Treatment of knee osteoarthritis: platelet-derived growth factors vs. hyaluronic acid. A randomized controlled trial

Abstract:

Objective:Aim of this trial was to compare efficacy of activated platelet-rich plasma against hyaluronic acid as intra-articular injections to people with osteoarthritis of the knee.

Design: Phase-2 randomized controlled trial, with blind patients and outcome assessors.

Setting: Outpatient rehabilitation service; years 2011–2013.

Subjects: Patients with knee osteoarthritis grades 2–3 at magnetic resonance imaging (MRI) were included after consent and randomized. Target sample size was 25 patients per group.

Interventions: Patients received three activated platelet-rich plasma (intervention group) or hyaluronic acid (controls) intra-articular injections at 4-week intervals.

Main measures: Main outcome measure was proportion of patients with >1 grade improvement at six months from last injection, as assessed by a radiologist blind to study group. Patients were evaluated over time clinically and with functional scales (Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Lysholm, Tegner, American Knee Society Score (AKSS), Lequesne, visual analogue scale (VAS) for pain).

Results: Overall, 30 patients were randomized to intervention and 28 to control group. For primary outcome, 28 patients (29 knees) in the intervention and 22 (25 knees) in the control group were available. Patients with at least 1 grade improvement at repeat MRI were 14 (48.3%) in the intervention and 2 (8%) in the control group (P < 0.003). Improvement in symptoms and functional scales was consistently higher in the intervention group. No side-effects were observed in either group.

Conclusion: Activated platelet-rich plasma reduces articular damage as evident at MRI, as soon as six months after treatment; it reduces pain and improves patient’s function and overall quality of life.

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Platelet-Rich Fibrin Facilitates Rabbit Meniscal Repair by Promoting Meniscocytes Proliferation, Migration, and Extracellular Matrix Synthesis

Abstract:

Although platelet-rich fibrin (PRF) has been used in clinical practice for some time, to date, few studies reveal its role as a bioactive scaffold in facilitating meniscal repair. Here, the positive anabolic effects of PRF on meniscocytes harvested from the primary culture of a rabbit meniscus were revealed. The rabbit meniscocytes were cultured with different concentrations of PRF-conditioned medium, and were evaluated for their ability to stimulate cell migration, proliferation, and extracellular matrix formation. In vivo, meniscal defects were created via an established rabbit animal model and were evaluated by a histology-based four-stage scoring system to validate the treatment outcome three months ostoperatively. The in vitro results showed that PRF could induce cellular migration and promote proliferation and meniscocyte extracellular matrix (ECM) synthesis of cultured meniscocytes. In addition, PRF increased the formation and deposition of cartilaginous matrix produced by cultured meniscocytes. Morphological and histological evaluations demonstrated that PRF could facilitate rabbit meniscal repair. The data highlight the potential utility of using PRF in augmenting the healing of meniscal injuries. These advantages would benefit clinical translation, and are a potential new treatment strategy for meniscal repair.

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Intradiscal O2O3: Rationale, Injection Technique, Short- and Long-term Outcomes for the Treatment of Low Back Pain Due to Disc Herniation

Abstract:

The management of low back pain should always start with a conservative approach; however, when it fails, intervention is required and at that moment the most appropriate choice remains unclear. Before invasive surgery, minimally invasive techniques can be adopted. In European trials and in a trans-Canadian clinical trial 03 ozone has been used successfully. In total over 50,000 patients have been treated safely. Ozone is a gas normally present in the atmosphere with potent oxidizing power; it has been used for percutaneous intradiscal injection combined with oxygen (O2O3) at very low concentrations for 15 years in Europe. The main indication is back pain with or without radicular pain but without motor deficits, which is refractory to 4-6 weeks of conservative therapies. Its mechanism of action on the disc is mechanical (volume reduction by subtle dehydration of the nucleus pulposis) and antinflammatory. The intradiscal ozone injection is performed with a thin needle (18-22 gauge) image guided by computed tomography or angiofluoroscopy and is usually complimented by periganglionic injection of corticosteroids and anesthetics. This combination gives immediate pain relief and allows time for the ozone to act. It is a cost-effective procedure that presents a very low complication rate (0.1%). The radicular pain is resolved before the back pain does, as is seen with microdiscectomy. Peer-reviewed publications of large randomized trials, case series, and meta analysis from large samples of patients have demonstrated the procedure to be safe and effective in the short and the long terms, with benefits recognized up to 10 years after treatment. We aim to review the principles of action of O2O3 and report the injection techniques, complications, and short- and long-term outcomes.

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The Histological Effects of Ozone Therapy on Sciatic Nerve Crush Injury in Rats

Abstract:

Objective: Peripheral nerve injury is a common, important problem that lacks a definitive, effective treatment. It can cause neurologic deficits ranging from paresthesia to paralysis. This study evaluated the effect of ozone therapy on sciatic nerve crush injury in rats.

Materials and Methods: Twenty-four male rats were divided into control sham surgery, sciatic nerve injury, and sciatic nerve injury with ozone groups (each n = 8). The sciatic nerve injury was inflicted via De Koning’s crush-force method. The sciatic nerve injury group received medical air and the sciatic nerve injury ozone group received 0.7 mg/kg ozone. Sciatic nerve samples were obtained 4 weeks after injury. Vascular congestion, vacuolization, edema formation, S100 expression, and the thicknesses of the perineurium and endoneurium and diameter of the injured sciatic nerves were evaluated.

Results: The diameter of the sciatic nerve and thicknesses of the perineurium and epineurium were significantly greater in the sciatic nerve injury group (P < 0.05) and significantly less in the sciatic nerve injury with ozone group (P < 0.001). High S100 immunoreactivity was seen in the sciatic nerve injury group compared with the other 2 groups (P < 0.05). The distributions of vascular congestion and vacuolization were significantly less in the sciatic nerve injury with ozone group (P < 0.05).

Conclusions: Ozone therapy improved sciatic nerve injury recovery without causing an increase in fibrotic tissue. Ozone reduced fibrosis, vascular congestion, vacuolization, and edema in rodents. Ozone treatment might be used to assist in sciatic nerve injury.

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Does platelet-rich plasma have a favorable effect in the early stages of steroid-associated femoral head osteonecrosis in a rabbit model?

Abstract:

Objectives: This study aims to investigate the effect of platelet-rich plasma (PRP) on femoral head osteonecrosis and compare it with bone marrow injection and core decompression.

Materials And Methods: A total of 30 healthy, adult, male New Zealand white rabbits (mean weight 2.25±0.15 kg; range 2.0 to 2.5 kg) were used in the study. To create experimental osteonecrosis in all rabbits, 40 mg/kg methylprednisolone acetate was applied intramuscularly. Rabbits were randomly allocated into three groups with 10 rabbits in each: drilling group, PRP group, and bone marrow group. The non-drilled hips of the drilling group were identified as the control group.

Results: Rate of necrotic bone was lower in the PRP group compared to other groups. Highest rate of necrotic bone was detected in the control group. New bone formation rate was higher in the PRP group compared to other groups. Lowest new bone formation rate was determined in the control group. Inflammatory reaction rate was higher in the PRP group compared to other groups.

Conclusion: Platelet-rich plasma injection may play a positive role in the treatment of steroid-associated osteonecrosis in a rabbit model.

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Six-month Efficacy of Perineural Dextrose for Carpal Tunnel Syndrome

Abstract:

Objective: To assess the 6-month effectiveness of ultrasound-guided perineural injection therapy (PIT) using 5% dextrose (D5W) in patients with mild-to-moderate carpal tunnel syndrome (CTS).

Patients and Methods: A prospective, randomized, placebo-controlled, and double-blind study was conducted between May 1, 2016, through March 30, 2017. A total of 49 participants diagnosed with mild-to-moderate CTS were randomized into D5W and control groups. Participants in the D5W group received 1 session of ultrasound-guided PIT with 5 cc of D5W, and the control group received PIT with normal saline. The visual analog scale measured pain as a primary outcome. Secondary outcomes were Boston Carpal Tunnel Syndrome Questionnaire scores, the cross-sectional area of the median nerve, and electrophysiological measurement results. Assessment was performed before injection and at 1, 3, and 6 months post-injection.

Results: All patients (data from 30 wrists in each group) completed the study. Compared with the control group, at all post-injection time points, the D5W group had a significant reduction in pain and disability, improvement on electrophysiological response measures, and decreased cross-sectional area of the median nerve.

Conclusion: Our study reveals that ultrasound-guided PIT with D5W is an effective treatment for patients with mild-to-moderate CTS.

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A Novel Treatment for Carpal Tunnel Syndrome?

Abstract:

Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy and is caused by chronic compression of the median nerve as it enters the carpal tunnel. Although the prevalence and incidence of CTS vary widely depending on the diagnostic criteria used, it is thought that, clinically, approximately 1 in 10 people have development of carpal tunnel syndrome.1,2 At this time, there is no consensus for the treatment of mild to moderate carpal tunnel syndrome. The American Academy of Orthopedic Surgeons has stated that nonsurgical treatments, such as splinting of the wrist to a neutral position and local corticosteroid injections, are reasonable options for patients early in the course of symptoms when there is no evidence of median nerve denervation.

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The Role of Platelet-Rich Plasma in Promoting Cartilage Integration and Chondrocyte Migration

Abstract:

Objectives: Current therapies for cartilage repair either do not result in regeneration of articular cartilage, or there is inadequate integration with the host tissue leading to failure of the repair. Thus, there is an interest in developing alternative approaches. The mechanisms of cartilage integration remain relatively unknown, however it is believed that chondrocyte migration is crucial to this process. Previously, we showed that platelet rich plasma (PRP) enhances in vitro cartilage tissue formation. We hypothesized that PRP will enhance the integration of bioengineered cartilage with native cartilage due to increased matrix accumulation at the interface and that PRP could promote chondrocyte migration.

Methods: Isolated bovine chondrocytes were seeded on a porous bone substitute and grown in vitro to form osteochondral-like tissue. After 7 days the biphasic constructs were soaked in PRP for 30 minutes prior to implantation into the core of a ring-shaped osteochondral explant. Controls were not soaked in PRP. The resulting implant-explant construct was cultured in a stirring bioreactor for 2 weeks (contact model). Alternatively, the PRP soaked biphasic construct was placed 2mm away from a native cartilage/bone plug of equal dimensions to assess chondrocyte migration between the two tissues (non-contact model). The integration zone was visualized histologically. A push-out test was performed to assess the strength of integration. Matrix accumulation at the zone of integration was assessed biochemically and the gene expression of the cells in this region was assessed by RT-PCR. Cell migration was evaluated by video microscopy over 8 days. Significance (p<0.05) was determined by a χ2 test, a student’s t-test or one-way ANOVA with tukey’s post hoc.

Conclusion: PRP soaked bioengineered cartilage implants showed improved integration with native cartilage compared to non-soaked implants perhaps due to increased matrix accumulation. Chondrocytes grew out from the in vitro formed tissue and migrated along fibers after PRP soaking. The contribution of these cells to integration requires further study.

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The effectiveness of platelet-rich plasma injections in gluteal tendinopathy – a randomised, double-blind controlled trial comparing a single platelet-rich plasma injection with a single corticosteroid injection.

Abstract:

Importance: Gluteus medius/minimus tendinopathy is a common cause of lateral hip pain or greater trochanteric pain syndrome.

Objective: There would be no difference in the modified Harris Hip score between a single Platelet-Rich-Plasma (PRP) injection compared to a corticosteroid injection (CSI) in the treatment of gluteal tendinopathy.

Design: Randomised Controlled Clinical Trial; Level of evidence 1, recruitment 29 May 2013 to May 2015, follow-up September 2016. Treating/assessing clinicians and subjects were blinded to treatment. PARTICIPANTS: 228 consecutive patients referred with gluteal tendinopathy were screened to enrol 80 participants. 148 excluded (refusal 48, previous surgery 39, sciatica 28, osteoarthritis 17, full thickness tears tendons 17, other 22).

Conclusion: Patients with chronic gluteal tendinopathy >4 months, diagnosed with both clinical and radiological examinations, achieved greater clinical improvement at 12 weeks when treated with a single PRP injection than those treated with a single corticosteroid injection.

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Is osteoarthritis a metabolic disease?

Abstract:

Obesity, together with aging and injury, is among the main risk factors for osteoarthritis. Obesity-related osteoarthritis can affect not only the weight-bearing joints, but also the hands, suggesting a role for circulating mediators released by the adipose tissue and known as adipokines. Thus, osteoarthritis may have a systemic metabolic component. Evidence from both epidemiological and biological studies support the concept of metabolic osteoarthritis, defined as a broad clinical phenotype that includes obesity-related osteoarthritis. Thus, osteoarthritis can be related to metabolic syndrome or to an accumulation of metabolic abnormalities. In addition, studies have demonstrated associations linking osteoarthritis to several components of the metabolic syndrome, such as hypertension and type 2 diabetes, independently from obesity or any of the other known risk factors for osteoarthritis. Both in vitro and in vitro findings indicate a deleterious effect of lipid and glucose abnormalities on cartilage homeostasis. Chronic low-grade inflammation is a feature shared by osteoarthritis and metabolic disorders and may contribute to the genesis of both. Thus, osteoarthritis is emerging as a disease that has a variety of phenotypes including a metabolic phenotype, in addition to the age-related and injury-related phenotypes.

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