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Patients with osteoarthritis are at increased risk for developing Parkinson's disease, a longitudinal Taiwanese study found.

Incidence rates for developing Parkinson's disease were 0.99 (95% CI 0.87-1.12) per 1,000 person-years among patients with osteoarthritis compared with 0.71 (95% CI 0.62-0.81) per 1,000 for controls, reported Shin-Liang Pan, MD, PhD, and colleagues from the National Taiwan University in Taipei.

Accordingly, the risk among patients with osteoarthritis was 41% higher compared with controls, with an adjusted HR of 1.41 (95% CI 1.16-1.70, P=0.0004), the researchers wrote online in .

It is now recognized that inflammation plays a major role in the development of osteoarthritis, while neuroinflammation is characteristic of Parkinson's disease.

"Because a growing body of literature reports that peripheral inflammation may induce neuroinflammation in the brain, leading to neurodegeneration, we hypothesized that having osteoarthritis may increase people's risk of later developing Parkinson's disease," Pan and colleagues wrote.

Therefore, they analyzed data from Taiwan's National Health Insurance system, which covers more than 97% of the population, identifying 33,360 individuals ages 50 to 64 who were diagnosed with osteoarthritis during the years 2002 to 2005, matching them by age and sex with the same number of controls.

Almost two-thirds of participants were women, and mean age was 57. Patients with osteoarthritis had more comorbidities such as hypertension, coronary heart disease, diabetes, chronic obstructive pulmonary disease, and gout.

Follow-up time averaged 7.74 years in the osteoarthritis group and 8.67 years among controls. During that time, 256 patients in the osteoarthritis group developed Parkinson's disease, as did 205 controls.

While the risk for Parkinson's disease was significantly higher among osteoarthritis patients, there was no significant difference in all-cause mortality (HR 1.01, 95% CI 0.95-1.08).

After adjustment for comorbidities, as well as geographic and socioeconomic factors, the risk for Parkinson's disease was increased in all subgroups of osteoarthritis:

• Knee or hip osteoarthritis, HR 1.55 (95% CI 1.14-2.11, P<0.05)
• Non-knee or hip, HR 1.42 (95% CI 1.06-1.89, P<0.05)
• Uncategorized, HR 1.32 (95% CI 1.05-1.64, P<0.05)

The investigators then analyzed risks according to sex and age, and found that the adjusted risk was elevated for women (HR 1.57, 95% CI 1.24-1.98) but not for men (HR 1.18, 95% CI 0.85-1.62). There was no difference in risk among patients who were younger (50 to 57) at baseline compared with those who were older (57 to 64), with nonsignificant point estimates of 1.38 and 1.42.

A sensitivity analysis that included prevalent cases of osteoarthritis at baseline to provide a longer follow-up time period found an adjusted HR for Parkinson's disease of 1.42 (95% CI 1.20-1.69), which was very similar to what was seen in the main analysis.

In discussing their findings, Pan and colleagues noted that patients with osteoarthritis have increased levels of proinflammatory cytokines, such as interleukin-6 and tumor necrosis factor alpha, which not only contribute to cartilage breakdown in the joints but also exacerbates neuroinflammation and the activation of microglia in the vulnerable midbrain.

Also contributing to the elevated risk for Parkinson's among patients with osteoarthritis is a lack of physical activity associated with pain in the weight-bearing joints. Physical activity can help inhibit neurodegeneration and protect dopaminergic neurons.

Furthermore, many patients with osteoarthritis have low levels of vitamin D, which can further raise the risk.

"Recent research has revealed that vitamin D can enhance the synthesis of dopamine by increasing tyrosine hydroxylase activity. In addition, this vitamin may promote the expression of glial cell line-derived neurotrophic factor, a critical protein for the survival of dopaminergic neurons," the researchers explained.

An additional impediment to the early recognition of Parkinson's disease among patients with osteoarthritis is that knee and hip involvement can result in Parkinson's-like characteristics such as slowing of movement and short walking strides. "Therefore, our findings suggest that clinicians need to be more vigilant about the risk of Parkinson's disease among their osteoarthritis patients," they wrote.

Further studies should explore potential underlying mechanisms in greater detail, they noted.

A limitation of the study was the fact that the database did not include potentially relevant lifestyle information such as smoking and alcohol use.

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