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Macrophage Involvement in Medication-Related Osteonecrosis of the Jaw (MRONJ): A Comprehensive, Short Review
Ioannis Gkouveris1, Akrivoula Soundia1, Panagiotis Gouveris2
1Division of Diagnostic and Surgical Sciences, UCLA School of Dentistry, Los Angeles, CA 90095, USA.
Abstract:
Antiresorptive agents such as bisphosphonates (BP) and denosumab are commonly prescribed for the management of primary bone malignancy, bone metastasis, osteoporosis, Paget disease, or other bone disorders. Medication-related osteonecrosis of the Jaws (MRONJ) is a rare but significant complication of antiresorptive medications. Duration, dose, and antiresorptive potency as well as concomitant diseases, additional medications, and local factors affect MRONJ incidence and severity. MRONJ pathophysiology is still poorly understood. Nevertheless, decreased bone resorption due to osteoclastic inhibition along with trauma, infection/inflammation, or blood supply inhibition are considered synergistic factors for disease development. In addition, previous data research examined the effects of antiresorptive medication on immune system components and introduced potential alterations on immune response as novel elements in MRONJ pathogenesis. Considering that macrophages are the first cells in the nonspecific immune response, it is not surprising that these multifaceted players attracted increased attention in MRONJ research recently. This current review attempted to elucidate the effects of antiresorptive medications on several aspects of macrophage activity in relation to the complex inflammatory microenvironment of MRONJ. Collectively, unravelling the mode of action and extent of macrophages' potential contribution in MRONJ occurrence will provide novel insight in disease pathogenesis and potentially identify intrinsic therapeutic targets.
Insights
Antiresorptive medications, like bisphosphonates, can cause Medication-related Osteonecrosis of the Jaws (MRONJ). This review explores how these drugs affect macrophages, key immune cells, potentially revealing new therapeutic targets for MRONJ.
Area of Science:
- Immunology
- Pharmacology
- Oral and Maxillofacial Surgery
Background:
- Antiresorptive agents (bisphosphonates, denosumab) are crucial for bone disorders but can cause Medication-related Osteonecrosis of the Jaws (MRONJ).
- MRONJ pathophysiology remains unclear, with theories involving impaired bone resorption, trauma, infection, and altered blood supply.
- Emerging research suggests immune system dysregulation, particularly macrophage activity, may play a role in MRONJ development.
Purpose of the Study:
- To review the impact of antiresorptive medications on macrophage activity.
- To explore the role of macrophages in the inflammatory microenvironment of MRONJ.
- To identify potential therapeutic targets for MRONJ by understanding macrophage contributions.
Main Methods:
- Literature review of studies investigating antiresorptive medications and macrophage function.
- Analysis of current understanding of MRONJ pathogenesis.
- Synthesis of data on immune response alterations in relation to antiresorptive drug use.
Main Results:
- Antiresorptive medications can modulate various macrophage functions, influencing the inflammatory milieu.
- Macrophages are implicated as significant players in the complex pathogenesis of MRONJ.
- Altered macrophage behavior may contribute to the development and severity of MRONJ.
Conclusions:
- Understanding the intricate effects of antiresorptive drugs on macrophages is crucial for elucidating MRONJ pathogenesis.
- Macrophages represent a promising area for future research and potential therapeutic intervention in MRONJ.
- Further investigation into macrophage-mediated mechanisms could lead to novel strategies for preventing or treating MRONJ.
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