SEATTLE (FRONTLINE MEDICAL NEWS) – Patients with osteoarthritis often have other common chronic conditions, a scenario that has implications for both clinical care and research, according to Dr. Gillian Hawker.

“This is a critically important topic in our field,” she told attendees of the World Congress on Osteoarthritis. “We know from myriad studies that there are major challenges to the diagnosis and management of osteoarthritis … But probably now what’s becoming a major issue is the high occurrence of coexisting medical problems, which have been shown to present competing demands to patients and physicians who are trying to balance a number of conditions in a single patient and contraindications to osteoarthritis therapies.”

Today, 90% of individuals aged 65 years and older with osteoarthritis have at least one other chronic condition, according to Dr. Hawker, the Sir John and Lady Eaton Professor and chair of medicine at the University of Toronto. Most commonly, those conditions are cardiovascular disease, diabetes, and hypertension, but about one-third of patients have depressed mood, which may affect adherence to and effectiveness of therapies.

Two main hypotheses have been proposed for the association of osteoarthritis and other common chronic conditions, according to Dr. Hawker. According to the first hypothesis, the shared risk factors of aging and obesity independently lead to both osteoarthritis, with resultant physical inactivity, and a cluster of metabolic perturbations including hypertension, hyperglycemia, and dyslipidemia. Collectively, these conditions increase risk for cardiovascular disease and diabetes.

In support of this hypothesis, “we have lots of data from qualitative research showing that people manage their osteoarthritis symptoms by giving up activities that exacerbate them, partly because they are afraid of taking painkillers and partly because nobody offers them anything that’s more effective,” Dr. Hawker noted. In addition, when patients juggle multiple health conditions, exercise is the most frequently dropped activity.

“Many have hypothesized that inability to walk, climb stairs, and be mobile would potentially impact the ability to self-manage physical activity, impacting numerous chronic conditions,” she said. Compelling evidence comes from research such as a cohort study of patients with symptomatic hip or knee osteoarthritis that found walking disability predicted a 30% increase in the risk of all-cause death and a 17% increase in the risk of cardiovascular events; among the subset with comorbid diabetes, walking disability and grip strength predicted the risk of hospitalization for diabetic complications ( PLoS One 2014;9:e91286 ).

“These are large, well-controlled observational studies that do show consistent independent relationships between walking disability and cardiovascular events, diabetes complications, and all-cause death,” Dr. Hawker said, while acknowledging that the research is still hypothesis generating.

Of note, recent attention has focused on systemic inflammation and a metabolic osteoarthritis phenotype. When it comes to the pathogenesis of osteoarthritis, “we now are very comfortable understanding the local biomechanical effects separately from the systemic effects on our joints,” she said. Obesity is among the systemic factors implicated, with some data suggesting that adipokines affect joint tissues in a manner similar to mechanical stress.

According to the second main hypothesis proposed to explain the association between osteoarthritis and common chronic conditions, aging and obesity give rise to a cluster of metabolic factors (hypertension, hyperglycemia, and dyslipidemia) that independently increase the risk of symptomatic osteoarthritis. Again, the arthritis may result in the loss of physical activity and disability, which exacerbates the metabolic situation.

Evidence in support of this hypothesis comes from a variety of studies. For example, one has shown that the number of components of the metabolic syndrome is related to the adjusted risk of development and progression of knee osteoarthritis ( Osteoarthritis Cartilage 2012;20:1217-26 ).

Overall, Dr. Hawker said, “we have some independent associations between metabolic syndrome and its components, and osteoarthritis – more so in the knee and hand, more so in women than in men, and more so in younger than in older individuals. And we have some data that suggest that symptomatic and disabling osteoarthritis has an association with increased risk of cardiovascular events and diabetes complications.” Here again, the studies have limitations, so the relative contributions of disability and systemic inflammation remain unknown, she cautioned.

Hypotheses aside, the association of osteoarthritis with common chronic conditions has implications for clinical care, Dr. Hawker said at the meeting, which was sponsored by the Osteoarthritis Research Society International. “Clearly, all of these data, irrespective of the relationships, point to a pivotal role for physical activity, a combination of physical activities,” she said, noting that benefits include reductions in both metabolic alterations and physical impairment, and possibly alleviation of depressed mood and improved sleep.

Osteoarthritis may be an independent risk factor for cardiovascular disease. “Many are suggesting that, in fact, if it is the fifth component of metabolic syndrome, this should really influence how we think about cardiovascular disease prevention, that osteoarthritis patients should be screened and we should be thinking more seriously about how we use various therapies,” such as nonsteroidal anti-inflammatory drugs, she said.

Dr. Hawker endorsed future research on these topics. “In the 2014 OARSI guidelines, we showed collectively as a community that we don’t have enough trials in this population, which is the majority of our patients with osteoarthritis. So yes, conservative therapy is good, but I’d say that we need way more evidence for effective interventions in the population with osteoarthritis who are living with other chronic conditions.”

Specifically needed are large prospective studies of the temporal relationships that look at mechanisms beyond age and body mass index, she explained. These studies should assess incidence and progression separately, structure and symptoms separately, and both weight-bearing and non–weight-bearing joints.

“To date, I haven’t seen any evidence to show that treatment of metabolic syndrome or its components influences the incidence or progression of osteoarthritis. And I think we should be thinking about asking those questions as they may in fact be modifiable risk factors for osteoarthritis,” she said.

Also needed are trials assessing the impact of aggressive treatment of osteoarthritis disability, according to Dr. Hawker, who disclosed that she had no relevant conflicts of interest. “If we reduce osteoarthritis disability, particularly walking disability, can we actually impact the outcomes of cardiovascular disease and diabetes? I think that’s an important question,” she concluded.


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