Primary OsteoarthritisPrimary Osteoarthritis

Primary Osteoarthritis (OA): Outline Overview Epidemiology Pathogenesis Genetics Clinical Features Imaging Management Thank you to Dr P/K!

Overview: What is OA? Conditions leading to joint signs & symptoms assoc. with:

- Loss of integrity articular cartilage & subchondral bone-Joint changes (cysts/geodes, sclerosis, osteophytes)

Associated with aging but not due to aging

Dynamic biochemical, mechanical & cellular processes

Can be defined clinically, pathologically, radiographically

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

Overview: Comparison of OA and Aging

Osteoarthritis Aging↑Cartilage hydration

↓Proteoglycan concentration

↓Collagen concentration

↑Chondrocyte proliferation

↑Metabolic activity

↑Subchondral bone thickness

↓Cartilage hydration

↔Proteoglycan concentration

↔Collagen concentration

↔or↓Chondrocyte proliferation

↔Metabolic activity

Normal subchondral bone

Loeser RF Jr. Rheum Dis Clin North Am 2000; 26:547-567

Overview: 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

Overview: Clinical Features of OA1. Pain in typically involved joints2. Pain worse with activity, improved with rest3. Morning stiffness <30 minutes4. Stiffness after immobility (gelling)5. Joint enlargement6. Joint instability7. Limitation of joint mobility8. Peri-articular muscle atrophy9. Crepitus (noise made by rubbing of irregular cartilage)

Rheumatology Secrets Second edition. Sterling West. Hanley and Belfus Inc. 2002.

Overview: Risk Factors for OA

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

Knuckle Cracking Question: Why do people crack knuckles?

Answer: Cracked knuckles feel looser and enjoy more mobility for a while after cracking. It is also possible that as kids people realize that cracking knuckles produces a funny noise and may repeat cracking just to produce the sound. This may make some people habitual “knuckle crackers”.

Question: What causes the sound?Answer: Joints (knuckles) are covered by a capsule (the joint capsule or synovial capsule). Within the space of this capsule the synovial fluid is contained which acts as a lubricant and also contains nutrients for the adjacent bone surfaces. A variety of gases are continuously dissolved in this fluid. When one cracks a knuckle, the stretching of the capsule lowers the pressure inside the joint and creates a vacuum which is filled by the gas previously dissolved in the synovial fluid. This creates a “bubble” which then bursts producing the characteristic “popping” or “cracking” sound. It takes a while until these gases are re-dissolved in the synovial fluid which explains why knuckles cannot be “re-cracked” immediately.

Question: Are there any side effects to cracking knuckles?There is no evidence that cracking knuckles causes any damage such as arthritis in the joints. However, a couple of reports in the medical literature are available associating knuckle cracking with injury of the ligaments surrounding the joint or dislocation of the tendons (attachments of muscles to bones) which improved with conservative treatment. A study found that after many years of cracking habitual knuckle crackers may have reduced grip strength compared with people not cracking their knuckles.

http://www.hopkins-arthritis.org/arthritis-news/2007/knuckle-cracking-and-arthritis.html

Epidemiology Most common type of arthritis

-Affected 21 million Americans in 1990

Most limitation, work loss & disability among chronic diseases

OA of the knee and hip assoc. with considerable medical costs-Cost to US approx $15.5 billion-2010 DOD budget $680 billion-478,000 total knee replacements (2004)-234,000 total hip replacements (2004)

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

Epidemiology Aging population & ↑ obesity…burden will skyrocket Incidence and prevalence women>men (esp. after 50)

Relationship to estrogen Hormone replacement decreases incidence of OA

Racial/ethic differences have been recognized: ↑Knee OA in Chinese due to squatting ↑Hip OA in Caucasians

Many have symptoms without x-ray changes & vice versa

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

Epidemiology

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

Pathogenesis to Development of 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

http://www.thiyaga.com/KNEE%20OA%20COMPARE.jpg

Pathognesis: Articular Cartilage Function

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

http://patientsites.com/media/img/972/knee_meniscus_surgery_anatomy02.jpg

Three Basic Components of Cartilage (CCP)

Chondrocytes: Manufacture and degrade collagen and proteoglycans Embedded within cartilage

Collagen Principally type II, gives articular cartilage its tensile

strength

Proteoglycans Aggregates of chondroitin sulfate and keratan sulfate High density/fixed neg. charge = properties of coiled spring

Dr Kortan Collagen and Proteoglycans Lecture 2010

http://www.hss.edu/images/corporate/osteoarthritis-ido-1.jpg

Pathogenesis: 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

Figure 164.12. Rheumatology, 4th ed. Hochberg et al, eds. Copyright © 2009 Elsevier Inc.

http://www.med.nyu.edu/medicine/labs/abramsonlab/images/Fig-1-pathogenesis_osteoarthritis-orig.jpg

Pathogenesis: 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

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

Genetic Predisposition to OA Genetic factors play a major role in osteoarthritis May be site and sex specific Estimated to be of the order of 50-65% First-degree relatives have a two- to three-fold increased risk

of disease Familial forms of OA that segregate as a simple Mendelian

genetic trait Likely involves combination of effects

Structure (i.e. collagen) Alterations in cartilage, bone metabolism,inflammation

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

Pain in OA

http://www.existentialpunk.com/.a/6a00d83452358069e20105369ff04a970c-800wi

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 Impingement

CNS Depression, fibromyalgia, coping

skills, ethnicity

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

Imaging in OA Anatomical Imaging

Conventional radiography (plain radiographs) Most important imaging method in OA

Physiologic Imaging MRI

What is the Role of Imaging in OA?

Figure 166.1. Rheumatology, 4th ed. Hochberg et al, eds. Copyright © 2009 Elsevier Inc.

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

Standardized views to better compare serial exams Hand bilateral arthritis Foot bilateral weight-bearing Shoulder bilateral two view Knee bilateral weight bearing and sunrise Hip bilateral C/L Spine 2 -3 view

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

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

Imaging: Pitfalls Odds of knee pain increase with increasing

radiographic severity -Osteophytes >> joint space narrowing-Radiographic changes≠pain≠ loss of function

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

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

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

ACR Slide Set, copyright 2009.

IP OA

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

1st CMC OA

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

C-spine OA

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

ACR Slide Set, copyright 2009.

MRI More Sensitive but not Cost-Effective for OA

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

Management of OA: Non-pharmacologic Patient education Self-management programs

(e.g., Arthritis Foundation Self Management Program)

Personalized social support (telephone contact)

Weight loss (if overweight) Aerobic exercise programs Physical therapy Muscle-strengthening

exercises

Assistive devices for ambulation

Patellar taping *Appropriate footwear Lateral-wedged insoles (for

genu varum) Bracing *Occupational therapy Joint protection & energy

conservation Assistive devices for

activities of daily living

http://www.rheumatology.org/practice/clinical/guidelines/oa-mgmt.asp

Management of OA: Pharmacologic Oral

Acetaminophen COX-2-specific inhibitor Nonselective NSAID plus misoprostol or a proton pump inhibitor** Tramadol Opioids

Intraarticular Glucocorticoids (3 months) Hyaluronan (6 months)

Topical Capsaicin Methylsalicylate Topical NSAID patch

http://www.rheumatology.org/practice/clinical/guidelines/oa-mgmt.asp

Management of OA: SurgicalSurgical interventions in OA three groups: Improving current symptoms (e.g. lavage/debridement)

Lavage removes debris (cartilage or calcium phosphate crystals) Debridement smoothing rough articular/meniscal surfaces, shaving tibial spine

osteophytes Weak symptomatic efficacy despite RCT’s

Preventing risk structural progression (e.g. osteotomy) Painful condition, moderate cartilage loss, specific localization. Genu varum Lack of evaluation of safety/efficacy

Improving symptoms/advanced OA (e.g. joint replacement) Level symptomatic severity/structural severity Level of required symptomatic therapies Comorbidity Patient's willingness

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

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.

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 Familial predisposition

Begins abruptly with pain, swelling and tenderness Small joints of the hands DIPs, PIPs, 1st CMC, scaphotrapezial joints Often symmetric/associated with deformities

Labs Modestly elevated ESR Serologies negative or low-titer positive Synovial fluid usually non-inflammatory

DDx: classical OA, RA, and PsA Requires radiographic confirmation Kellgren’s Disease

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.

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

Erosive Osteoarthritis

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

Radiologic changes include a combination of bony proliferation and erosion.

Erosive Osteoarthritis Treatment Nonpharmacologic therapies

Physical therapy, occupational therapy Pharmacologic therapies

No definitive therapeutic approach Corticosteroid 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

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 Also known as Forrestier’s Disease

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

Most patients present with stiff back or non-specific back pain

Complications from advanced disease: Dysphagia Stridor Chronic pneumonia Vascular compression

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

DISH Clinical Criteria Flowing calcifications/ossifications along anterolateral

aspect of 4 contiguous vertebral bodies, with or without osteophytes

Preservation of disk height in involved areas & absence of excessive disk disease

Absence of bony ankylosis of facet joints and absence of sacroiliac erosion, sclerosis, or bony fusion (narrowing and sclerosis of facet joints ok)

Khozaim Nakhoda Diffuse Idiopathic Skeletal Hyperostosis. emedicine .com

Etiology of DISHUnknown however there are some associations:-Hyperglcyemia and Diabetes- Dyslipidemia-Hyperuricemia -Vitamin A derivatives used to treat acne-Chronic fluoride intoxication

Vezyroglou G, Mitropoulos A, Antoniadis C. A . J Rheumatol. Apr 1996;23(4):672-6.DiGiovanna JJ SO J Am Acad Dermatol 2001 Nov;45(5):S176-82. Utsinger PD; Resnick D; Shapiro R . Arch Intern Med 1976 Jul;136(7):763-8.

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

ACR Slide Set, copyright 2009.

Questions/Concerns?