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Hyperbaric Therapy In Knee Osteonecrosis

Medical information reviewed by: ANDREI BOGDAN, MD, Orthopedics-traumatology doctor

i.php?p=11.Terapia hiperbara in osteonec

Discover the hyperbaric medicine center opened in our clinic. Centrokinetic has the top-performing hyperbaric chamber in Bucharest, with multiple medical and anti-aging uses. The Baroks chamber has 5 seats, and operates at a constant pressure of 2.5 atmospheres, being fully automated and having protocols for each condition, and can be used individually for each patient. 

Hyperbaric oxygen therapy - benefits

Patients who use the clinic's hyperbaric therapy services benefit from:

  • The only medically accredited hyperbaric therapy chamber in Bucharest, which operates at 2.5 atmospheres (those for aesthetic use go to 1 atmosphere and have no medical benefits).
  • A safe medical procedure, without irradiation, without pain, without other side effects. 
  • The specialized medical team consists of recovery doctors, orthopedists, rheumatologists, neurologists, and neurosurgeons, meaning a multidisciplinary team specialized in all diseases that can be treated with hyperbaric therapy. 
  • Premium conditions at a fair price. Our clinic is recognized for the conditions offered and for the care of each patient. But we do not need to pay exorbitant prices to have access to quality medical services. At Centrokinetic you can find an affordable and fair price. But note that we do not have a contract with the National Health Insurance House (we do not offer state reimbursed services)

Centrokinetic is keeping contact with prestigious clinics and universities in Belgium, the Netherlands, France, and Greece to constantly update treatments to provide patients with the best medical solutions.

What is knee osteonecrosis?

Osteonecrosis of the knee (ONK) is a form of aseptic necrosis resulting from ischemia to subchondral bone tissue. Typically, treatment is invasive. Hyperbaric oxygen therapy (HBOT) may provide a noninvasive alternative by improving oxygenation and reperfusion of ischemic areas. This study evaluates the efficacy of HBOT in a series of ONK patients.

Methods

This retrospective study evaluates 37 ONK patients (29 male, 8 female; mean age ± 1 standard deviation: 54 ± 14); 83.7% of patients presented with Aglietti stage I-II; 16.3% presented with Aglietti stage III. Patients were treated with HBOT once a day, 5 days a week, at 2.5 atmospheres absolute with 100% inspired oxygen by mask for an average of 67.9 ± 15 sessions. Magnetic resonance imaging was performed before HBOT, within 1 year after completion of HBOT, and in 14 patients, 7 years after treatment. Oxford Knee Scores (OKSs) were recorded before HBOT and at the end of each HBOT treatment cycle.

Results

After the 30 sessions of HBOT, 86% of patients experienced an improvement in their OKS, 11% worsened, and 3% did not change. All patients improved in OKS after 50 sessions. Magnetic resonance imaging evaluation 1 year after HBOT completion showed that edema at the femoral condyle had resolved in all but 1 patient.

Introduction

The knee is the second most frequent location for aseptic osteonecrosis after the femoral head. Despite the high prevalence, literature regarding this disease process and its treatment remain limited in size and scope. Osteonecrosis is a debilitating ischemic disease process that results in localized pain and tissue death of the subchondral bone. While initially, synovial fluid is able to keep the overlaying cartilage intact, the underlying necrotic tissue will eventually result in an inflammatory response that damages articular surfaces. If untreated the decrease in blood supply to the load-bearing bone structure of joints can result in joint collapse. Without early recognition and proper management of the disease, invasive procedures such as total knee replacement may be necessary.

Current characterization and staging for osteonecrosis of the knee (ONK) are often performed using the 5 stages of the Aglietti Radiographic Scale. The Aglietti Scale evaluates radiographic characteristics of the knee and, if applicable, measures the area of the necrotic lesion by multiplying the greatest width in the anteroposterior view by the greatest length in the lateral view. Although this is a valuable tool for prognosis and plan of care, it is a poor tool for early diagnosis as radiographic evidence of osteonecrosis is often absent in the early stages of the disease. Generally, early Aglietti staging (I-II) is associated with the reversibility of the disease process. This can be accomplished through reperfusion and oxygenation of the ischemic tissue. Invasive interventions described include core decompression, bone grafting, and tibial osteotomy. Post-collapse cases require more radical operations like total knee arthroplasty. To date, several noninvasive therapies have been evaluated to increase tissue perfusion and oxygenation including the use of extracorporeal shockwave therapy, anticoagulants, vasoactive substances, and hyperbaric oxygen therapy.

Oxygen breathing (100%) in a hyperbaric chamber, or HBOT, has been shown to improve tissue oxygenation in ischemic and pre-necrotic areas. HBOT increases the partial pressure of oxygen, which as stated in Henry's law is directly proportional to the amount of oxygen dissolved in blood plasma. Increased plasma O2 allows for greater tissue oxygenation. In addition, HBOT has been shown to increase the level of reactive oxygen species in tissue. Reactive oxygen species can trigger a set of cellular responses that improve neovascularization and modulate impaired proinflammatory cytokine production. While repetitive exposure to HBOT may induce otic barotrauma in approximately 10% of patients, this is a tolerable side effect that can be managed with decongestants. Although aseptic necrosis of bone the primary disease process of ONK, has yet to be approved as an indication by the Undersea and Hyperbaric Medical Society, we described successful utilization of HBOT in the early stages of avascular necrosis of the femoral head (AVNF). Thus, we reasoned that HBOT can also be used effectively in the conservative management of ONK. This study aims to evaluate the efficacy of HBOT as a treatment modality for ONK.

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Materials and methods

This study comprises a retrospective chart review of patients with ONK; the institutional review board approval was obtained through the Local Ethics Committee of the University of Padova, Italy. The cohort of patients described in this study was treated with HBOT per criteria accepted as appropriate by the local health consortium, USL-5 in Fidenza, Italy. In this region of northern Italy, HBOT has been successfully used to alleviate symptoms of ONK. Patient enrollment dates range from November 1999 to February 2012. Patients received treatment after referral by their orthopaedic surgeon. The prevalent presenting symptom in this cohort was unilateral knee pain. Patients included in the study had no history of trauma, knee arthroplasty, or steroid use. Patients who accepted for treatment received a physical evaluation, pain assessment, plain anteroposterior and lateral knee radiograph, and magnetic resonance imaging (MRI). Owing to our resource limitations, the time between a patient's initial visit and completion of the first MRI reached 102 days on average. 

Patients who received MRI were staged using the Aglietti Scale as described: stage I, radiographs appear normal; stage II, flattening of the condyle can be visualized (lesion size 0-2.0 cm2); stage III, a radiolucent lesion of the subchondral bone can be seen (lesion size 2.1-4.5 cm2); stage IV, perifocal sclerosis is evident, and the subchondral bone has collapsed and is visibly calcified (lesion size 4.6-6.0 cm2); and stage V, secondary degenerative changes are present on both femur and tibia such as osteophyte formation, subchondral sclerosis, and visible bone erosion (lesion size ≥6.1 cm2). MRIs, and therefore Aglietti staging, were obtained before HBOT, after completion of HBOT (within 1 year after initiating HBOT), and 7 years after HBOT.

Pain was assessed using the Oxford Knee Evaluation, a survey consisting of 12 questions regarding patient subjective pain and active range of motion. The survey was used to determine a pretreatment Oxford Knee Score (OKS) for the patient. Traditionally, when grading an OKS, a score of 0 to 19 indicates severe knee arthritis and suggests the need for surgical intervention. A score of 20-29 indicates moderate-to-severe knee arthritis and suggests the need for an orthopaedic consult. A score of 30-39 indicates mild-to-moderate knee arthritis and suggests conservative management through moderate exercise, anti-inflammatory drugs, and weight loss. A score of 40-60 indicates normal joint function. The OKS was subsequently used to track treatment progression. Oxford knee evaluations were taken after each cycle of HBOT treatments.

The HBOT protocol used had been previously developed to treat AVNF, and has shown reproducible results. Patients were placed inside a multiplace hyperbaric chamber where they were compressed at 2.5 atmosphere absolute, once a day, 5 days a week. During compression at 2.5 atmosphere absolute, patients were exposed to 100% inspired oxygen by mask for 60 minutes. The mask was tightly sealed to ensure 100% oxygen was being delivered from the mask to the patient. The total length of the procedure including compression and decompression was 82 minutes. To minimize risk of flammability, the gas composition in the hyperbaric chamber was sampled every 5 minutes to detect any mask leakages and maintain a chamber oxygen gas composition of <23%. Ultimately, patients were to receive up to 4 cycles of treatment totaling 90 sessions. The first cycle consisted of 30 sessions, Monday to Friday for 6 weeks. After a 2-month break, patients received a second cycle consisting of 20 more sessions Monday to Friday for 4 weeks. The third and fourth cycles were identical, following a month break, and patients received 20 additional sessions Monday to Friday for 4 weeks. No additional treatments were used; patients were advised to avoid overly vigorous exercise.

i.php?p=16. Tratarea tinitusului cu oxig

Demographics

The study population consisted of 29 males and 8 females with a mean age of 54 ± 13 years. On average, patients received 68 treatments over 3 cycles (cycle 1: 30, 2: 20, and 3: 20); only 28 subjects completed the last cycle of treatments. The location of the necrotic lesion on the femoral condyles was characterized for the sample using radiographic imaging. Most patient's lesions were localized on the medial condyle (56.4%). There was no significant difference in treatment susceptibility based on the location of the lesion.

MRI findings

Patients were to receive an MRI for Aglietti staging pretreatment, post-treatment, and 7 years post-treatment. On pretreatment MRI, patients showed one of 3 patterns of necrosis: diffuse bone marrow edema (BME), focal geographic abnormality with T2 hyperintense signal, or edema surrounding a focal subchondral low signal area, often with an undulating serpiginous appearance. Post-treatment MRIs, in all but 1 case, showed a normal appearance of the femoral condyle with no visible signs of edema. Of the 37 patients, only 14 returned for their 7-year follow-up. Eleven of 14 (78.5%) patients showed no significant variation in their post-treatment MRI; the remaining 3 patients showed only a slight deterioration.

After the first cycle of treatments (30 HBOT sessions), 32 of 37 (86%) patients reported improvement from pretreatment OKS, 4 patients (11%) reported worsened OKS, and 1 patient (3%) reported no change in OKS. Interestingly, patients who reported worsened or unchanged OKS after the first cycle showed marked improvement in OKS after the second cycle of treatments. After the second cycle of treatments (50 HBOT sessions), 35 of 37 (94.6%) reported the maximum score of 60, 1 patient reported a score of 59, and 1 patient reported a score of 55. These scores remained unchanged for patients who received a third or fourth cycle.

Only 28 of the initial 37 patients received up to a third or fourth cycle of treatments (70 to 90 HBOT sessions). All 28 patients who received a third or fourth cycle of treatments reported no change in OKS since their second cycle of treatments. Twenty-six of 28 patients (93%) reported maintaining an OKS of 60, 1 patient reported maintaining a score of 55, and 1 patient reported maintaining a score of 59.

The difference in mean OKS was tested using a 1-tailed t-test. Mean OKS for the sample population showed clinically and statistically significant (P < .01) increases after the first cycle of treatments when compared to the baseline, bringing the average OKS from 13.9 ± 10 (or severe) to 30.2 ± 6.3 (or moderate to mild). This trend continues after the second cycle of treatments bringing the average OKS from 30.2 ± 6.3 (or moderate to mild) to 59.8 ± 0.8 (or normal), this again is statistically and clinically significant for both baseline (P < .0001) and post first cycle OKS (P < .01). For the 28 patients who remained in the study, no reduction in OKS was observed after the third cycle.

Most patients presented with Aglietti stages I-II each comprising 43.2% and 40.5% of the sample population, respectively. Aglietti stage III patients represent 16.3% of the sample population. No patients' baseline Aglietti staging exceeded stage III. Of the patients presenting with Aglietti stage I, 15 (93.75%) saw complete reversal to stage 0 on post-treatment MRI and 1 (6.25%) showed no improvement. Of the patients who presented with stage II, 10 (66.67%) saw complete reversal to stage 0, 4 (26.67%) saw an improvement by 1 clinical stage, and 1 (6.67%) saw no measurable improvement. Patients presenting with Aglietti stage III almost uniformly improved 3 clinical stages to stage 0 (n = 5, 83.33%) except 1 patient who only improved 1 clinical-stage to stage 2 (n = 1, 16.67%).

i.php?p=8. Terapia hiperabara in implant

Discussion


HBOT has already proven effective for AVNF. The 2010 paper on this topic shows a significant difference in pain relief and an increased range of motion after 20+ sessions of HBOT at 2.5 absolute atmospheres compared to other treatments. Radiographic improvements were evident after 30 HBOT sessions.

After the first cycle of HBOT, the study was repeated and HBOT was offered to the control group with similar results. No patients involved in the study required hip arthroplasty and patients did not report any pain at 7-year reassessment. Also, several other studies show a partial or complete recovery in the treatment of the early stages of the disease, as measured by improved subjective pain, good MRI results, and altered movement volume. 

A systemic review of the existing prospective literature for HBOT treatments applied to AVNF by Li et al. gave rise to 9 studies on 318 cases treated with HBOT. The clinical effect of HBOT for AVNF is 4.95 times greater than that of conventional treatments. Another retrospective study further confirms that HBOT is an effective treatment for AVNF. A retrospective study of 217 patients over 10 years showed significant improvements in subjective pain scores and radiographic findings in patients who received HBOT for AVNF.

Although the number of osteonecrosis studies is growing, it is currently not possible to determine and implement an optimized treatment protocol. This is caused by several issues, including the lack of a comprehensive standardized feature and staging scale, the lack of level 1 evidence for noninvasive therapies, and a rudimentary understanding of the mechanisms underlying the disease process. 

RANK is a transmembrane protein of osteoclasts and their precursor cells. The binding of RANKL to RANK induces osteoclast differentiation, activation, prolongation, and adhesion to bone surfaces. OPG modulates this process by acting as a decoy receptor to RANKL. As a decoy receptor, OPG prevents RANK binding by decreasing the receptor-free levels of RANKL. Decreased levels of OPG or increased levels of RANKL can lead to bone degradation and collapse. A 19-patient study, conducted in 2016, suggests that blood levels of serum OPG can be influenced by HBOT. OPG levels were measured before and during HBOT for treatment of ANFH. HBOT not only did reduce pain symptoms in all patients and significantly reduce lesion size in all stage I and stage II patients but also found to significantly increase OPG levels in patients.

This, however, is a very narrow view of the mechanisms involved in the regulation of bone remodeling. Other controls of osteoclastic differentiation also exist tumor necrosis factor-alpha, interleukin-6, and interleukin-1. Furthermore, HBOT may play a role in stimulating osteogenesis. Okubo et al. has demonstrated the positive effects of HBOT on osteoinduction via recombinant human bone morphogenetic protein-2 in rats; HBOT was shown to increase the alkaline phosphatase levels, an indication of bone growth.

The main types of osteonecrosis

HBOT provides another conservative alternative to patients who are poor surgical candidates. However, at present surgery is the most common intervention for ONK. To date, 3 primary types of ONK have been described:
  • Primary or spontaneous osteonecrosis (SONK) typically involves a single condyle, most often the medial femoral condyle. Average SONK patients are over 55 years of age, obese, and female; the ratio of female-to-male SONK patients being 3:1. SONK patients describe onset as a sudden and severe knee pain localized in the load-bearing portion of the medial femoral condyle. Pain is usually described as worse at night and patient history does not include trauma. A literature review of ONK illustrates prognosis for SONK based on lesion size: Aglietti I was associated with general reversibility, Aglietti III studies showed ∼32% required surgical intervention, Aglietti IV-V 100% required surgical intervention if left untreated, and Aglietti stages III-V will progress to subchondral collapse. The treatments available for SONK are limited given that physical activity is restricted, and anti-inflammatory drugs have minimal effect. Management of care relies mainly on the size of the necrotic area. While smaller lesions can be managed with a combination of non-surgical therapies, lesions that take up 50% or more of the femoral condyle require joint preservative and/or partial/total knee arthroplasty.
  • Secondary or idiopathic osteonecrosis (IONK) primarily affects young people. It is commonly associated with alcoholism, steroid use, and other hematologic diseases. Similar to SONK, it has female predominance. However, in contrast to SONK, the onset of IONK is generally described by patients as a vague pain. Despite a milder onset, lesions are severe and multiple. Lesion foci are localized in the lateral region of the joint, femoral condyles, and/or tibial plateaus. Furthermore, because of its roots in chronic hematological or endocrinological disease, IONK may be bilateral. Symptomatic IONK patients typically require surgical intervention, >70% progressing to the point where total knee arthroplasty is necessary.
  • Post-arthroscopic osteonecrosis (ONPK) is less common than the other types of ON. Although it has been described as a complication of arthroscopic knee surgery with resulting subchondral fractures, the exact etiology of ONPK is still under debate. Because of its association with prior surgical history, none of the subjects within this study meet the criteria for ONPK.
These classifications are relatively new in the literature and were not utilized at the inception of this study; we did not incorporate the endpoints needed to successfully stratify patients into these categorizations. With a predominantly older male cohort of patients, the demographics of this study do not align perfectly with any of the descriptions mentioned previously. However, as a majority of the patients in this study presented with individual knee pain and medial lesion localization, it can be inferred that at least a majority of these patients presented with SONK.

What are the effects of oxygen therapy on the body?

  • Decreases inflammation
  • Increases the body's oxygen saturation by 20-30%
  • Increases the body's immunity
  • Increases blood circulation and stimulates the formation of new capillaries
  • Decreases toxins in the body
  • Stimulates the production of new blood cells
  • Increases healing rate

Limitations of the study

Recent literature has shown that primary BME is a significant pain generator and a primary contributor to disease. Because this information was not available at the beginning of this study, primary BME was not accounted for in the study design. Although it is not yet certain whether primary BME represents the early stages of osteonecrosis, we recognize that there is the potential for it to be a separate condition and that a percentage of patients classified as stage I Aglietti may have had primary BME. However, similar to primary BME, Aglietti I is associated with general reversibility in 70% of cases; thus, the accidental inclusion of primary BME could not have affected the analysis of the study.

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While this study is limited in the scope of the disease due to its retrospective nature and lack of a control group or alternative treatment group comparators, it is evidence of the concept. As the sample consisted of stages I-III Aglietti, it remains uncertain whether HBOT will be an effective treatment for patients with stages IV-V Aglietti who have already progressed to joint collapse. Also, additional data on the efficacy of HBOT in stage III treatment must be obtained.

Conclusions

Based on the findings of this study, HBOT should be further investigated for its therapeutic effects in ONK. Most patients (95.4%) showed a dramatic improvement with the first cycle of HBOT and all patients showed improvements after the second cycle.

IN CASE YOU HAVEN'T ALREADY HEARD ABOUT US

Centrokinetic is the place where you will find clear answers and solutions for your motricity problems. The clinic is dedicated to osteoarticular diseases and is divided into the following specialized departments:

  • Orthopedics , a department composed of an extremely experienced team of orthopedic doctors, led by Dr. Andrei Ioan Bogdan, primary care physician in orthopedics-traumatology, with surgical activity at Medlife Orthopedic Hospital, specialized in sports traumatology and ankle and foot surgery. .
  • Pediatric orthopedics , where children's sports conditions are treated (ligament and meniscus injuries), spinal deformities (scoliosis, kyphosis, hyperlordosis) and those of the feet (hallux valgus, hallux rigidus, equine larynx, flat valgus, hollow foot).
  • Neurology , which has an ultra-performing department, where consultations, electroencephalograms (EEG) and electromyography (EMG) are performed. 
  • Medical recovery  for adults and  children , department specialized in the recovery of performance athletes, in spinal disorders, in the recovery of children with neurological and traumatic diseases. Our experience is extremely rich, treating over 5000 performance athletes.
  • Medical imaging , the clinic being equipped with ultrasound and MRI, high-performance devices dedicated to musculoskeletal disorders, and complemented by an experienced team of radiologists: Dr. Sorin Ghiea and Dr. Cosmin Pantu, specialized in musculoskeletal imaging.

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