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      Steroid induced osteonecrosis: An analysis of steroid dosing risk

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          Abstract

          Osteonecrosis is a serious condition involving bone destruction that frequently requires surgical treatment to rebuild the joint. While there is an abundance of literature documenting corticosteroid related osteonecrosis, there is no consensus as to the relative risk of osteonecrosis after administration of steroids via parenteral, oral, topical, inhaled and other routes. This risk is an important prognostic indicator because identification and conservative intervention can potentially reduce morbidity associated with aggressive surgical treatment of osteonecrosis. This paper provides insight into establishing guidelines related to the risk of developing osteonecrosis as a result of corticosteroid use. Case studies, retrospective studies and prospective studies in humans on different corticosteroids and varied dosages were assessed. Most cases of osteonecrosis are secondary to systemically administered corticosteroids and/or high dose daily therapy, particularly in patients with underlying comorbidities including connective tissue diseases, hyperlipidemia, or previous trauma. Previous case reports of osteonecrosis related to inhaled or topical use of steroids are complicated by the fact that in the great majority of cases, the patients are also treated with systemic steroids prior to the development of osteonecrosis. Based on the literature, a set of recommendations regarding the risk of osteonecrosis in patients on steroids was formulated.

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          Most cited references134

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          Nontraumatic necrosis of bone (osteonecrosis).

          H Mankin (1992)
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            Damage in systemic lupus erythematosus and its association with corticosteroids.

            To evaluate the association between corticosteroid use and organ damage in patients with systemic lupus erythematosus (SLE). The occurrence and date of organ damage, as measured by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, were determined for 539 patients enrolled in the Hopkins Lupus Cohort Study. The risk of damage associated with the cumulative prednisone dose, high-dose prednisone (> or =60 mg/day for > or =2 months), and pulse methylprednisolone (1,000 mg intravenously for 1-3 days) was estimated using Cox proportional hazards regression analyses, controlling for age, race, and sex. Risk estimates for the cumulative prednisone dose were based on a reference dose of 36.5 gm (e.g., 10 mg of prednisone daily for 10 years [or equivalent]). The cumulative prednisone dose was significantly associated with the development of osteoporotic fractures (relative risk [RR] 2.5, 95% confidence interval [95% CI] 1.7, 3.7), symptomatic coronary artery disease (RR 1.7, 95% CI 1.1, 2.5), and cataracts (RR 1.9, 95% CI 1.4, 2.5). Each intravenous pulse was associated with a small increase in the risk of osteoporotic fractures (RR 1.3, 95% CI 1.0, 1.8); however, this result failed to reach statistical significance (P = 0.07). Each 2-month exposure to high-dose prednisone was associated with a 1.2-fold increase in the risk of both avascular necrosis (95% CI 1.1, 1.4) and stroke (95% CI 1.0, 1.5). SLE patients receiving long-term prednisone therapy were at significant risk of morbidity due to permanent organ damage. Additional research is required to determine the relative contributions of SLE disease activity and corticosteroids to the pathogenesis of specific types of organ damage. Furthermore, new steroid-sparing therapies are needed in order to treat disease activity and minimize cumulative and high-dose prednisone exposure.
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              Osteonecrosis as a complication of treating acute lymphoblastic leukemia in children: a report from the Children's Cancer Group.

              To determine the incidence, risk factors, and morbidity for osteonecrosis (ON) in children with acute lymphoblastic leukemia (ALL) treated with intensive chemotherapy including multiple, prolonged courses of corticosteroid. The occurrence of symptomatic ON was investigated retrospectively in 1, 409 children ages 1 to 20 years old receiving therapy for high-risk ALL on Children's Cancer Group (CCG) protocol CCG-1882. ON was diagnosed in 111 patients (9.3% +/- 0.9%, 3-year life-table incidence). The incidence was higher for older children (> or = 10 years: 14.2% +/- 1.3% v < 10 years: 0.9% +/- 0.4%; P: <.0001), especially females 10 to 15 years old and males 16 to 20 years old (19.2% +/- 2.3% and 20.7% +/- 4.7%, respectively). In patients 10 to 20 years old, the incidence of ON was higher for females versus males (17.4% +/- 2.1% v 11.7% +/- 1.6%, respectively; P: =.03) and for patients randomized to receive two 21-day dexamethasone courses versus one course (23.2% +/- 4.8% v 16.4% +/- 4.3%, respectively; P: =.27). Among ethnic groups, whites had the highest incidence and blacks the lowest, with other groups intermediate (16.7% +/- 1.4% v 3.3% +/- 2.3% v 6.7% +/- 2.2%, respectively; P: =.003). There was no difference in event-free survival in patients with or without ON. ON was diagnosed within 3 years of starting ALL therapy in all but one patient, involved weight-bearing joint(s) in 94% of patients, and was multifocal in 74% of patients. Symptoms of pain and/or immobility were chronic in 84% of patients, with 24% having undergone an orthopedic procedure and an additional 15% considered candidates for surgery in the future. Children ages 10 to 20 years who receive intensive ALL therapy, including multiple courses of corticosteroid, are at significant risk for developing ON.
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                Author and article information

                Contributors
                Journal
                Autoimmun Rev
                Autoimmun Rev
                Autoimmunity Reviews
                Elsevier B.V.
                1568-9972
                1873-0183
                9 July 2010
                September 2010
                9 July 2010
                : 9
                : 11
                : 721-743
                Affiliations
                [a ]Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, 451 Health Sciences Drive, Suite 6510, Davis, CA 95616, United States
                [b ]1585 Railroad Avenue, Crescent City, CA 95531, United States
                Author notes
                [* ]Corresponding authors. Chang is to be contacted at Pacific Coast Allergy, 1585 Railroad Avenue, Crescent City, CA 95531, United States. Tel.: + 1 707 464 3430; fax: + 1 707 464 4668. Gershwin, Tel.: + 1 530 752 2884; fax: + 1 530 752 4669. c3chang@ 123456yahoo.com megershwin@ 123456ucdavis.edu
                [1]

                Contributed equally to the preparation of this paper.

                Article
                S1568-9972(10)00125-4
                10.1016/j.autrev.2010.06.007
                7105235
                20621176
                ad964504-1e2e-4931-b065-eeccdc84fb79
                Copyright © 2010 Elsevier B.V. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 12 June 2010
                : 20 June 2010
                Categories
                Article

                Immunology
                avascular necrosis,corticosteroids,bone death,autoimmune disease,transplantation
                Immunology
                avascular necrosis, corticosteroids, bone death, autoimmune disease, transplantation

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