Primary Osteoarthritis. Primary Osteoarthritis (OA): Outline Epidemiology Classification Pathogenesis Genetics Clinical Features Imaging

Primary OsteoarthritisPrimary Osteoarthritis

Primary Osteoarthritis (OA): Outline Epidemiology Classification Pathogenesis Genetics Clinical Features Imaging Management

What is OA? “ . . . a heterogeneous group of conditions that lead to

joint symptoms and signs which are associated with defective integrity of articular cartilage, in addition to related changes in the underlying bone and at the joint margins.”

Associated with aging but not due to aging OA ≠ degenerative joint disease

Involves dynamic biochemical/-mechanical & cellular processes Can be defined pathologically, radiographically or clinically

Altman RD, et al. Arthritis Rheum 1986; 29:1039-1049.

Epidemiology OA is a condition found worldwide

Most common type of arthritis Affected 21 million Americans in 1990 Projected to affect 25% of the population (67 million) by 2030

Accounts for more functional limitation, work loss and physical disability than any other chronic disease

Due to its effect on ambulation/mobility, OA of the knee and hip is associated with considerable medical costs Costs range from 1-3% of GNP in developed countries 478,000 total knee replacements and 234,000 total hip replacements in 2004 Aggregate expenditures increased by $185.5 billion per year in 2007

Due to our aging population and the epidemic of obesity, the burden is only expected to increase

Kotlarz H et al. Arthritis Rheum 2009; 60(12):3546-3553.

Epidemiology Incidence and prevalence higher in women than men,

especially after age 50

Racial/ethic differences have been recognized Absence of hip OA in Asians Differences between African- and Caucasian-Americans

Many persons in the population have joint symptoms without x-ray changes and vice versa

Epidemiology

Figure 162.3, Rheumatology, 4th ed. Hochberg et al, eds. Copyright © 2009 Elsevier Inc.

Mortality Overall, slight increase in mortality rates compared with

the general population Increased proportionate mortality from CV and GI conditions

Singh G. Am J Med 1998; 105(1B):31S-38S.

Classification for Subsets of OA

Altman R et al. Arthritis Rheum 1986; 29(8):1039-1049.

Primary OA DIP joints PIP joints CMC joints AC joints Hip joints Knee joints 1st MTP joints Facet/apophyseal joints

of the C- and L-spine

ACR Classification Criteria – Knee (1996)


ACR Classification Criteria – Hand (1990)

Altman R et al. Arthritis Rheum 1990; 33(11):1601-1610.ACR Slide Set, copyright 2009.

ACR Classification Criteria – Hip 1991


Interrelationship of Risk Factors for OA

Figure 162.4, Rheumatology, 4th ed. Hochberg et al, eds. Copyright © 2009 Elsevier Inc.

Genetic Predisposition to OA Familial aggregation

Generalized OA (BLSA, GARP) 2-8 fold increase in risk for siblings for TJR for OA

High heritability in twin studies Candidate genes

AGC1, ASPN, COL9A2, COL9A3, COL11A2, ESR1, FZRB, IL1A, IL1PN, PTGS2 and VDR genes

Genome wide linkage analyses Areas on chromosomes 2, 6 and 11

Valdes AM and Spector TD. Med Clin N Am 2009; 93(1):45-46.

Etiopathogenesis of OA Complex

Changes in bone and cartilage integral components of process Inflammation plays an important role in the production of

symptoms and signs as well as the progression of disease

Affects all of the tissues of the joint

“OA can be thought of as a mechanically driven but chemically mediated active disease process of joints in which attempted (or aberrant) repair is one of the dominant aspects of the process”

Dieppe P. Stepping away from OA. 1999 NIH conference.

Pathways to OA

Abnormal StressNormal Physiology

Normal StressAbnormal Physiology

ObesityAltered joint loadingAbnormal anatomyBone remodeling

Trauma

JointDestruction

PainDisability

Matrix destructionAberrant repair response

Mechanical failure

InflammationImmune responses

AgingGenetic factors

Normal Joint Function and Loading

Figures 164.1 and 164.3. Rheumatology, 4th ed. Hochberg et al, eds. Copyright © 2009 Elsevier Inc.

Balance is Key

Figures 164.4. Rheumatology, 4th ed. Hochberg et al, eds. Copyright © 2009 Elsevier Inc.

http://www.chelationtherapyonline.com/articles/images/Cart1.jpg

Articular Cartilage Function

Take up and distribute load applied to the joint Provide for low friction movement

Structure Matrix

Territorial (class to cells) Inter-territorial

Chondrocytes

http://www.netterimages.com/images/vpv/000/000/013/13483-0550x0475.jpg

Chondrocytes Synthesize and secrete matrix components

Collagens (Types II, IX, XI, also Types X and VI) Aggrecan (link and core proteins, KS, CS) Leucine rich repeat (LRR) proteins (e.g. decorin) Other macromolecules (e.g. COMP, CMP [matrilin-1])

Figure 164.9. Rheumatology, 4th ed. Hochberg et al, eds. Copyright © 2009 Elsevier Inc.


Figures 9.3 and 164.10. Rheumatology, 4th ed. Hochberg et al, eds. Copyright © 2009 Elsevier Inc.

Chondrocytes Synethesize & secrete the substances that degrade the

matrix Aggrecanases (e.g. ADAMTS-4, ADAMTS-5) Matrix metalloproteinases (MMPs)

Collagenase, stromelysis, gelatinase, etc. Cytokines and other inflammatory mediators


Pathologic Features of OA OA may affect all parts of a joint and periarticular tissues

Old dogma that OA is primarily and predominately a cartilage abnormality is no longer true

Articular Cartilage Changes in OA

ACR Slide Set, copyright 2009.

Above: Normal hip articular cartilage. Stains red due to abundance of acid mucopolysaccharide except for superficial zone.

Right: Degenerative changes seen. Diffuse hypercellularity and extensive loss of acid mucopoly-saccharide from matrix.

Wieland HA et al. Nat Rev Drug Dis Apr 2005; 4:331-344.

Evidence for Inflammation in OA Arthroscopic synovitis near cartilage defects

Synovial hyperplasia, increased lining cells Increased expression of IL-1, TNF, COX-2, MMPs

Synovitis correlates to pain Synovitis predicts OA progression Elevated proinflammatory genes in cartilage from OA pts

http://img.medscape.com/fullsize/migrated/editorial/clinupdates/2006/5602/images/fig3.gif

Many Facets of Osteoarthritis


Potential Mechanisms of Pain in OA Bone

Periostitis associated with osteophyte formation

Subchondral microfractures Bone angina due to decreased

blood flow and elevated intraosseous pressure

Synovium Irritation of sensory nerve endings

within synovium and/or joint capsule from osteophytes

Synovial inflammation due to release of PGs, LTs & cytokines

Joint effusion causing stretching of joint capsule

Periarticular Muscle spasm and weakness Joint instability and/or subluxation Bursitis

Anserine and/or prepatellar Trochanteric and/or ischial

Tendonitis IT band syndrome

Neuropathic

http://www.painstudy.com/images/KneePain.jpg

Imaging in OA Anatomical Imaging

Conventional radiography (plain radiographs) Most important imaging method in OA Widely available, inexpensive and readily understood

Establish the diagnosis and/or severity of OA Monitor disease progression and possible therapeutic responses Look for complications of the disorder or of treatment

Physiologic Imaging MRI Radionucleotide scans

Plain Radiographs Quality influenced by sensitivity of imaging system & radiographic view(s)

Standardized views to better compare serial exams WB views sometimes needed to evaluate joint space

Radiologic features associated with OA Osteophytosis Subchondral bone sclerosis Joint space narrowing (JSN) Subchondral lucencies Remodeling and attrition of bone

Not perfect Observational studies have demonstrated that although odds of knee pain

increase with increasing radiographic severity (osteophytes >> JSN), the relation between radiographic changes and pain and function in OA is not strong

Further confounding this relation, recent data suggest that knee pain itself can modify the measurement of joint space width (JSW) in weight-bearing extended-view radiographs

Hunter DJ and Conaghan PG. Curr Opin Rheum Mar 2006;18:157-162.

What is the Role of Imaging in OA?


Kellgren & Lawrence Grading System: Knee OA

Kellgren JH and Lawrence JS. Ann Rheum Dis 1957; 16:494-502.

0 No osteophytes, no OA1 Doubtful osteophytes2 Minimal osteophytes,

possibly with narrowing, cysts and sclerosis

3 Moderate or definite osteophytes with moderate joint space narrowing

4 Severe with large osteophytes and definite joint space narrowing

Hip OA JSN typically

superior >> medial



IP OA


1st CMC OA



C-spine OA



MRI More Sensitive but not Cost-Effective for OA

Gupta KB et al. Radiol Clin N Am 2004; 42:11-41.

What are Clinically Relevant Outcomes in OA?

Pham T et al. J Rheum 2003; 30(7):1648-1654.Table 167.2. Rheumatology, 4th ed. Hochberg et al, eds. Copyright © 2009 Elsevier Inc.

Management of Osteoarthritis


OARSI Recommendations for Knee & Hip OA Optimal management requires combination of

nonpharmacologic and pharmacologic modalities (SOR 96%; 95% CI 93-99)

Acupuncture may be of symptomatic benefit in knee OA (SOR 59%; 95% CI 47-71)

Zhang W et al. Osteoarthritis Cartilage 2008; 16:137-162.ACR Subcommittee on OA Guidelines. Arthritis Rheum Sep 2000; 43(9):1905-1915.

OARSI Recommendations for Knee & Hip OARecommendation SOR 95% CI

Acetaminophen (paracetamol) (up to 4 g/d) can be effective initial oral analgesic for treatment of mild to moderate pain in pts with knee or hip OA 92% 88-89

NSAIDs should be used at lowest effective dose but long-term use should be avoided is possible. In pts with increased GI risk, either a COX-2 or nonselective NSAID with coprescription of a PPI or misoprostol for gastroprotection may be considered. NSAIDs should be used with caution in pts with CV risk factors.

93% 88-89

Topical NSAIDs and capsaicin can be effective as adjunctives and alternatives to oral analgesic/anti-inflammatory agents in knee OA. 85% 75-95

IA injections with corticosteroids can be used in the treatment of knee or hip OA, and should be considered particularly when pts have moderate to severe pain not responding satisfactorily to oral analgesics/anti-inflammatory agents and in pts with symptomatic knee OA with effusions or other physical signs of local inflammation.

78% 61-95

Injections of IA hyaluronate may be useful in pts with knee or hip OA. They are characterized by delayed onset, but prolonged duration, of symptomatic benefit when compared to IAC injections. 64% 43-85

Treatment with glucosamine and/or chondroitin sulphate may provide symptomatic benefit in pts with knee OA. If no response is apparent within 6 months treatment should be discontinued. 63% 44-82

The use of weak opioids and narcotic analgesics can be considered for the treatment of refractory pain in pts with hip or knee OA, where other pharmacologic agents have been ineffective or are contradicted. Stronger opioids should only be used for the management of severe pain in exceptional circumstances. Nonpharmacologic therapies should be continued in such pts and surgical tmts should be considered.

82% 74-90

Zhang W et al. Osteoarthritis Cartilage 2008; 16:137-162.

OARSI Recommendations for Knee & Hip OARecommendation SOR 95% CI

Pts with hip or knee OA who are not obtaining adequate pain relief and functional improvement from a combination of nonpharmacological and pharmacological treatment should be considered for joint replacement surgery. Replacement arthroplasties are effective, cost-effective interventions for pts with significant symptoms, and/or functional limitations associated with a reduced health-related QOL, despite conservative therapy.

96% 94-98

Unicompartmental knee replacement is effective in pts with knee OA restricted to a single compartment. 76% 64-88

Osteotomy and joint preserving surgical procedures should be considered in young adults with symptomatic hip OA, especially in the presence of dysplasia. For the young and physically active pt with significant symptoms from unicompartmental knee OA, high tibial osteotomy may offer an alternative intervention that delays the need for joint replacement some 10 yrs.

75% 64-86

The roles of joint lavage and arthroscopic debridement in knee OA are controversial. Although some studies have demonstrated short-term symptom relief, others suggest that improvement in symptoms could be attributable to placebo effect.

60% 47-82

In pts w/knee OA, joint fusion can be considered as a salvage procedure when jt replacement has failed. 69% 57-82

Zhang W et al. Osteoarthritis Cartilage 2008; 16:137-162.

Prevention of Osteoarthritis in the Future?

Bay-Jensen A-C et al. Rheumatol Int 09 Oct 2009; epub.

Prevention of Osteoarthritis in the Future?

Bay-Jensen A-C et al. Rheumatol Int 09 Oct 2009; epub.

DMOADs? Potential disease-modifying drugs for OA

Anti-resorptive agents N-containing bisphosphonates Calcitonin Strontium ranelate

Cytokine inhibitors Diacerein, IL1-R antagonist, ICE inhibitors

Matrix metalloprotease inhibitors Doxycycline

Nutritional supplements Glucosamine sulfate and chrondroitin sulfate

Growth factors

Hunter DJ. Med Clin N Am Jan 2009; 93(1):223-234.Qvist P et al. Pharmacol Res Jul 2008; 58:1-7.

Other Forms of Idiopathic Other Forms of Idiopathic Osteoarthritis Osteoarthritis

Erosive Osteoarthritis (eOA) Disorder that most often involves

hands of post-menopausal women F:M ratio 10:1 to 12:1 Mean age of onset 50.5 (range extends 36-83) Familial predisposition

Usually begins abruptly with pain, swelling and tenderness of the small joints of the hands DIPs, PIPs, 1st CMC, scaphotrapezial joints Often symmetric Often associated with deformities

Labs Modestly elevated ESR Serologies negative or low-titer positive SF usually non-inflammatory but may be

mildly inflammatory (WBC 2-16K) DDx: classical OA, RA, and PsA Requires radiographic confirmation

Belhorn LR and Hess EV. Sem Arthritis Rheum Apr 1993; 22(5):298-306.Gupta KB et al. Radiol Clin N Am 2004; 42:11-41.

Erosive Osteoarthritis

Gupta KB et al. Radiol Clin N Am 2004; 42:11-41.

Radiologic changes include a combination of bony proliferation and erosion.

Punzi L et al. Best Pract Res Clin Rheum 2004; 18(5):739-758.

Erosive Osteoarthritis Treatment Nonpharmacologic therapies

Physical therapy, occupational therapy ROM exercises, moist heat (paraffin baths)

Pharmacologic therapies No definitive therapeutic approach

IA steroid injections can be efficacious in reducing symptoms NSAIDs (especially if there appears to be an inflammatory component) Analgesics (acetaminophen, capsaicin)

Possible use – inconclusive studies, investigational therapies Hydroxychloroquine Glucosamine and chondroitin sulfate Methotrexate Gold salts Others – anakinra, intraarticular infliximab, systemic adalimumab

Surgical intervention Synovectomy, arthrodesis of destroyed actively inflamed joints

Belhorn LR and Hess EV. Sem Arthritis Rheum Apr 1993; 22(5):298-306.

DISH Diffuse idiopathic skeletal hyperostosis

AKA ankylosing hyperostosis or Forestier's disease

2:1 male predominance Prevalence increases with age and weight in both sexes

Criteria depends on radiologic appearance of Tspine New bone formation which bridges 4 contiguous vertebral bodies Uninterrupted bone “flows” from one vertebra to another Anterior longitudinal ligament over the anterior 2/3 of the vertebral bodies dictates

the distribution of the new bone formation More prominent on R side of Tspine (?pressure from L-sided aorta)

Table 169.2. Rheumatology, 4th ed. Hochberg et al, eds. Copyright © 2009 Elsevier Inc.


DISH Can occur at other joints as well Clinical features

Deposition of bone usually asymptomatic apart from stiffness of neck, back, or peripheral joints

Can have a peripheral enthesopathy which can cause pain Symptoms may arise from compression of important structures

Dysphagia with C-spine DISH Myelopathy/quadriplegia with ossification of posterior longitudinal ligament Spinal stenosis due to marked osteophytosis

Can co-exist with inflammatory arthritis Associated with diabetes, IGT, obesity DDx includes AS or other SpA, DDD, primary OA, acromegaly

Management of DISH Prevention

Weight reduction Treat hyperinsulinemia

Specific Interventions Symptomatic only, sometimes steroid injections can help

Table 169.3. Rheumatology, 4th ed. Hochberg et al, eds. Copyright © 2009 Elsevier Inc.

Not OA but on the Boards:Pellegrini Steida Syndrome (Here you go, JRo!)


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Primary Osteoarthritis. Primary Osteoarthritis (OA): Outline Epidemiology Classification Pathogenesis Genetics Clinical Features Imaging