May 2016

Smoking & knee OA: From clinical controversy to therapeutic possibility

iStock_000023074274Experts say perplexing studies suggesting that smoking may be protective against the development of knee osteoarthritis (OA) should not deter clinicians’ efforts to discourage smoking—even in patients who are at risk for OA. But, if researchers can pinpoint specific ingredients associated with the protective effect, that could have significant implications for the development of new OA therapies.

By Barbara Boughton

Smoking tobacco has long been recognized as the most preventable cause of morbidity and early mortality in the US.1 Smoking contributes to many poor lower extremity outcomes, including increased risk of osteoporosis-related fractures, complications following orthopedic surgery, and musculoskeletal pain.2

Yet smoking remains a persistent and widespread habit among Americans—including patients who need healthcare for orthopedic and musculoskeletal conditions. In fact, studies have estimated that one out of every five patients who receive outpatient physical therapy smoke or use tobacco.1,3 Organizations such as the American Academy of Orthopaedic Surgeons (AAOS) have begun to recommend that clinicians should take a more active role in screening patients for smoking and counseling them about smoking cessation.2

At the same time, a number of controversial but large review and population-based scientific studies have reported that smoking may be protective against the development of osteoarthritis (OA), particularly knee osteoarthritis. Several large studies in China and Australia have also found that, among OA patients, smokers are less likely than nonsmokers to undergo total knee arthroplasty for severe symptoms.

The research has generated controversy, as well as concern among lower extremity clinicians who are well acquainted with years of research showing poor outcomes among patients with OA who also smoke.

“The research that shows a protective effect of smoking on knee osteoarthritis is intriguing and interesting, but I’m not convinced that there’s enough evidence to support the notion that smoking has a beneficial effect,” said Janet Bezner, PhD, PT, DPT, associate professor of physical therapy at Texas State University in San Marcos. “There really isn’t enough information in the research studies I’ve seen to support the conclusion that smoking has a protective effect on knee osteoarthritis—or to change our advice to patients about the hazards of tobacco.”

5Cover-iStock3665279-copySmokers are at increased risk for nonunion of fractures and delayed healing after orthopedic surgery,2,4-6 said AAOS spokes­person Alan Reznik, MD, an orthopedic surgeon and sports medicine specialist in New Haven, CT, and one of the authors of the recent AAOS statement on smoking.

Since smoking damages the inner walls of arteries and slows down microcirculation, blood flow that aids healing is often compromised, Reznik added. Smokers are also at increased risk for mortality and serious morbidities such as deep infection, heart attack, and stroke and sepsis after surgery, including orthopedic surgery,7-10 he said.

“Smokers who have other risk factors such as obesity and diabetes are often not candidates for elective orthopedic surgeries such as arthroplasties, because they are at such heightened risk for complications,” he said.

Smokers who quit just weeks or months before surgery appear to reduce their risk for adverse events, and that risk decreases further if the patients quit smoking a year or more before surgery, according to the AAOS statement.2,10,11

“The hazards of smoking are well documented,” Bezner said. “We know that smokers are more likely to have back pain and chronic musculoskeletal pain—and smokers heal more slowly from tendon and muscular injuries.”12-14

A protective effect?

Yet in recent years, a great deal of research has begun to show a modest to significant protective effect of smoking on knee OA. No one, of course, is arguing that lower extremity clinicians should encourage their patients to smoke, or refrain from counseling smoking cessation. Researchers hope that learning more about the possible link between tobacco and OA will lead to insights about specific ingredients in tobacco or nicotine that may be protective, so those components could be isolated for the development of new arthritis medications.

In one of the largest recent studies on OA and smoking, published in Osteoarthritis and Cartilage in 2014, researchers in Singapore found smokers had a significantly lower risk for severe knee OA resulting in total knee arthroplasty than nonsmokers in a cohort of more than 63,000 Chinese men and women. Smokers had a 51% decreased risk of total knee arthroplasty compared with people who had never smoked.15

“Our study is limited in that it used total knee replacement as a surrogate for knee osteoarthritis—so you can’t really say from our study whether smoking was associated with onset or progression of osteoarthritis,” said Katy Leung, MBChB, director of research in the department of rheumatology and immunology at Singapore General Hospital. “Yet, an important strength of our study is that we had very detailed data on patients who quit smoking, and we found that the protective effective of smoking declined quickly after quitting.”

Recent basic science experiments indicate that nicotine can aid collagen synthesis in chondrocytes,16 which suggests to Leung and colleagues that there could be practical implications drawn from their study’s findings.

5Cover-iStock44340762-copy“The development of chemopreventive agents from nicotine analogues may provide an effective means to reduce the progression and lessen the burden of severe OA,” they wrote in their paper.

That line of thinking, however, is still in the very early stages.

“There are hundreds of ingredients in cigarettes, so it’s not yet appropriate at this time to make any conclusions about which ingredients might have a protective effect,” Leung said. “More research on this question needs to be done.”

In 2011, researchers performed a meta-analysis of 48 studies and found a significant inverse association between smoking and the development of knee OA.17 Yet a large population-based study of 9064 Koreans older than 50 years, published in 2016, did not find a significant association between knee and hip OA and smoking or indirect or side stream smoke.18

Two large population-based studies conducted in Australia found a beneficial effect of smoking on knee OA, as well. This research concluded smoking decreased the risk for lower limb total joint replacement, and the association held true when the researchers controlled for age, comorbidities, body mass index (BMI), and socioeconomic status.19,20

“Both of our studies were consistent in their findings,” said lead researcher of both studies George Mnatzagainian, PhD, MPH, an epidemiologist at Australian Catholic University in Melbourne. “There was a protective effect of smoking, and both male and female smokers had less risk for lower limb total joint replacement than nonsmokers. We also found a dose-response effect between years of smoking and reduced risk for having a total joint replacement [with more years of smoking linked to a greater decrease in risk for TKA than fewer smoking years].”

Contradictory findings

In a 2015 editorial in Osteoarthritis & Cartilage that analyzed recent studies and reports on the link between OA and smoking,21 David Felson, MD, a professor of medicine and epidemiology at Boston University in Massachusetts, noted that a “preponderance of evidence suggests that smokers are modestly protected against developing radiographic OA in the knee and hip.” Yet Felson and Zhang also observed that smoking may have contradictory effects on OA. Research such as the 2011 meta-analysis indicated that, while smokers had less OA disease than nonsmokers, they were at “modestly increased risk of painful OA,” Felson and Zhang wrote.

A recent study highlighted the contradictory and complex effects of smoking on knee OA.22 In 2250 patients with radiographic evidence of knee OA, researchers from the University of Massachusetts Medical School in Worcester studied the effect of smoking history on knee pain, stiffness, physical function, and OA progression as indicated by joint space width. Changes in knee-specific symptoms, such as pain, stiffness, and physical function were measured at baseline and annually over 72 months. Joint space width was evaluated by x-ray at baseline and annually over 48 months. In their analyses, the researchers controlled for potential confounders, such as age, gender, education, income, race, BMI, symptom-related multijoint OA, alcohol consumption, and Short Form-12 physical and mental health scores.

In a cross-sectional analysis performed at baseline, the researchers found patients with a history of greater than 15 pack-years of smoking had worse pain and stiffness than patients who had never smoked. Their findings also revealed a contradictory result: Patients with fewer than 15 pack-years of smoking at baseline had better joint space width than patients who never smoked—but they had worse overall function.

The researchers also measured changes in WOMAC (Western Ontario and McMaster Universities Arthritis Index) symptoms from baseline to 72 months, and changes in joint space width from baseline to 48 months. This more robust longitudinal analysis found no association between smoking history or pack-years of smoking and changes in OA symptoms or joint space width.

“We suspect that the small and conflicting findings from the cross-sectional study are [less reliable and] due to residual confounding,” the researchers wrote in their paper.

“Our study showed clearly that there was no relationship between smoking and knee osteoarthritis,” said lead author Catherine Dubé, EdD, research associate professor in the Department of Quantitative Health Sciences at the University of Massachusetts Medical School. “We do not believe there is a protective effect of smoking on osteoarthritis.”

Dubé acknowledged that previous population-based studies had found a strong association between smoking and reduced prevalence of knee OA, as well as a reduced risk for total knee arthroplasty.

“It’s difficult to assess the quality of these studies, and the generalizability of their results,” she said.

Dubé also noted a number of studies have actually found that, because smoking has a negative effective on bone mineral density, the habit can cause increased cartilage loss.23,24

“Chronic smoking also creates a pro-inflammatory state, and since inflammatory mediators play an important role in osteo­arthritis, one would expect that smoking would have an overall negative effect on symptoms and disease progression,” she said.

In their paper, Dubé and colleagues noted that, while some chemical exposures in cigarette smoking could be beneficial, it might be almost impossible to narrow down which ingredients were protective.

Cigarettes have hundreds of ingredients associated with at least 69 known carcinogens, and more than 7000 chemicals when burned, Dubé and colleagues noted in their study.

Still, it’s important for research to provide more clarity about the relationship between smoking and OA, so that smokers do not find a reason to continue smoking, Dubé said.

Cessation counseling

Other clinicians interviewed by LER also emphasized the importance of continuing to counsel OA patients who smoke about the health hazards of their habit. A discussion about smoking before elective surgery, such as total knee arthroplasty, presents an opportunity to intervene and discuss smoking cessation methods and programs, said V. Franklin Sechriest II, MD, chief of orthopedic surgery at the Minneapolis Veteran Affairs Health Center System.

5Cover-iStock_43787028-copy“It’s crucial to discuss the risks of smoking with any patient undergoing surgery,” Sechriest said. “If patients can’t quit smoking before undergoing surgery, then it’s vital to aggressively counsel them afterward about tobacco cessation. I usually tell my patients that, if they want a good outcome after surgery without complications, it will help to quit smoking.”

Sechriest also noted that smokers should be monitored more closely than nonsmokers after orthopedic surgeries to ensure healing.

Bezner emphasized the important role that physical therapists can play in helping patients to stop smoking.

“We should be screening patients for smoking, and asking if we can help with quitting,” she said. “Although we can’t prescribe stop-smoking medications, we can refer patients to stop-smoking programs.”

But Bezner has found that physical therapists often don’t take advantage of opportunities to address smoking cessation with their patients.1

“Physical therapists have reported that they do not feel prepared to provide smoking cessation counseling, although they feel that they should ask patients about smoking habits and provide advice to stop smoking,” Bezner wrote in a 2015 review article on promoting health and wellness in physical therapy.1

Bezner advises taking an educational approach to patients who smoke, and informing them about the risks of smoking, as well as the benefits and rewards of quitting. Patients should also be asked to identify any barriers or roadblocks they’ve encountered when trying to quit, and advised about ways they might be able to overcome these roadblocks, she added.

If an OA patient is both obese and a smoker, or if an obese patient who smokes is at risk for OA, it’s often best to start by advising them about starting an appropriate exercise program—as long as they can handle physical activity.

“Once they take that first step and start exercising,” Bezner said, “they realize pretty quickly how much smoking is limiting them.”

Barbara Boughton is a freelance writer based in the San Francisco Bay Area.

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