Osteoarthritis

Osteoarthritis
Classification and external resources
ICD-10	M15-M19, M47
ICD-9	715
OMIM	165720
DiseasesDB	9313
MedlinePlus	000423
eMedicine	med/1682 orthoped/427 pmr/93 radio/492
MeSH	D010003

Osteoarthritis (OA) also known as degenerative arthritis or degenerative joint disease, is a group of mechanical abnormalities involving degradation of joints,^[1] including articular cartilage and subchondral bone. Symptoms may include joint pain, tenderness, stiffness, locking, and sometimes an effusion. A variety of causes—hereditary, developmental, metabolic, and mechanical—may initiate processes leading to loss of cartilage. When bone surfaces become less well protected by cartilage, bone may be exposed and damaged. As a result of decreased movement secondary to pain, regional muscles may atrophy, and ligaments may become more lax.^[2]

Treatment generally involves a combination of exercise, lifestyle modification, and analgesics. If pain becomes debilitating, joint replacement surgery may be used to improve the quality of life. OA is the most common form of arthritis,^[2] and the leading cause of chronic disability in the United States.^[3] It affects about 8 million people in the United Kingdom and nearly 27 million people in the United States.

Classification

Osteoarthritis can be classified into either primary or secondary depending on whether or not there is an identifiable underlying cause.

Signs and symptoms

Bouchard's nodes and Heberden's nodes may form in osteoarthritis

The main symptom is pain, causing loss of ability and often stiffness. "Pain" is generally described as a sharp ache, or a burning sensation in the associate muscles and tendons. OA can cause a crackling noise (called "crepitus") when the affected joint is moved or touched, and patients may experience muscle spasm and contractions in the tendons. Occasionally, the joints may also be filled with fluid. Humid and cold weather increases the pain in many patients.^[4][5]

OA commonly affects the hands, feet, spine, and the large weight bearing joints, such as the hips and knees, although in theory, any joint in the body can be affected. As OA progresses, the affected joints appear larger, are stiff and painful, and usually feel better with gentle use but worse with excessive or prolonged use, thus distinguishing it from rheumatoid arthritis.

In smaller joints, such as at the fingers, hard bony enlargements, called Heberden's nodes (on the distal interphalangeal joints) and/or Bouchard's nodes (on the proximal interphalangeal joints), may form, and though they are not necessarily painful, they do limit the movement of the fingers significantly. OA at the toes leads to the formation of bunions, rendering them red or swollen. Some people notice these physical changes before they experience any pain.

OA is the most common cause of joint effusion, sometimes called water on the knee in lay terms, an accumulation of excess fluid in or around the knee joint.^[6]

Causes

Some investigators believe that mechanical stress on joints underlies all osteoarthritis, with many and varied sources of mechanical stress, including misalignments of bones caused by congenital or pathogenic causes; mechanical injury; overweight; loss of strength in muscles supporting joints; and impairment of peripheral nerves, leading to sudden or uncoordinated movements that overstress joints.^[7] However exercise, including running in the absence of injury, has not been found to increase one's risk of developing osteoarthritis.^[8] Nor has cracking ones knuckles been found to play a role.^[9]

Primary

Primary osteoarthritis of the left knee. Note the osteophytes, narrowing of the joint space (arrow), and increased subchondral bone density (arrow).

Primary osteoarthritis is a chronic degenerative disorder related to but not caused by aging, as there are people well into their nineties who have no clinical or functional signs of the disease. As a person ages, the water content of the cartilage decreases^[10] as a result of a reduced proteoglycan content, thus causing the cartilage to be less resilient. Without the protective effects of the proteoglycans, the collagen fibers of the cartilage can become susceptible to degradation and thus exacerbate the degeneration. Inflammation of the surrounding joint capsule can also occur, though often mild (compared to that which occurs in rheumatoid arthritis). This can happen as breakdown products from the cartilage are released into the synovial space, and the cells lining the joint attempt to remove them. New bone outgrowths, called "spurs" or osteophytes, can form on the margins of the joints, possibly in an attempt to improve the congruence of the articular cartilage surfaces. These bone changes, together with the inflammation, can be both painful and debilitating.

A number of studies have shown that there is a greater prevalence of the disease among siblings and especially identical twins, indicating a hereditary basis.^[11] Up to 60% of OA cases are thought to result from genetic factors.

Both primary generalized nodal OA and erosive OA (EOA. also called inflammatory OA) are sub-sets of primary OA. EOA is a much less common, and more aggressive inflammatory form of OA which often affects the DIPs and has characteristic changes on X-Ray.

Secondary

This type of OA is caused by other factors but the resulting pathology is the same as for primary OA:

• Congenital disorders of joints
• Diabetes.
• Inflammatory diseases (such as Perthes' disease), (Lyme disease), and all chronic forms of arthritis (e.g. costochondritis, gout, and rheumatoid arthritis). In gout, uric acid crystals cause the cartilage to degenerate at a faster pace.
• Injury to joints, as a result of an accident or orthodontic operations.
• Septic arthritis (infection of a joint )
• Ligamentous deterioration or instability may be a factor.
• Marfan syndrome
• Obesity
• Alkaptonuria
• Hemochromatosis and Wilson's disease

Diagnosis

Diagnosis is made with reasonable certainty based on history and clinical examination.^[12][13] X-rays may confirm the diagnosis. The typical changes seen on X-ray include: joint space narrowing, subchondral sclerosis (increased bone formation around the joint), subchondral cyst formation, and osteophytes.^[14] Plain films may not correlate with the findings on physical examination or with the degree of pain.^[15] Usually other imaging techniques are not necessary to clinically diagnose osteoarthritis.

In 1990, the American College of Rheumatology, using data from a multi-center study, developed a set of criteria for the diagnosis of hand osteoarthritis based on hard tissue enlargement and swelling of certain joints. These criteria were found to be 92% sensitive and 98% specific for hand osteoarthritis versus other entities such as rheumatoid arthritis and spondyloarthropathies.^[16]

Related pathologies whose names may be confused with osteoarthritis include pseudo-arthrosis. This is derived from the Greek words pseudo, meaning "false", and arthrosis, meaning "joint." Radiographic diagnosis results in diagnosis of a fracture within a joint, which is not to be confused with osteoarthritis which is a degenerative pathology affecting a high incidence of distal phalangeal joints of female patients.

Treatment

Lifestyle modification (such as weight loss and exercise) and analgesics are the mainstay of treatment. Acetaminophen / paracetamol is used first line and NSAIDS are only recommended as add on therapy if pain relief is not sufficient.^[17] This is due to the relative greater safety of acetaminophen.^[17]

Lifestyle modification

Exercise

For most people with OA, graded exercise should be the mainstay of their self-management. Moderate exercise leads to improved functioning and decreased pain in people with osteoarthritis of the knee.^[18][19]

Education

For overweight people, weight loss may be an important factor. Patient education has been shown to be helpful in the self-management of arthritis. It decreases pain, improving function, reducing stiffness and fatigue, and reducing medical usage.^[19] A meta-analysis has shown patient education can provide on average 20% more pain relief when compared to NSAIDs alone in patients with hip OA.^[19]

Physical

There is sufficient evidence to indicate that physical interventions can reduce pain and improve function.^[20] There is some evidence that manual therapy is more effective than exercise for the treatment of hip osteoarthritis, however this evidence could be considered to be inconclusive.^[21] Functional, gait, and balance training has been recommended to address impairments of proprioception, balance, and strength in individuals with lower extremity arthritis as these can contribute to higher falls in older individuals.^[22] Splinting of the thumb for OA of the base of the thumb leads to improvements after one year.^[23]

Medication

Analgesics

Acetaminophen is the first line treatment for OA.^[17][24] For mild to moderate symptoms effectiveness is similar to NSAIDs, though for more severe symptoms NSAIDs may be more effective.^[17] Non-steroidal anti-inflammatory drugs (NSAID) such as ibuprofen while more effective in severe cases are associated with greater side effects such as gastrointestinal bleeding.^[17] Another class of NSAIDs, COX-2 selective inhibitors (such as celecoxib) are equally effective to NSAIDs but no safer in terms of side effects. They are however much more expensive. There are several NSAIDs available for topical use including diclofenac. They have fewer systemic side-effects and at least some therapeutic effect.^[25] While opioid analgesic such as morphine and fentanyl improve pain this benefit is outweighed by frequent adverse events and thus they should not routinely be used.^[26]

Other

Oral steroids are not recommended in the treatment of OA because of their modest benefit and high rate of adverse effects. Injection of glucocorticoids (such as hydrocortisone) leads to short term pain relief that may last between a few weeks and a few months.^[27] Topical capsaicin and joint injections of hyaluronic acid have not been found to lead to significant improvement.^[25][28][29]

Tanezumab, a monoclonal antibody that binds and inhibits nerve growth factor, appears to relieve joint pain enough to improve function in people with osteoarthritis of the knee, according to research published online Sept. 29 in the New England Journal of Medicine. The FDA is reviewing the safety of tanezumab that could still emerge as an effective treatment for the pain of osteoarthritis.^[30][31]

While electrostimulation techniques (NEST) have been used for twenty years to treat osteoarthritis in the knee, a Cochrane Review of studies determined that there is no evidence to show that it reduces pain or disability.^[32]

A double-blind, randomized controlled trial using radiofrequency ablation (RF) for the treatment of chronic knee pain due to osteoarthritis of the knee in 38 elderly patients (control n=18, RF n= 17) demonstrated improved visual analogue scale scores (VAS) and Oxford knee scores (OKS) in the RF group at 1, 4, and 12 weeks from baseline. The VAS at baseline was 77.2 ± 7.5 in the control group and 78.2 ± 13.8 in the RF group. At 12 weeks post-procedure the VAS was 77.9 ± 9.8 in the control group and 42.4 ± 25.4 in the RF group. The OKS at 12 weeks was 38.9 ± 4.9 in the control group and 27.4 ± 10.2 in the RF group. In addition, ten participants in the RF group (59%) achieved a primary outcome of at least 50% knee pain relief at 12 weeks, whereas no participants in the control group achieved this primary outcome.^[33]

Surgery

If the above management is ineffective, joint replacement surgery or resurfacing may be required in advanced cases. Arthroscopic surgical intervention for osteoarthritis of the knee however has been found to be no better than placebo at relieving symptoms.^[34]

Alternative medicine

Many alternative medicines are purporting to decrease pain associated with arthritis. However, there is no evidence supporting benefits for most alternative treatments including: vitamin A, C, and E, ginger, turmeric, omega-3 fatty acids, chondroitin sulfate and glucosamine. These treatments are thus not recommended.^[35][36] Glucosamine was once believed to be effective^[37], but a recent analysis has found that it is no better than placebo.^[38] S-Adenosyl methionine may relieve pain similar to nonsteroidal anti-inflammatory drugs.^[37][39]

Acupuncture

A Cochrane review found that while acupuncture leads to a statistically significant improvement in pain, this improvement is small and may be of questionable clinical significance. Waiting list-controlled trials for peripheral joint osteoarthritis do show clinically relevant benefits, but these may be due to placebo effects.^[40] Acupuncture does not seem to produce long-term benefits.^[41]

Glucosamine

Controversy surrounds glucosamine.^[42] A 2010 meta-analysis has found that it is no better than placebo.^[38] Some older reviews conclude that glucosamine sulfate was an effective treatment^[43][44] while some others have found it ineffective.^[45][46] A difference has been found between trials involving glucosamine sulfate and glucosamine hydrochloride, with glucosamine sulfate showing a benefit and glucosamine hydrochloride not. The Osteoarthritis Research Society International (OARSI) recommends that glucosamine be discontinued if no effect is observed after six months.^[47]

Mud pack therapy

Mud pack therapy has been suggested to temporarily relieve pain in patients with osteoarthritis of the knees. According to researchers of the Ben Gurion University of the Negev, treatment with mineral-rich mud compresses such as that of those extracted from the Dead Sea, can be used to augment conventional medical therapy in these patients.^[48]

Epidemiology

Disability-adjusted life year for osteoarthritis per 100,000 inhabitants in 2004.^[49]

  no data

  ≤ 200

  200-220

  220-240

  240-260

  260-280

  280-300

  300-320

  320-340

  340-360

  360-380

  380-400

  ≥ 400

Osteoarthritis affects nearly 27 million people in the United States, accounting for 25% of visits to primary care physicians, and half of all NSAID prescriptions. It is estimated that 80% of the population have radiographic evidence of OA by age 65, although only 60% of those will have symptoms.^[50] In the United States, hospitalizations for osteoarthritis increased from 322,000 in 1993 to 735,000 in 2006.^[51]

Etymology

Osteoarthritis is derived from the Greek word "osteo", meaning "of the bone", "arthro", meaning "joint", and "itis", meaning inflammation, although the "itis" of osteo arthritis is somewhat of a misnomer—inflammation is not a conspicuous feature.

Fossil record

Main article: Paleopathology

Evidence for osteoarthritis found in the fossil record is studied by paleopathologists, specialists in ancient disease and injury. Osteoarthritis has been reported in fossils of the large carnivorous dinosaur Allosaurus fragilis.^[52]

Gallery

• 

  Damaged cartilage in gross pathological specimen from sows. (a) cartilage erosion (b)cartilage ulceration (c)cartilage repair (d)osteophyte (bone spur) formation.

• 

  Histopathology of osteoarthrosis of a knee joint in an elderly female patient.

• 
• 
• 
• 

  Severe osteoarthritis and osteopenia of the carpel joint and 1st carpometacarpel joint.

See also

• Eburnation
• Osteoarthritis in Canines

References

1. ^ "osteoarthritis" at Dorland's Medical Dictionary
2. ^ ^{a b} Conaghan, Phillip. "Osteoarthritis - National clinical guideline for care and management in adults" (PDF). http://www.nice.org.uk/nicemedia/pdf/CG059FullGuideline.pdf. Retrieved 2008-04-29. 
3. ^ Centers for Disease Control and Prevention (CDC) (February 2001). "Prevalence of disabilities and associated health conditions among adults—United States, 1999". MMWR Morb Mortal Wkly Rep. 50 (7): 120–5. PMID 11393491. 
4. ^ McAlindon, T., Formica, M., Schmid, C.H., & Fletcher, J. (2007). Changes in barometric pressure and ambient temperature influence osteoarthritis pain. The American Journal of Medicine, 120(5), 429-434.
5. ^ MedlinePlus Encyclopedia Osteoarthritis
6. ^ Water on the knee, MayoClinic.com
7. ^ Brandt KD, Dieppe P, Radin E (January 2009). "Etiopathogenesis of osteoarthritis". Med. Clin. North Am. 93 (1): 1–24, xv. doi:10.1016/j.mcna.2008.08.009. PMID 19059018. 
8. ^ Bosomworth NJ (September 2009). "Exercise and knee osteoarthritis: benefit or hazard?". Can Fam Physician 55 (9): 871–8. PMC 2743580. PMID 19752252. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2743580. 
9. ^ Deweber, K; Olszewski, M, Ortolano, R (2011 Mar-Apr). "Knuckle cracking and hand osteoarthritis.". Journal of the American Board of Family Medicine : JABFM 24 (2): 169–74. doi:10.3122/jabfm.2011.02.100156. PMID 21383216. 
10. ^ Simon, H; Zieve D (2005-05-08). "Osteoarthritis". University of Maryland Medical Center. http://www.umm.edu/patiented/articles/what_osteoarthritis_000035_1.htm. Retrieved 2009-04-25. 
11. ^ Valdes AM, Spector TD (August 2008). "The contribution of genes to osteoarthritis". Rheum Dis Clin North Am. 34 (3): 581–603. doi:10.1016/j.rdc.2008.04.008. PMID 18687274. 
12. ^ Zhang W, Doherty M, Peat G, et al. (March 2010). "EULAR evidence-based recommendations for the diagnosis of knee osteoarthritis". Ann. Rheum. Dis. 69 (3): 483–9. doi:10.1136/ard.2009.113100. PMID 19762361. 
13. ^ Bierma-Zeinstra SM, Oster JD, Bernsen RM, Verhaar JA, Ginai AZ, Bohnen AM. Joint space narrowing and relationship with symptoms and signs in adults consulting for hip pain in primary care. J Rheumatol. 2002;29:1713-1718
14. ^ "Osteoarthritis (OA): Joint Disorders: Merck Manual Professional". http://www.merck.com/mmpe/sec04/ch034/ch034e.html. 
15. ^ Phillips CR and Brasington RD (2010). "Osteoarthritis treatment update: Are NSAIDs still in the picture?". Journal of Musculoskeletal Medicine 27 (2). http://www.musculoskeletalnetwork.com/display/article/1145622/1517357. 
16. ^ Altman R, Alarcón G, Appelrouth D, et al. (1990). "The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hand". Arthritis Rheum. 33 (11): 1601–10. doi:10.1002/art.1780331101. PMID 2242058. 
17. ^ ^{a b c d e} Flood J (March 2010). "The role of acetaminophen in the treatment of osteoarthritis". Am J Manag Care 16 Suppl Management: S48–54. PMID 20297877. 
18. ^ http://www.cfp.ca/cgi/content/abstract/55/9/871?etoc
19. ^ ^{a b c} Hip Pain and Mobility Deficits – Hip Osteoarthritis: Clinical Practice Guidelines Linked to the International Classification of Functioning, Disability, and Health from the Orthopaedic Section of the American Physical Therapy Association J Orthop Sports Phys Ther 2009;39(4):A1-A25. doi:10.2519/jospt.2009.0301
20. ^ Page CJ, Hinman RS, Bennell KL (2011). "Physiotherapy management of knee osteoarthritis.". Int J Rheum Dis 14 (2): 145-152. PMID 21518313. 
21. ^ French HP, Brennan A, White B, Cusack T (2011). "Manual therapy for osteoarthritis of the hip or knee - a systematic review". Man Ther 16 (2): 109–117. PMID 21146444. 
22. ^ Sturnieks DL, Tiedemann A, Chapman K, Munro B, Murray SM, Lord SR. Physiological risk factors for falls in older people with lower limb arthritis. J Rheumatol. 2004;31:2272-2279
23. ^ "Splint for Base-of-Thumb Osteoarthritis: A Randomized Trial -- Rannou et al. 150 (10): 661 -- Annals of Internal Medicine". http://www.annals.org/cgi/content/abstract/150/10/661. e
24. ^ Zhang W, Moskowitz RW, Nuki G, et al. (September 2007). "OARSI recommendations for the management of hip and knee osteoarthritis, part I: critical appraisal of existing treatment guidelines and systematic review of current research evidence". Osteoarthr. Cartil. 15 (9): 981–1000. doi:10.1016/j.joca.2007.06.014. PMID 17719803. 
25. ^ ^{a b} Altman R, Barkin RL (March 2009). "Topical therapy for osteoarthritis: clinical and pharmacologic perspectives". Postgrad Med 121 (2): 139–47. doi:10.3810/pgm.2009.03.1986. PMID 19332972. 
26. ^ Nüesch E, Rutjes AW, Husni E, Welch V, Jüni P (2009). Nüesch, Eveline. ed. "Oral or transdermal opioids for osteoarthritis of the knee or hip". Cochrane Database Syst Rev (4): CD003115. doi:10.1002/14651858.CD003115.pub3. PMID 19821302. 
27. ^ Arroll B, Goodyear-Smith F (April 2004). "Corticosteroid injections for osteoarthritis of the knee: meta-analysis". BMJ 328 (7444): 869. doi:10.1136/bmj.38039.573970.7C. PMC 387479. PMID 15039276. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=387479. 
28. ^ Arrich J, Piribauer F, Mad P, Schmid D, Klaushofer K, Müllner M (April 2005). "Intra-articular hyaluronic acid for the treatment of osteoarthritis of the knee: systematic review and meta-analysis". CMAJ 172 (8): 1039–43. doi:10.1503/cmaj.1041203. PMC 556045. PMID 15824412. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=556045. 
29. ^ Richette P, Ravaud P, Conrozier T, et al. (March 2009). "Effect of hyaluronic acid in symptomatic hip osteoarthritis: a multicenter, randomized, placebo-controlled trial". Arthritis Rheum. 60 (3): 824–30. doi:10.1002/art.24301. PMID 19248105. 
30. ^ Tanezumab Is Effective Osteoarthritis Treatment. Doctors Lounge Website. Located at http://www.doctorslounge.com/index.php/news/pb/14401. Last accessed on September 29, 2010.
31. ^ Nancy E. Lane, M.D., Thomas J. Schnitzer, M.D., Ph.D., Charles A. Birbara, M.D. et al. Tanezumab for the Treatment of Pain from Osteoarthritis of the Knee. NEJM. Sept 15, 2010.
32. ^ Rutjes AW, Nüesch E, Sterchi R, et al. (2009). Rutjes, Anne WS. ed. "Transcutaneous electrostimulation for osteoarthritis of the knee". Cochrane Database Syst Rev (4): CD002823. doi:10.1002/14651858.CD002823.pub2. PMID 19821296. 
33. ^ Choi, Woo-Jong; Hwang, Song, Leem, Kang, Park, Shin (March 2011). "Radiofrequency treatment relieves chronic knee osteoarthritis pain: A double-blind randomized controlled trial". Pain 152 (3): 481–487. doi:10.1016/j.pain.2010.09.029. PMID 21055873. 
34. ^ Moseley JB, O'Malley K, Petersen NJ, et al. (2002). "A controlled trial of arthroscopic surgery for osteoarthritis of the knee is proven to bring an improvement lasting for about two years". The New England journal of medicine 347 (2): 81–8. doi:10.1056/NEJMoa013259. PMID 12110735. http://content.nejm.org/cgi/content/full/347/2/81. 
35. ^ Rosenbaum CC, O'Mathúna DP, Chavez M, Shields K (2010). "Antioxidants and antiinflammatory dietary supplements for osteoarthritis and rheumatoid arthritis". Altern Ther Health Med 16 (2): 32–40. PMID 20232616. 
36. ^ Reichenbach S, Sterchi R, Scherer M, et al. (2007). "Meta-analysis: chondroitin for osteoarthritis of the knee or hip". Ann. Intern. Med. 146 (8): 580–90. PMID 17438317. 
37. ^ ^{a b} Hardy ML, Coulter I, Morton SC, et al. (August 2003). "S-adenosyl-L-methionine for treatment of depression, osteoarthritis, and liver disease". Evid Rep Technol Assess (Summ) (64): 1–3. PMID 12899148. 
38. ^ ^{a b} "Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis -- Wandel et al. 341 -- bmj.com". http://www.bmj.com/content/341/bmj.c4675. 
39. ^ De Silva, V; El-Metwally, A, Ernst, E, Lewith, G, Macfarlane, GJ, Arthritis Research UK Working Group on Complementary and Alternative, Medicines (2011 May). "Evidence for the efficacy of complementary and alternative medicines in the management of osteoarthritis: a systematic review.". Rheumatology (Oxford, England) 50 (5): 911–20. PMID 21169345. 
40. ^ Manheimer E, Cheng K, Linde K, et al. (2010). Manheimer, Eric. ed. "Acupuncture for peripheral joint osteoarthritis". Cochrane Database Syst Rev (1): CD001977. doi:10.1002/14651858.CD001977.pub2. PMID 20091527. 
41. ^ Wang, S; Kain ZN; White PF (2008). [www.thecochranelibrary.com/.../file/Acupuncture.../CD001977.pdf "Acupuncture Analgesia: II. Clinical Considerations"]. Anesth Analg 106 (2): 611–21. doi:10.1213/ane.0b013e318160644d. PMID 18227323. www.thecochranelibrary.com/.../file/Acupuncture.../CD001977.pdf. 
42. ^ The effects of Glucosamine Sulphate on OA of the knee joint. BestBets.
43. ^ Poolsup N, Suthisisang C, Channark P, Kittikulsuth W (2005). "Glucosamine long-term treatment and the progression of knee osteoarthritis: systematic review of randomized controlled trials". The Annals of pharmacotherapy 39 (6): 1080–7. doi:10.1345/aph.1E576. PMID 15855241. 
44. ^ Black C, Clar C, Henderson R, et al. (November 2009). "The clinical effectiveness of glucosamine and chondroitin supplements in slowing or arresting progression of osteoarthritis of the knee: a systematic review and economic evaluation". Health Technol Assess 13 (52): 1–148. doi:10.3310/hta13520 (inactive 2010-07-30). PMID 19903416. 
45. ^ McAlindon T, Formica M, LaValley M, Lehmer M, Kabbara K (November 2004). "Effectiveness of glucosamine for symptoms of knee osteoarthritis: results from an internet-based randomized double-blind controlled trial". Am J Med 117 (9): 643–9. doi:10.1016/j.amjmed.2004.06.023. PMID 15501201. 
46. ^ Vlad SC, Lavalley MP, McAlindon TE, Felson DT (2007). "Glucosamine for pain in osteoarthritis: Why do trial results differ?". Arthritis & Rheumatism 56 (7): 2267–77. doi:10.1002/art.22728. PMID 17599746. 
47. ^ Zhang W, Moskowitz RW, Nuki G, et al. (February 2008). "OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines". Osteoarthr. Cartil. 16 (2): 137–62. doi:10.1016/j.joca.2007.12.013. PMID 18279766. http://www.oarsi.org/pdfs/part_II_OARSI_recommendations_for_management_of_hipknee_OA_2007.pdf. 
48. ^ Therapy With Mud Compresses for Knee Osteoarthritis: Comparison of Natural Mud Preparations With Mineral-Depleted Mud. Flusser, Daniel; Abu-Shakra, Mahmoud; Friger, Michael; Codish, Shlomi; Sukenik, Shaul. Journal of Clinical Rheumatology. August 2002 - Volume 8 - Issue 4 - pp 197-203
49. ^ "WHO Disease and injury country estimates". World Health Organization. 2009. http://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html. Retrieved Nov. 11, 2009. 
50. ^ Green GA (2001). "Understanding NSAIDs: from aspirin to COX-2". Clin Cornerstone 3 (5): 50–60. doi:10.1016/S1098-3597(01)90069-9. PMID 11464731. 
51. ^ Hospitalizations for Osteoarthritis Rising Sharply Newswise, Retrieved on September 4, 2008.
52. ^ Molnar, R. E., 2001, Theropod paleopathology: a literature survey: In: Mesozoic Vertebrate Life, edited by Tanke, D. H., and Carpenter, K., Indiana University Press, p. 337-363.

External links

• Arthritis Ireland
• American College of Rheumatology Factsheet on OA
• Osteoarthritis The Arthritis Foundation
• Osteoarthritis at WebMD
• [1] American Chiropractic Association