

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.

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

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.

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

overdoing can damage

the knee further.

Free cycling for 5 10

minutes at zero resistance.
Can be repeated twice a day.

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

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.

Patello-femoral pain

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

Life style modification

Unilateral joint unloading
braces are not
recommended for general
use. They are commonly
prescribed for unicompartmental disease of
the knee.

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.

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

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

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

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

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

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

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.

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.

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.

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

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

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.

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.

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.

Arthroscopy Procedures

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

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.

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.

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

Autologous chondrocyte transplantation

Mosaicplasy - Technique
The patients 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.

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.

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

Mosaicplasy

Chondroplasty

Chondroplasty

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.

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.

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).

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.

High Tibial Osteotomy

High Tibial Oateotomy

Spontaneous correction due to stress

fracture

Replacement Surgery

Total knee replacement

Patients specific knee replacement
Unicondylar replacement
Patello-femoral replacement
Meniscus replacement
Metallurgy - replacing biology

Metallurgy has a date of expiry

Uni-condylar replacement

Patello femoral replacement

oxidised zirconium oxinium

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.

INOR TKR

Bilateral TKR

An interesting case

1995 - 2012

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

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.

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.

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.

Experimental
intra-articular injection of growth factors, such as
transforming growth factor-1, insulin-like
growth factor-1, bone morphogenetic proteins,
fibroblast growth factor, and epidermal growth
factor.
A single injection of transforming growth factor1 stimulated a persistent increase in cartilage
proteoglycan synthesis and content, but multiple
injections induced substantial synovitis, synovial
hyperplasia, and formation of osteophytes .

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.

Future - Dolly

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.

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.

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)

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.

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.

Journey Continue.

It is a crime to think small

- A.P.J. Abdul Kalam

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