Document Type

Article

Publication Date

5-23-2025

Comments

This article is the author’s final published version in Bone, Volume 198, September 2025, Article number 117542.

The published version is available at https://doi.org/10.1016/j.bone.2025.117542. Copyright © 2025 The Authors. Published by Elsevier Inc.

Abstract

Debilitating pain is the primary clinical feature of osteoarthritis (OA) that drives the enormous healthcare costs. Osteoarthritis-related pain is often treated with non-steroidal anti-inflammatory drugs (NSAIDs), which effectively relieve pain and inflammation by inhibition of prostaglandin synthesis. Antibodies directed against nerve growth factor (NGF) were tested some time ago as an alternative potential analgesic for musculoskeletal pain, including osteoarthritis-related pain. Unfortunately, clinical development of these drugs was put on hold due to adverse outcomes - primarily rapidly progressive osteoarthritis. Both prostaglandin synthesis and NGF have been implicated as critical mediators of strain adaptive bone remodeling, which may play a role in rapid osteoarthritis progression. Therefore, this study was designed to investigate the effects of celecoxib, an NSAID, and muMab911, an anti-NGF antibody, as well as the combination therapy on strain adaptive bone remodeling, bone mass and geometry, and bone healing in a murine model. Adult female C57BL/6 J mice received celecoxib through drinking water, up to 3 IP injections of muMab911, or both treatments over a period of two weeks. As expected, all treatments were effective for relieving injury-associated pain. Consistent with previous studies, we found that celecoxib alone and in combination with muMab911 impaired periosteal load-induced bone formation induced by axial forelimb compression. Furthermore, both treatments had minimal effects on osteoblast and osteocyte populations, bone structural and material properties, and cortical and trabecular bone mass. Moreover, treatment did not impair fracture healing or callus morphology, though both treatments suppressed NGF expression during healing. Together, these findings suggest that celecoxib and anti-NGF therapy diminish strain adaptive bone remodeling without broadly compromising bone mass or repair, potentially contributing to the accelerated OA progression observed clinically by weakening the subchondral bone's adaptive capacity.

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Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

Additional Files
Supplementary Data 1.docx (1091 kB)

PubMed ID

40414473

Language

English

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