Abstract
Abstract
Background
An effective prevention strategy for osteonecrosis of the femoral head (ONFH) has yet to be established. We previously reported that the innate immune system via the toll-like receptor (TLR) response induced by corticosteroids leads to the development of ONFH and that repression of IRF7 activity by an inhibitor could interfere with the development of ONFH while maintaining the therapeutic effect of the corticosteroids.
Objective
In the present study, we hypothesize that lansoprazole has the potential to suppress IRF7 activity and prevent corticosteroid-induced ONFH in rats. Furthermore, we conducted a preliminary clinical trial to prevent corticosteroid-induced ONFH in autoimmune disease patients.
Methods
Male Wistar rats were randomly divided into four groups. On Day 1, each rat was injected with TLR4 ligand (LPS) or TLR7 ligand (imiquimod), followed by methylprednisolone with or without lansoprazole on Day 2. They were killed at 1 or 14 days after the last injection.We prospectively recruited 30 patients requiring primary high-dose corticosteroid treatment for immune diseases. All patients were administered lansoprazole, starting the night before corticosteroid treatment began. MRI was performed before corticosteroid treatment, and at 4, 12 and 24 weeks afterward.
Results
In rats, co-treatment of lansoprazole with corticosteroids significantly repressed both IRF7 activity and the development of ONFH. Moreover, in the human patients, the incidence of ONFH was significantly decreased from 53.4 to 13.3%.
Conclusions
Although the present study is preliminary, the results show that co-treatment of lansoprazole with corticosteroids prevents ONFH development. Lansoprazole may be both safe and effective in preventing osteonecrosis of the femoral head in patients needing corticosteroid treatment.
Funder
the Japanese Society for the Promotion of Science.
Publisher
Springer Science and Business Media LLC
Subject
Orthopedics and Sports Medicine,Surgery
Reference31 articles.
1. Matsuo K, Hirohata T, Sugioka Y, Ikeda M, Fukuda A (1988) Influence of alcohol intake, cigarette smoking, and occupational status on idiopathic osteonecrosis of the femoral head. Clin Orthop Relat Res 234:115–123
2. Takahashi S, Fukushima W, Yamamoto T, Imamoto Y, Kubo T, Sugano N et al (2015) Temporal trends in characteristics of newly diagnosesd nontraumatic osteonecrosis of the femoral head from 1997 to 2011: a hospital-based sentinel monitoring system in Japan. J Epidemiol 25:437–444
3. Fukushima W, Fujioka M, Kubo T, Tamakoshi A, Nagai M, Hirota Y et al (2010) Nationwide epidemiologic survey of idiopathic osteonecrosis of the femoral head. Clin Orthop Relat Res 468:2715–2724
4. Aaron RK, Gray RRL (2007) Osteonecrosis: etiology, natural history, pathophsiology, and diagnosis. In: Callaghan JJ, Rosenberg AG, Rubash HE (eds) The adult hip, 2nd edn. Lippincott Williams & Wilkins a Wolters Kluwer Business, Philadelphia, pp 465–476
5. Shah KN, Racine J, Jones LC, Aaron RK (2015) Pathophysiology and risk factors for osteonecrosis. Curr Rev Musculoskelet Med 8:201–209
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