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European Journal of Orthopaedic Surgery & Traumatology
Published in: European Journal of Orthopaedic Surgery & Traumatology 4/2020

Open Access 01-05-2020 | Lansoprazole | Original Article

The proton pump inhibitor, lansoprazole, prevents the development of non-traumatic osteonecrosis of the femoral head: an experimental and prospective clinical trial

Authors: Ima Kosukegawa, Shunichiro Okazaki, Motohisa Yamamoto, Satoshi Nagoya, Chisako Suzuki, Junya Shimizu, Hiroki Takahashi, Toshihiko Yamashita

Published in: European Journal of Orthopaedic Surgery & Traumatology | Issue 4/2020

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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.
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Metadata
Title
The proton pump inhibitor, lansoprazole, prevents the development of non-traumatic osteonecrosis of the femoral head: an experimental and prospective clinical trial
Authors
Ima Kosukegawa
Shunichiro Okazaki
Motohisa Yamamoto
Satoshi Nagoya
Chisako Suzuki
Junya Shimizu
Hiroki Takahashi
Toshihiko Yamashita
Publication date
01-05-2020
Publisher
Springer Paris
Published in
European Journal of Orthopaedic Surgery & Traumatology / Issue 4/2020
Print ISSN: 1633-8065
Electronic ISSN: 1432-1068
DOI
https://doi.org/10.1007/s00590-020-02622-5

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