Vinod Naneria

Osteoarthritis of Knee

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.

Don’t 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

overdoing can damage the knee further.

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.

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 uni-compartmental 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 non-pharmacological 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 supplementsNot 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 anti-inflammatory 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 transplantationMosaicplasy - 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.

Autologous chondrocyte transplantationMosaicplasy - 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• Patient’s specific knee replacement• Unicondylar replacement• Patello-femoral replacement• Meniscus replacement

Metallurgy - replacing biology

Metallurgy has a date of expiry

Patello – femoral replacement

oxidised zirconium” oxinium”

Uni-condylar replacement

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 (so-called 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-ß1, insulin-like growth factor-1, bone morphogenetic proteins, fibroblast growth factor, and epidermal growth factor.

• A single injection of transforming growth factor-ß1 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