Team approach: Management of osteonecrosis in children with acute lymphoblastic leukemia.

With current treatments for acute lymphoblastic leukemia (ALL), the overall prognosis for survival is favorable. Increasing emphasis is placed on recognizing and managing the long-term consequences of ALL and its treatment, particularly involving osteonecrosis. Early osteonecrosis diagnosis and management may improve outcomes and is best accomplished through coordinated teams that may include hematologic oncologists, radiologists, orthopedic surgeons, physical therapists, and the patient and their family. Magnetic resonance imaging is the "gold standard" for diagnosis of early-stage and/or multifocal osteonecrosis. Treatments for osteonecrosis in ALL patients are risk stratified and may include observation, corticosteroid or chemotherapy adjustment, and pharmaceutical or surgical approaches.

Bone manifestations in neuronopathic Gaucher disease while receiving high-dose enzyme replacement therapy.

Avascular necrosis (AVN), one type of bone infarction, is a major irreversible complication of Gaucher disease (GD). In this report, two pediatric patients with GD type 3, homozygous for the L483P pathogenic variant (formerly L444P), developed AVN despite treatment on long-term, high-dose enzyme replacement therapy (ERT). ERT was initiated in both patients, who had intact spleens, shortly after diagnosis with an initial dramatic response. However, both patients exhibited AVN after 5.5 and 11 years on high-dose ERT, respectively, despite good compliance and normalized hematological findings and visceral symptoms. This report demonstrates the importance of careful, regular surveillance of the musculoskeletal system in addition to monitoring the neurological symptoms associated with neuronopathic GD. Additionally, it highlights the limitations of ERT in terms of targeting certain sanctuary sites such as bone marrow and suggests the need for new treatment modalities other than ERT monotherapy to address these limitations.

Cumulative Burden of Glucocorticoid-related Adverse Events in Patients with Systemic Lupus Erythematosus: Findings from a 12-year Longitudinal Study.

OBJECTIVE: The aim of this population-based study is to examine the adverse events (AE) associated with longitudinal systemic glucocorticoid (GC) use among an ethnic Chinese systemic lupus erythematosus (SLE) cohort. METHODS: Our study subjects were patients with newly diagnosed SLE aged 18 and older who received at least 1 prescription of systemic GC between 2001 and 2012 from Taiwan's National Health Insurance Research Database (NHIRD). The earliest prescription date of systemic GC for each subject was defined as the index date. For each subject, we calculated the average prednisolone-equivalent dose and the medication possession ratio (MPR) of GC use every 90 days for each patient after the index date. Patients with a diagnosis of AE (defined by the International Classification of Diseases-9-Clinical Modification diagnosis code) during the followup were also identified from the NHIRD. Generalized estimating equations adjusted for propensity score were applied to examine the association between longitudinal GC use and risks of prespecified AE (musculoskeletal, gastrointestinal, ophthalmologic, infectious, cardiovascular, neuropsychiatric, metabolic, and dermatologic diseases). RESULTS: We identified 11,288 patients with SLE (mean followup: 6.28 yrs). Higher doses and higher MPR of GC were associated with increased risk of osteonecrosis [adjusted OR (aOR) 2.87-9.09]. Similar results were found regarding the risk of osteoporosis (aOR 1.71-3.67), bacterial infection (aOR 2.12-3.89), Cushingoid syndrome (aOR 6.51-62.03), and sleep disorder (aOR 1.42-3.59). CONCLUSION: To our knowledge, this is the first study to show that the dose and intensity of longitudinal use of GC were both associated with risk of AE among a nationwide Asian SLE cohort.

The role of hyperbaric oxygen therapy in the prevention and management of radiation-induced complications of the head and neck - a systematic review of literature.

Radiation therapy for the treatment of head and neck cancer can injure normal tissues and have devastating side effects. Hyperbaric oxygen (HBO) is known to reduce the severity of radiation-induced injury by promoting wound healing. While most of the research in literature has focused on its efficacy in osteonecrosis, HBO has other proven benefits as well. The aim of this review was to identify the various benefits of hyperbaric oxygen therapy in patients who have undergone radiation for head and neck cancer. An electronic database search was carried out to identify relevant articles and selected articles were reviewed in detail. The quality of evidence for each benefit, including preserving salivary gland function, preventing osteonecrosis, dental implant success, and overall quality of life, was evaluated. Evidence showed that HBO was effective in improving subjective symptoms of xerostomia, swallowing, speech and overall quality of life. There was no conclusive evidence to show that HBO improved implant survival, prevented osteonecrosis, or improved salivary gland function. The high costs and accessibility of HBO therapy must be weighed against the potential benefits to each patient.

Hyperbaric oxygen therapy and osteonecrosis.

Osteonecrosis of the jaw may be caused by radiation, medication, or infection. Optimal therapy requires a multimodal approach that combines surgery with adjuvant treatments. This review focuses on the use of adjunctive hyperbaric oxygen therapy for this condition. In addition to evidence regarding the basic and clinical science behind hyperbaric oxygen therapy, controversies in the field and economic implications are discussed.

Osteonecrosis of the jaw during sorafenib therapy for hepatocellular carcinoma.

INTRODUCTION: Sorafenib is an oral multiple tyrosine kinase inhibitor and is currently the only evidence-based treatment recommended for advanced hepatocellular carcinoma. We report a case of osteonecrosis of the jaw that occurred during sorafenib therapy in a patient with advanced hepatocellular carcinoma not treated with bisphosphonates or other antiangiogenic drugs. METHODS: A systematic search in PubMed yielded some cases of osteonecrosis of the jaw in patients treated with antiangiogenic agents, alone or in combination with bisphosphonates, for metastatic renal cell carcinoma. The only case of osteonecrosis observed during sorafenib therapy not combined with other predisposing agents was described by Guillet et al. RESULTS: A 74-year-old man diagnosed with hepatocellular carcinoma ensuing in hepatitis C virus infection, who was treated with sorafenib at a daily dose of 400 mg, developed osteonecrosis of the right mandibular body. The lesion was documented by a dental CT scan and surgical evaluation did not lead to an indication for curettage treatment. Sorafenib was discontinued because of the radiological and laboratory features of hepatocellular carcinoma progression and the high risk of jaw fracture. CONCLUSIONS: To our knowledge, this is the first description of osteonecrosis of the jaw detected in a cirrhotic patient on sorafenib therapy not combined with bisphosphonates.

Bone disease in post-transplant patients.

PURPOSE OF REVIEW: Mineral and bone disorders are common problems in organ transplant recipients. Successful transplantation solves many aspects of abnormal mineral and bone metabolism, but the degree of improvement is frequently incomplete. Posttransplant bone disease can affect long-term outcomes as well as increase the likelihood of fracture. In this article, we reviewed the major posttransplant bone diseases and recent advances in treatment strategies. RECENT FINDINGS: Pretransplant bone disease and immunosuppressants are important risk factors for posttransplant bone disease. Corticosteroid withdrawal may result in minimal or no protection against fractures, with increased risk for acute rejection. Vitamin D analogue and bisphosphonate are frequently used to prevent and treat posttransplant osteoporosis. Posttransplant hyperparathyroidism increases the risk for all-cause mortality and graft loss, but not major cardiovascular events. Cinacalcet was well tolerated and effectively controlled hypercalcemic hyperparathyroidism; however, it did not improve bone mineral density and discontinuation led to parathyroid hormone rebound. Six-month paricalcitol supplementation reduced parathyroid hormone levels and attenuated bone remodeling and mineral loss in case of posttransplant hyperparathyroidism. SUMMARY: Posttransplant bone diseases present in various forms, including osteoporosis, hyperparathyroidism, adynamic bone disease, and osteonecrosis. Prophylactic and therapeutic approaches to both pretransplant and posttransplant periods should be considered.

Beneficial effect of grape seed proanthocyanidin extract in rabbits with steroid-induced osteonecrosis via protecting against oxidative stress and apoptosis.

BACKGROUND: Oxidative damage and apoptosis play dominant roles in the pathogenesis of steroid-induced osteonecrosis (ON). Grape seed proanthocyanidin extract (GSPE) demonstrates antioxidant and antiapoptotic properties. Our aim was to demonstrate the effects of GSPE in preventing steroid-induced ON in rabbits. METHODS: Osteonecrosis was induced by high-dose methylprednisolone (40 mg/kg). Rabbits in the preventive medicine group were treated with 100 mg/kg/day GSPE for 14 consecutive days, and the presence or absence of ON was examined histopathologically. Oxidative damage in bone tissue was assessed by immunohistochemical staining of 8-oxo-2'-deoxyguanosine (8-OHdG), malondialdehyde (MDA) levels, and activities of antioxidant enzymes Cu/Zn superoxide dismutase (SOD) and phospholipid hydroperoxide glutathione peroxidase (GSH-Px). Apoptosis was detected via quantitative terminal deoxynucleotidyl transferase (TdT) deoxyuridine triphosphate nick end labelling (TUNEL) staining and activated caspase 3 immunoblotting and activity. RESULTS: GSPE significantly attenuated the changes of immunohistochemical staining of 8-OHdG, MDA levels, and antioxidant enzymes activities, which were caused by methylprednisolone administration. Quantitative TUNEL and caspase 3 assay showed lower apoptosis with GSPE application. Simultaneously, GSPE reduced the incidence of steroid-induced ON in an established rabbit model to 17.6 %, compared with 87.5 % in the steroid-only group. CONCLUSION: These results reveal that GSPE treatment could inhibit oxidative damage and apoptosis to exert beneficial effects on reducing the incidence of steroid-induced ON in rabbit models.

Dysbaric osteonecrosis: a literature review of pathophysiology, clinical presentation, and management.

OBJECTIVE: To perform a general literature review of dysbaric osteonecrosis (DON) to describe its pathophysiology, prevalence in scuba divers, prognosis, and treatment options. DATA SOURCES: A literature search on PubMed was performed using the term "dysbaric osteonecrosis" yielding 67 results. There was no exclusion based on dates. Articles that mainly dealt with decompression sickness secondary to tunnel work, mining, or airplane travel were not selected. An additional search on PubMed using the terms "(osteonecrosis diving) NOT dysbaric" was performed to identify other publications not picked up in the initial search. MAIN RESULTS: Dysbaric osteonecrosis is associated with prolonged hyperbaric exposure and rapid decompression that cause nitrogen bubbles to enter the fatty marrow-containing shafts of long bones leading to reduction in blood flow and subsequent osteonecrosis. Patients may present asymptomatically, and typical radiographic findings of DON include: decalcification of bone, cystic lesions, osteosclerotic patterns, nontraumatic fractures, bone islands, and a subchondral crescent sign. Surgical treatment options are comprised of core decompression and free vascularized fibular graft, whereas nonsurgical treatment options consist of monitoring, physical therapy, and bisphosphonate therapy. CONCLUSIONS: Although the incidence of DON has decreased significantly over the past 2 decades, the lack of timely diagnosis and optimal management keeps DON relevant in the orthopedic and sport medicine community.

Necrosis avascular bilateral del escafoides (enfermedad de Preiser), una causa infrecuente de dolor de muñeca / Bilateral avascular necrosis of the scaphoid (Preiser’ Disease), a rare cause of wrist pain

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An update on the recent literature on sickle cell bone disease.

PURPOSE OF REVIEW: To summarize the findings of the recent publications on sickle cell bone disease (SBD). RECENT FINDINGS: Individuals with sickle cell disease (SCD) are living longer and develop progressive organ damage including SBD with age. Recent studies suggest alternative radiological diagnostics such as ultrasound and scintigraphy can detect and differentiate between different forms of SBD. MRI with or without diffusion-weighted sequences remains the gold standard. Case reports of cranio-orofacial SBD highlight the rarity of this presentation. Vitamin D deficiency is highly prevalent at all ages, but may not be an independent risk factor for avascular necrosis (AVN). Gene polymorphisms of the Annexin A gene may predict AVN in SCD. A recent study demonstrated reduced days with pain and improved physical activity quality of life following high-dose vitamin D therapy. The high rates of osteopenia and osteoporosis in SCD support the need for research addressing this rising public health problem. Lastly, results of total hip arthroplasty for AVN in SCD has improved significantly over time with the use of cementless prosthetic material and improved supportive care. SUMMARY: SBD remains poorly studied. Prospective randomized studies targeting predictors, diagnostics, prevention, and treatment options for SBD are sorely needed.

HIV and its effects on bone: a primer for rheumatologists.

PURPOSE OF REVIEW: As patients with HIV are living longer because of effective treatments, rates of comorbid chronic diseases such as bone complications are increasing. There is a growing body of literature showing increased rates of osteopenia and osteporosis in the HIV population. Less is known about the risk of fracture, as well as other bone complications, such as avascular necrosis (AVN). RECENT FINDINGS: Increased rates of osteopenia and osteoporosis are seen in the HIV population, likely secondary to an interaction of traditional osteoporotic and HIV-specific risk factors, and possibly the effect of antiretroviral therapy (ART). There are conflicting recent data as to whether the decrease in bone mineral density seen in the HIV population, specifically with particular ART regimens, translates into an increased risk of fracture. Conflicting evidence emerges from recent studies exploring whether supplementation of vitamin D and calcium can prevent the bone loss seen with specific ART regimens. SUMMARY: Bone disease is common in the HIV population, and will likely be a medical problem increasingly seen by rheumatologists. The role of ART regimens on bone complications such as fracture and AVN is unclear, and further research in this area as well as possible prevention strategies are needed.

[Central-medullary nailing of proximal humerus fractures using T2 nails. A retrospective study of 38 cases]. / Enclouage centromédullaire des fractures de l'extrémité proximale de l'humérus par clou T2. Etude rétrospective de 38 cas.

The intramedullary nailing of humerus has emerged as one of the treatments of reference for proximal fractures. We have reviewed 38 patients aged 64.2 on average with a mean follow of 18 months. The functional scores used were the Constant and Murley's score as well as the DASH self-administered quality of life questionnaire. Radiological criteria have been analyzed, namely the cephalic angle noted alphaF and the presence of any osteolysis of the major tuberosity. Patients were grouped by type of fracture, according to Neer's classification, with nine cases in Neer 2 group, 19 in Neer 3 group, and ten in Neer 4 group. The unrefined Constant score was 53.4 points on average, balanced to 71.6%. The joint mobilities were an average forward elevation of 108 degrees, an average abduction of 100 degrees and an external rotation of 27 degrees. These scores were even worse than the fracture was comminuted. It was not found a radioclinical correlation between value of the angle alphaF and clinical outcome, but the presence of osteolysis of the major tuberosity was significantly associated with poor late functional results. Five cases of osteonecrosis have been counted, divided with 10.5% in the Neer stage 3, and 30% in the Neer stage 4. The average unrefined Constant score from these patients was 38.5 points on average, balanced to 57.7%. Intramedullary nailing allows fixation of comminuted fractures with three or four fragments, but control of fixing and strength of assembly were not always practiced. In young patients, where tuberosities consolidation is essential, screwed plates seem to be a favorable alternative. Moreover, total reverse prosthesis seems to have more and more arguments to impose itself like the preferred treatment towards fractures in four fragments in people aged over 75 years.

Resolution of cavitational osteonecrosis through NeuroModulation Technique, a novel form of intention-based therapy: a clinical case study.

OBJECTIVES: This study evaluated the possibility of using NeuroModulation Technique (NMT), a form of intention-based medicine, to induce osteogenesis and healing of cavitational osteonecrosis, a common progressive form of ischemic disease of the alveolar arch. DESIGN: Eleven (11) adult patients were enrolled based on the presence of lesions in the jawbone. Ten (10) subjects underwent NMT therapy for up to 10 months, while 1 subject received no treatment. OUTCOME MEASURES: A sensitive analysis of bone density in the alveolar processes of maxilla and mandible was performed before and after therapy using the U.S. Food and Drug Administration-approved Cavitat system of through-transmission ultrasonography and computer imaging. RESULTS: All subjects presented between one and six cavitational lesions at the first scan, most of which (92%) were associated with sites of previous tooth extraction. NMT-treated patients demonstrated significant improvement in bone density in 27 of the 34 lesions analyzed (79%). The median number of lesions per patient was 4 pretreatment and 0 post-treatment (p < 0.01). One NMT-treated patient, 1 surgically treated patient, and the control subject were also imaged at later time points, showing a durable healing of the lesions through NMT comparable to that of surgery, as opposed to disease persistence in the untreated control. CONCLUSIONS: NMT therapy provides a safe and potentially effective treatment for jawbone osteonecrosis. Preclinical placebo-controlled trials are encouraged to investigate in depth the potential of NMT for treating inflammatory and degenerative pathologies.

Hyperthermia associated osteonecrosis in young patients with pelvic malignancies.

INTRODUCTION: Progressive and non-juvenile avascular osteonecrosis (AVN) is a rare condition in children. During the last decade, some data indicate that regional deep hyperthermia therapy (RHT) combined with either chemo- and / or radiotherapy in malignancies is associated with AVN in young patients. In this study, we present our data on AVN following RHT in children with intra-pelvic malignancies. MATERIAL AND METHODS: Localization, extent of AVN, and associated joint effusions were evaluated via MRI and X-ray findings in 37 patients treated with RHT and chemotherapy +/- additional radiotherapy for intra-pelvic malignancies in our study. AVN was classified in accordance to the Association Research Circulation Osseus (ARCO). In addition, the recurrence of sarcoma after RHT, the number of total joint replacements, and level of activity including sport activities were recorded in all patients. The mean follow-up was 6.2 years (SD: 4.1, range: 1-12 years). RESULTS: Eight out of 37 pediatric patients treated with RHT and chemotherapy +/- additional radiotherapy showed AVN of the femoral head within our follow-up period. Five out of the eight children developed bone marrow edema within 6 months after RHT procedure and three additional patients within the first year. All patients except one showed a rapid progression of AVN from ARCO stage 0 to the post-collapse-stages III and IV in our study. Seven out of eight AVN patients survived without evidence of further malignancy. Although advanced stages of AVN were observed in our patient group, they were able to still maintain a high quality of life. No patients in our group have undergone total hip replacement thus far. CONCLUSION: Based on our findings, we hypothesize a high risk of AVN in young children who receive RHT for pelvic sarcoma. However, further clinical investigation needs to be done to prove our hypothesis.

Prevention of avascular necrosis in displaced talar neck fractures by hyperbaric oxygenation therapy: a dual case report.

Talar neck fractures are a rare injury that account for less then 2% of all foot fractures. Displaced fractures are associated with an exceedingly high rate of avascular necrosis (AVN). The incidence of AVN following Hawkins Type 3 fractures of the talar neck may approach 100%, particularly if diagnosis and reduction are delayed. Severe cases may present as pain and disability of the ankle and the subtalar joints due to a talar dome collapse, resulting in degenerative changes that usually require hind foot arthrodesis. We present two cases of traumatic displaced talar neck fractures which were treated surgically more than 2 weeks following injury due to a delay in diagnosis. Both patients underwent hyperbaric oxygen therapy (HBOT) after the operation and neither resulted in AVN of the talus in a three-year follow-up. We suggest that this favorable result may be due to the beneficial effects of HBOT.

MRI screening of dysbaric osteonecrosis in hyperbaric-chamber inside attendants.

Inside attendants are medical staff who accompany patients during hyperbaric oxygen treatments. Dysbaric osteonecrosis (DON) is a well-known consequence of hyperbaric exposure. The aim of this study was to evaluate DON in inside attendants using magnetic resonance imaging (MRI). The bilateral shoulder, hip and knee joints of 12 inside attendants (four men, eight women; mean age 29 years; age range 22 - 36 years) were investigated. The mean +/- SD duration of employment as an inside attendant was 3.8 +/- 3.0 years (range 1 - 9 years) and the mean +/- SD number of hyperbaric exposures was 198 +/- 267 (median 96; range 30 - 950). None of the inside attendants had a history of decompression sickness. The MRIs of the attendants did not reveal bone lesions consistent with DON. This study failed to find an increased risk for DON in inside attendants. Additional multicentre epidemiological studies are warranted to investigate the occupational safety of inside attendants.

Reconstruction of post-orthognathic aseptic necrosis of the maxilla.

We present the reconstruction of near total aseptic necrosis of the maxillary alveolus that occurred after a Le Fort I osteotomy eight years previously.