Family History Raises Knee OA Risk

— Twofold increase in risk if parent had knee arthroplasty.
by Nancy Walsh, Senior Staff Writer, MedPage Today December 9, 2014

Genetic factors appear to play a role in the development of osteoarthritis (OA)-related knee pain, with higher rates of worsening knee pain being identified in the offspring of parents who had knee arthroplasty, Australian researchers found.

Compared with controls whose parents had no history of knee OA, those who had at least one parent who had undergone total knee replacement more often reported worsening knee pain over a period of 8 years (66% versus 41%), according to Graeme Jones, MD, PhDopens in a new tab or window, of the University of Tasmania in Hobart, and colleagues.

And after adjustment for age, sex, body mass index, and smoking, individuals with a parental history of knee replacement had a more than twofold greater likelihood of worsening total knee pain (OR 2.46, 95% CI 1.35-4.51), the researchers reported online in Annals of the Rheumatic Diseases.opens in a new tab or window

“OA-related pain is a complex integration of sensory, affective and cognitive processes, driven by nociceptive and neurobiological mechanisms, each of which involves a number of proteins throughout the peripheral and central nervous systems, whose effects have been shown to be affected by the interplay between environmental and genetic factors,” they observed.

Previous research has identified genetic factors relating to pain sensitivity, and a cross-sectional studyopens in a new tab or window by Jones and colleagues suggested that knee pain was more common among individuals with a parent who had undergone knee arthroplasty. But there have been no studies of changes in risk for knee pain over time among individuals with a family history of OA.

To address this question, the researchers enrolled 219 participants, 115 of whom were offspring of parents who had knee replacement because of severe, primary OA, and 104 controls.

Offspring and controls were initially seen in 2000-2001, and had knee pain assessed on a self-reported pain questionnaire. Then, 2 years later, they had their knee pain rated on the Western Ontario and McMaster Osteoarthritis Index (WOMAC), which includes several subscales such as pain while walking on a flat surface, on stairs, and standing upright.

The third assessment took place 8 years later, and an increase of one point on the WOMAC was considered worsening knee pain.

Radiographs were obtained at baseline and scored for joint space narrowing and the presence of osteophytes, and MRIs were used to evaluate cartilage defects, bone marrow lesions, and meniscal pathology.

Participants’ mean age was 48, and more than half were women. Prevalent knee pain was present in 45% of offspring at the first assessment compared with 20% of controls (P<0.001), in 56% and 54% at the second assessment (P=0.764), and in 74% and 54% at year 10 (P=0.002).

On multivariable analyses that adjusted for standard factors such as age and sex, and also for radiographic and MRI abnormalities, significant associations were seen for offspring versus controls for all WOMAC subscales except pain while walking on a flat surface and while standing:

  • Pain on stairs, OR 3.30 (95% CI 1.66-6.60)
  • Pain in bed at night, OR 2.46 (95% CI 1.29-4.71)
  • Pain sitting, OR 1.95 (95% CI 1.01-3.74)
  • Total pain, OR 2.16 (95% CI 1.14-4.12)

The finding that the association persisted even after adjustment for structural abnormalities within the joint seen on imaging studies “implies that the genetic contribution to knee pain may be mediated through factors outside the joint, possibly involving pain processing,” Jones and colleagues wrote.

Limitations of the study included a sizable number of participants having been lost to follow-up at year 10 and the possibility of recall bias.

Disclosures

The authors reported no financial disclosures.

Primary Source

Annals of the Rheumatic Diseases

Source Reference: opens in a new tab or windowPan F, et al “The offspring of people with a total knee replacement for severe primary knee osteoarthritis have a higher risk of worsening knee pain over 8 years” Ann Rheum Dis 2014; DOI: 10.1136/annrheumdis-2014-206005.

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