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Written by: Dr Jeremy Steinberg – created: 15 August 2021; last modified: 26 February 2023

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Osteoarthritis (OA) is a degenerative joint disease that is characterised by cartilage loss, subchondral bone remodelling, and osteophytosis. It is a final common pathway for a variety of risk factors. Clinically there may be variable reduced range of motion, swelling, and joint pain.



Osteoarthritis is a common condition that affects a significant proportion of the global population. According to the WHO, an estimated 240 million individuals worldwide have symptomatic OA. The prevalence of OA is higher in women than in men, with 18% of women over the age of 60 and 10% of men over the age of 60 experiencing symptoms of OA. In New Zealand, the prevalence of OA is approximately 10%. The prevalence rates of OA among different ethnic groups in New Zealand vary, with Māori experiencing a prevalence of 7%, Pacific peoples 4.8%, Asian populations 2.5%, and European 12.5%.

In North America, African Americans have a higher prevalence and severity of OA compared to white Americans. Chinese women also have a higher prevalence of knee OA than white American women, although hip OA is less common in Chinese women. Additionally, lower socioeconomic status and rural communities are associated with an increased prevalence of OA. Age is a significant risk factor for OA, with the prevalence increasing over time, particularly among women. However, the increasing prevalence of OA is not fully explained by the aging population or the rising rates of obesity, suggesting that other factors may also contribute to its development.[1][2]

Prevalence by Site

OA prevalence by site in >45-50 year olds[3]
Body Part Radiographic Prevalence Symptomatic Prevalence
Knee ~35% ~13.8-17.4%
Hip ~20% ~4.2-10%
Hand ~30-70% ~7-20%
Foot and ankle 0-97% Data less accurate

Risk Factors

There is no single distinct aetiology. Rather there are a variety of risk factors.

Person-Level and Joint-Level Risk Factors
Person-Level Factors Joint-Level Factors




Rural Residence

Family History and Genetic Factors



High Bone Mineral Density

Metformin Use


Joint Injury (shaft or joint fracture)

Joint Malalignment†

Joint Deformity/Abnormal Joint Shape

Muscle Weakness†

Leg Length Discrepancy

Physically Demanding Occupations

Previous Disease (RA, gout, etc)

† Mixed evidence

Person Level Risk Factors

There is a clear association between weight and the risk of developing OA, especially in the knee joint. Obesity, in particular, has been shown to increase the risk of OA by up to threefold. The effects of obesity are stronger for some joints than others (for example stronger for knee than hip) Excess weight puts additional stress on the joints and increases inflammation. There is mixed evidence for metabolic syndrome as a risk factor when controlling for weight.[4]

Any diseases that effect synovial joints such as rheumatoid arthritis and gout, which can alter the shape of the joint and predispose to the development of secondary osteoarthritis

Vitamin D has been the subject of numerous studies on its potential impact on osteoarthritis. However, the results of these studies have been conflicting, with some showing positive effects and others showing no significant differences. While supplementation with vitamin D did not show any significant differences in outcomes, those who maintained adequate vitamin D levels tended to have better outcomes. It is possible that Vitamin D and K are important in combination.[4]

There is some evidence to suggest that certain dietary factors may have a positive influence. For instance, higher dietary fiber intake has been associated with better outcomes for individuals with OA. Additionally, consuming soy milk and following a Mediterranean diet have also been linked to improved OA outcomes. However, the evidence for these dietary factors is less extensive than that for vitamin D and requires further investigation.[4]

Several studies have revealed that higher bone mineral density is linked to an increased risk of radiographic knee and hip osteoarthritis (OA). However, the majority of studies have not observed a correlation between high bone mineral density and the progression of the disease. This suggests that while high bone density may contribute to the onset of OA, it may not necessarily impact its severity or rate of progression.[4]

Other factors include smoking (mixed evidence), metformin (possibly reduced medial compartment loss), high blood pressure (mixed evidence), low birth weight (likely association), and lead and organic pollutants (likely association).[4]

Joint Level Risk Factors

Developmental risk factors include abnormal biomechanics (such as valgus and varus knee alignment), and abnormal joint morphology (such as hip dysplasia, slipped epiphysis, Perthes). Acetabular dysplasia, cam-type deformity and acetabular retroversion/excess anteversion are independently associated with incident or progressive hip OA. A recent extensive genetic epidemiology review suggests specific genes are linked to both joint shape and OA, including Growth Differentiating Factor 5, SOX9, Parathyroid hormone-like hormone, Collagen type XI, and Astrotactin 2.[4][5]

Previous injury, for example fracture of a shaft leading to a joint can result in abnormal forces on the joint, and fracture of a joint itself altering its shape altering the mechanical loading. Trauma also includes surgical intervention such as meniscectomy which predisposes to osteoarthritis. Injury and subsequent surgery are strong risk factors. The most evidence exists for the knee with ACL rupture (OR 4.2), isolated meniscal injury (OR 6.3), and combined ACL and meniscal injury (OR 6.4). There is mixed evidence that surgery alone could be a risk factor.[4][5]

Multiple studies demonstrate an association between limb length inequality and prevalent radiographic, incident symptomatic, and progressive radiographic hip and knee OA. Radiographic OA may be more common in the shorter limb.[4]

There is mixed evidence for muscle weakness. Knee extensor weakness has an OR of 1.7 for developing knee OA over a follow up of 2-14 years. Those with knee OA are 4 times more likely to have knee extensor or flexor weakness. Lower strength may be associated with progression of symptoms and function, but probably not radiographic changes/structural deterioration.[4]

Coronal malignment is a strong predictor of progression of OA. However there is mixed evidence if varus or valgus is associated with increased incidence or prevalence of OA.[4]

Physically demanding occupations are associated with higher risk of OA. Some studies suggest a dose-response relationship. At risk occupations include: farmer, builder, metal worker, floor layer, carpenter, miner, houseworker, service worker and craftsman. Higher exposures to occupational lifting, kneeling, climbing, squatting, and standing were potential mechanisms.[4]

Participation in physical activity generally not associated with OA and likely reduces risk of OA in most circumstances. Recreational runners are likely to be protected compared to competitive runners and non-runners.[4]

Increased T2 signal on MRI is associated with radiographic knee OA at 2 years and total knee replacement at 5 years, suggesting an early biomarker in the diagnosis and prediction of OA. Infrapatella fat pad signal alterations were associated with incident OA over 4 years, as well as progression of OA over 2 years and arthroplasty amongst those with OA over 5 years.[4]


There is a current interest in defining and understand OA phenotypes. The purpose is to identify subgroups of patients who may respond differently to treatment strategies. There are clinical vs structural aspects to differentiation.[4]

A review identified six main phenotypes, and when applied to a large cohort there is ~20% overlap between groups:

  1. Chronic pain in which central mechanisms are prominent
  2. Inflammatory
  3. Metabolic syndrome
  4. Bone and cartilage metabolism
  5. Mechanical overload/varus malalignment
  6. Minimal joint disease


The pathophysiology of osteoarthritis is often described as "wear and tear." A more accurate statement is "tear, flare, and repair" because joints are metabolically active structures and not simply mechanical structures. The term tear reflects factors such as obesity, overuse, and malalignment. Flare represents inflammation. The repair process can lead to a symptom free but structurally altered joint, or can be suboptimal with a mismatch between repair and degradation resulting in persistent pain and disability.

Extracellular Matrix Components

Main article: Fibrous Connective Tissues

The extracellular matrix of cartilage is made up of two main macromolecules: type II collagen and aggrecan. Aggrecan is a large aggregating proteoglycan which retains water. The type II collagen provides intrinsic resistance to tension, and allows the proteoglycans to swell against it to provide resistance to compression. There are other more minor components that also play a role in matrix structure such as other forms of collagen (e.g. types IX, XI, and VI collagen), proteoglycans (e.g. biglycan, decorin), and cartilage oligomerix matrix protein.

Matrix Synthesis and Degradation

See also: Synovial Joints

In the normal state there is an equilibrium between synthesis and degradation of the extracellular matrix. Synthesis refers to the production of the collagens and proteoglycans, and this process is stimulated by a variety of factors such as IGF, TGF, and FGF.

In osteoarthritis there is a change in the ratio of the KS/CS ratio with a preference for keratan sulphate which has only one compared to two negative charge sites and so has less ability to retain water.

Degradation refers to the production of a variety of MMPs and ADAMTs proteinases whose function is to degrade the matrix. Degradation allows for clearing of old components so that fresh components can be synthesised. The degradative process is controlled by the TIMP compounds. The chondrocyte is continuously metabolically active with continuous synthetic and degradative processes.

The classic degradative enzymes, produced in the chondrocyte and synovium, are the metalloproteinases (MMPs) which facilitate the turnover of the extracellular matrix in both normal and osteoarthritic states. It is thought that MMP-1 is the primary collagenase in rheumatoid arthritis, and MMP-13 is the primary collagenase in osteoarthritis. The role of MMP-1 may be distinct in each joint, being elevated in knee osteoarthritis, and reduced in hip osteoarthritis. MMP-3 on the other hand is reduced in osteoarthritis, and elevated in rheumatoid arthritis. There are various other changes in MMP expression in osteoarthritis.[6]

The A Disintegrin And Metalloproteinase with Thrombospondin Motifs (ADAMTS) group of proteinases were discovered later and are involved in both the synthesis and degradation of the extracellular matrix. ADAMTS enzymes include the procollagen propeptidases (ADAMTS-2, -3, and -14) that are involved in collagen biosynthesis, and the aggrecanases (ADAMTS-1, -4, -5, -9, and -15) that are involved in aggrecan degradation. There are various changes seen in osteoarthritis with the expression and activity of these proteinases.[7] ADAMS-4 and -5 are key proteinases active in early OA. They act to cleave the interglobular region between G1 and G2, leaving a shortened aggrecan with fewer fixed charges.

In the arthritides there is a disruption of this balance so that the degradative processes are favoured with elevated levels of active proteinases leading to the destruction of collagen and aggrecans in the cartilage. In osteoarthritis it is the proteinases that are produced by chondrocytes that play a major role. While in the highly inflamed rheumatoid joint, it is the chondrocytes, synovial cells, and inflammatory cells that all contribute to degradation.

There is initially a gradual loss of proteoglycans, and this results in the collagen of the matrix being exposed. After exposure of the collagen fibres, these can be acted on by proteinases.

There are also important inhibitors, and the tissue inhibitors of metalloproteinases (TIMPs) are able to inhibit the activity of MMPs and potentially ADAMTS. In osteoarthritis there can be an imbalance between metalloproteinase and TIMP activities[6]

Cartilage oligomerix protein (COMP) is also known as thrombospondin 5. It's exact function remains unclear but it appears to be an important regulator of extracellular matrix assembly and stabilisation of the matrix through interacting between collagen fibrils and matrix components. It appears to be a marker of cartilage turnover and has been studied as both a diagnostic and prognostic indicator of osteoarthritis.[8]

Synovial Membrane and Fluid

The degradative products of proteoglycans and collagens are found in the synovial fluid and contribute to the debris characteristic of an osteoarthritic joint. Leftover proteinases are also found in the synovial fluid.

The debris causes a reaction in the synovial membrane. There may be hyperplasia of the tissue with the formation of villi, and there may be inflammatory episodes which can cause overt synovitis. Inflammation can eventually lead to fibrosis of the synovial membrane and the joint capsule which can cause clinical stiffness.

Degradative enzymes can be stimulated by various inflammatory mediators such as interleukin-1 and TNF-alpha. These enzymes can also suppress the synthetic arm of matrix homeostasis, and this is their main function.


As there is a decrease in the matrix, there is reaction at the joint margins in the form of osteophytosis. Blood vessels grow into the sides of the joints to furnish this new bone. Osteophyte development can be viewed as an attempt to improve the efficiency of the joint. This is because of an increase in the surface are of the joint, leading to a reduction in the force per unit area. An analogy is walking on snow with snow shoes versus high heels.

Hyaluronan Cysts

These are cysts not bone growths on the edges of the weakened cartilage.


In viewing changes in the expression of various genes, it is important to remember that such changes don't necessarily mean that a particular enzyme is causative in the pathogenesis of osteoarthritis. There may be different factors involved across the spectrum of osteoarthritis from mild to end-stage.[7]


Main article: Cartilage Biomechanics

Synovial joints are supported by fluid pressure and solid matrix in a 20 to 1 ratio. With the above pathological processes there is a change in the biomechanics of the osteoarthritic joint.

In early osteoarthritic change, there is increased water content and decreased proteoglycan content. This leads to increased tissue permeability, which in turn reduces the fluid pressurisation mechanism of load support in cartilage. In this setting, the solid matrix is called upon to bear more of the load, which is detrimental to the long term viability of cartilage. The disordered matrix is weaker and is less able to take on load.

End-stage Changes

Macroscopically, initial changes are fibrillation which are small cracks. These then progress to larger cracks and eventually cartilage erosion. Ultimately the underlying bone is exposed. At this point the bone attracts a hyperaemia undergoes sclerosis. The hyperaemia may be a cause of intraosseous venous hypertension.

As the exposed bone is exposed to forces it experiences eburnation (polishing due to rubbing, which may underlie the clinical feature of crepitus through vibration), the formation of subchondral bone cysts, and with sufficient forces it may undergo necrosis. Bone is poorly designed to experience intermittent compressive loads, it is more suited to static loads and it needs the cartilage for protection.

Relationship to Pain

While osteoarthritis can be a cause of pain, there is a very poor relationship between abnormalities on plain films and symptoms.[9] Osteoarthritis is more common with age regardless of pain. Psychological factors explain very little of the variance between symptoms and structure.[10]

In the lumbar spine. there is no difference in the grade of arthropathy between painful and non-painful zygapophyseal joints as determined by controlled intra-articular blocks. Similarly there is a clinically insignificant correlation between back pain and lumbar degenerative disc changes, with such changes not being related to pain the majority of the time.[11]

One hypothesis of how an osteoarthritic joint may be painful is the theory of intraosseous venous hypertension. Because of the hyperaemia, the veins in the subchondral bone are distended and the pain results in increased tension in the adventitia of those veins.


A working diagnosis of pain can be made without an x-ray if:

  1. Age 45 years or over.
  2. Chronic (lasting 3 months or more) joint pain that is worse with use.
  3. Morning stiffness lasting no more than half an hour.
  4. Alternative diagnosis is unlikely.


Despite the rapid improvement of treatment options and strategies for inflammatory arthritis there remain very limited effective options for treating osteoarthritis.


The response to analgesics is usually disappointing. Only a third of people will benefit from analgesics, even opioids.[12][13][14]



Corticosteroid injections can be effective in the short but not long term. A 2009 systematic review found evidence for significant relief at one week.[15]

There is some concern about chondrotoxicity of corticosteroids. A 2017 RCT compared intra-articular triamcinolone versus saline injected every three months for 24 months in patients with symptomatic knee osteoarthritis. At 24 months they found a significant loss of cartilage in the treatment group (MRI cartilage thickness change of -0.21 vs -0.10 mm) with no significant difference in knee pain (-1.2 vs -1.9).[16]

Hyaluronic Acid

This is not commonly used in New Zealand due to lack of funding and lack of evidence of clinically significant efficacy over placebo. The most generous trials indicate that there is a small but clinically meaningless benefit over placebo.

Platelet Rich Plasma

Another controversial treatment option with mixed trial results.


Arthroplasty does not predictably relieve pain.


See the following open access "Year in Review" series published by Osteoarthritis and Cartilage:


  1. Allen, K. D.; Thoma, L. M.; Golightly, Y. M. (2022-02). "Epidemiology of osteoarthritis". Osteoarthritis and Cartilage. 30 (2): 184–195. doi:10.1016/j.joca.2021.04.020. ISSN 1522-9653. PMID 34534661. Check date values in: |date= (help)
  2. Lao, Chunhuan; Lees, David; Patel, Sandeep; White, Douglas; Lawrenson, Ross (2019-09-20). "Geographical and ethnic differences of osteoarthritis-associated hip and knee replacement surgeries in New Zealand: a population-based cross-sectional study". BMJ open. 9 (9): e032993. doi:10.1136/bmjopen-2019-032993. ISSN 2044-6055. PMC 6756428. PMID 31542769.
  3. Allen, K. D.; Thoma, L. M.; Golightly, Y. M. (2022-02). "Epidemiology of osteoarthritis". Osteoarthritis and Cartilage. 30 (2): 184–195. doi:10.1016/j.joca.2021.04.020. ISSN 1522-9653. PMID 34534661. Check date values in: |date= (help)
  4. 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 4.13 Allen, K. D.; Thoma, L. M.; Golightly, Y. M. (2022-02). "Epidemiology of osteoarthritis". Osteoarthritis and Cartilage. 30 (2): 184–195. doi:10.1016/j.joca.2021.04.020. ISSN 1522-9653. PMID 34534661. Check date values in: |date= (help)
  5. 5.0 5.1 Quicke, J. G.; Conaghan, P. G.; Corp, N.; Peat, G. (2022-02). "Osteoarthritis year in review 2021: epidemiology & therapy". Osteoarthritis and Cartilage. 30 (2): 196–206. doi:10.1016/j.joca.2021.10.003. ISSN 1522-9653. PMID 34695571. Check date values in: |date= (help)
  6. 6.0 6.1 Kevorkian L, Young DA, Darrah C, Donell ST, Shepstone L, Porter S, Brockbank SM, Edwards DR, Parker AE, Clark IM. Expression profiling of metalloproteinases and their inhibitors in cartilage. Arthritis Rheum. 2004 Jan;50(1):131-41. doi: 10.1002/art.11433. PMID: 14730609.
  7. 7.0 7.1 Yang, C-Y et al. “ADAMTS and ADAM metalloproteinases in osteoarthritis - looking beyond the 'usual suspects'.” Osteoarthritis and cartilage vol. 25,7 (2017): 1000-1009. doi:10.1016/j.joca.2017.02.791
  8. Tseng, Susan et al. “Cartilage Oligomeric Matrix Protein (COMP): A Biomarker of Arthritis.” Biomarker insights vol. 4 33-44. 17 Feb. 2009, doi:10.4137/bmi.s645
  9. Creamer, P.; Hochberg, M. C. (1997-07). "Why does osteoarthritis of the knee hurt--sometimes?". British Journal of Rheumatology. 36 (7): 726–728. doi:10.1093/rheumatology/36.7.726. ISSN 0263-7103. PMID 9255104. Check date values in: |date= (help)
  10. Creamer, P.; Hochberg, M. C. (1998-02). "The relationship between psychosocial variables and pain reporting in osteoarthritis of the knee". Arthritis Care and Research: The Official Journal of the Arthritis Health Professions Association. 11 (1): 60–65. doi:10.1002/art.1790110110. ISSN 0893-7524. PMID 9534495. Check date values in: |date= (help)
  11. Bogduk N. Degenerative joint disease of the spine. Radiol Clin North Am. 2012 Jul;50(4):613-28. doi: 10.1016/j.rcl.2012.04.012. PMID: 22643388.
  12. Bjordal, Jan Magnus; Klovning, Atle; Ljunggren, Anne Elisabeth; Slørdal, Lars (2007-02). "Short-term efficacy of pharmacotherapeutic interventions in osteoarthritic knee pain: A meta-analysis of randomised placebo-controlled trials". European Journal of Pain (London, England). 11 (2): 125–138. doi:10.1016/j.ejpain.2006.02.013. ISSN 1090-3801. PMID 16682240. Check date values in: |date= (help)
  13. Zhang, W.; Jones, A.; Doherty, M. (2004-08). "Does paracetamol (acetaminophen) reduce the pain of osteoarthritis? A meta-analysis of randomised controlled trials". Annals of the Rheumatic Diseases. 63 (8): 901–907. doi:10.1136/ard.2003.018531. ISSN 0003-4967. PMC 1755098. PMID 15020311. Check date values in: |date= (help)
  14. Krebs, Erin E.; Gravely, Amy; Nugent, Sean; Jensen, Agnes C.; DeRonne, Beth; Goldsmith, Elizabeth S.; Kroenke, Kurt; Bair, Matthew J.; Noorbaloochi, Siamak (2018-03-06). "Effect of Opioid vs Nonopioid Medications on Pain-Related Function in Patients With Chronic Back Pain or Hip or Knee Osteoarthritis Pain: The SPACE Randomized Clinical Trial". JAMA. 319 (9): 872–882. doi:10.1001/jama.2018.0899. ISSN 1538-3598. PMC 5885909. PMID 29509867.
  15. Hepper, C. Tate; Halvorson, Jason J.; Duncan, Stephen T.; Gregory, Andrew J. M.; Dunn, Warren R.; Spindler, Kurt P. (2009-10). "The efficacy and duration of intra-articular corticosteroid injection for knee osteoarthritis: a systematic review of level I studies". The Journal of the American Academy of Orthopaedic Surgeons. 17 (10): 638–646. doi:10.5435/00124635-200910000-00006. ISSN 1067-151X. PMID 19794221. Check date values in: |date= (help)
  16. McAlindon, Timothy E.; LaValley, Michael P.; Harvey, William F.; Price, Lori Lyn; Driban, Jeffrey B.; Zhang, Ming; Ward, Robert J. (2017-05-16). "Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and Pain in Patients With Knee Osteoarthritis: A Randomized Clinical Trial". JAMA. 317 (19): 1967–1975. doi:10.1001/jama.2017.5283. ISSN 1538-3598. PMC 5815012. PMID 28510679.

Literature Review