Effect of methotrexate on bone and wound healing

ABSTRACT

Introduction: Methotrexate (MTX) is one of the most commonly used disease modifying drugs administered for wide spectrum of conditions. Through the expansion of the indications of MTX use, an increasing number of patients nowadays attend orthopaedic departments receiving this pharmacological agent. The aim of this manuscript is to present our current understanding on the effect of MTX on bone and wound healing.

Areas covered: The authors offer a comprehensive review of the existing literature on the experimental and clinical studies analysing the effect of MTX on bone and wound healing. The authors also analyse the available literature and describe the incidence of complications after elective orthopaedic surgery in patients receiving MTX.

Expert opinion: The available experimental data and clinical evidence are rather inadequate to allow any safe scientific conclusions on the effect of MTX on bone healing. Regarding wound healing, in vitro and experimental animal studies suggest that MTX can adversely affect wound healing, whilst the clinical studies show that lose-dose MTX is safe and does not affect the incidence of postoperative wound complications.

KEYWORDS:

• Methotrexate
• mesenchymal stem cells
• fibroblasts
• osteoblasts
• wound healing
• bone healing
• fracture

Article highlights

• In vitro studies on the effect of MTX on bone cells reveal significant variability and conflicting results. MTX does not affect the chondrocytes in vitro. MTX inhibits the proliferation of fibroblasts and induces their apoptosis.

• The experimental animal studies are limited. High doses of MTX could inhibit bone healing in animals, while low doses were found to have no effect. Wound healing in animals was negatively affected by MTX.

• The clinical studies in humans on the effect of MTX on bone healing are limited. MTX should be considered as a potential risk factor for delayed union or nonunion.

• MTX does not affect the incidence of postoperative wound complications.

• It is safe to continue low dose MTX throughout the perioperative period. However, if there is deterioration in the renal function postoperatively, MTX should be discontinued.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

No funds were received in support of this study.