Osteoarthritis

Osteoarthritis (OA) is a musculoskeletal disorder that increases in prevalence with age and is the major cause of rheumatic disease in geriatric patients. (1,2) Since the very old (age 85 and older) are now the most rapidly growing segment of the population, proper understanding of diagnosis, disease expression, signs and symptoms, and treatment of OA is important for primary care providers and in the design of health care delivery. This article begins a series of reviews in geriatric rheumatology, including relevant orthopedic issues and therapeutic strategies.

Scope of the problem

OA encompasses 60% to 70% of joint diseases overall, is second among causes of permanent incapacity among people over age 50, and has a prevalence that increases exponentially beyond age 45. It is not a distinct disease, but rather a final common pathway which may be triggered by a complex interplay of environmental and genetic (3) factors, accounting for clinical heterogeneity with regional or generalized presentations.

Risk factors for OA include age, congenital deformities (eg, slipped capital epiphyses in the hip), joint derangement (eg, meniscal disease in the knee), crystal deposition disease, obesity (knee), and heredity (primary idiopathic OA). OA may be accelerated in the face of trauma (especially fractures involving the joint) and when metabolic (eg, obesity, diabetes) or neurologic disorders are comorbidities. For example, diabetic patients may manifest an increased incidence of OA in weight-bearing joints as a concomitant of obesity, or develop an exaggerated form of OA, ie, Charcot arthropathy, as a function of neuropathy.

OA is characterized by a slow progression, and has traditionally been considered a pain syndrome caused by mechanical derangement of the joint rather than an inflammatory disorder. (4)

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The incidence of regional forms of OA is age-dependent, presenting radiographically:

* after age 25 in the first metatarsophalangeal joint (big toe),

* after age 35 in the first carpometacarpal joint (base of thumb),

* after age 45 in the distal (Heberden's nodes) and proximal (Bouchard's nodes) interphalangeal joints of the hand, and

* after age 50 in the knee and hip.

Knee OA remains the most common cause of disability in older persons. Overall, OA is projected to become the fourth most common cause of disability by 2020. (5)

By retirement (age 60 to 65), approximately 80% of individuals have some type of musculoskeletal complaint (eg, back pain, regional pain syndromes) only some of which are due to arthritis (table). Self-reported arthritis in the community increases from 337 per 1,000 among those age 55 to 64 to approximately 600 per 1,000 for those age 85 and older. For each subgroup, rates of arthritis are higher among women than men, and higher among African-Americans than whites.

Twenty-five percent to 50% of older persons have significant pain (up to 80% when nursing home residents are sampled), with arthritis being a predominant, although not exclusive, cause. (1,2,5) Regional pain syndromes involving the shoulders, back, or feet may be due to mechanical disorders, such as rotator cuff disease, spinal stenosis, or plantar fasciitis. These syndromes may occur with OA and their effects on functional deficits of activities of daily living (ADLs) need to be evaluated.

Among ambulatory persons age 75 or older, back pain is the third most frequently mentioned symptom, and the most common musculoskeletal complaint. Low back pain is more commonly due to structural abnormalities of the spine in older than in younger persons; however, systemic diseases (eg, metastases, metabolic bone disorders) are twice as frequent a cause of low back pain in older adults and need to be considered in the differential diagnosis.

Confounding the pain issue is the fact that by age 65, most of the population has radiographic changes of degenerative arthritis, making pain and disability difficult to assess. Estimates indicate that 10% of adults are homebound, most commonly due to arthritis. Not incidentally, arthritis, osteoporosis, cervical spondylosis, and lumbar stenosis contribute to the increased incidence of falls and hip fractures in the geriatric population. (6,7)

Musculoskeletal aging

Correlates of normal aging include loss of lumbar lordosis and mild-to-moderate kyphoscoliosis or pelvic tilt; such changes may be of cosmetic concern, but do not necessarily denote pathology or need for corrective measures. There is increased stiffening and cross-linking of connective tissue matrix components, and accumulation of post-translational modifications, such as advanced glycation end-products. (8) Aging is associated with changes in composition of glycosaminoglycans, specifically an increase in the ratio of keratan sulfate to chondroitin sulfate, variable proteolytic cleavage of core proteins, and increased levels/decreased molecular size of hyaluronan. (9)

OA is a consequence of the interplay between these correlates of aging and environmental and genetic factors; indeed, studies of knee menisci indicate that characteristic histologic changes may start as early as the second decade of life. Whereas radiographic evidence of OA increases dramatically with age, clinical correlates are inexact, underscoring the importance of careful rheumatologic history and physical examination. Such a history and examination may be incorporated into a multidisciplinary vehicle for geriatric assessment that includes comorbid diseases and multiple medications (Take-home Points). (4,10)

Muscle loss: A progressive loss of muscle mass affects the lower extremities more than the upper. Muscle mass decreases from approximately 30% body weight at age 30 to approximately 15% at age 75, largely due to a selective loss of type 2 (fast-twitch) fibers. Pathologic changes include increased lipofuchsin, reduction in size and number of myofibrils, and increased Golgi activity. As a consequence, maximum isometric contraction force is approximately 20% lower by age 60, and approximately 50% lower by age 80. These changes result in decreases in muscle mass, strength, and endurance, contributing significantly to joint instability and falls.

There is a major risk for prolonged inactivity (eg, during hospitalizations), which can result in further loss of muscle mass and strength of approximately 1.5% per day; deconditioning occurs rapidly with inactivity and may require weeks of reconditioning to return to baseline. (9)

Recent studies in older persons using moderate- and high-intensity resistance exercises have shown that functional deterioration is not an inevitable consequence of intrinsic aging, and that proper regimens of exercise (eg, Tai Chi, weight training) can significantly impact ADLs and reduce the incidence of falls by 30% to 40%. (11)

Immunosenescence and autoimmunity

Evaluation of the geriatric patient with rheumatic disease requires an appreciation of patterns of immunosenescence, as well as understanding the prevalence of autoimmune phenomena. Aging affects the B- and T-cells, the latter more profoundly. (12) While B-cell numbers are generally normal, there is increased synthesis of IgG/IgA/IgG1/IgG3, a decline in specific antibody responses, and generation of low-affinity antibodies, but these are rarely of clinical significance. There is also an increased incidence of B-cell clonality, manifesting as monoclonal gammopathies that may be found on routine laboratory evaluation. (13)

Thymic atrophy is reflected in decreased T lymphopoeisis overall as decreasing numbers of T-cells carrying the pan-T marker CD3. Recent studies have shown clonal expansions of CD8 and gamma-delta cells (the T-cell equivalent of gammopathy) in older persons without evidence of underlying disease. Functionally, there is loss of T-cell proliferative response to mitogens and antigens, which has been ascribed to defects in signal transduction. Clinical consequences are hypoergy on testing for delayed hypersensitivity and increased production of some cytokines by T- and other cells. The former may cause decreased reactivity on tuberculin skin testing; uncontrolled release of proinflammatory cytokines leads to increased levels of acute-phase reactants (APR). The APR fibrinogen is the major determinant of the Erythrocyte Sedimentation rate (ESR), normal values of which increase with age; consequently, mild elevations of the ESR in an older person do not have the same significance as in a younger individual. (14)

Age-related defects in programmed cell death (apoptosis) may cause accumulation of functionally impaired T-cells and weaken host response to transformed or infected cells. One consequence is loss of self-tolerance and an increased incidence of autoimmune phenomena. Older persons may have low levels of autoantibodies to nuclear antigens (ie, antinuclear antibodies), IgG (ie, rheumatoid factor) or thyroid antigens, without any evidence of connective tissue or autoimmune disease; the incidence of such autoimmune phenomena increases with each decade of life. Such tests should not be over-interpreted in the evaluation of rheumatic disease in older persons. (15)

Pathologic, radiologic correlates

The pathology of OA is a consequence of an abnormal concentration of force on a normal articulation, or as the result of a normal force on abnormal cartilage or weakened or stiffened subchondral bone. Malalignment and aberrant bone repair are characteristic.

Most studies regarding the pathogenesis of OA have focused on the articular cartilage, although the entire joint, including subchondral bone, synovial membrane, and surrounding muscles, are involved.

Characteristic pathology includes:

* fibrillation (fissuring of cartilage)

* denudation (erosions/ulcers of fibrillated cartilage)

* eburnation (new subchondral bone formation in an area of denudation)

* osteophyte formation (new bone covered with hyaline or fibrocartilage, usually occurring at the margin of the joint), and

* geodes (cysts occurring in the bone below eburnated surfaces due to increased intra-articular pressure).

Radiographic correlates include:

* loss of joint space

* sclerosis

* bony collapse

* osteophytes

* subchondral cysts

* intra-articular osseous bodies

* disruption and distortion of ligamentous structures, and

* deformity/malalignment.

Enlargement of the joint is due to bone remodeling, accentuated by atrophy of surrounding muscles.

Pain may originate in bone (peri-osteal elevation associated with spur formation, increased intraosseous pressure), from periarticular structures (capsule, ligaments, tendon insertions, bursae), and from within the joint space (increased intra-articular pressure due to fluid accumulation, synovitis). Neither grade of joint space narrowing nor the presence of subchondral sclerosis correlate well with pain severity, in part due to the difficulty of measuring apposing articular surfaces by routine radiographs.

Treatment

Treatment of the osteoarthritic joint includes:

* patient education and reassurance,

* avoidance of excessive strain,

* strengthening the supporting muscle groups,

* weight loss,

* physical/occupational therapy, and

* therapy directed to specific joints.

Examples include the unloading of weight-bearing through use of braces or a cane carried in the contralateral hand, or aquatics exercises. For the knee, quadriceps muscle weakness has been identified as a factor for instability, responsive to isometric strengthening (16) by three times weekly exercises with increasing amounts of ankle weights.

Analgesics administered orally (acetaminophen, neurontin, tramadol) or topically (capsaicin, lidoderm) may provide significant relief. Cyclooxygenase (COX)-2-selective inhibitors or "classic" nonselective nonsteroidal (NSAIDs) may be appropriate for moderate-to-severe pain. Although COX-2 selective NSAIDs have a lower incidence of peptic ulcer disease, patients should still be placed on cytoprotective agents (misoprostol or a proton pump inhibitor) and monitored regularly (ie, every 2 to 3 months) for GI toxicity.

Adjunctive therapies for mild-to-moderate disease are the use of chondroprotective agents (ie, intra-articular hyaluronans). (17)

Nutraceuticals. There remains considerable professional and public interest in the use of disease-modifying agents for OA. Glucosamine

and chondroitin sulfate have been reported in laboratory studies to stimulate proteoglycan synthesis and inhibit degradative enzymes. Although quite different in molecular weight, both appear to be significantly absorbed after oral administration, with a low toxicity profile and delayed onset of action. Limited controlled clinical data offers support for efficacy with regard to symptom modification (ie, pain relief), with less support for actual joint structure modification. (18) The results of a large NIH-sponsored comparator trial for knee OA are expected in the near future.

The manufacture of nutriceutical/dietary supplements is not regulated, and therefore the various products available are not standardized, and also not subsidized by insurance. (18)

Conclusion

Long neglected as an "inevitable" disease of aging, OA is emerging as a disease of multiple genetic and environmental facets, the molecular bases of which are increasingly understood. A careful rheumatalogic history and thorough physical examination remain the hallmarks for diagnosing this "wear-and-tear" disorder. Managing the pain and disability that accompany OA remains an art.

Take Home points

Select features of the geriatric rheumatologic assessment

* Physician's ability to assess pain may be significantly limited by patient cognitive deficits

* Some features of intense inflammation (eg, fever) may be blunted, particularly in debilitated patients, or those on medications containing acetaminophen or nonsteroidal antiinflammatory drugs (NSAIDs)

* Limitation of motion may reflect an active disease process (eg, shoulder pain due to pseudogout), be a consequence of remote disease or injury (eg, rotator cuff disease due to prior falls), or both

* Careful attention should be paid to the functional consequences of foot and hand complaints--have the older adult remove their shoes and socks/stockings for evaluation frequently

* Activities of Daily Living (ADL) includes an evaluation for fall risk

* Careful consideration needs to be given to the effects of comorbidities and concomitant medications (including OTC and alternative therapies)

* Depression may be primary, a feature of disease (eg, PMR/GCA), medication-related, or reactive

* Evaluation may benefit from an interdisciplinary (eg, orthopedic, rehabilitation, pain management) approach

* Potential value of focused physical therapy and exercise training

* Importance of adequate pain control

Source: Created for Geriatrics by PD Gorevic, MD.

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Detach or photocopy this page, place an X in the boxes that correspond to your answers, fill in your name and address, and mail (see address below). Answers must be received by February 1, 2005. A score of at least 80% must be earned to receive CME credit.

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References

(1.) Lawrence RC, Helmick CG, Arnett FC, et al. Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis Rheum 1998; 41(5):778-99.

(2.) Centers for Disease Control. Public Health and Aging: Projected Prevalence of Self-Reported Arthritis or Chronic Joint Symptoms Among Persons Aged >65 Years--United States, 2005--2030. Morbidity and Mortality Weekly Report 2003; 52(21):489-91.

(3.) Aigner T, Dudhia J. Genomics of osteoarthritis. Curr Opin Rheumatol 2003; 15(5):634-40.

(4.) Loeser RF, Shakoor N. Aging or osteoarthritis: which is the problem? Rheum Dis Clin North Am 2003; 29(4):653-73.

(5.) Woolf AD, Pfleger, BP. Burden of major musculoskeletal conditions. Bull World Health Organ 2003; 81(9): 646-56.

(6.) Loeser RF, Jr., O'Rourke KS (Eds). Geriatric Rheumatology. Rheum Dis Clin North Am 2000; 26:415-691.

(7.) Landefeld CS. Improving Health Care for Older Persons. Ann Intern Med 2003; 139(5 pt 2):421-4.

(8.) DeGroot J, Verzijl N, Wenting-Van Wijk, BJG, et al. Accumulation of advanced glycation end products as a molecular mechanism for aging as a risk factor in osteoarthritis. Arthritis Rheum 2004; 50(4):1207-15.

(9.) Leveille SG. Musculoskeletal aging. Curr Opin Rheumatol 2004; 16(2):114-8.

(10.) McGann PE. Geriatric assessment for the rheumatologist. Rheum Dis Clin North Am 2000; 26(3):415-32. 11. Seguin R, Nelson M E. The benefits of strength training for older adults. Am J Prev Med 2003; 25(3 Suppl 2): 141-9.

(12.) Linton PJ, Dorshkind K. Age-related changes in lymphocyte development and function. Nat Immunol 2004; 5(2):133-9.

(13.) Ghia P, Prato G, Scielzo C, et al. Monoclonal CD5+ and CD5- B-lymphocyte expansions are frequent in the peripheral blood of the elderly. Blood 2004; 103(6):2337-42.

(14.) Bruunsgaard, H, Pedersen, M, Pedersen BK. Aging and proinflammatory cytokines. Curr Opin Hematol 2001; 8(3): 131-6.

(15.) Ramos-Casals M, Garcia-Carrasco M, Brito MP, et al. Autoimmunity and geriatrics: clinical significance of autoimmune manifestations in the elderly. Lupus 2003; 12(6):341-55.

(16.) Sharma L, Dunlop DD, Cahue S, Song J, Hayes KW. Quadriceps strength and osteoarthritis progression in malaligned and lax knees. Ann Intern Med 2003; 138(8):613-9.

(17.) Recommendations for the Medical Management of Osteoarthritis of the Hip and Knee: 2000 Update. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Arthritis Rheum 2000; 43(9): 1905-15.

(18.) Zerkak D, Dougados M. The use of glucosamine therapy in osteoarthritis. Curr Rheumatol Rep 2004; 6(1):41-5.

Dr. Gorevic is professor of medicine and director of rheumatology, Mount Sinai Medical Center, New York, NY. Disclosures: The author has no real or apparent conflict of interest due to affiliation with any company or manufacturer whose products or devices are mentioned in this article.

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