Where does arthritis come from? The Mechanotransduction Theory and Nanoplasty with MicroCore explained.
A Physical Therapy Algorithm in the Setting of Orthopeadic Immunobiologics for Unicompartmental Knee Osteoarthritis
Signaling cell treatments, often referred to erroneously as “stem cell treatments” and “regenerative therapies” are not uniform between clinics and often do not even represent scientifically justified management strategies. In fact, a recent article in the Journal of Bone and Joint surgery illustrated that of the more than 895 clinics claiming to offer “regenerative treatments”, 96% were in violation of both ethical and legal professional standards by making false treatment claims. Sadly, widespread provider unfamiliarity with molecular mechanisms over the last decade has led to widespread patient exploitation with appropriate treatments delayed and patient trust defeated in many settings. Gaining a better understanding of the immunological signaling basis for autologous orthopedic immunobiologics provides the knowledge to make sound clinical decisions where signaling cell treatments are considered.
An adequate work up includes thorough history and physical with appropriate clearance obtained from primary physicians when indicated. Initially, patients with poor alignment or multi-compartment involvement with extensive joint disease on radiographs were not considered good candidates for cell treatments. Recently, these concerns have been refuted by us and other authors who point to clinical and molecular evidence otherwise including excellent clinical results in the setting of more prounounced Kellgren-Lawrence stages. Patients who have “bone-on-bone” changes can be expected to have up to two to five years of at least fifty percent pain relief. Having an unaffected weight bearing compartment facilitates the subchondral healing response and when managed exquisitely, can lead to clinical regression of osteoarthritis symptoms reflected by structural changes. Subchondral nanoplasty techniques that restore Young’s modulus to the stiff bone seek to accomplish that end.
Patients are typically indicated as likely appropriate by history, examination and appropriate weight bearing radiographs including long-standing films. Magnetic resonance imaging Cartigram® (GE Healthcare®, Chicago, IL) sequencing including T2 wetmap and Terracon images define proteoglycan parameters and suggests the potential for chondrocyte differentiation, specialization and migration into new matrix. Patients are not offered the procedure until they are declared candidates and fully understand all risks, benefits and options to treatment, including no treatment. Full informed consent is established and the procedure is described using the word, “experimental” during full disclosure. Patients are made aware that in spite of our clinically proven success based on prospectively collected data, the procedure is used off-label in this setting and there is no third-party indication or reimbursement for signaling cell arthritis treatment.
In the pre-procedure setting, there is nutrition consultation and patients are trained on the potential benefits of an alkaline diet. Dietary supplementation may be provided and typically includes N-acetylcysteine, ubiquinone, quercetin and NAD+ that patients typically subscribe to for twelve weeks. Clinical consultation prompts laboratory studies and focuses evaluation. An executive lab panel plus is drawn. The labs are necessary and obtained to exclude blood born cancers, infection, anemia and to ensure there is no platelet deficiency (thrombocytopenia). The labs also demonstrate any nutritional deficiency requiring supplementation.
Patients have an advanced concept MR imaging study called a CartiGram® (GE Health®, Chicago, IL) that clearly provides in living color the greatest detail in the extracellular matrix where cartilage cells reside. This advancement in appendicular imaging technology is consistent with the ongoing paradigm shift from reactive to proactive medicine. The axial imaging counterpart, apparent diffusion coefficient (ADC)/diffusion weighted imaging has recently worked its way into clinical medicine and promises to play a big role in the regenerative techniques that presently in use and on the horizon. These advanced imaging techniques predict the clinical onset of arthritis symptoms long before patients present for treatment and should play a larger role in the prevention of disease.
An ideal initial cell harvest is critical to achieve the most therapeutically valuable cell counts. While isopycnic separation is the current gold standard, other looming FDA approved technologies promise to eclipse current cell isolation methods and provide an order of magnitude greater cell delivery, which may further enhance results. Orthopedic and neurosurgeons have the most experience harvesting bone marrow from the anterior iliac crest, where bone turnover is high due to gravitational impact loading along the gluteal pillar with locomotion from heel strike to toe off. Techniques to extract immune cells, mesenchymal stem cells, hematopoietic stem cells, dendritic cells, endothelial cells, pericytes, inflammatory and nucleated cells have been elaborated on at length elsewhere and are beyond the scope of the article. Total nucleated cell counts should be obtained in all patients who undergo signaling cell treatments. Samples from bone marrow aspirate, platelet poor plasma, growth factor concentrate and bone marrow concentrate should be kept for enzyme linked immunosorbent assay. Samples of effusate may indicate the stage of arthritis and ELISA correlates well to clinical report and condition. Most patients experience two to four years of symptoms after the onset of knee pain due to clinical arthritis, after which joint destruction is eminent. Proteome cytokine shifts in the effusion account for clinical experience of symptoms and wax and wane over a four-year period during which the joint undergoes continual and ultimately end stage destruction. At this point, the opposite weight bearing compartment of the same joint is mechanically involved and disease progression is rapid, leading to deformity and transfer lesions to other articulations.
Multimodality ancillary involvement is critical to achieve long term results and patient satisfaction with their investment. Patients must re-establish normal concavity compression in full extension of the knee joint prior to becoming candidates for the procedure. This ensures full surface area of contact. Failure to accomplish this leads to rim/edge loading akin to internal rotation contracture at the glenohumeral joint. Edge loading equates to third body wear from a physical standpoint. Edge loading is biomechanically coupled to plasma membrane bound second messenger systems through integrin and cadherin mechanoreceptors that incite immunomodulatory catabolic signaling pathways and lead to joint destruction. Patients often initially present with contracture of the posteromedial (varus knee) or posterolateral (valgus knee) corner of the knee that must undergo manual stretching to accomplish results and can take 6-12 weeks of a formal therapy program. Patients must achieve their full range of motion or cannot become excellent candidates for signaling cell based nanoplasty procedures.
Static and dynamic unloader bracing is extremely helpful in the pre-procedural setting. All of our patients undergo evaluation by a physical therapist with expertise in gait and locomotion. Balance and gait optimization in all degrees of freedom in stance and throughout locomotion are primary. Subchondral remodeling is the key to a good result in all patients who undergo signaling cell treatments and the weight bearing mechanical axis must be tuned at the time of signaling cell treatment using a combination of unloader bracing for six weeks when gravity dependent following the procedure and an additional six-week period of brace use with impact activities. Patients typically use the appropriate heel wedge orthotics for one to two years to maintain the new mechanical axis and facilitate subchondral bone remodeling.
Ideally, in most patients over sixty, a three-week pre-habilitation phase focuses on balance and gait patterns, core range of motion and strengthening and appendicular range of motion and strengthening including weight bearing frontal and transverse plane hip strengthening and stabilization. Patient treatment is critically individualized and the prehabilitation phase may last longer based on circumstance. Often, patients find adequate relief with an exercise program and conservative management strategies even when they have been told their only option is knee replacement. It must be understood that restoration of full passive and active knee extension range of motion must be achieved to avoid expectation/result mismatch following the procedure. Often, manual stretching is indicated and can take 8-12 weeks to achieve the desired resolution of posteriorly-based capsular and intrinsic ligamentous contractures.
Younger, more active impact athletes may be more resistant to prehabilitation until they understand the importance of subchondral remodeling in restoring tissue elasticity (Young’s Modulus). The attached infographic is helpful in educating patients on the concepts behind both the disease and the treatment.
Below, we describe our basic rehabilitation program for arthritic knee pain patients who elect to undergo signaling cell treatment with primed marrow concentrates. The program is meant to serve as a guide and/or platform that can be modified as the field evolves and is not exhaustive.
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