AndrasHeijink • Andreas H. Gomoll •Henning Madry • MatejDrobnicˇ • Giuseppe Filardo •Joa˜oEspregueira-Mendes • C. Niek Van Dijk,Knee Surg Sports TraumatolArthrosc (2012) 20:423–435DOI 10.1007/s00167-011-1818-0
Viscosupplementation for Osteoarthritis of the Knee: A Systematic Review and Meta-analysis ONLINE FIRSTAnne W.S. Rutjes, PhD; Peter Jüni, MD; Bruno R. da Costa, MSc; Sven Trelle, MD; EvelineNüesch, PhD; and Stephan Reichenbach, MD, MSc[+-] Article and Author InformationAnn Intern Med. 12 June 2012
Subchondral Drilling, Abrasion, or Microfracture Articular chondrocytes reside in an avascular environment and do not usually effect healing when damage to the joint surface is limited to the layer of cartilage(27,47,129). Many investigators have attempted to stimulate cartilage-healing by drilling, abrading, or producing so-called microfractures in the subchondral bone(2,3,19,70,102,116,130,138,191,236). All of these techniques have in common the goal of recruiting pluripotential stem cells from the marrow by penetration of the subchondral bone.
Survivorship of high tibialosteotomy in the treatment of osteoarthritis of the knee Finnish registry-based study of 3195 kneesT. T. Niinimäki, MD, Orthopaedic Surgeon1 ; A. Eskelinen, MD, PhD, Orthopaedic Surgeon2; B. S. Mann, FRCS(Tr & Orth), Orthopaedic Surgeon3; M. Junnila, MD, Orthopaedic Surgeon4; P. Ohtonen, MSc, Statistician1; and J. Leppilahti, MD, PhD, Orthopaedic Surgeon1+ Author Affiliations1Oulu University Hospital, PL 21, 90029 OYS, Oulu, Finland. 2Coxa Hospital for Joint Replacement, PL 652, 33101 Tampere, Finland. 3Southmead Hospital, Southmead Road, Westbury-on-Trym, Bristol BS10 5NB, UK. 4Turku University Hospital, PL52, 20521 Turku, Finland. Correspondence should be sent to Mr T. T. Niinimäki; e-mail: firstname.lastname@example.orgAbstractPrevious studies from single centres or single-surgeon series report good early and mid-term results for high tibialosteotomy (HTO) in the treatment of osteoarthritis of the knee. However, the survivorship of HTO at a national level is unknown. This registry-based study included 3195 high HTOs performed between 1987 and 2008. Kaplan-Meier analysis revealed an overall survivorship of 89% (95% confidence interval (CI) 88 to 90) at five years and 73% (95% CI 72 to 75) at ten years, when conversion to total knee replacement was taken as the endpoint. Females and patients aged > 50 years had worse survivorship than males or patients aged ≤ 50 years (hazard ratio (HR) 1.26 (95% CI 1.11 to 1.43) and HR 1.41 (95% CI 1.23 to 1.64), respectively). The survivorship of HTOs performed between 1998 to 2008 was worse than for those performed between 1987 and 1997.
Improvements in the surgical technique of total knee replacement (TKR) are continually being sought. There has recently been interest in three-dimensional (3D) pre-operative planning using magnetic resonance imaging (MRI) and CT. The 3D images are increasingly used for the production of patient-specific models, surgical guides and custom-made implants for TKR. The users of patient-specific instrumentation (PSI) claim that they allow the optimum balance of technology and conventional surgery by reducing the complexity of conventional alignment and sizing tools. In this way the advantages of accuracy and precision claimed by computer navigation techniques are achieved without the disadvantages of additional intra-operative inventory, new skills or surgical time.
Mr Rees is one of a few surgeons in the UK currently using a revolutionary new material called oxidised zirconium also known as oxinium. Oxinium is produced as a result of a chemical process that allows oxygen to absorb into zirconium metal thereby changing only its surface from metal to ceramic. This new material may be considered for young patients (under 65 years of age) undergoing total knee replacement.The actual procedure involves two separate operations. The first involves a day case knee arthroscopy during which the cartilage defect is visualised. The defect is usually on the femur but can be located on the undersurface of the patella or kneecap. The defect has to have certain characteristics in order for the procedure to be suitable in terms of its size (less than 10cm2) and exact location. A very small biopsy of undamaged cartilage is taken from the side of the knee in an area that will not compromise the knee’s function.The biopsy is then immediately transferred into a transport container and sent to a laboratory in Austria where the biopsy is mixed with a liquid collagen matrix (the protein building blocks of cartilage) and incubated for two weeks. A transplant (the new cartilage) is then formed and is fully adjustable in size and thickness to suit the exact defect in the injured knee.At the second operation the knee is opened to expose the defect, which is prepared, and the edges freshened up. The tailor-made transplant is then attached with biological glue called fibrin glue onto the base of the cartilage defect. The operation usually takes about one hour. It will involve a 1-2 day stay in hospital.
team of Duke Medicine researchers has engineered cartilage from induced pluripotent stem cells that were successfully grown and sorted for use in tissue repair and studies into cartilage injury and osteoarthritis. The finding is reported online in the Proceedings of the National Academy of Sciences, and suggests that induced pluripotent stem cells, or iPSCs, may be a viable source of patient-specific articular cartilage tissue."This technique of creating induced pluripotent stem cells -- an achievement honored with this year's Nobel Prize in medicine for Shimya Yamanaka of Kyoto University -- is a way to take adult stem cells and convert them so they have the properties of embryonic stem cells," said FarshidGuilak, PhD, Laszlo Ormandy Professor of Orthopaedic Surgery at Duke and senior author of the study."Adult stem cells are limited in what they can do, and embryonic stem cells have ethical issues," Guilak said. "What this research shows in a mouse model is the ability to create an unlimited supply of stem cells that can turn into any type of tissue -- in this case cartilage, which has no ability to regenerate by itself."Articular cartilage is the shock absorber tissue in joints that makes it possible to walk, climb stairs, jump and perform daily activities without pain. But ordinary wear-and-tear or an injury can diminish its effectiveness and progress to osteoarthritis. Because articular cartilage has a poor capacity for repair, damage and osteoarthritis are leading causes of impairment in older people and often requires joint replacement.In their study, the Duke researchers, led by Brian O. Diekman, PhD, a post-doctoral associate in orthopaedic surgery, aimed to apply recent technologies that have made iPSCs a promising alternative to other tissue engineering techniques, which use adult stem cells derived from the bone marrow or fat tissue.One challenge the researchers sought to overcome was developing a uniformly differentiated population of chondrocytes, cells that produce collagen and maintain cartilage, while culling other types of cells that the powerful iPSCs could form.To achieve that, the researchers induced chondrocyte differentiation in iPSCs derived from adult mouse fibroblasts by treating cultures with a growth medium. They also tailored the cells to express green fluorescent protein only when the cells successfully became chondrocytes. As the iPSCs differentiated, the chondrocyte cells that glowed with the green fluorescent protein were easily identified and sorted from the undesired cells.The tailored cells also produced greater amounts of cartilage components, including collagen, and showed the characteristic stiffness of native cartilage, suggesting they would work well repairing cartilage defects in the body."This was a multi-step approach, with the initial differentiation, then sorting, and then proceeding to make the tissue," Diekman said. "What this shows is that iPSCs can be used to make high quality cartilage, either for replacement tissue or as a way to study disease and potential treatments."Diekman and Guilak said the next phase of the research will be to use human iPSCs to test the cartilage-growing technique."The advantage of this technique is that we can grow a continuous supply of cartilage in a dish," Guilak said. "In addition to cell-based therapies, iPSC technology can also provide patient-specific cell and tissue models that could be used to screen for drugs to treat osteoarthritis, which right now does not have a cure or an effective therapy to inhibit cartilage loss."In addition to Guilak and Diekman, study authors include Nicolas Christoforou; Vincent P. Willard; Alex Sun; Johannah Sanchez-Adams; and Kam W. Leong.The National Institutes of Health (AR50245, AR48852, AG15768, AR48182, Training Grant T32AI007217) and the Arthritis Foundation funded the study.Brian O. Diekman, Nicolas Christoforou, Vincent P. Willard, Haosi Sun, Johannah Sanchez
Osteoarthritis of the Knee joint
Osteoarthritis of Knee
• The name osteoarthritis comes from three
Greek words meaning bone, joint, and
• It is a progressive disorder of the joints
caused by gradual loss of articular cartilage
with secondary changes in the bone and
Osteoarthritis – oldest
• Remains of the
show evidence of
million years ago.
• Earliest evidence of
has been found in the
remains of Neanderthal
man. ( 0.6 – 0.03 M)
New man from a valley
• 10% adult population
across the world
• About a quarter of all
consultations in general
• Symptoms of the disease
manifest much late.
• There is no known cure of
Progress can be controlled or delayed
Articular cartilage - unique
No blood supply,
No lymphatic drainage,
No neural elements,
Chondrocytes are shielded from
• 60 – 80% of human cartilage is water.
• Chondrocytes are the
sites of cartilage and
are responsible for the
maintenance of the
surrounding matrix .
• Protein macromolecules
that contain characteristic
helical amino acid chains.
• Provide the tensile strength
and form of cartilage
• Proteoglycans are attached
to the collagen framework.
• 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,
Articular Cartilage Matrix Organization
between zones based
on depth from articular
• Superficial – shearing
• Deep - compression
Pathogenesis of osteoarthritis of the knee
• Chronological age is the single most important
• In younger patients unfavourable
biomechanical environment at the joint is the
• 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
• 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 Option - Medical
Treatment Option - invasive
Injections (Hydrocortisone – Hyaluronic acid)
Alignment corrective surgery (HTO)
Total / partial joint replacement
Regenerative medicine ( cartilage transplantation)
Life style modification:
Sitting on ground
Shoe modification (lateral
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
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
Pain: Heat therapy, SWD, US
ROM: bicycle, CPM, free swing, Stretching
Correction of deformity,
Strengthening of Quad + Hamstrings
Improvement in gait & Balance,
Resistive exercises – with weights?
Choice of modalities should be left to physiotherapist
Exercises – 4 Ds
• Golden rules:
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.
damage the knee
• 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
• Can be repeated twice a day.
• Bicycling for knee arthritis is not a weight
reduction tool, overdoing can damage the
ZERO - RESISTANCE
overdoing can damage
the knee further.
Free cycling for 5 – 10
minutes at zero resistance.
Can be repeated twice a day.
• Soft surface – in garden or wooden platform
• Avoid high impact.
• Climbing uphill
increases loading on the
damaged cartilage and
at times precipitate
acute pain and effusion
• It is a high impact
• Specially precipitate PF
Life style modification
• Unilateral joint unloading
braces are not
recommended for general
use. They are commonly
prescribed for unicompartmental disease of
• 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
• Patients with symptomatic OA of the knee can
receive one of the following analgesics for
pain unless there are contraindications to this
• NSAIDs only in acute flare for short term.
• Avoid them in cases of hypertension, CRF and
• 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
Approved by FDA as food supplements
Not recommended by AAOS for OA
• Recommendations for or against Glucosamine
and/or Chondroitin sulfate or hydrochloride
are inconclusive for symptomatic OA of the
• There are proteoglycons synthesised by
chondrocytes in normal cartilage, there
supplementation logically have no effect in
FDA – food supplements
Diacerein (interleukin alpha 1 blocker)
• The IL-1 mediated enhancement of collagenase
production in chondrocytes is actively inhibited by
• 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
Inflammation is a response to disease and not the cause of disease
• Inhibition of IL-1, which distinguishes it from
other drugs indicated for the treatment of
• 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
• A weak muscle increases mechanical
overloading on the knee articular surface.
• There can be disuse quadriceps weakness due
• 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
• Visco supplementations.
• Benefit of viscosupplementation in patients
with symptomatic osteoarthritis is minimal or
• Increased risks for serious adverse events and
local adverse events, the administration of
these preparations should be discouraged.
• Intra-articular corticosteroids for short-term pain
relief for patients with symptomatic OA of the
• 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
• Known anti-inflammatory, but their
mechanism of action is not completely known.
• Corticosteroids inhibit the accumulation of
inflammatory cells, such as leukocytes and
• They prevent phagocytosis, lysosomal enzyme
release, and the synthesis of several
Ideal for elderly who are sedentary and not fit for surgery
• The name derived from the Greek word hyalos
meaning vitreous, and uronic acid.
• Normally secreted in the synovium by Type B
• Act as a lubricant and shock absorber.
• It is made of approximately 12,500 disaccharide
units and have molecular weight of 5 million
• In pathological condition, the concentration and
molecular weight of indigenous hyaluronic acid is
• Hyaluronic acid has both viscous and elastic
• At high shear forces, hyaluronic acid exhibits
increased elastic properties and reduced
• 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.
• The use of HA as VS began in the late 1960s by
Biotrics, Inc. The material was taken from human
• 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.
• 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.
• 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
• 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
Proteoglycon are resistant to neovascularization
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.
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.
• 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
• 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
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
High Tibial Osteotomy
• Improved instrumentation and fixation plates for
medial opening / lateral closing wedge
• Dynamic external fixation for medial opening
• 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.
Total knee replacement
Patient’s specific knee replacement
Metallurgy - replacing biology
Metallurgy has a date of expiry
• 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
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.
• 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
• 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 .
• 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.
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
• 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
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)
are murine induced
pluripotent stem cells
addition to type II
collagen (red), F-actin
(magenta), and nucleus
express green fluorescent
protein under the control
of a chondrocyte-specific
promoter. Diekman et al.
employed cell sorting to
cartilage for potential use
in treating cartilage
defects or discovering new
drugs for osteoarthritis.
• 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.
It is a crime to think “small”
- A.P.J. Abdul Kalam
• 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
• 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
• 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