Bone Medication May Save Knees

According to research presented this week at the American College of Rheumatology Annual Meeting in Washington, D.C., a daily dose of strontium ranelate -- a medication prescribed for osteoporosis -- may delaBone Medication May Save Kneesy knee osteoarthritis progression. The study also revealed that taking strontium ranelate may improve knee pain, reduce joint damage and the need for surgery. Knee osteoarthritis is caused by cartilage breakdown in the knee joint. Factors that increase the risk of knee osteoarthritis include obesity, age, prior injury to the knee, extreme stress to the joints, and family history. In 2005, 27 million Americans suffered from osteoarthritis, and one in two people will have symptomatic knee arthritis by age 85. Strontium ranelate is an osteoporosis treatment proven to prevent vertebral and hip fractures. In non-clinical studies, strontium ranelate was shown to stimulate bone mass by slowing the breakdown of bone and stimulating new bone growth, having a positive effect on cartilage. Current OA treatments focus on improving disease symptoms through a combination of medication and non-pharmaceutical therapy, but there is currently no treatment approved to delay the progression of the disease. An international group of researchers recently evaluated if strontium ranelate was effective in reducing joint damage and symptoms caused by knee OA. "Osteoarthritis is the most common disease in the elderly and there are currently major unmet medical needs in OA disease management," says Jean-Yves Reginster, MD, PhD, lead investigator in the study and president and chair, department of public health sciences at the University of Liège in Belgium. "There is currently no medication, approved by regulatory authorities to prevent the structural progression of the disease." The Strontium Ranelate Knee Osteoarthritis Trial (also called SEKOIA) studied 1,683 participants with symptomatic primary knee OA over a three-year period. Participants were divided into three groups and randomly selected to receive strontium ranelate or placebo. Participants given strontium ranelate received one or two gram(s) daily dosage. Joint damage was evaluated yearly using digital X-rays. Also, using a computer assisted method, researchers measured knee joint space width, which correlates with cartilage loss. Researchers also evaluated symptoms such as pain, stiffness and changes in physical function using validated tools such as the WOMAC questionnaire. Of the 1,683 participants, 82 percent (or 1,371) completed the study. Sixty-nine percent of the participants were female with average age 63 years-old, average body mass index (also called BMI) of 30±5 kg/m2, and average joint space width measuring 3.5 millimeters. Based on a test that measured disease progression, 60 percent of the patients had mild (stage two) and 40 percent moderate (stage three) knee OA. Researchers noted that strontium ranelate was associated with a decrease in joint damage. After one year, cartilage loss in both groups assessed by the joint space width was -0.23±0.56 mm with 1g/day;-0.27±0.63 mm with 2g/day and -0.37±0.59 mm with placebo. The differences between treatment and placebo groups were 0.14 mm for 1g/day and 0.10 mm for 2g/day. Researchers also noted that strontium ranelate was effective in reducing pain and improving physical function. Overall, treatment with strontium ranelate was well tolerated, with no significant difference in adverse events between both treatment groups and placebo. Additionally, the safety of strontium ranelate was consistent with what was previously observed in osteoporosis. "Strontium ranelate is a drug approved in 102 countries for the management of post-menopausal osteoporosis, which has been proven to be safe when used for ten years in this particular indication. Results of the present trial show also its ability to reduce the progression of osteoarthritis. This could be a major step in the global management of musculo-skeletal disorders in the elderly subjects," says Dr. Reginster. Patients should talk to their rheumatologists to determine their best course of treatment.

Knee Replacement Lowers Risk for Mortality and Heart Failure

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New research presented at the 2012 Annual Meeting of the American Academy of Orthopaedic Surgeons (AAOS) highlights the benefits of total knee replacement (TKR) in elderly patients with osteoarthritis, including a lower probability of heart failure and mortality.

Investigators reviewed Medicare records to identify osteoarthritis patients, separating them into two groups – those who underwent TKR to relieve symptoms, and those who did not. Outcomes of interest included average annual Medicare payments for related care, mortality, and new diagnoses of congestive heart failure, diabetes and depression. Differences in costs and risk ratios were adjusted for multiple variables including age, sex, race and region. The results (adjusted for underlying health conditions) were compared at fixed periods of one year, three years, five years and seven years after surgery.

The seven-year cumulative average Medicare payments for all treatments were $63,940 for the non-TKR group, and $83,783 for the TKR group, for an incremental increased seven-year cost of $19,843. The cost does not include prescription drugs, which are reportedly much higher in the non-TKR group.

There were significant positives in the osteoarthritis TKR group: the risk of mortality was half that of the non-TKR group and the congestive heart failure rate also was lower, at three, five and seven years after surgery. There was no difference in diabetes rates among both groups. Depression rates were slightly higher in the TKR group during the first three years after surgery, though there was no difference at five and seven years.

“These patients had improved survivorship and reduced risk for cardiovascular conditions,” said Scott Lovald, PhD, MBA, lead investigator and senior associate at Exponent, Inc. “More specifically, total knee replacement in osteoarthritis patients may reduce patient mortality by half. There are few health care investments that are so cost effective.”

Patients at risk of knee joint complications when new technology is used

Introducing a new knee replacement model increases the likelihood of early revision surgery


Orthopaedic surgeons face a steep learning curve to get used to new prostheses, and the instruments and methods that go with them, before new total knee replacement procedures are as safe and effective as conventional methods. Patients who undergo the first 15 operations using a new device in a hospital are 48 percent more likely to need early revision surgery, than patients undergoing an operation to fit a prosthesis previously used in the hospital. The work by Mikko Peltola from the National Institute for Health and Welfare in Finland, and colleagues, is published online in Springer's journal, Clinical Orthopaedics and Related Research.

Total knee arthroplasty, or replacement, is an established treatment for patients with severe osteoarthritis of the knee. There are numerous brands and models of endoprostheses (a prosthesis used internally) available and new models continue to emerge as a result of a combination of new technology, marketing efforts and the increasing number of patients requiring the surgery.

Hospital staff makes important decisions when choosing the implants and instruments they use, and these decisions carry consequences for patients' health. According to the research team, however, new equipment and techniques are often used in clinical practice, occasionally without evidence of effectiveness and safety.

Peltola and team looked at the risk of early revision surgery following the introduction of a new endoprosthesis model for total knee arthroplasty. They studied data from the Finnish Arthroplasty Register to identify centers that had performed total knee replacement operations for primary osteoarthritis between 1998 and 2004. Of the 23,707 total number of patients who underwent the surgical procedure, 22,551 were followed up for five years.

The researchers found that the introduction of an endoprosthesis model in a hospital put the first patients at greater risk of revision surgery. The effect was substantial for the first 15 patients operated on with the new model, who were at 48 percent greater risk than patients having undergone an operation to implant a conventional endoprosthesis. Overall, the likelihood of needing revision surgery was greatest during the first two years after the surgery. The learning curve smoothed quickly, however, with no increased risk after the first 15 operations with the new model.
The authors conclude: "Patients should be informed if there is a plan to introduce a new model and offered the option to choose a conventional endoprosthesis instead. Although introducing potentially better endoprosthesis models is important, there is a need for managed uptake of new technology."

Reference

Peltola M et al (2011). Introducing a knee endoprosthesis model increases risk of early revision surgery. Clinical Orthopaedics and Related Research.DOI 10.1007/s11999-011-2171-9

Patients who use narcotics prior to knee replacement experience worse results

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Patients who are dependent on opioids (narcotic pain relievers) for pain management before knee replacement surgery have much more difficulty recovering, a study recently published in the Journal of Bone and Joint Surgery (JBJS) has found. These patients tend to have longer hospital stays, more post-surgical pain, a higher rate of complications, and are more likely to need additional procedures, than patients who are not opioid-dependent.

"We expected to find that the opioid-dependent patients have worse outcomes," says orthopaedic surgeon Michael A. Mont, M.D., the principal investigator and Director of the Center for Joint Preservation and Reconstruction at the Rubin Institute for Advanced Orthopaedics at Sinai Hospital of Baltimore. "But the differences between the two groups of patients were even greater than we thought they would be. The chronic narcotics users did significantly worse in every category."

Study Findings:

Patients included in the study were matched according to age, sex, body-mass index, insurance type, as well as a variety of medical factors. When those factors were accounted for, the study still found that chronic opioid users:

• had to remain in the hospital longer after surgery
• were more likely to need referrals for pain management
• were more likely to suffer unexplained pain or stiffness
• had lower function and less motion in the replaced knee

"This doesn't mean that opioid users shouldn't have the surgery," Mont says. "But those patients and their physicians should know that their results may not be as optimal. It might be possible that we can work with these patients to improve their surgical outcomes."

Dr. Mont and his co-authors outline several strategies to help improve patient outcomes; including:

• weaning patients off strong opioid medications prior to surgery
• prescribing alternate, non-opioid pain medications
• considering non-pharmaceutical pain management strategies

The study's authors acknowledge that some patients who become dependent on opioids before surgery may have lower pain thresholds than those who do not. In addition, those patients may be less compliant with rehabilitation plans and other post-surgical treatments. However, the results of this study are important enough to warrant attention to this issue.

"Previous studies have found that patients who use opioids are more dissatisfied after surgery," Mont says. "But these are more powerful findings since patients require additional surgeries. This is a topic our orthopaedic community and other care providers need to address together."

Glucocorticoid Treatment May Prevent Long Term Damage to Joints,

Joint injury can result in irreversible damage of cartilage which, despite treatment and surgery, often eventually leads to osteoarthritis (OA) in later life. New research published in BioMed Central's open access journal Arthritis Research & Therapy demonstrates that short term treatment of damaged cartilage with glucocorticoids can reduce long term degenerative changes and may provide hope for prevention of OA after injury.

A normal joint is covered by a layer of cartilage containing proteoglycans such as aggrecan and lubricating fluid containing glycosaminoglycans (GAG) such as hyaluronic acid. In a double whammy, after injury proteoglycans and other molecules in cartilage begin to break down and the synthesis of these proteoglycans within cartilage is reduced. Additionally proinflammatory cytokines such as TNFα, IL-1β, and IL-6 are released into the synovial fluid after injury and further increase GAG loss from cartilage.

Using a 'worst-case scenario' system in which cartilage was subjected to mechanical injury and bombarded with immune system-stimulating bio-molecules (TNFα and IL-6) the glucocorticoid dexamethasone (DEX) was able to reduce GAG loss and restore proteoglycan synthesis levels to normal.

Prof Alan Grodzinsky from the MIT Center for Biomedical Engineering said, "Glucocorticoid injections are sometimes used to relieve the pain of established osteoarthritis, but there are concerns about long-term use. Our results suggest that short-term glucocorticoid treatment after joint injury may help restore components of cartilage to preinjury levels and consequently may prevent the long term changes which lead to osteoarthritis."

Infected prosthetic knees cause problems

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The number of people that undergo an operation to have a prosthetic knee joint is increasing. One reason is that the population is getting older, another is that people are also getting heavier, which is a factor in the development of osteoarthritis. The number of knee replacement operations has increased by 9 per cent a year in recent years.

"So if 1-2 per cent of the operations lead to bacterial infection, then the need for revision – re-operation – will also increase", says Anna Stefánsdóttir.

This often involves two operations. First, the old prosthesis is removed and temporarily replaced with bone cement, while the patient is treated with antibiotics to eradicate the infection. This takes 6𔃆 weeks and during this time the patient can usually remain at home. Then a further operation follows to insert a new prosthesis.

In some cases it is not possible to put in a new prosthesis. These patients can be treated with an arthrodesis, or removal of the prosthesis (which leaves the leg without a real knee joint, often confining the patient to a wheelchair). In exceptional cases the infection leads to amputation.

Anna Stefánsdóttir has reviewed almost 480 cases of revision knee replacement between 1986 and 2000.

"Over time more patients have received a new knee prosthesis and fewer are treated with an arthrodesis, but still there are many people who do not get rid of the infection. Other studies show that those who have to have a second operation because of an infection are less satisfied than those who have to have their knee joint changed because the prosthesis has come loose or become worn", she says.

Therefore it is important that the healthcare service does its utmost to avoid infection in the wound. This means having good ventilation in the operating theatre, ensuring the doors are tightly closed, and ensuring that preventive antibiotics are given at exactly the right time before the operation.

"It is also important to be observant of wound complications. If an infection is discovered in time, it is possible to open the wound and clean out the bacteria before they have had chance to spread. Newly operated patients should have a 'VIP lane' so that they can go straight to the hospital orthopaedics department and not have to go via primary care", says Anna Stefánsdóttir.

In Ms Stefánsdóttir's view, re-operations due to infection should be centralised to specialist units, because they require such close cooperation between orthopaedists and infectious disease specialists.

Nowadays, there are orthopaedics clinics that only carry out one such operation a year, which makes it more difficult to establish the right routines.

Lubricating the knee cartilage after ACL injury may prevent osteoarthritis

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PROVIDENCE, RI – An injury to the anterior cruciate ligament (ACL) is fairly common, especially among young athletes. While it can often be corrected through surgery, the injury can lead to increased risk of developing degenerative joint diseases, including osteoarthritis (OA). The problem is that fluid in the knee joint, which lubricates the cartilage, is impacted by the trauma of the injury and begins to deteriorate. A new study from Rhode Island Hospital researchers identifies options for restoring that lubrication to potentially prevent development of OA. The study is published in the August 2010 edition of the journal Arthritis & Rheumatism and is now available online ahead of print.

The study was led by Gregory Jay, MD, PhD, an emergency medicine physician and researcher at Rhode Island Hospital. Jay says, "We know that acute ACL injury is a significant risk factor for the development of post-traumatic osteoarthritis. We also know why that occurs, due to the degeneration of the fluids in the joint and cartilage and joint instability, among other things. Our goal for this study was to determine an effective way to counter that process to prevent the development of OA."

The most movable joints in the body, known as synovial joints, contain synovial fluid (SF). This fluid acts as a lubricant to reduce friction between cartilage in the joint during movement. Following a traumatic injury to the ACL, SF concentration of the natural lubricant, lubricin, in the injured joints is significantly lower in those joints than in the healthy, uninjured joint.

The goal was to identify biologic methods to address the loss of lubricin. In their study, they used animal models with torn ACLs to test three types of fluids that could be injected into the joints and could serve as a substitute for the lost SF. The first was human synoviocyte lubricin that was created in a culture and then purified to be injected into the injured knees. The second is recombinant protein, with a change in the genetic make-up of the cell so that it makes a molecule of interest. The reasoning behind using a recombinant protein is that if it is commercialized, that is likely how it will be manufactured. The third was lubricin from human SF that would otherwise be discarded. The human SF is then purified before injection, and because it is more closely aligned with the natural lubricin, it represents a positive control in the study.

Through their study, the researchers report three key findings. Jay, who is also a professor of emergency medicine and engineering at The Warren Alpert Medical School of Brown University says, "First and foremost, we found that you can limit cartilage deterioration. This is evident by using a well-accepted OA biomarker which shows that the breakdown of cartilage collagen type 2 and recovered in the urine has been muted by treating the knee joint with lubricin." The human synoviocyte lubricin was the most effective form in this experiment, however, the recombinant form also had a good degree of success.

Second, the study results indicate that when lubricin is placed back into the traumatized joint, it encourages the joint to make its own lubricin. Jay explains, "We found that you are limiting deterioration of the joint endogenously by the greater secretion of the lubricin molecule. Basically, by placing the lubricin there, it encouraged the joint's normal activity to produce this molecule."

Jay, who is also a physician with University Emergency Medicine Foundation in Providence, stresses that this study is important for another reason. "This is a huge advance over the existing technology of viscosupplementation injections. The concept was good, but the chemistry isn't there to support it." Jay continues, "When viscosupplements were approved as devices in the 90s, it was thought then that hyaluronic acid used in this treatment was tied to joint lubrication because it was viscous. We now know that joint lubrication has little to do with viscosity. We are inventing a new type of joint lubrication strategy: Tribosupplementation, taken from the Greek, meaning to wear or to rub" "

Jay notes, "Viscosupplementation is a $500 million per year device market that just doesn't work particularly well. Past studies by us and others indicate this. We now need a paradigm shift in how we are thinking about preventing and treating arthritic diseases."

Jay and his colleagues believe the study findings represent that paradigm shift. Jay says, "We found that lubricin may prevent the fundamental process that can lead to OA following an ACL injury. It is a promising biologic candidate since it is a replacement for a normally occurring glycoprotein. This is very germane to the health care bill, which supports the creation of new therapeutic biologics." Biologics are important and their development is encouraged because they are very specific and have low toxicity profiles, meaning they are better for patients in terms of better results with fewer complications.

Jay concludes that this and related papers are key to future treatment of joint trauma. "In the peri-injury period following joint trauma, joint surfaces are vulnerable to enhanced wear. This study is pointing us in the right direction, and has shown that this can potentially be mitigated by simply reintroducing the joint's natural lubricant." He continues, "We are confident that further studies will perfect the technology and this will be the way that joints will be treated in the future to prevent OA."