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Source: Wikimedia Commons and National Human Genome Research

Study: Prebiotics Can Slow OA Progression; Bone Marrow Aspirate Enhances OCA Integration; Multimodal Analgesia Cuts Narcotic Use

Elizabeth Hofheinz, M.P.H., M.Ed. • Mon, October 2nd, 2017

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Study: Prebiotics Slow OA Progression

Working in a mouse model, researchers from the University of Rochester have shown that by altering prebiotics in the gut microbiome it is possible to slow the progression of osteoarthritis (OA). The research was presented at the Orthopaedic Research Society’s annual meeting by researchers from the university’s Center for Musculoskeletal Research (CMR).

Michael J. Zuscik, Ph.D. associate professor of orthopedics and director of educational programs at the Center for Musculoskeletal Research at the University of Rochester, told OTW, “Osteoarthritis (OA) is the greatest cause of disability in the U.S., and obesity is a major risk factor for its development. Despite the comorbid association, the mechanisms linking obesity to the development of OA have not been fully elucidated.”

“For the past few years, our lab has been investigating obesity induced systemic inflammation as a possible explanation for the greater disease prevalence in the obese population. Recently, the gut microbiome has become a hot topic across multiple areas of disease research, including obesity.”

“In obese subjects, the gut microbiome is significantly different from lean, healthy patients, characterized by less diversity and an increase in bacteria associated with inflammation. The obese gut microbiome has been suggested as causal in adipose tissue accumulation and elevated levels of circulating pro-inflammatory cytokines.”

“Moreover, these alterations are correctable through the use of prebiotic supplements, which are non-digestible dietary fibers that promote the proliferation of beneficial, commensal microbes. Thus, we hypothesized, targeting the gut microbial community in obesity could be useful to address the accelerated joint degeneration in this context.”

“In most cases, studies investigating the impact of prebiotics on obesity and type 2 diabetes initiate the prebiotic supplementation at a young age, coinciding with the initiation of the high-fat diet. In these studies, the mice on a high-fat diet supplemented with prebiotic do not gain as much weight as mice on control supplement, and have improved glucose tolerance. In our experiment, we did not want weight to be a variable, so we delayed initiation of prebiotic supplementation until the mice were already obese. Remarkably, mice supplemented with oligofructose were protected from OA progression despite not losing weight, so weight was not a factor in OA progression.”

“This study is the first to investigate the impact of the gut microbiome on the progression of osteoarthritis.”

“We found that from the colon, to the circulation, to the knee specifically, oligofructose was able to reduce inflammation, presumably through increases in certain populations of Bifidobacteria.”

“The most significant finding was that obese mice supplemented with oligofructose were completely protected from the accelerated cartilage degeneration following injury typically observed in the OA of obesity. Even though prebiotic and control supplemented mice had equal body mass and body fat percentage, obese mice on oligofructose had significantly more cartilage remaining at the end of the experiment.”

“These results provide the first direct evidence that gut microbiome shifts can influence inflammation and degeneration in diarthrodial joints, and support targeting of the gut microbiome as a viable disease modifying therapeutic strategy to address the OA of obesity that warrants deeper investigation.”

“This study has laid the foundation for the development of new OA therapeutic targets. Currently, there are no disease modifying therapeutic options for OA. This study provides evidence that manipulation of the gut microbiome is a novel therapeutic strategy to address the OA of obesity.”

“If orthopedic surgeons take nothing else away from this study, it is important to understand how important diet can be to the progression of OA. I don’t think they can stress enough to their patients how important it is to eat a healthy diet that promotes a healthy gut microbiome.”

Bone Marrow Aspirate Enhances OCA Integration

Researchers at the University of Missouri School of Medicine have found that using autogenous bone marrow aspirate concentrate (BMC) before joint restoration improved bone integration and speeded recovery.

"Surgeons performing biologic joint restoration surgeries typically only wash the donor bone to remove the marrow as a pretreatment before implanting the graft," said James Cook, D.V.M., Ph.D., O.T.S.C., the William and Kathryn Allen Distinguished Chair in Orthopaedic Surgery at the MU School of Medicine, in the September 25, 2017 news release. "Once implanted, the recipient's bone has to grow into the donor bone for the surgery to be successful. This graft integration involves a long process called 'creeping substitution' that can take more than a year to complete. The first six months are the most critical for success, so we have been studying ways to make this process better and faster."

Dr. Cook told OTW, “Osteochondral allograft (OCA) transplantation can be an excellent treatment option for patients with large articular cartilage defects in the knee, hip, ankle and shoulder. A biologic joint repair often can return patients back to full activity, including the return of 89% of patients back to their athletic sport of choice. Biologic joints also can function very well for 10 to 15 years in 75 to 80% of patients. With the growing number of people suffering from these extremely common joint problems, this treatment option is becoming more attractive. However, unsuccessful outcomes often are associated with failure of OCA bone integration into the patient. Therefore, it is critical that we explore ways to minimize this issue and increase the chance for success in patients receiving OCA transplants. This line of research is a major focus at MU’s Thompson Laboratory for Regenerative Orthopaedics and the Mizzou BioJoint Center.”

The researchers compared 17 biologic knee joint grafts without BMC to 29 grafts pretreated with BMC. Postoperatively, the team looked at x-ray images at six weeks, three months and six months in order to determine graft integration and healing.

"The use of BMC is approved by the Food and Drug Administration for bone healing therapies," Dr. Cook said in the news release. "It has not been used specifically for biologic joint restoration procedures. I believe this is the first clinical study to directly examine the effects of BMC on bone integration for biologic joint restoration surgeries. Our data show that donor grafts pretreated with BMC were associated with earlier and better bone integration. This means that pretreatment with BMC reduces the risk of bone graft failure and improves the patients' chances for long term success."

Dr. Cook told OTW, “Patients who received OCAs pretreated with their own (autogenous) BMC showed significantly faster and better OCA bone integration during the critical first six month healing period when compared to patients who received OCAs pretreated using the current standard of care irrigation technique alone.”

“This was a prospective clinical cohort study comparing the current standard of care to a new FDA-approved method of pretreating OCAs, so the results are directly applicable to real patients.”

“Based on the basic science, translational and now clinical data, we pretreat all of our OCAs with autogenous BMC at the Mizzou BioJoint Center and continue to see improvements in outcomes as detailed in this study.”

Multimodal Analgesia Cuts Narcotic Use

A complex problem such as chronic spinal pain requires a sophisticated approach...and ideally, one that doesn’t involve narcotics. Surgeons from Rush University Medical Center have developed a multidisciplinary manner of managing such pain.

Kern Singh, M.D., a spine surgeon at Midwest Orthopaedics at Rush and Professor at Rush University Medical Center, and Asokumar Buvanendran, M.D. of Rush University Medical Center, have developed a new postoperative spine anesthesia protocol that decreases and/or eliminates the need for post-surgical narcotics. Their approach—multimodal analgesia (MMA)—uses a combination of medications administered before, during and right after surgery to more effectively control pain. Their MMA protocol completely eliminates the need for a morphine pump after spine surgery…all patients go home with only oral medications. And in many cases they go home the day after surgery.

Dr. Singh told OTW, “Minimally invasive spinal surgeries are done with almost no narcotic medications in our outpatient Surgery Center. Patients are able to undergo a fusion or disk replacement to the neck or back and go home the same day. Minimally invasive techniques are only one aspect of pain management. The perfect combination of different modalities to address pain before it sets in is equally important.”

Asked if other practices were using a multidisciplinary approach to postop pain management/narcotic reduction, Dr. Singh said, “Most practices do NOT use this management as it is a newer concept and most physicians are not familiar with it.”

As for the process of developing this protocol, Dr. Singh told OTW, “Working closely with a pain specialist/anesthesiologist we went through a series of protocol iterations. Understanding pharmacology and medication interactions was key in creating a pathway to reduce narcotic consumption.”

“It’s very safe, established and becoming more wide spread. In addition, all the medications are safe and available in every hospital in the country at very low cost.”

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