osteoarthritis

see also:

• arthritis - clinical patterns

• a “degenerative” or inflammatory disorder of joints arising from the breakdown of articular (hyaline) cartilage
• radiographic hand OA is present in approximately 40–60% of adults over age 55, while symptomatic hand OA affects about 13–26% of individuals in the same age group¹⁾
• 80-90% of individuals older than 65 years have evidence of radiographic primary osteoarthritis
• 50% of women and 25% of men develop symptomatic hand OA by age 85yrs - half of these will have inflammation
  • currently there are no effective medications to reduce this
• menopause-induced loss of oestrogen and progesterone promotes extracellular matrix degradation and chondrocyte deterioration in knee OA ²⁾

• historically divided into:
  • primary OA:
    • usually refers to OA involving DIP joints of fingers resulting in Heberden's nodes (at the DIPjts) &/or Bouchard nodes (PIPjts)
    • type 1 nodal polyarticular primary OA
      • involves DIPjts, PIP jts of hands as well as medial compartment knee and 1st MTP jts
      • generally has a familial predisposition
    • type 2 polyarticular primary OA
      • initial MCPjt of 2nd, 3rds fingers (MCP2,3 OA), and possible also primary ankle OA
      • usually associated with HFE gene mutations
      • closely resembling the arthropathy described in haemochromatosis
    • thumb CMCjt OA
  • secondary OA:
    • generally refers to all other OA, particularly the weight bearing joints or when there has been preceding articular trauma or disease

• age
  • prevalence increases dramatically among persons older than 50 years
• obesity
  • particularly, hip, knee and ankle OA
• type II diabetes
• genetics
  • the presence of Heberden or Bouchard nodes is strongly familial and often associated with medial knee and 1st MTPjt OA
    • it is hypothesized that the familial incidence of “nodal OA” reflects the familial inheritance of the anatomical characteristics that determine the level of resistance to osteophyte growth,and not the familial incidence of a different form of OA³⁾
    • finger DIPjts and PIPjts combined with 1st MTP jts (hallus rigidus):
      • autosomal dominant patterns with incomplete penetrance drive familial clustering, raising first-degree relative risk 2-10 fold across these sites
      • IL1A/IL1B/IL1RN haplotypes: Increase risk for DIP OA via heightened inflammation, with potential overlap to MTP under mechanical stress.⁴⁾
      • NOD/RIPK2 pathway variants: Novel mutations tied to familial hand OA, potentially extending to MTP through inflammatory signaling.⁵⁾
  • genes in the BMP (bone morphogenetic protein) and WNT (wingless-type) signaling cascades have been implicated, in particular, GDF5 (growth and differentiation factor 5) and FRZB (frizzled related protein)
  • MCF2L gene is associated with large joint OA
  • a 2025 study found over 900 genetic associations with OA ⁶⁾
    • 175 for osteoarthritis at any site, 151 for hip osteoarthritis, 146 for knee osteoarthritis, 131 for hip and/or knee osteoarthritis, 4 for spine osteoarthritis, 14 for hand osteoarthritis, 7 for finger osteoarthritis, 5 for thumb osteoarthritis, 136 for total hip replacement, 92 for total knee replacement and 101 for total joint replacement
    • highest scoring effector gene was ALDH1A2
  • genetic mechanisms:
    • bone morphology and geometric parameters risking areas of increased cartilage stress
    • NOD/RIPK2 signalling pathway
    • chondrogenesis factors
    • tendinopathy factors, tenocytes
    • retinoic acid signalling (thumb OA)
    • TGFβ signalling - six effector genes that are linked to OA
    • BMP signalling
    • WNT signalling
    • Fibroblast growth factor signalling (knee OA)
    • ECM organisation and assembly
    • circadian rhythm disruption in repair processes
    • Glial-cell-related pathways
• dietary fats
  • long term use of animal fat, butter, and palm oil can weaken the cartilage in rats but lauric acid may be protective ⁷⁾
• the GIT microbiome
  • individuals with symptomatic hand OA had an increased relative abundance of the genera Bilophila and Desulfovibrio, both sulfate-reducing bacteria, and a lower relative abundance of Roseburia. Bilophila induces the expression of inflammatory cytokines, IFN-γ and IL-6, in various tissues as well as LBP (lipopolysaccharide binding protein), A-SAA (SAA acute-phase reactant serum amyloid A), TNF-α, and IL-6 in serum, suggesting Bilophila drives both local and systemic inflammation. Desulfovibrio has been shown to induce the transcription of inflammatory genes and activate the NF-κB pathway via LRRC19. Desulfovibrio also stimulates the production of IL-6 and IL-8 in human oral epithelial and gingival fibroblast cells in response to its bacterial products, such as lipopolysaccharides. Roseburia, in contrast, is typically associated with anti-inflammatory effects.⁸⁾
• women are more prone to:
  • OA of the DIP joints of the fingers
  • OA of the knees (1.7x risk)
  • erosive OA (12x risk)
• ethnic differences
  • knee OA is very common in China
• reduced levels of sex hormones
• muscle weakness
  • reduces protection of joint, and increases joint movement range to risk damage to the joint
• repetitive use
  • microtrauma may also cause damage, especially in individuals whose occupation or lifestyle involves frequent squatting, stair-climbing, or kneeling
• malalignment such as varus deformity of knees
  • weight bearing forces passing through higher risk parts of the joint
• secondary to other bone conditions such as gout, intra-articular fractures, infections
• presence of nodal OA of digits may be a indicator of future OA elsewhere
  • the number of Heberden's nodes, their locations, and symmetry were associated with knee OA incidence and progression over 8 years ⁹⁾
• possible role of the cartilage protective protein SHP (NR0B2)
  • SHP protects cartilage by suppressing the production of matrix-degrading enzymes, specifically MMP-3 and MMP-13, which are known to break down cartilage tissue, via regulating the IKKβ/NF-κB pathway¹⁰⁾

• symptom relief:
  • simple analgesics such as oral or topical non-steroidal anti-inflammatory drugs (NSAIDs) (with cover of proton pump inhibitors (PPIs) if at risk as this reduces dyspepsia relative risk by 67% and absolute risk by 9%)
  • topical capsaicin reduces pain by 50% and 0.025% is better tolerated than 0.075%
  • i/articular steroid injections may have a role BUT:
    • should not be given more often than every 4 months as risk of cartilage and joint damage
    • risk of joint sepsis
  • NB. paracetamol (acetaminophen) is no longer 1st line Rx as for chronic pain of OA, it does not appear to be better than placebo, and recent studies suggest chronic use may have significant adverse effects such as GIT, RR 1.4x of cardiovascular events (although this is similar to NSAIDs) ¹¹⁾
  • whilst effective in short term, long term use of opiates and opioids is problematic resulting in fractures (RR 4.5), cardiovascular events (RR 1.8), all cause mortality (RR 1.9), constipation, and dependence and tolerance
  • duloxetine appears to be a useful adjunct to NSAIDs, but does cause nausea, constipation, fatigue, dry mouth and anorexia.
  • 20mg methotrexate weekly for 6 months appears to provide moderate relief compared with placebo for hand OA with inflammation (Lancet 2023)
• weight reduction if obese
• knee braces if knee OA
• maintain muscle strength
• Genicular artery embolization (GAE) appears to he highly effective for knee OA and is minimally invasive ¹²⁾
• joint replacement is a last resort as these generally only last 10-15yrs in younger patients, particularly total knee replacements (TKR)
• daily glucosamine and chondroitin supplements for 2 years in 45-75 yr olds appears to slow joint space narrowing but no evidence of reduced pain vs placebo¹³⁾