LAS VEGAS – One of the most intriguing clues that suggest the metabolic syndrome or one of its components might cause hand osteoarthritis comes from a recent study of middle-aged HIV-positive patients, David T. Felson, MD, asserted at the World Congress on Osteoarthritis.

“This is an important study. The identification of an unusual cohort, which otherwise wasn’t supposed to get a particular disease, has really helped us to determine the cause of diseases in other circumstances,” said Dr. Felson, a rheumatologist who is professor of medicine and epidemiology and director of the clinical epidemiology research and training unit at Boston University. He cited an example that also happens to have been related to HIV: Kaposi’s sarcoma in gay men “that alerted us initially to the existence of HIV infection,” he commented.

Dr. Felson was a coinvestigator in the cross-sectional hand osteoarthritis (HOA) study, which included 152 HIV-positive patients with metabolic syndrome matched by age and gender to 149 HIV-infected individuals without it, with individuals in the Framingham (Mass.) Osteoarthritis Study serving as controls drawn from the general population. The prevalence of hand OA was 64.5% in HIV-positive subjects with metabolic syndrome – significantly greater than the 46.3% prevalence in HIV-positive patients without metabolic syndrome, and the 38.7% prevalence in the Framingham cohort.

In addition, the radiographic severity of hand OA was greater in the HIV-positive group with metabolic syndrome. In a logistic regression analysis, the presence of metabolic syndrome was associated with a 2.23-fold increased risk of hand OA in HIV-infected subjects (Ann Rheum Dis. 2016 Dec;75[12]:2101-7).

“It’s circumstantial evidence, but I would say that the report on this cohort provides us with potentially very important clues,” Dr. Felson said at the congress sponsored by the Osteoarthritis Research Society International.

Other evidence to suggest that metabolic factors are causally related to hand OA comes from animal models, as well as from large population-based cohort studies, including the Netherlands Epidemiology of Obesity (NEO) study. NEO involved 6,673 middle-aged Dutch men and women. Metabolic syndrome was associated with increased rates of both hand OA and knee OA in analyses unadjusted for body weight. However, when the Leiden University investigators adjusted for body weight, the association between metabolic syndrome and knee OA went away, whereas the association between metabolic syndrome and hand OA remained strong (Ann Rheum Dis. 2015 Oct;74[10]:1842-7).

This has uniformly been the case in other cohort studies reporting an association between metabolic syndrome and knee OA: upon adjusting for body mass index (BMI), there is no longer a residual relationship between metabolic syndrome and knee OA.

“One of the challenges in studying metabolic syndrome and knee osteoarthritis is that all the components of the metabolic syndrome are strongly correlated with obesity, and obesity is a major risk factor for knee osteoarthritis through its effects on joint loading. So obesity – at least for knee osteoarthritis – is an enormous confounder,” Dr. Felson said.

The findings from NEO and other large cohort studies underscore a key point: “Metabolic syndrome is not a risk factor for knee osteoarthritis, despite a lot of hullabaloo to the contrary. It doesn’t emerge in cohort studies as an important factor,” according to the rheum

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atologist.

“I’m not suggesting that there are different ultimate causes in the biology of hand osteoarthritis and knee osteoarthritis. I’m suggesting that the epidemiologic findings are different because joint load-bearing is a critical factor in knee osteoarthritis and that factor overwhelms much else. The message with regards to hand osteoarthritis is nowhere near as clear as it is for knee osteoarthritis, and the possibility that metabolic syndrome may cause hand osteoarthritis probably needs to be pursued further,” he continued.

Also worth pursuing is the possibility that hypertension increases the risk of OA. Several studies, including Framingham, have shown a modest signal of a relationship with both knee OA and hand OA that persists after adjusting for BMI. A hypothetical mechanism for such an effect might be reduced blood flow to the joints of hypertensive patients, with resultant adverse structural effects.

“Look at all the varied consequences of high blood pressure: stroke, blindness, MI, heart failure, kidney failure. Is osteoarthritis another one we need to be thinking about? I don’t know the answer, but I think it remains an open question based on the available data,” Dr. Felson observed.

As for the possibility that diabetes is causally linked to OA, he pronounced himself a skeptic.

“The diabetes association has been heralded by some, but in multiple studies, after adjustment for BMI the association goes away. I would strongly suggest to you that diabetes is not associated with osteoarthritis,” he declared.

He stressed that the possibility that metabolic factors are involved in the pathogenesis of OA isn’t simply of academic interest.

“We’re struggling in this field to find prevention and treatment opportunities. At present, there is no treatment that’s been shown to slow progression of osteoarthritis. If a causative metabolic factor could be identified, we might hope that it could reveal effective treatments for abrogating the disease,” he said.

Dr. Felson reported having no financial conflicts of interest.

bjancin@frontlinemedcom.com

HIV-positive patients with metabolic syndrome have high rate of hand OA