The effect of immunomodulatory drugs on bone metabolism of patients with multiple myeloma

ABSTRACT

Introduction

Immunomodulatory drugs (IMiDs) are widely used in the management of newly diagnosed and relapsed/refractory multiple myeloma patients. These agents show their potential effect on myeloma bone disease (MBD), including inhibition of osteoclasts activity and effects on osteoblasts differentiation. It is unclear whether these effects are direct, which may have an impact on bone formation markers when combined with proteasome inhibitors.

Areas covered

This review summarizes the available evidence on the role of IMiDs in microenvironment regulation and their potential effects on bone metabolism. The literature search methodology consisted of searching PubMed for basic and clinical trials using medical subject terms. Included articles were screened and evaluated by the coauthors of this review.

Expert Opinion

As a therapeutic option, IMiDs directly affect preosteoblast/osteoclast differentiation. The combination of proteasome inhibitors may counteract the short-term up-regulation of osteogenic activity markers, and therefore intravenous zoledronic acid is recommended, however, obtaining a more significant myeloma response will have a long-term positive impact on myeloma bone disease.

KEYWORDS:

• Multiple myeloma
• bone metabolism
• immunomodulatory drugs
• osteoclast
• osteoblast

Article highlights

• IMiDs directly inhibit early osteoclasts differentiation.

• Potential up-regulation of osteogenic activity markers when lenalidomide is used at high doses (25 mg) or in combination with proteasome inhibitors.

• Intravenous zoledronic acid is recommended over oral clodronate in reducing skeletal-related events.

• A regimen of IMiDs combined with proteasome inhibitors is recommended, although this regimen counteracts short-term upregulation of osteogenic activity markers, clinical studies have demonstrated improved myeloma response and reduced risk of skeletal-related events.

• More focus needs to be put on developing methods to stimulate osteoblast activation and administration to improve bone formation.

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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This study was supported by Luzhou Municipal Government—Southwest Medical University Cooperation Application Foundation (grant no. 2023LZXNYDJ045) and Academic Research Projects of Southwest Medical University (grant no. 2023QN042).