Osteoarthritis

CHAPTER 312 OSTEOARTHRITIS OA ~ Degenerative joint disease • Failure of diarhtrdial (movable, synovial-line) joint • Primary/Idiopathic OA is the most common form • Secondary OA due to underlying cause Classification Diseases Idiopathic Hands Heberden’s nodes Bouchard’s nodes Erosive IP arthritis 1st CMC joint Feet Hallux valgus Hallux rigidus Contracted toes (hammer/cock-up toes) Talonavicular Knee Medial compartment Lateral compartment Patellofemoral compartment Hip Eccentric (superior) Localized Concentric 9axial, medial) Diffuse (coxae senilis) Spine Apophyseal joints Intervertebral joints (disks) Spondylosis (osteophytes) Ligamentous (hyperostosis, Forestier’s disease, diffuse idiopathic skeletal hyperostosis Other Glenohumoral single Acromioclavicular sites Tibiotalar Sacroiliac Tempormandibular Generalized Includes 3 or more of the areas listed above Secondary Acute Trauma Chronic (occupational, sports) Legg-Calve-Perthes Congenital hip Localized disease dislocation Slipped epiphysis Unequal LE length Valgus/varus Congenital Mechanical factors deformity Hypermobility syndromes Epiphyseal dysplasia Spondyloepiphyseal Bone dysplasias dysplasia Osteonychondystrophy Onchronosis (alkaptonuria) Hemochromatosis Metabolic Wilson’s disease Gaucher’s disease Acromegaly Hyperparathyroidism Endocrine DM Obesity Hypothyroidism Calcium deposition Calcium pyrophosphate dihydrate deposition diseases Apatite arthropathy Fracture Avascular necrosis Localized Infection Gout Other bone and joint disease RA Paget’s disease Diffuse Osteopetrosis Osteochondritis Neuropathic Charcot joints Kashin-Beck Endemic Mseleni Miscellaneous Frostbite Caisson’s disease

Hemoglobinopathies EPIDEMIOLOGY AND RISK FACTORS • Most common joint disease • Knee OA: leading cause of chronic disability in developed countries

•

Age (in older individuals) → MOST POWERFUL RISK FACTORS

  •



Mother and sister of a woman with DIP OA (herberden’s nodes) have higher possibility of having OA

Major Joint Trauma

     •

Chinese: lower incidence for hip OA than whites South African least common for IP OA especially hip OA

Genetic factors

 •

Women: OA of IP joints and thumb base

Race

 •

Men: hip OA

Anterior cruciate insufficiency or meniscus damage → OA Trimalleolar fracture → ankle OA Ballet dancer : Ankle OA Baseball players : Elbow OA Prize fighters : MCP OA

Obesity  Knee and hand OA  Women > Men Age Female sex Race Genetic factors Major joint trauma

Risks Factors for OA Repetitive stress 9vocational) Obesity Congenital/developmental defects Prior inflammatory joint disease Metabolic/endocrine disorders

PATHOLOGY • Loss of articular cartilage, organ AO, synovial joint, subchondral bone, synovium , meniscus, ligaments, neuromuscular apparatus • In load-bearing areas of the articular cartilage Thickening of cartilage (with patchy synovitis) ↓ Breached integrity of joint (cartilage softens and bone thins) ↓ Fibrillation (vertical clefts) ↓ Deep cartilage ulcers that may extend to bone ↓ Weak fibrocarilaginous bone ↓ Metabolically active cartilage (osteophytes) ↓ Hypocellular cartilage ↓ Remodelling and hypertrophy Appositional bone growth in subchondral region (sclerosis in x-ray) Bone abrasion like ivory (eburnation) Periarticular muscle wasting

PATHOGENESIS

• •

•

•

Stimulators of matrix biosynthesis

Load on articular cartilage is generated by contraction of them muscles that stabilize or move the joint However it is too thin to serve as a sole shock absorber in the joint that additional protective mechanisms are provded by subchondral bone and periarticular muscles



Functions of articular cartilage  Provides smooth bearing surface so that bones glide effortlessly over each other with joint movement (with help of synovial fluid)  Prevents concentration of stresses so that bones tdo not shatter when the joint is loaded

 

•

Settings at which OA develops  Normal biomaterial properties + excessive loading of the joint causes the tissues to fail  Reasonable load + inferior material properties

•

Predisposing factors for OA  Repeated oscillation  Repetitive impact loading

•

OA changes  Occurs at sites subject to greatest compressive loads  Due to subtle congenital or developlmental defects

•

Clinical conditions that reduce the ability of the cartilage or subchondral bone to deform

  

Ochronosis: accumulation of homogentistic acid polymers → stiffening of cartilage Osteopetrosis: stiffness of subchondral trabeculae Osteoporosis: abnormally soft bone; protective against OA

THE EXTRACELLULAR MATRIX OF NORMAL ARTICULAR CARTILAGE • Components of articular cartilage  Proteoglycans: Responsible for the compressive stiffness of the tissue and ability to withstand load  Collage: provides tensile strength and resistance to shear

 









Cartilage loss  “Wear” contributes to cartilage loss  Nitric Oxide  IL-1, TNF & shear stress stimulate synthesis of NO by chondrocytes  NO stimulates synthesis of MMPs  MMPs accounts for loss of cartilage in matrix  IL-1, MMPs, plasmic and cathepsin areinvlveed in breakdown of articular cartilage

•

Repair of cartilage  TIMP & PAI-1 stabilizethe systemic temporarily

 •

•

Plasminogen and stromelysin: activate latent MMPs

Pathophysiology

  

Tissue inhibitor of metalloproteinase (TIMP) and plasminogen activator inhibitor-1 (PAI-1): synthesized by chondrocyte and limits degradative activity of MMPs and plasminogen activator TIMP and PAI-1 is destroyed or present in concentrations that are insufficient relative to those fa tive enzymges, stromelysin and plasmin Stromelysin: degrade protein core of PG and activate latent collagenase Stromelysin + Plasmin = active protease responsible for matrix degradation

Traumatic injury  Swelling  Alteration in biomechanical properties  Cell death  Changes in biosynthesis of matrix macromolecules  Loss of PGs  Degradation of collagen



Inhibitors of matrix degrading enzymes



GFs (IGF-1& TGF-β) repair, heal or stabilize process

Cartilage damage ↓ ↑PG concentration → Thickening of cartilage (Compensated OA) ↓ Repair tissue does not hold well under mechanical stress ↓ ↓PG synthesis → full thickness loss of cartilage (End-stage OA)



•

Irreversible

•





Loads of relatively brief duration may sitmulate matrix biosynthesis

PATHOPHYSIOLOGY OF CARTILAGE CHANGES IN OA • Primary changes in OA  Change in arrangement and size of collagen fibers  Biochemical data consistent with the presence of a defect in the collagen network of the matrix due to disruption of the “glue” that binds adjacent fibers

Lysosomal proteases (cathepsins): Degrade the components of intracellular matrix at low pH Metalloporteinases (stromelysin, collagenase, gelatinase): Degrade the components of extracellular matrix at neutral pH IL-1  Normal cartilage turnover Stimulates synthesis and secretion of latent MMPs and of tissue plasminogen activator  Suppresses PG syntheis by chondrocyte, inhibiting matrix repair Plasminogen: synthesized by chondrocyte or may enter the cartilage from the synovial fluid

Polypeptide mediators (IGF-1 & TGF-β)  Stimulate PG biosynthesis  Regulate matrix metabolism in normal cartilage  Play a role in matrix repair in OA  Modulate catabolic and anabolic pathways of chondrocytemetabolism Mechanical loading: modulates chondrocyte metabolism Static laoding inhibits synthesis of PGs and protein

•

↑MMP gene expression

Extent of above changes due to direct mechanical damage vs. cell-mediated degradation



Injury → ↑responsiveness of the chondrocyte to stimulation by cytokines



Injury → diffusion of cytokines into the matrix Unlike in knee cartilage: GAGs loss from ankle cartilage is not increased after mechanical injury of the tissue and exposure to cytokines



CLINICAL FEATURES • Deep ache localized to the involved joint

• • • •

Aggravated by use and relieved by rest Octurnal apin in advanced oA of the hip andmay be enervating (+) Morning stiffness (<20 minutes) Usually NO systemic manifestations Causes of joint Pain and Patients with OA Source Mechanisms Synovium Inflammation (due to)



Phagocytosis of shards of cartilage and bone from the abraded joint surface



Release from the cartilage of soluble matrix macromolecules or crystals of calcium pyrophosphate or hydroxyapatite)



Antigens derived from cartilage matrix sequestered in collagenous tissues of the join → low-grade synovitis Subchondral bone Medullary hypertension, microfractures Osteophyte Stretching of periosteal nerve endings Ligaments Stretch Capsule Inflammation, distention Muscle Spasms • Physical examination  Localized tenderness  Bony or soft tissue swelling  Bony crepitus  Synovial effusions  Warmth over joint  Periarticular muscle atrophy IN ADVANCED CASES  Gross deformity  Bony hypertrophy  Subluxation  Marked loss of joint motion LABORATORY AND RADIOGRAPHIC FINDINGS • Radiographic findings  Joint space narrowing  Subchondral bone sclerosis  Subchondralcysts  Osteophytosis  Change in contour due to bony remodling  Subluxation •

Laboratory testing (For secondary OA)  ESR  Serum chemistry  Blood counts  Urinalysis  Synovial fluid analysis

 

WBC < 2,000/µL Mononuclear predominance

OA AT SPECIFIC JOINT SITES INTERPHALANGEAL JOINTS

• • • •

Heberden’s nodes (DIP): most common form of idiopathic OA Bouchard’s nodes (PIP) May present with pain, redness, swelling Gelatinous dorsal cysts may develop at the insertion of the digital extensor tendon into the base of the distal phalanx

Erosive OA  DIP and PIP invoveld  More destructive  X-ray: collapse of subchondral plate with bony ankylosing  Severe deformity and functional impairment  Extensively infiltrated with mononuclear cell Generalized OA

  

Involves 3 r more joints (DIP, PIP) Evident Heberden’s nodes (+)Flare’ups ofinflammation marked by soft tissue swelling, redness and warmth



↑ESR but (-)RF

THUMB BASE

   



2nd most frequently affected area Swelling, tenderness and crepitation Loss of motion and strength X-ray: squared appearance due to osteophytes Pain with pinch → adduction of the thumb and contracture of the 1st web space or compensatory hyperextension of the first MCP and swan-neck deformity of the thumb

HIP • Due to congenital or developmental defects of the hip • Pain referred to inguinal area, buttock or proximal thigh • Pain invoked through flexion (initially) and internal rotation (exacerbation of pain)

•

Limited ROM: internal rotation → extension → adduction → flexion (due to capsular fibrosis and/or buttressing osteophytes)

KNEE • May involve medial or lateral femorotibial compartment and/or patellofemoral compartment • Bony hypertrophy (osteophytes) and tenderness • Small effusions • Bony crepitus • Medial : varus (bowleg) :: Lateral : valgus (knock knee) • (+)Shrug sign (pain with manual compression of patella agains femur during quadriceps contraction) = Patellofemoral OA • Chondromalacia patellae  Syndrome of patellofemoral pain in teenagers and young adults  More common in females  Due to abnormal quadriceps angle, patella alta, trauma  Softening and fibrillation of cartilage on posterior aspect of patella  Anterior knee pain & (+)Shrug sign  Tx: Analgesics or NSAIDs and physical therapy SPINE • Involve apophyseal joints, IVD and paraspinous ligaments • Spondylosis: degerative disk disease • Diagnosis: reserved in patients with apophyseal involvement • Localized pain and stiffness

•

•

Nerve root compression → radicular pain & motor weakness  From osteophyte blockade of a neural foramen  From prolapse of degenerated disk  From subluxatio of an apophyseal joint OA similar to DISH but DISH…  Occur in middle-aged and elderly  Men > Women

  

Ligamentous classification and ossification in anterior spinal ligaments (flowing wax) on anterior vertebral bodies (+)RADIOLUCENCY BETWEEN NEWLY DEPOSITED BONE AND VERTEBRAL BODY Preserved disk spaces and normal sacroiliac * apophyseal joints

TREATMENT Goals:

• • •

Reduce pain Maintain mobility Minimize disability

PHARMACOLOGIC THERAPY NSAIDs and Acetaminophen

NONPHARMACOLOGIC MEASURES (KEYSTONE IN OA) Reduction Of Joint Loading • Correction of poor posure • Support for excessive lumbar lordosis • Avoid excessive loading • Avoid prolonged standing, kneeling and swatting • Lose weight • Rest periods during the day • Thermoplastic splint blocks flexion can reduce pain, improve overall hand function and reduce muscle spasm • Use of cane/crutches or walker Patellar Taping • For OA of patellofemoral compartment • Medial taping to reduce pain on kneeling, squatting or climbing stairs • Simple and inexpensive • Maintain with isometric exercises to strengthen the vastus medialis obliquus component of the quadriceps muscle • Facilitates realignment of the patella ona long-term basis Wedged Insoles/Orthoses

• • •

• •

For patients with medial compartment knee OA and medial tibial femoral compartment Pain on external adduction Reduce excessive loading on medial compartment of thek nee ands train on the lateral collateral ligament Lateral wedge insoles → ↓NSAID consumption

Propylene mesh: Practical, inexpensive and washable Thermal Modalities • Heat: reduce pain and stiffness • Ice: better analgesia Exercise

•

•

• • • •

Patient Education • Encouragement, reassurance, advice about exercise recommendation of measures to unload arthritic joint • Self-management

and

Tidal Irrigation Of The Knee • Copius irrigation of the OA knee through a large-bore needle • Flush out fibrin, cartilage shards and debris Arthrosopic Debridement And Lavage • Alleviate knee pain • Improve function • Indications:  OA with loose bodies  OA with flaps of cartilage  OA with disruption of the meniscus

 

Patients with symptomatic knee Asymptomatic patients that pharmacologic threapy

do

Disadvantages: GI symptoms, ulceration, hemorrhage and death Risk Factors For Upper Gastrointestinal Adverse Events in Patients Taking NSAIDs Increasing age History of UGIT bleeding Comorbidity (poor or fair general health) Anticoagulation Oral glucocorticoids Combination NSAID therapy History of peptic ulcer Increasing NSAID dose Selective COX-2 Inhibitors • For patients NSAIDs-associated GI catastrophe • No greater efficacy than nonselective NSAIDs but with lower incidence of GI bleeding Glucocorticoid Injection • Symptomatic relief, given intra-articularly Intraarticular Injection of Hyaluronan • For patients who have failed a program of nonpharmacologic therapy and simple analgesics Opioids • Indications:  Acute flares (when APAP or NSAID does not provide adequate pain relief)  Chronic OA pain  Nausea/Vomiting  Constipation  Urinary retention  Mental confusion  Drowsiness

 





from

µ-opioid agonist Inhibits reuptake of norepinephrine and serotonin

Drug Interactions → Convulsions  TCA  SSRI  MAOI

Rubefacients/Capsaicin • For patients who can’t take systemic analgesics and NSAIDs due to risk of adverse effects • Topical irritants/local heat to provide pain releif GLUCOSAMINE, CHONDROITIN SULFATE • Symptomatic benefit • Chondroprotective? ORTHOPEDIC SURGERY • For patients with advanced OA in whom aggressive medical management has failed •

benefit

Respiratory depression Mechanism of Action



•

not

Anti-inflammatory/Analgesic Decrease joint pain Improve mobility

•

Since OA due to overuse, not much exercise → ↑ risk for hypertension, obesity, diabetes and cardiovascular disease  Aerobic conditioning  Walking, cycling, aquatic exercises  For cardiovascular fitness  Improve function and quality of life  Exhibit improved gait and walking speed Disuse → Muscle atrophy  Strengthening exercise

Slow cartilage damage?

Arthroplasty: Relieve pain, increasing mobility Osteotomy: eliminate concentration ofpeak dynamic loads and provide effective pain relief

CARTILAGE REGENERATION • Disadvantage: fibrocartilage that resurfaces isinferior to normal hyaline cartilage in its ability to withstand mechanical laods

RATIONAL APPROACH TO NONSURGICAL MANAGEMENT OF OA • Nonpharmacologic management: foundation of treatment of OA pain • Pharmacologic management: adjunctive or complementary role in management of this disease • Individualized approach

Week 0

Instruction in joint protection principles

Week 2

Thermal modalities

Shoes with wellcushioned soles

←

Doing well ↓ Reduce acetaminophen dose

cane

Exercise: Range of motion Quadriceps strengthening Aerobic conditioning

Intraarticular steroid infection if effusion present

→

Telephone call 2wks

Weight loss (if obsess)

Insufficient pain control ↓

↓ Capsaicin cream 0.025% qid Continue acetaminophen 1g q 4-6h prn up to 4g/d

Reinforce compliance with nonpharmacologic measures

Doing well

←

→

Telephone call 4wks

WEEK 10

←

Doing well

Continue tramadol or acetaminophen/ codeine prn

WEEK 14

Reinforce compliance with nonpharmacologic measures

Doing well Decrease salsalate dose to prn

WEEK 18

Increse salsalate to 1500mg BIDif tolerated, increase dose to achieve serum concentration of 20-25 mg/d

Reinforce compliance with nonpharmacologic measures

Follow-up visit → 4wks

Reinforce compliance with nonpharmacologic measures

←

Telephone call 4wks

→

Reinforce compliance with nonpharmacologic measures

Doing well ↓ Continue pharmacologic and nonpharmacologic measures

←

Telephone call 4wks

←

↓ d/c Capsaicin d/c ibuprofen/naproxen d/c selective Cox-2 inhibiotr

→

Insufficient pain control

d/c salsalate

→

↓ NO: Ibuprofen 400mg TD or QID or Naproxen 250-75 mg BID YES: Salsalate 1g BID or Naproxen 250-375 mg BID + Misoprostol or PPI or Selective COX-2inhibitor

Insufficient pain control ↓

Reduce ibuprofen or salsalate dose to prn after 4 wks

Risk factors for GI adverse eveny?

→

Reinforce compliance with nonpharmacologic measures

WEEK 6

Acetaminophen 1g q4-6h up to 4g daily

Tramadol 25 mg/d titrated to 200300mg/d or acetaminophen/codeine

Insufficient pain control ↓ d/c tramadol or acetaminophen/codeine

←

↓ Reinforce compliance with nonpharmacoloic measures

Medial RF OA? Or PF OA? ↓ Medial TF OA: wedged insole PF OA: pateollar taping

Risk factors for GI adverse event? ↓ NO: Naproxen 375-50mg BID Reinforce compliance with YES: Naproxen 375-500mg BID + ← nonpharmacologic measures Misoprostolor or PPI or selective COX-2 inhiibtor Insufficient pain control ↓ Referreal to orthopedic surgeon →