Many factors may influence incidence of disease, effectiveness of treatment in women

Osteoarthritis (OA) of the knee develops at a greater rate in women than in men as they age. In fact, says Mary I. O’Connor, MD, the incidence of knee OA is 1.7 times greater in women overall. Although multiple factors may contribute to this increased prevalence, it’s logical, she says, to consider the influence of hormones and estrogen in postmenopausal women.

“We know articular cartilage has estrogen receptors,” says Dr. O’Connor. “As such, it is reasonable to suggest that the decline in estrogen with menopause may contribute to this upsurge in knee OA in older women.

“In one study of elderly women taking estrogen replacement,” she continues, “knee OA incidence and progression risk was 60 percent lower than women who had never used estrogen replacement therapy, although this finding was not statistically significant.”

Insulin-like growth factor 1 (IGF-1)—a hormone that is important for maintaining muscle, bone density, and regulation of fat metabolism—may also play an important role in the risk for development of knee OA. Dr. O’Connor notes that lower levels of IGF-1 are found in healthy women compared to healthy men; however, women undergoing total knee arthroplasty (TKA) had markedly lower levels of IGF-1 compared to healthy female controls, whereas IGF-1 levels did not differ between men who underwent TKA and healthy male controls.

Dr. O’Connor also reports that women may be more physically disabled at the time of TKA compared to men.

“Women self-report that they have more symptoms than men who have the same degree of knee OA,” she says. “Some studies report that women have worse preoperative pain compared to men.”

In one study, arthroplasty candidates performed tests that measured normalized strength and the ability to climb stairs and walk.

“The researchers’ data suggested that women undergo arthroplasty at a more advanced disease state then men do,” says Dr. O’Connor.

What’s keeping women away from TKA?
Surgery for severe hip or knee OA is underutilized by both sexes, says Dr. O’Connor, but the degree of underutilization is three times greater in women.

A study performed by Carlos J. Lavernia, MD, of 300 patients found that TKA patients’ anxiety levels in the perioperative period were higher among blacks, Hispanics, and women than among Caucasian males, she says.

When Dr. O’Connor sees female patients who are reasonable candidates for TKA, but who are unsure whether they want to have the surgery, she warns them about the “never catch up syndrome,” a term Dr. Lavernia coined.

“Let’s say a female patient has a Knee Society Score of 50 prior to surgery and a male patient has a score of 60,” she says. “If both improve 30 points, her score will be 80 and his score will be 90. The male patient didn’t wait long to have surgery, but the female patient delayed. While she improves the same amount of points, she may never reach the same maximum score of the male patient. Thus, she can ‘never catch up’ to a male patient who had surgery sooner.”

She also points to the results of a study performed in 2008 that focused on two standardized patients, a male and female, with identical clinical presentations and moderate knee OA.

“When the study first began, it also included two standardized patients with severe knee OA,” explains Dr. O’Connor. “They were removed from the study early on because researchers found no difference in terms of recommendations—both men and women with severe knee OA were equally recommended for surgery.

“Over a span of 5 years,” continues Dr. O’Connor, “the standardized patients with moderate knee OA visited 38 family physicians and 33 orthopaedic surgeons. The family practice physicians were twice as likely to recommend TKA to the male patient than to the female patient; the orthopaedic surgeons were 22 times more likely to recommend TKA to the male patient than to the female patient.”

The researchers concluded that unconscious gender bias may have played a role in the difference among the recommendations for surgery.

“Women tend to be more narrative and personal, while men are sometimes more businesslike, factual, and reserved—perhaps that may have influenced the physician-patient interaction and the recommendation for surgery. The authors of the study do not have an explanation for the discrepancy in recommendations for TKA,” notes Dr. O’Connor.

Effectiveness of TKA
Much conflicting data exist about the effectiveness of TKA in both female and male patients.

“Some studies report that 15 percent to 30 percent of patients have little or no improvement after surgery,” she says, acknowledging that many orthopaedists may not see this level of dissatisfaction at their practices. “It’s important to remember that unhappy patients may not come back to you—they may seek care elsewhere.”

A 2008 study found that women who underwent TKA had equal or better implant survival compared with male TKA patients. The study was based on a literature review of studies with at least 400 patients and 2 to 5 year follow-up.

“The study focused on implant survival, meaning whether the implants failed and needed revision,” she says. “The results don’t necessarily mean that the female patients were doing as well clinically or that they’re as satisfied with their outcomes.”

Female patients’ satisfaction with the results of TKA, says
Dr. O’Connor, may be linked to preoperative function, which studies have suggested is adversely affected the longer a patient waits to have surgery.

“Data support that the best predictors of postoperative outcomes are preoperative function and quadriceps strength,” she says.

Dr. O’Connor also notes that a study performed by the Mayo Clinic in Rochester, Minn., found that women reported more moderate to severe pain after TKA.

“This study concluded that female gender, young age, and worse preoperative pain were predictors for a greater risk of moderate to severe postoperative pain in primary and revision TKA,” says Dr. O’Connor.

“When female TKA patients come into the office and say they’re unhappy with their knee, you may be able to identify a problem, such as instability,” she adds. “The data show, however, that there’s a 28.9 percent chance of moderate to severe pain 5 years after revision surgery in a female patient compared to an 18.3 percent chance in a male patient. I tell all my female patients that their risk for continued pain after revision knee arthroplasty is 1 in 4, and I tell my male patients that it is 1 in 5.”

Is a gender-specific implant necessary?
“I’m personally not for or against a gender-specific implant—I just want the implant to fit the patient, which is why we need multiple sizes,” says Dr. O’Connor.

Clearly, anatomic differences between men and women can affect TKA outcomes. “Women have a differently shaped distal femur,” says Dr. O’Connor. “Because women’s femurs tend to be narrower at the medial-lateral plane, selection of a component that avoids medial-lateral overhang may result in overresection of the posterior femoral condyles and instability of the knee in flexion. Conversely, using a larger component will not compromise resection of the posterior bone, but could result in medial-lateral overhang, which causes soft tissue irritation. Using a knee system with multiple sizes and good medial-lateral to anterior-posterior ratios will minimize this risk.”

Dr. O’Connor was part of an AAOS task force that studied clinical data regarding the need for a gender-specific implant. Their results were published in a Technology Overview in 2008, which was approved by the AAOS Board of Directors.

“We did not find clear clinical data to suggest that gender-specific implants affect clinical outcomes,” she says. “I add the caveat that our findings were based on current measurement tools.”

Those who support gender-specific implants, she says, contend that current clinical tools are not sophisticated enough to find differences among different implant designs regarding satisfaction and outcomes.

More data, better measurement tools needed
According to Dr. O’Connor, new methods to assess the risk of knee OA progression are needed.

“What I really want is to be able to say to a female patient with knee arthritis is, ‘I know you don’t want to have knee surgery right now, but we need to monitor your condition. Perhaps you can delay a year without compromising your outcome; however, if you delay for 2 years, our data suggest that you will have a more significant loss of quadriceps strength that will keep you from going up and down stairs well, and will make it difficult for you to rise from a seated position.’ It would be really nice to have some sort of predictive model.”

“We also need new strategies for pre- and postoperative rehabilitation to improve the ‘never catch up patients,’” she adds, “and we must counter potential biases in treatment recommendations.”

Dr. O’Connor receives royalties from DePuy and Zimmer, and research support from DePuy.

Jennie McKee is a staff writer for AAOS Now. She can be reached at mckee@aaos.org

Gender-Specific Knee Replacements Technology Overview (PDF)

Editor’s Note: “Sex and Gender Differences in Knee Osteoarthritis (OA): Impact on Clinical Practice” was an instructional course lecture held at the 2009 AAOS Annual Meeting. The AAOS co-branded the course, which was moderated by Barbara Boyan, PhD, with the Women’s Health Issues Advisory Board and the Ruth Jackson Orthopaedic Society. Faculty members included Mary I. O’Connor, MD; Wendy M. Kohrt, PhD; and Daniel P. Nicolella, PhD.

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