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12 Articles in Volume 18, Issue #4
A New Frontier in Migraine Management: Inside CGRP Inhibitors & Migraine Prevention
Assessment of Patients with Rheumatoid Arthritis or Osteoarthritis
Biosimilars in Rheumatology: How Popular Will They Be?
Case Studies in Regenerative Cellular Therapy: Tendinopathy and Osteoarthritis
Commentary: Make the Easy Choice for Care
Editorial: The Emergence of Trackable Pill Technology: Hype or Hope?
Editorial: The Practicality of Pain Acceptance
How to Avert Government Scrutiny When Prescribing Opioids
Letters to the Editor: DEA and Prescribing, the War on Statistics, Failing Treatments, Patients' Options
Meet the Migraine Game-Changers
Platelet-Rich Plasma and Stem Cell-Rich Prolotherapy for Musculoskeletal Pain
With concerns over opioids, could novel receptors be useful?

Case Studies in Regenerative Cellular Therapy: Tendinopathy and Osteoarthritis

The authors discuss patient outcome and pain relief after administering orthobiologic treatments using platelet-rich plasma and bone marrow aspirate concentrate.
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Case #1: Advanced Tendinopathic Disease

A 29-year-old male recreational soccer player who still enjoys regular participation in league play, presents with progressive right knee pain for several years. The pain is anterior, worse with descending stairs and with running when accelerating. There is no history of significant injury. He participated in two physical therapy programs over the prior three years, as well as various courses of anti-inflammatories. At the time, each would provide modest relief and allow him to continue playing. However, symptoms have progressed to the point of preventing active participation. He now reports pain with daily activities, such as stair climbing, which can “make him wince.” He avoids long walks and deep bending. He rates his pain as high as 7/10 on the visual analog scale.

Physical examination demonstrated a well-developed, healthy male who entered the examination room without antalgic gait. On examination, the right knee was without effusion. Range of motion was full. There is no significant medial or lateral joint line tenderness, and ligamentous testing was stable in the anterior, posterior, and lateral planes. There was mild crepitus with knee extension. There was pain with resisted knee extension, but not flexion. Palpation at the inferior pole of the patella extending into the first 2 cm of the patella tendon reproduced his pain. There is mild local soft-tissue edema.

A musculoskeletal ultrasound evaluation was performed. The ultrasound images shown in Figures 1 and 2 demonstrate advanced tendinopathic disease. Note the considerable thickening, diffuse hypoechoic change, and central anechoic lesions signifying intrasubstance tearing.

Figure 1: Pre-treatment, Case #1: long and short axis views of the patella tendon demonstrating significant thickening, diffuse hypoechoic changes, and anechoic areas consistent with intrasubstance tearing.

Figure 2: Pre-treatment, Case #1: long and short axis views of the patella tendon demonstrating significant thickening, diffuse hypoechoic changes, and anechoic areas consistent with intrasubstance tearing.

As the patient had already engaged in two bouts of physical therapy, the last including an attempt at eccentric exercise, he presented to our facility to discuss available options. He had investigated platelet-rich plasma (PRP) and was rather well read on that treatment modality. He was not interested in a surgical consultation.

Tendinopathy Pathophysiology& Changing Treatment Paradigms

The term tendinitis denotes inflammation of a tendon, most commonly from overuse but also from infection or rheumatic disease. It was as early as 1976 that Paddu et al. recognized a lack of inflammatory cells, bringing into question inflammation as the underlying pathology of chronic tendon pain.1 Evidence mounted until the early 1990s when an editorial by Khan et al. pronounced it is time “to accept the irrefutable evidence that the term tendinitis must be abandoned to highlight a new perspective on tendon disorders."2 This tipping-point drove clinicians and therapists into a new era of thinking about the structural forces and mal-adaptations that lead to what is now properly termed tendinosis. Various pathologic theories arose including angiogenic, neural, biochemical, and structural alterations that led to new treatments aimed at these theoretical models, such as eccentric strengthening, sclerosing agents, blood products, and extra-corporeal shockwave therapy.3

Each of the treatments has demonstrated various levels of success without any option rising to clear superiority. The current models of pain generation in tendinosis accept contribution from all of these mechanisms, without favoring either as the priority pain generator. Recent publications have cited central sensitization as playing a role in recalcitrant tendinopathies.4

Phases of Healing

The healing cascade in tendon injury and repair has been well described and will be briefly summarized. There are three phases which overlap and are not independent of each other, not including hemostasis which occurs in the first few minutes after injury, and whose purpose is platelet aggregation, coagulation, and fibrin plug formation to stop bleeding.

The inflammatory phase typically spans the first one to three days. Inflammation is heralded by the presence of large quantities of red and white blood cells. Platelets are emptying alpha and dense granules, dispersing cytokines and growth factors. Macrophages are activated and digest necrotic debris, while tenocytes migrate and begin replication.

The second stage is the proliferative or repair stage, beginning roughly 48 to 72 hours after injury. Macrophages shift from catabolic or phagocytic to anabolic or reparative functions. Tenocytes attempt to provide early structural support and deposit a temporary, mechanically inferior matrix composed mostly of collagen III.5,6

Remodeling begins 30 to 60 days after injury and can last up to one year before tissue is matured. However, it is important to know that the original structure, metabolic, and biomechanical qualities may never be fully restored. Tendon modulus of elasticity and tensile strength are diminished, and an increased mechanical stiffness often remains. Both the extracellular matrix and native cellular metabolism may be decreased compared to the uninjured state. Compounded, these characteristics increase the chance of ultimate tendon failure.6,7

Considerations in PRP

As mentioned, platelets are known to contain alpha and dense granules, which release multiple growth factors and cytokines that promote wound healing. Authors of in vitro studies have reported an enhancement of the recruitment, proliferation, and differentiation of the cells involved in soft-tissue regeneration. When injecting platelet-rich plasma (PRP), most clinicians also fenestrate the tendon. The local trauma promotes bleeding and release of collagen fragments. Collagen is a potent platelet activator, and when the PRP is introduced, the concentrated platelets are activated and immediately release their growth factors and chemokines. This converts a stagnant, non-healing state in an active inflammatory environment with a renewed healing potential.8-10

Platelet-rich plasma is safe, accessible, and has limited downtime. A 2013 meta-analysis by Mautner et al. concluded most patients reported a moderate (ie, 50%) improvement in pain symptoms.11 Prior to the rise of PRP utilization, surgery had been considered the final option for recalcitrant tendinopathies despite highly variable clinical outcomes – satisfaction estimated at approximately 80% depending on the type of tendon surgery.12,13 An updated meta-analysis of randomized controlled trials by Fitzpatrick et al. concluded “there is good evidence to support the use of a single injection of LR-PRP [leukocyte-rich platelet-rich plasma] under ultrasound guidance in tendinopathy. The authors also noted that “both the preparation and intra-tendinous injection technique of PRP appear to be of great clinical significance."14

Last updated on: June 8, 2018
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Biosimilars in Rheumatology: How Popular Will They Be?