Osteoarthritis

Definition

A degenerative joint disorder in which there is progressive loss of articular cartilage accompanied by new bone formation and capsular fibrosis.

Aetiology

Still obscure
Increased frequency with age but not an expression of senescence
Progression of cartilage lesions probable requires stiffened subchondral bone
Cartilage aging ® splitting and flaking of the surface and decreased cellularity, decreased proteoglycan ground substance and loss of elasticity with a decrease in breaking strength
Mechanical changes in subchondral bone ® stiffer and transmits more load to the cartilage
May be biological change secondary to a disturbance in lubrication of the joint and hence nutrition of cartilage
Two forms of degeneration:
  1. Limited cartilage loss seen mainly away from load bearing areas and probably due to wear and tear.
  2. Progressive cartilage destruction always maximal in the major load bearing area and associated with symptomatic OA

Hereditary aspects of OA:
  1. Joint congruity, CSH / CDH / DDH, Perthes, SFCE
  2. Gait and posture
  3. Joint / ligament laxity
  4. Pagets, inflammatory arthropathies

Incidence

People > 60 years old ® moderate to severe OA in 8%
25% of females and 16% of males have symptomatic OA
80% people > 80 years have radiological evidence of OA
Male = Female incidence but females more symptomatic
The hip, knee and spine most commonly affected
OA of the hip more common in males than females and often unilateral, 20% eventually ® involvement of the other side

Classification

Primary Osteoarthritis: (When no cause is obvious)

Poly-arthritis affecting finger joints, (chiefly distal, thumb (basal), big toe (MTP) and often also the knees and facet joint of the spine
Usually starts in the hands but many joints become involved
Stiffness and deformity may be marked but pain usually mild or in time becomes painless
Mainly affects post menopausal women and has a marked familial incidence
Heberdens nodular arthropathy ® distal IP joint of the hands only
Sometimes, particularly in men the DIP joint changes are absent but other joints symmetrically involved and spinal changes pronounced
Primary generalised OA is associated with increased incidence of CTS and tenosynovitis
The arthropathy of the individual joints has the same pathology as mono-articular OA
Differentiate spinal changes from DISH, and distal IP joint changes from psoriatic arthropathy and gout

Secondary Osteoarthritis: (When it follows a demonstrable abnormality)

Secondary OA estimated to account for 80% of osteoarthritis
Articular degeneration results from a disparity in the stress applied to articular cartilage and the ability of the cartilage to withstand that stress.
Solomon (1976); Aetiology of OA
  1. Failure of normal cartilage subject to abnormal or incongruous loading for long periods
  2. Damaged or defective cartilage failing under normal conditions of loading
  3. Break up of articular cartilage due to defective subchondral bone

Classification of cartilage degeneration: (Jackson)
Class 1: Softening of articular cartilage
Class 2: Fibrillation and fissuring of articular cartilage
Class 3: Partial thickness cartilage loss, clefts and chondral flaps
Class 4: Full thickness cartilage loss with bone exposed

Clinically

Usually history of previous injury or pathology evident
History of intermittent disability
Usually present with pain
May experience decreased pain as the disease ® decreased ROM
Often worse on rising from bed and at the end of the day, aggravated by activity
Exaggerated by extremes of movement
Early ® relieved by rest, later ® pain at rest

Source of pain Helal (1965)

  1. Capsular; due to stretch at extremes of movement
  2. Muscular: following effort
  3. Venous congestion: ® rest pain?

Movement may be associated with crepitus
Joint effusion or osteophytes may be evident
Muscle wasting may also be a feature
Deformity may precede the development of OA, but may also result from secondary muscle imbalance, capsular contracture or joint instability.
In the hip abduction, extension and internal rotation are affected first
Hip pain referred to the knee due to the fact that the obturator nerve supplies both joints (the sciatic and femoral do as well)

X-Rays

Joint space narrowing
Sub-articular sclerosis
Bone cysts
Osteophytes
Bone density is either normal or increased
There may be evidence of other pathology eg, old trauma, congenital anomalies, RA, chondrocalcinosis etc
Rapid and severe joint changes may occur, especially in patients taking analgesics and NSAIDs

Pathology

Capsule

Capsular ligament is supplied by both myelinated and non-myelinated nerves, the synovial layer by only non-myelinated nerves

Synovium

Secrete Hyaluronate (+ lubricin)

Two cell types
Type A: phagocytosis
Type B: secretory role
Complete absence of a basement membrane
Regulates movement of solutes, electrolytes and proteins
Synovial fluid a dialyslate of plasma and hyaluronate but has less high molecular weight proteins (eg fibrinogen) and more low molecular weight protein (eg albumin)
Cartilage is connective tissue derived from the mesenchyme
Articular cartilage is avascular, aneural and alymphatic, and a small number of chondrocytes are surrounded by a large quantity of extracellular matrix
The structure of this intercellular matrix determines the type of cartilage

Normal cartilage matrix

70 - 80% water
Of the remainder
70% is collagen
20% Proteoglycans
10% non collagenous protein

Proteoglycans: (Mucopolysaccharides)

Hyaluronic acid secreted by the Type B cells of the synovium and finds its way into the cartilage
Gylcosaminoglycans, chondroitin and keratan sulphate
Proteoglycan aggregates are complex in structure consisting of a long protein core with a molecular weight up to 300,000 to which are attached about 100 carbohydrate side chains of chondroitin 4 & 6 or keratan sulphate
These proteoglycan complexes aggregate in groups of 20 to 50 by attachment via a link protein to hyaluronic acid filament
The relative amounts of each varying with age and area of cartilage
Chondroitin 4 is higher in children
Keratin sulphate is higher in older individuals and in the deeper parts of articular cartilage
High fixed negative charge ® hold enormous amounts of water ® shock absorbing properties
Proteoglycans are strongly bound to collagen and can withstand compression
Responsible for elasticity and resistance to compression of articular cartilage
Increased concentration in deeper layers of cartilage
There is a decrease in the size of the proteoglycan aggregate with age but no change in the hyaluronic acid back-bone
Constant turnover of the matrix is controlled by the chondrocyte
Decreased proteoglycan leads to decreased stiffness (chondromalacia) and collagen will tend to break and fray (fibrillate)
Proteoglycan synthesis is increased by growth hormone (somatomedins), PTH and calcitonin, and decreased by oestrogen, testosterone and glucocorticoids
Tamoxifen has been shown to decrease osteoarthritis in experiments with the rabbit model

Collagen

At least 14 types of collagen have been identified
Fibre network largely made up of Type II collagen representing 90-95% of all collagen found in cartilage
Characterised by 3 ?1 chains in a triple helix
Has more hydroxylysine residues than type I ® finer diameter of these collagen fibres
There is more collagen at the surface, and it is of finer diameter and tighter weave
Collagen is continuous across the tidemark
50% dry weight and 90% total protein content of cartilage
Types I, IV, IX, X & XII are also present
Arc shaped arrangement supported by additional collagen on the surface ® tensile strength and acts as a constrainer of the proteoglycan matrix
Adult articular cartilage turnover time is around 300 days, this decreases markedly in joint inflammation (particularly at a cartilage pannus interface)

Chondrocytes

Make up 5% or less of the volume of articular cartilage
Metabolically active ® producing and maintaining the matrix
Most matrix synthesis occurring in the deep non-calcified zone
Respond to increased compressive force by significantly increasing production of proteoglycan
Nourished principally by diffusion from synovial fluid, a lesser amount comes from subchondral bone
Tissue environment ® higher level of carbon dioxide and cells tolerate lower O2 tension (relatively insensitive to hypoxia)
Cartilage cells survive up to 48 hours or longer after death
As cartilage is avascular unable ® inflammatory response
Cartilage has limited potential for repair

Functions of Articular Cartilage

Must withstand high loads (2-7 times body weight)

Histology of Articular Cartilage

Average thickness 2-4mm
Consists of chondrocytes enmeshed in super hydrated matrix of collagen and proteoglycans
Cartilage is keyed into irregular surface of bone
Cartilage adjacent to bone is calcified and the "tidemark" represents the junction between calcified and non calcified cartilage
Thin fibrous membrane (lamina splendens) on surface of articular cartilage (probably an artefact)
Fluid flux or creep with indentation / loading of cartilage takes up to 4 hours therefore not seen during walking etc

Zones of articular cartilage

  1. Superficial (tangential) Zone ® cells are flat and parallel to the surface
  2. Transitional zone ® cells are arranged randomly
  3. Deep or radial zone ® cells are smaller and arranged in short columns perpendicular to the surface
  4. Calcified zone cells are pyknotic

Chondrocytes are metabolically active in all zones but do not synthesise DNA or divide unless their micro-environment is altered
There is however less metabolic activity in the calcified zone
Chondrocyte synthesis of glycosamino-glycans varies depending on the load they are subjected to
Intermittent load and motion essential for cartilage nutrition, immobilisation ® atrophy of cartilage
Water flux occurs under load ® cartilage nutrition
The compressive stiffness of cartilage is directly proportional to the aggregate (proteoglycan) content
Self lubrication
High load ® squeeze film
Low load ® boundary lubrication
Coefficient of friction of 0.002, (the best artificial joint is 30 times higher)

Response to injury

  1. Injury limited to cartilage ® no healing process
  2. Injury extending to subchondral bone ® fibro-cartilage repair occurs (fibro-cartilage = collagen with little proteoglycan)

Superficial injury:
Ghost cells (lacunae with dead chondrocytes)
Within 24/24 mitotic activity is seen in the cartilage cells adjacent to the margins of the defect associated with increased synthesis of matrix components
Within 2/52, back to normal levels of activity with no further progression to healing
Short lived inadequate response which fails to provide sufficient numbers of new cells or matrix to repair even a small defect. ® But no progression to OA
Deep Penetrating injury: (crosses the tidemark)
Damage involves vasculature ® granulation tissue
Bone heals up to its old level
At the margins of the defect chondrocytes show a brief burst of mitotic and synthetic activity
Initially the tissue looks like hyaline cartilage but has an increase in Type I collagen
By 12 months appearance is of fibro-cartilage
Size and shape of defect important in terms of likelihood to heal and progress to degeneration

V shaped defects more likely to heal with hyaline like cartalage than U shaped defects

These defects do progress to focal OA

Response to blunt trauma
Increase in bone stiffness
Loss of proteoglycan
Cellular degeneration
Chondrocyte clumping
Cartilage fibrillation which ® increased water content and softening

Repetitive loading ® changes akin to early OA
Salter (1980) Motion is important for articular repair ® stimulates fluid flux and nutrition of cartilage

Aging

Thickness of cartilage unaltered if otherwise normal
Tensile strength, fracture resistance and fatigue strength deteriorate (loss of elasticity)
Decreased cellularity of cartilage
Metabolic activity overall decreases
Alteration in proteoglycans produced
Proteoglycan turnover probably unchanged
Pigmentation ? aetiology
Cartilage Degeneration:
Deterioration in any of the interdependent components of cartilage tend to trigger off a cycle of cartilage breakdown
? stimulus for cartilage to change
? may be secondary to development of micro fractures of subchondral bone ® thickening and stiffening ® decreased energy absorption ® chondrocytes under increased pressure ® stimulate cell division and synthesis of DNA, collagen and proteoglycans as well as degenerative enzymes
Initially repair process keeps pace with degradation process but ® degradation predominates

Collagen content normal but ® loss of proteoglycan and decreased proteoglycan aggregation associated with fatigue fracture of cartilage collagen network enables greater water influx
Derangement of the collagen architecture ® proteoglycan aggregates take up more water and the cartilage swells becoming softer and losing its compressive stiffness and tensile strength

Degenerative change ® stimulation of mitosis in chondrocytes ® clumping or formation of columns (cloning) ® collagen synthesis and proteoglycan synthesis is initially increased but this process eventually fails
There is less keratin sulphate and more chondroitin sulphate which is of a more
Immature type

Cartilage becomes oedematous and soft ® secondary damage to chondrocytes ® further matrix breakdown ® abrasive wear
Progressive cartilage matrix deformation ® further stress to collagen network
These early changes of softening and fibrillation are referred to as "chondromalacia"

Attempts of repair with chondrocyte clumping (clones) and increased proteoglycan synthesis
Later ® decreased number of chondrocytes
Thickening and sclerosis of subchondral bone due to increased stress becomes evident on X-Ray
Steep stiffness gradient in the subchondral bone secondary to repeated trauma may ® precipitation of cartilage degeneration
Crack in subchondral bone ® transmission of pressure to cancellous bone ® cyst formation
Progressive cartilage disintegration ® bone exposure and eburnation
As instability increases intact cartilage in the periphery ® proliferates and ossifies, producing bony outgrowths (osteophytes)

Wear types

Abrasive
Irregular hard surfaces moves on a softer surface and ploughs grooves in it
Corrosive
Follows the disruption of the protective surface oxide layer of metals
Adhesive
Repetitive sliding movements ® fragments are pulled from one surface and adhere to the other

Cartilage debris in the form of chondrocytes, fragments of collagen fibres and proteoglycan molecules act as a kind of emery sandpaper ® produce further wear ® conditions favourable for the development of synovitis
Synovial membrane and capsule usually show some degree of inflammation usually from deposition of cartilage and bone debris into the synovium ® incite an inflammatory response ® fibrosis in sub-synovial layers ® capsular thickening and reduced ROM
Degeneration usually associate with only a mild increase in the number of inflammatory cells in the joint

The common occurrence of chronic mononuclear cell infiltrates in the synovium in conjunction with immuno-fluorescent evidence for immune reactant products in cartilage of surgical case specimens has suggested the local involvement of immune processes in arthritis

Harris (CORR 1986) found that 90% of patients with so-called primary idiopathic OA of the hip actually had growth related abnormalities of the hip and he believes that primary OA of the hip does not exist or if it does is extra-ordinarily rare
Lubrication:
In the clinical setting lubrication of articular cartilage involves

  1. Boundary lubrication, specialised molecules attached to the cartilage surface ® make them smooth
  2. Hydrostatic lubrication, Pressure causes water to move (weep) from cartilage into the joint space producing a lubricant film
  3. Squeeze film, non compressible fluid trapped between joint surfaces and its viscosity prevents it being squeezed out

Osteophytes

Increase the joint area
? related to healing trabecular fracture
? related to venous congestion

Fibrillation

Exposure of collagen fibres or fibrils following the loss of proteoglycans ® roughening and eventually cracking of the cartilage surface
Often occurs in areas around points of hydrostatic stress in areas where forces are tangential to the surface. ® Generation of tensile strain may promote the degenerative process and vascular ingrowth, cartilage degeneration and osteophyte formation

Eburnation

Process in which bone becomes hard and dense like ivory (Latin ebur = ivory) and occurs where bone becomes exposed and subjected to wear

Differential Diagnosis

Mono-arthritis (inflammatory such as Reiters) but no X-Ray changes in the acute setting
Crystal arthropathy
AVN ® joint space preserved

Treatment

Early

Relieve pain ® analgesics and anti-inflammatories, heat
Increase movement ® exercise program
Reduce load ® weight loss, stick, avoid stress (jogging)

Intra-articular steroid injection may help (not > 3/yr/joint)
Studies indicate that several NSAIDs including salicylates, suppress proteoglycan synthesis in articular cartilage in vitro. ® The effect on OA cartilage is more marked than that on normal cartilage, the effect being inversely related to the proteoglycan content of the tissue
NSAIDs may aggravate the normal decrease in proteoglycan content caused by the disease

Intermediate

Realignment osteotomy

Late

Reconstructive surgery
Arthrodesis if stiffness not a problem and other joints OK

Arthroplasty if not too young

Haemophilic Arthropathy

A group of clinical states manifest by an abnormality of the coagulation mechanism caused by functional deficiencies of specific clotting factors
Only 2 bleeding disorders ® repeated haemarthrosis

Classical haemophilia or Haemophilia A (deficiency of factor VIII)
Christmas disease or Haemophilia B (deficiency of factor IX)

Clotting factor activity of 40% is compatible with normal clotting
Activity of 20 - 40% may ® prolonged bleeding after injury or accident
Activity below 5% ® spontaneous bleeding

Incidence

1 / 10,000 male births
Inheritance: X linked recessive
25 -30% mutation rate

Clinically

Percentage of normal clotting factor activity:

1% Sever spontaneous bleeds often crippling
1-5% Severe bleeds after minor injury occasional spontaneous bleeding
5-25% Severe bleeding after surgery
25-50% Bleeding after major surgery
50-100% Normal

Severity of the disease is the same as other affected family members
Haemarthrosies begin at the age of 12 to 18 months
Usually affects the knee, hips, elbows, shoulders or ankles
Results in severe pain , warmth, boggy swelling and tenderness, loss of movement, joint usually flexed and may have a mild fever

May ® compartment syndrome occasionally but fasciotomy is unwise unless clotting factors have been given
Joint degeneration usually begins before the age of 15 ® cartilage degeneration

Muscle haemorrhage most common in the psoas, thigh ,calf and forearm, may ® permanent contracture (Volkmans)
Haemarthrosis : Intramuscular bleeds 4:1
Associated with neurological damage in 25%

Femoral nerve most commonly ® Iliacus syndrome ® flexion contracture of the hip and a tender mass in the iliac fossa (recovery may take several weeks to months)
Muscle wasting and fixed deformities are a feature

X-Rays

(Cornell Medical Centre, NY)
  1. Soft tissue swelling
  2. Osteoporosis, epiphysial overgrowth but joint integrity maintained
  3. Disorganisation of the joint, subchondral cysts, squaring of patella and inter-condylar and trochlear widening
  4. Narrowing of the joint space and cartilage destruction
  5. Marked narrowing of the joint and fibrous capsular contracture ® decreased ROM
    Up to stage III control of bleeds can stop progression
    Haemophilic pseudo-tumour results from bony erosion secondary to slowly increasing swelling following a bleed (cystic appearance resembles GCT)
    If large may ® skin necrosis, ulceration and infection

Pathogenesis

Direct irritant effect of blood on cartilage ® synovial reaction and inflammation

Bleeds may be spontaneous from sub-synovial vascular tissue or traumatic

Pathology

Synovial lining is heavily laden with haemosiderin
Repeated haemarthrosis ® chronic synovitis and hypertrophy, accumulation of haemosiderin, release of lysosomal enzymes (cathepsin D), release of plasmin, fibrosis of synovium and cartilage destruction
Synovial changes ® synovium easily damaged ® further bleeds
Also subchondral haemorrhage with loss of cartilage support and hyperaemic stimulation of epiphysial growth
Enzymatic processes and intracellular iron deposits ® inflammatory response which ® continued breakdown of articular cartilage
Chondrocytes also exhibit iron deposition which may ® necrosis

Treatment

Aims

Control bleeding ® give clotting factor
Restore and maintain joint function
Prevent arthropathy
Half life of factor VIII is 12 hours

Aim to keep the factor level about 60% initially and gradually tailor off administration

15% to prevent spontaneous haemorrhage
30% to prevent re-bleeding
60% post surgery

Haemarthrosis, intramuscular haematomas and simple fractures aim for 2-4 days above 40%
Major locomotor surgery subject to strains, major injuries aim for 2-4 days at above 60% then above 40% for some weeks
Aspiration avoided unless distension is severe and only under control of factor replacement

Use a removable splint until comfortable ® encourage movement
NSAIDs may be helpful along with analgesics (aspirin is contraindicated due to its platelet inhibiting effect)
Intramuscular injection is relatively contraindicated
May ultimately need operation to correct fixed deformity eg osteotomy for deformity or arthrodesis for severe arthropathy in the young
THR or TKR in appropriate patients for secondary degeneration
Fractures ® control bleeding and treat as appropriate for the fracture (union is not delayed)

Acute Haemarthrosis:

  1. Splintage 24 - 48 hours and give clotting factors
  2. Isometric exercise
  3. Active movement after 48 hours
  4. Night splints (many bleeds occur over night)
  5. Aspirate tense haemarthrosies only

Subacute Haemarthrosis:

  1. Immobilise 3 - 4 weeks
  2. Isometric exercises
  3. Gentle mobilisation and gentle serial splintage to limit deformity

Neuropathic Joints

A Joint where the appreciation of pain and position sense is lost ® rapid progressive joint degeneration
Martin Charcot (1868) noted relationship between syphilis and severe arthropathy

Aetiology

Central
Tabes dorsalis
Syringomyelia
Myelomeningocoele
Multiple Sclerosis
Charcot Marie Tooth
Central neurological injury
Peripheral
Trauma
Peripheral neuropathies (diabetes, alcohol, amyloidosis, pernicious anaemia)
Infection (Leprosy, Yaws, TB)
Other
Congenital indifference to pain
Dysautonomia
Repeated hydrocortisone injections into RA joints

Clinically

Tabes usually over 45 years
Argyll Robertson pupils (accommodate but will not react)
Knee jerk often lost
No pain on squeezing achilles tendon
Syringomyelia typically dissociated sensory loss (loss of pain and temperature but not touch)

Complain of weakness, instability, swelling and deformity of the affected joint
Pain may not be absent but certainly less than expected from the pathology evident

Symptoms progress rapidly
Joint may be subluxated or even dislocated
Effusion evident as are extra or loose bits of bone (osteophytes or LBs)

Treatment

As appropriate for the underlying condition
External splintage, callipers
Arthrodesis but operation is not advised due to high failure rate

Hypertrophic Osteodystrophy

Characterised by

  1. Periosteal new bone formation
  2. Clubbing of digits
  3. Arthritis

Associated with

Pulmonary neoplasm
Chronic lung disease or carcinoma
Chronic liver disease
Cyanotic heart disease and bacterial endocarditis
Hyperthyroidism may be associated with clubbing

Aetiology

Unknown
May be primary or secondary

Pathology

Periosteum elevated
Mononuclear cell infiltration in adjacent soft tissues
Sub-periosteal new bone formation and some endosteal resorption
Occurs primarily at distal ends of metacarpals, metatarsals and long bones
Occasionally scapula, clavicles, ribs and pelvic bones affected
Proliferation of connective tissue in nail bed and volar digital pad ® clubbing of fingers

Treatment

That appropriate for the underlying condition
May resolve completely after treatment
NSAIDs may help to control symptoms