Department of Orthopedic Surgery, Sapporo Medical University School of Medicine, S1 W16, Chuo-ku, Sapporo, 060-8543, Japan.
Department of Orthopedic Surgery, Hokkaido Ohno Memorial Hospital, Sapporo, Japan.
Eur J Orthop Surg Traumatol. 2020 May;30(4):713-721. doi: 10.1007/s00590-020-02622-5. Epub 2020 Jan 14.
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.
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.
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.
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%.
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.
目前尚未建立有效的股骨头坏死（ONFH）预防策略。我们之前的研究报告称，糖皮质激素通过 Toll 样受体（TLR）反应诱导的固有免疫系统导致 ONFH 的发生，而通过抑制剂抑制 IRF7 活性可以在维持糖皮质激素治疗效果的同时干扰 ONFH 的发生。
本研究假设兰索拉唑具有抑制 IRF7 活性和预防大鼠糖皮质激素诱导的 ONFH 的潜力。此外，我们进行了一项初步的临床试验，以预防自身免疫性疾病患者的糖皮质激素诱导的 ONFH。
雄性 Wistar 大鼠随机分为四组。在第 1 天，每只大鼠注射 TLR4 配体（LPS）或 TLR7 配体（咪喹莫特），然后在第 2 天注射甲泼尼龙和/或兰索拉唑。在最后一次注射后 1 天或 14 天处死大鼠。我们前瞻性地招募了 30 名需要原发性大剂量皮质类固醇治疗免疫疾病的患者。所有患者均在皮质类固醇治疗前一晚开始服用兰索拉唑。在皮质类固醇治疗前、治疗后 4、12 和 24 周进行 MRI 检查。
在大鼠中，兰索拉唑与皮质类固醇的联合治疗显著抑制了 IRF7 活性和 ONFH 的发生。此外，在人类患者中，ONFH 的发生率从 53.4%显著降低至 13.3%。
尽管本研究尚属初步，但结果表明兰索拉唑与皮质类固醇的联合治疗可预防 ONFH 的发生。兰索拉唑可能在预防需要皮质类固醇治疗的患者的股骨头坏死方面既安全又有效。
