Clinical Pain Medicine

ISSUE: NOVEMBER 2014 | VOLUME: 12(11)

Paris—Triggers for knee and hand osteoarthritis (OA) are different, a new study suggests. Mechanical stress appears to be the most important factor for knee OA, and systemic processes appear to have the most effect on the development of hand OA, according to the researchers.

The study was a retrospective review of records from the NEO (Netherlands Epidemiology of Obesity) study, which was designed to examine pathways to common diseases and conditions in overweight and obese adults.

“It is not clear how obesity contributes to OA, but several mechanisms have been proposed, including mechanical stress and systemic processes that are related to adipose tissue,” said Margreet Kloppenburg, MD, who presented the study at the 2014 European League Against Rheumatism Congress (abstract OP0144).

“Adipose tissue produces mediators, proinflammatory proteins and hormones that influence inflammation, lipids, glucose metabolism and insulin resistance,” said Dr. Kloppenburg, from Leiden University Medical Center in the Netherlands. “The hypothesis is that these processes could contribute to the development of OA. We wanted to understand the association between obesity and OA in order to develop new therapeutic approaches.”

There were 6,628 participants in the NEO study, and 56% were women. The participants had a mean age of 56 years and a mean body mass index of 26 kg/m2. Ten percent of the subjects had knee OA; 8% had hand OA; and 4% had both.

Participants were divided into three weight categories: less than 75 kg, 75 to 90 kg and more than 90 kg. Odds ratios (ORs) were calculated between surrogates for mechanical stress and systemic processes and knee OA, hand OA, or OA of the knees and hands. Surrogates for mechanical stress were body weight and fat-free mass. The surrogate for systemic processes was the metabolic syndrome.

After adjusting for metabolic factors, knee OA was significantly associated with body weight (OR, 1.49) and fat-free mass (OR, 2.05). Similar ORs for these factors were seen for both knee and hand OA. For hand OA alone, the converse was true: A significant association was found for metabolic syndrome and hand OA (OR, 1.46). This association was independent of body weight and fat-free mass.

Dr. Kloppenburg said the associations between mechanical stress and knee OA and surrogates for systemic processes and hand OA were as hypothesized. However, the finding that mechanical stress was associated with the presence of OA in both the hands and the knees was unexpected.

“This suggests that when hand and knee OA occur in one individual, there may not be a common underlying pathway, but may reflect the presence of two different types of OA,” she said.

The associations for knee OA and for both knee and hand OA were strongest in the highest body weight category, whereas the associations were not stronger for hand OA alone with increased weight.

“These findings support the role of weight loss and exercise in persons with knee OA, since these measures modify mechanical stress,” Dr. Kloppenburg said. She noted that it would be interesting to see the effects of weight loss on hand OA as well.

New Disease Mechanisms

“Until now, the respective impact of overweight and metabolic disturbances on OA joints was not clearly delineated. The study of M. Kloppenburg, et al is very original since it is the first one that deciphers which factors mainly impact on the knee and the hand, specifically. For the knees, excessive mechanical stress due to overweight/obesity seems to be the main factor, while systemic metabolic disturbances belonging to the metabolic syndrome is the main risk factor for hand OA. This study further elucidates the pathophysiology of [metabolic syndrome]–related OA, showing that pathophysiological mechanisms may vary according to localization,” said Jeremie Sellam, MD, a rheumatologist at Hôpital Saint-Antoine, and Université Pierre et Marie Curie, Paris, France.

Another message from this study is that OA is not a “wear and tear” disease, but a real systemic disease leading to cartilage degradation with pathophysiologic specificities depending on each phenotype (i.e., aging, obesity, trauma). “Such a new view of this old disease will open … new therapeutic perspectives,” Dr. Sellam said.

—Alice Goodman

Expert Commentary

Dr. Kloppenburg’s paper, “Rationale for Weight Loss in Knee OA,” provides more than an additional rationale for the benefit of weight loss in patients with knee OA. This paper helps to understand what is often raised as an apparent paradox where mechanical stress appears to be an obvious explanation for the association between OA and obesity for the knee; however, the association between hand OA and obesity confounds a purely mechanical explanation. Clearly, as Dr. Kloppenburg suggests, the elevated mediators—proinflammatory proteins and hormones that influence inflammation associated with obesity—could contribute to the development of OA. Surely, there is support for OA as a metabolic disease,1 as well as an inflammatory disease.2 However, there is equally strong support that OA is a disease of mechanics.3 The unexpected finding reported by Dr. Kloppenburg that mechanical stress was associated with the presence of OA in both the hand and the knee suggests that the metabolic, inflammatory and mechanical factors cannot be considered in isolation, but rather there is an interaction between each of these factors that influences the development of OA. A recent laboratory study4 has highlighted the potential negative interaction between mechanical stress and elevated levels of a proinflammatory cytokine (TNF-α). Thus, the possibility that elevated proinflammatory cytokines can produce a catabolic response even with a nominal mechanical stress supports the association between obesity and the increased incidence of hand OA. But at the knee, obesity creates a perfect storm of risk for OA through the interaction between elevated proinflammatory cytokines and increased mechanical stress. Thus, weight loss that reduces the biological effects of adipose tissue as well as mechanical stress on cartilage can yield a twofold benefit for knee OA.

—Thomas P. Andriacchi, MD,
research engineer, Department of Orthopedic Surgery,
Stanford University, Stanford, Calif.

Sellam J, Berenbaum F. Is osteoarthritis a metabolic disease? Joint Bone Spine. 2013;80:568-573.
Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthritis Cartilage. 2013;21:16-21.
Felson DT. Osteoarthritis as a disease of mechanics. Osteoarthritis Cartilage. 2013;21:10-15.
Bevill SL, Boyer KA, Andriacchi TP. The regional sensitivity of chondrocyte gene expression to coactive mechanical load and exogenous TNF-α stimuli. J Biomech Eng. 2014;136:091005.