Stem Cells Reduce Pain from Knee Osteoarthritis

By Pat Anson, PNN Editor

A small new study has demonstrated that stem cells collected from a patient’s own bone marrow can significantly reduce pain caused by osteoarthritis of the knee.

In the first clinical trial of its kind in Canada, researchers collected mesenchymal stromal cells (MSCs) from the spines of 12 middle-aged patients with moderate to severe knee osteoarthritis. These “autologous” cells – stem cells derived from a patient’s own fat or bone tissue – were then processed and injected back into the patients’ knees at different doses.

Researchers then followed the patients for the next 12 months, using MRI imaging, biomarkers, molecular fingerprinting and the patient's own assessment of how they felt.

"Our goal was to test for safety as well as to gain a better understanding of MSC dosing, mechanisms of action and donor selection," said lead author Sowmya Viswanathan, PhD, Arthritis Program at the Krembil Research Institute, University Health Network in Toronto.

At the end of the study period, researchers said there were significant improvements in all 12 patients’ pain levels, stiffness and quality of life. The study also showed that the MSCs were safe at all the doses tested and that the higher the dose, the more effective the outcome.

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"We also obtained novel insights into a potential anti-inflammatory mechanism of action of these cells in osteoarthritic knee joints. We noted that donor heterogeneity is an important factor, and our assembled panel of genes helps us identify cells which are potent in osteoarthritis. These are important findings which we hope to translate into a larger, powered clinical trial as part of our next steps," said Viswanathan, who reported the findings in the journal Stem Cells Translational Medicine.

Over 250 million people worldwide suffer from knee osteoarthritis (OA), which causes thinning of cartilage and progressive joint damage. Nearly 40 percent of Americans over the age of 45 have some degree of knee OA.

Knee replacement and arthroscopic knee surgeries are commonly used to treat knee OA, even though many studies show they have limited effectiveness. A 2017 study in The British Medical Journal  of over 7,400 patients who had knee replacement surgery found the procedure often had minimal effects on quality of life and wasn’t worth the cost.

Arthroscopic surgery is less invasive than a total knee replacement, but studies also show it is often not effective. In 2017, an international panel of experts reviewed 25 studies involving nearly two million patients and concluded that arthroscopic surgery does not improve long term pain or function in patients with knee conditions such as osteoarthritis.

Because these conventional treatments often fail, there is growing interest in the use of stem cells to treat knee problems. The FDA, however, takes a dim view of autologous stem cells and released guidance in 2017 that requires the cells to undergo “minimal manipulation.”

The FDA recently sent letters to 20 stem cell manufacturers and clinics warning them they were violating FDA regulations. The agency says the science behind autologous cells is still in its early stages and they have not been proven to be safe and effective.

“There’s a false premise being asserted by some in the field that a product derived from a person’s own body and then manipulated and reinserted for another use different from the one it played in its original location is not subject to FDA regulation just because it originated from the person it was given back to,” then FDA commissioner Scott Gottlieb, MD, and Biologics Center Director Peter Marks, MD, said in a statement.

“We’ve seen too many cases of sponsors claiming that cells aren’t subject to FDA regulation just because the cells originated from the same patient to whom the eventual manufactured product is being given. And we’ve seen too many cases of companies making unsubstantiated claims that these treatments prevent, treat, cure or mitigate disease where the products have sometimes led to serious patient harm.”

One Third of Knee Surgery Patients Still Have Pain

By Liz Szabo, Kaiser Health News

Danette Lake thought surgery would relieve the pain in her knees.

The arthritis pain began as a dull ache in her early 40s, brought on largely by the pressure of unwanted weight. Lake managed to lose 200 pounds through dieting and exercise, but the pain in her knees persisted.

A sexual assault two years ago left Lake with physical and psychological trauma. She damaged her knees while fighting off her attacker, who had broken into her home. Although she managed to escape, her knees never recovered. At times, the sharp pain drove her to the emergency room. Lake’s job, which involved loading luggage onto airplanes, often left her in misery.

When a doctor said that knee replacement would reduce her arthritis pain by 75 percent, Lake was overjoyed.

“I thought the knee replacement was going to be a cure,” said Lake, now 52 and living in rural Iowa. “I got all excited, thinking, ‘Finally, the pain is going to end and I will have some quality of life.’”

But one year after surgery on her right knee, Lake said she’s still suffering.

“I’m in constant pain, 24/7,” said Lake, who is too disabled to work. “There are times when I can’t even sleep.”

Most knee replacements are considered successful, and the procedure is known for being safe and cost-effective. Rates of the surgery doubled from 1999 to 2008, with 3.5 million procedures a year expected by 2030.

But Lake’s ordeal illustrates the surgery’s risks and limitations. Doctors are increasingly concerned that the procedure is overused and that its benefits have been oversold.

DANETTE LAKE (khn photo)

DANETTE LAKE (khn photo)

Research suggests that up to one-third of those who have knees replaced continue to experience chronic pain, while 1 in 5 are dissatisfied with the results. A study published last year in the BMJ found that knee replacement had “minimal effects on quality of life,” especially for patients with less severe arthritis.

One-third of patients who undergo knee replacement may not even be appropriate candidates for the procedure, because their arthritis symptoms aren’t severe enough to merit aggressive intervention, according to a 2014 study in Arthritis & Rheumatology.

“We do too many knee replacements,” said Dr. James Rickert, president of the Society for Patient Centered Orthopedics, which advocates for affordable health care, in an interview. “People will argue about the exact amount. But hardly anyone would argue that we don’t do too many.”

Although Americans are aging and getting heavier, those factors alone don’t explain the explosive growth in knee replacement. The increase may be fueled by a higher rate of injuries among younger patients and doctors’ greater willingness to operate on younger people, such as those in their 50s and early 60s, said Rickert, an orthopedic surgeon in Bedford, Ind. That shift has occurred because new implants can last longer — perhaps 20 years — before wearing out.

Yet even the newest models don’t last forever. Over time, implants can loosen and detach from the bone, causing pain. Plastic components of the artificial knee slowly wear out, creating debris that can cause inflammation. The wear and tear can cause the knee to break. Patients who remain obese after surgery can put extra pressure on implants, further shortening their lifespan.

The younger patients are, the more likely they are to “outlive” their knee implants and require a second surgery. Such “revision” procedures are more difficult to perform for many reasons, including the presence of scar tissue from the original surgery. Bone cement used in the first surgery also can be difficult to extract, and bones can fracture as the older artificial knee is removed, Rickert said.

Revisions are also more likely to cause complications. Among patients younger than 60, about 35 percent of men need a revision surgery, along with 20 percent of women, according to a November article in the Lancet.

Yet hospitals and surgery centers market knee replacements heavily, with ads that show patients running, bicycling, even playing basketball after the procedure, said Dr. Nicholas DiNubile, a Havertown, Pa., orthopedic surgeon specializing in sports medicine. While many people with artificial knees can return to moderate exercise — such as doubles tennis — it’s unrealistic to imagine them playing full-court basketball again, he said.

“Hospitals are all competing with each other,” DiNubile said. Marketing can mislead younger patients into thinking, “‘I’ll get a new joint and go back to doing everything I did before,’” he said. To Rickert, “medical advertising is a big part of the problem. Its purpose is to sell patients on the procedures.”

Rickert said that some patients are offered surgery they don’t need and that money can be a factor.

Knee replacements, which cost $31,000 on average, are “really crucial to the financial health of hospitals and doctors’ practices,” he said. “The doctor earns a lot more if they do the surgery.”

Ignoring Alternatives

Yet surgery isn’t the only way to treat arthritis.

Patients with early disease often benefit from over-the-counter pain relievers, dietary advice, physical therapy and education about their condition, said Daniel Riddle, a physical therapy researcher and professor at Virginia Commonwealth University in Richmond.

Studies show that these approaches can even help people with more severe arthritis.

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In a study published in Osteoarthritis and Cartilage in April, researchers compared surgical and non-surgical treatments in 100 older patients eligible for knee replacement.

Over two years, all of the patients improved, whether they were offered surgery or a combination of non-surgical therapies. Patients randomly assigned to undergo immediate knee replacement did better, improving twice as much as those given combination therapy, as measured on standard medical tests of pain and functioning.

But surgery also carried risks. Surgical patients developed four times as many complications, including infections, blood clots or knee stiffness severe enough to require another medical procedure under anesthesia. In general, 1 in every 100 to 200 patients who undergo a knee replacement die within 90 days of surgery.

Significantly, most of those treated with non-surgical therapies were satisfied with their progress. Although all were eligible to have knee replacement later, two-thirds chose not to do it.

Tia Floyd Williams suffered from painful arthritis for 15 years before having a knee replaced in September 2017. Although the procedure seemed to go smoothly, her pain returned after about four months, spreading to her hips and lower back.

She was told she needed a second, more extensive surgery to put a rod in her lower leg, said Williams, 52, of Nashville.

“At this point, I thought I would be getting a second knee done, not redoing the first one,” Williams said.

Other patients, such as Ellen Stutts, are happy with their results. Stutts, in Durham, N.C., had one knee replaced in 2016 and the other replaced this year. “It’s definitely better than before the surgery,” Stutts said.

Inappropriate Surgeries

Doctors and economists are increasingly concerned about inappropriate joint surgery of all types, not just knees.

Inappropriate treatment doesn’t harm only patients; it harms the health care system by raising costs for everyone, said Dr. John Mafi, an assistant professor of medicine at the David Geffen School of Medicine at UCLA.

The 723,000 knee replacements performed in 2014 cost patients, insurers and taxpayers more than $40 billion. Those costs are projected to surge as the nation ages and grapples with the effects of the obesity epidemic, and an aging population.

To avoid inappropriate joint replacements, some health systems are developing “decision aids,” easy-to-understand written materials and videos about the risks, benefits and limits of surgery to help patients make more informed choices.

In 2009, Group Health introduced decision aids for patients considering joint replacement for hips and knees.

Blue Shield of California implemented a similar “shared decision-making” initiative.

Executives at the health plan have been especially concerned about the big increase in younger patients undergoing knee replacement surgery, said Henry Garlich, director of health care value solutions and enhanced clinical programs.

The percentage of knee replacements performed on people 45 to 64 increased from 30 percent in 2000 to 40 percent in 2015, according to the Agency for Healthcare Research and Quality.

Because the devices can wear out in as little as a few years, a younger person could outlive their knees and require a replacement, Garlich said. But “revision” surgeries are much more complicated procedures, with a higher risk of complications and failure.

“Patients think after they have a knee replacement, they will be competing in the Olympics,” Garlich said.

Danette Lake once planned to undergo knee replacement surgery on her other knee. Today, she’s not sure what to do. She is afraid of being disappointed by a second surgery.

Sometimes, she said, “I think, ‘I might as well just stay in pain.’”

Kaiser Health News, a nonprofit health newsroom whose stories appear in news outlets nationwide, is an editorially independent part of the Kaiser Family Foundation.

Study Questions Value of Knee Replacement Surgery

By Pat Anson, Editor

New research is raising questions about the value of knee replacement surgeries, one of the fastest growing elective procedures in the United States.

In an analysis of over 7,400 patients with osteoarthritis who had knee replacement surgeries, researchers concluded the procedure often had minimal effects on quality of life and wasn’t worth the cost. But when the surgeries are performed on patients with more severe knee pain, their effectiveness increases, researchers reported in The BMJ.

The annual rate of total knee replacements in the U.S. has doubled since 2000, with more than 640,000 surgeries now performed annually at a cost of $10.2 billion.

"Given its limited effectiveness in individuals with less severely affected physical function, performance of total knee replacement in these patients seems to be economically unjustifiable," wrote lead author Bart Ferket, MD, an assistant professor at the Icahn School of Medicine at Mount Sinai in New York City.

"Considerable cost savings could be made by limiting eligibility to patients with more symptomatic knee osteoarthritis,"

Osteoarthritis is a joint disorder that leads to thinning of cartilage and progressive joint damage. Nearly 40 percent of Americans over the age of 45 have some degree of knee osteoarthritis, and those numbers are expected to grow as the population ages.

Ferket and his colleagues found that about a third of the patients who had their knees replaced continued to experience chronic pain after the procedure. Their quality of life generally improved, but the change was small. The improvement in quality of life was higher when patients with lower physical scores before surgery were operated on.

“The practice of total knee replacement as performed in a recent U.S. cohort of patients with knee osteoarthritis had minimal effects on quality of life. If the procedure were restricted to patients with more severe functional status, however, its effectiveness would rise, with practice becoming economically more attractive,” they concluded.

"Our findings emphasize the need for more research comparing total knee replacement with less expensive, more conservative interventions, particularly in patients with less severe symptoms.”

Previous studies have also questioned the value of many knee surgeries. A five year study of 175 knee replacement patients by the National Institutes of Health found that over a third of the surgeries were inappropriate. Many patients had pain and other symptoms that were too mild to justify having their knees replaced.  

Another study found that arthroscopic knee surgery is “not an economically attractive treatment option” compared to physical therapy, exercise and medication.

In arthroscopic surgery, a doctor makes a small incision in the knee and inserts a tiny camera and instruments to repair damaged ligaments or torn meniscus. Arthroscopic surgery is far less invasive than a total knee replacement. Depending on insurance, hospital charges and the surgeon, arthroscopic surgeries cost about $4,000.  A total knee replacement costs about $28,000 according to HealthCare Bluebook.

Hospitals Accountable for Joint Replacement Surgeries

By Pat Anson, Editor

Hospitals will be held accountable for the cost and quality of care given to Medicare patients who undergo hip and knee replacement surgery under a pilot program by the Center for Medicare and Medicaid Services (CMS).

Hip and knee replacements are the most common inpatient surgery for Medicare beneficiaries. In 2014, there were more than 400,000 such procedures, costing Medicare more than $7 billion for hospitalizations alone. Post-surgery complications such as pain and infection often lead to hospital readmissions and extended recovery periods.

Under the Comprehensive Care for Joint Replacement (CJR) model, the hospital where the surgery takes place will be accountable for all services from the time of the surgery through 90 days after hospital discharge. This “bundling” of payments for hospitals, physicians, physical therapists and other health providers is meant to encourage them to work together to deliver more effective and efficient care.

Depending on the hospital’s quality and cost performance, the hospital will either earn a financial reward or be required to refund Medicare for a portion of the cost.

The quality and cost of care for hip and knee replacement surgeries can vary greatly. Currently the average Medicare expenditure for surgery, hospitalization, and recovery ranges from $16,500 to $33,000 across geographic areas. The rate of complications from infections or implant failures can be more than three times higher at some facilities than others.

“Incentives to coordinate the whole episode of care – from surgery to recovery – are not strong enough, and a patient’s health may suffer as a result,” CMS said in a statement. “When approaching care without seeing the big picture, there is a risk of missing crucial information or not coordinating across different care settings. This approach leads to more complications after surgery, higher readmission rates, protracted rehabilitative care, and variable costs. These are not the health outcomes patients want.”

The CJR model is being tested in 67 metropolitan areas throughout the country, and nearly all hospitals in those areas are required to participate. Patients will still be able to choose their doctor, hospital, nursing facility, home health service, and other providers. A list of all 67 areas can be found here.

The aging of the U.S. population is causing a surge in hip and knee replacement surgeries. Over a million joint replacement surgeries are currently performed annually – a number expected to surpass four million by 2030. 

Joint replacement surgery is generally conducted on the elderly to relieve pain from osteoarthritis, a painful and disabling condition caused by a loss of cartilage and the degradation of joints. Twenty-seven million Americans suffer from osteoarthritis.

Recent studies have questioned whether many of the surgeries are appropriate. A five year study of 175 knee replacement patients by the National Institutes of Health found that over a third of the surgeries were inappropriate, according to researchers who found that many patients had pain and other symptoms that were too mild to justify having their knees replaced.  Less than half (44%) of the knee replacement surgeries were classified as appropriate, with 22% rated inconclusive and 34% deemed inappropriate.

Racial Disparities Found in Joint Replacement Surgery

By Pat Anson, Editor

Black, Hispanic and Medicaid patients are significantly more likely to be readmitted to the hospital after total joint replacement (TJR) surgery, while women are less likely to suffer complications, according to new studies presented at the annual meeting of the American Academy of Orthopaedic Surgeons in Las Vegas.

In one study, researchers analyzed race and ethnic data on nearly 53,000 patients admitted to Connecticut hospitals for TJR from 2008 to 2012. The average patient was 67 years of age, white, female and covered by Medicare.

Patients who were African-American were 62% more likely to be readmitted to the hospital within 30 days of TJR. Hispanic patients were 50% more likely and Medicaid patients were 40% more likely to be readmitted than patients with private insurance.

"Our study shows that black patients who undergo total knee replacement may have poorer outcomes," said lead study author and orthopedic surgeon Courtland Lewis, MD. "After controlling for two key variables implicated in race and ethnic disparities in hospital readmission -- preoperative comorbidities and type of insurance coverage -- black patients still have a 35 percent higher likelihood of all-cause, 30-day readmission compared to white patients.”

Lewis said the disparity with white patients may be due to black patients having less access to primary care and less communication with health care providers.

Racial disparities in health care have long been documented, including that black patients utilize hip and total knee replacement at rates nearly 40 percent less than white patients, despite having higher rates of osteoarthritis—a leading cause of joint deterioration. Total hip and knee replacements are common surgical treatments for late-stage arthritis.

The overall 30-day readmission rate for patients in the study was about 5 percent. The most common reasons for readmission were postoperative infection, inflammatory reaction due to a joint prosthesis, hematoma complications, and dislocation of a prosthetic joint.

A second study looked at nearly 60,000 knee and hip replacements at a hospital in Ontario, Canada. Researchers found that men were 15% likely than women to return to the emergency department within 30 days of TJR surgery – even though women who had the surgery were older and more likely to be frail. Over half the patients in the study were women.

The findings contradict the theory that TJR is underutilized in female patients because they have worse outcomes then men.

"Despite the fact that women have a higher prevalence of advanced hip and knee arthritis, prior research indicates that North American women with arthritis are less likely to receive joint replacement than men," said lead study author Bheeshma Ravi, MD, an orthopaedic surgery resident at the University of Toronto. "One possible explanation is that women are less often offered or accept surgery because their risk of serious complications following surgery is greater than that of men.

"In this study, we found that while overall rates of serious complications were low for both groups, they were lower for women than for men for both hip and knee replacement, particularly the latter" said Dr. Ravi. "Thus, the previously documented sex difference utilization of TJR cannot be explained by differential risks of complications following surgery." 

Men in the study were found to be up 70 percent more likely to have a heart attack within three months of TJR surgery and 70 percent more likely to have an infection or require revision surgery within two years of a total knee replacement.