Alteration of macrophage viability, differentiation, and function by bisphosphonates

Patntirapong, Somying; Poolgesorn, Mahatana

doi:10.1111/odi.12908

Cited by 36 publications

(30 citation statements)

References 36 publications

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“…The family of bisphosphonates is used in the treatment of osteoporosis, certain bone tumors, and bone metastasis. Bisphosphonates are capable of reducing the number and impairing function of monocytes and specialized macrophages ( 66 ). Treatment with a member of this family, clodronate disodium, has shown effectiveness in animal models of pulmonary coronavirus infections ( 67 ), but the impact of clodronate disodium on the microglia can also make animals more susceptible to neural damage in a coronavirus encephalitis model ( 68 ).…”

Section: Systemic Inflammatory Response Induced By Lung Inflammationmentioning

confidence: 99%

Overview: Systemic Inflammatory Response Derived From Lung Injury Caused by SARS-CoV-2 Infection Explains Severe Outcomes in COVID-19

Polidoro

Hagan

Santiago³

et al. 2020

Front. Immunol.

158

147

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Most SARS-CoV2 infections will not develop into severe COVID-19. However, in some patients, lung infection leads to the activation of alveolar macrophages and lung epithelial cells that will release proinflammatory cytokines. IL-6, TNF, and IL-1β increase expression of cell adhesion molecules (CAMs) and VEGF, thereby increasing permeability of the lung endothelium and reducing barrier protection, allowing viral dissemination and infiltration of neutrophils and inflammatory monocytes. In the blood, these cytokines will stimulate the bone marrow to produce and release immature granulocytes, that return to the lung and further increase inflammation, leading to acute respiratory distress syndrome (ARDS). This lung-systemic loop leads to cytokine storm syndrome (CSS). Concurrently, the acute phase response increases the production of platelets, fibrinogen and other pro-thrombotic factors. Systemic decrease in ACE2 function impacts the Renin-Angiotensin-Kallikrein-Kinin systems (RAS-KKS) increasing clotting. The combination of acute lung injury with RAS-KKS unbalance is herein called COVID-19 Associated Lung Injury (CALI). This conservative two-hit model of systemic inflammation due to the lung injury allows new intervention windows and is more consistent with the current knowledge.

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Section: Systemic Inflammatory Response Induced By Lung Inflammationmentioning

confidence: 99%

Overview: Systemic Inflammatory Response Derived From Lung Injury Caused by SARS-CoV-2 Infection Explains Severe Outcomes in COVID-19

Polidoro

Hagan

Santiago³

et al. 2020

Front. Immunol.

158

147

View full text Add to dashboard Cite

show abstract

“…As a functional immune system is proposed to be a vital factor in the development of MRONJ, this has been an area of active investigation. Recent in vitro studies have demonstrated the reduction of macrophage viability and monocyte differentiation as well as increased matrix metalloproteinase expression in the setting of BP exposure utilizing a THP-1 human monocytic cell model 23 , 24 . Further, analyses of osseous specimens from patients diagnosed with MRONJ have also demonstrated a marked increase in both macrophage infiltration as well as polarization toward a destructive M1, or classically-activated, phenotype mediated by BP exposure which may impair bone tissue homeostasis 25 .…”

Section: Discussionmentioning

confidence: 99%

The effect of pamidronate delivery in bisphosphonate-naïve patients on neutrophil chemotaxis and oxidative burst

Chadwick

Tenenbaum

Sun

et al. 2020

Sci Rep

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The pathogenesis of medication-related osteonecrosis of the jaw (MRONJ), a morbid condition associated with bisphosphonate administration, has not been fully elucidated. Recent research utilizing a murine model has revealed that the neutrophil becomes dysfunctional following exposure to bisphosphonates. Accordingly, the impairment of neutrophil function could play an important role in the pathogenesis of MRONJ via an infectious mechanism mediated by the suppression of the innate immune system. Currently, the existing human data are insufficient to substantiate this theory. To investigate, we isolated neutrophils from blood and oral rinse samples from bisphosphonate-naïve patients who were recently diagnosed with multiple myeloma both prior to and one month following their initial infusion of pamidronate, an intravenous bisphosphonate agent. Stimulated blood and oral neutrophil superoxide production and chemotactic capabilities were found to be impaired relative to baseline values. These results suggest that impaired neutrophil function may partially contribute to the aetiology underlying the pathophysiological processes linked to the development of MRONJ. Further, as the functional status of circulating neutrophils was reflected in the oral cavity where sampling can be accomplished in a non-invasive fashion, it is conceivable that neutrophil function could serve as a potential biomarker for MRONJ prognostication.

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“…The function of macrophages is disrupted by increased MMP expression, leading to impaired wound healing in MRONJ-affected areas. 32 Through the inhibition of RANKL, denosumab may affect the expression of RANK on immune cells, such as dendritic cells, monocytes, or macrophages. RANKL increases the production of proinflammatory cytokines and reduces monocyte apoptosis.…”

Section: Infection and Immunitymentioning

confidence: 99%

Pathogenesis and multidisciplinary management of medication-related osteonecrosis of the jaw

Sun

Liu

et al. 2020

Int J Oral Sci

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Medication-related osteonecrosis of the jaw (MRONJ) is a serious side effect of bone-modifying agents and inhibits angiogenesis agents. Although the pathogenesis of MRONJ is not entirely clear, multiple factors may be involved in specific microenvironments. The TGF-β1 signalling pathway may have a key role in the development of MRONJ. According to the clinical stage, multiple variables should be considered when selecting the most appropriate treatment. Therefore, the prevention and management of treatment of MRONJ should be conducted in patient-centred multidisciplinary team collaborative networks with oncologists, dentists and dental specialists. This would comprise a closed responsibility treatment loop with all benefits directed to the patient. Thus, in the present review, we aimed to summarise the pathogenesis, risk factors, imaging features, clinical staging, therapeutic methods, prevention and treatment strategies associated with MRONJ, which may provide a reference that can inform preventive strategies and improve the quality of life for patients in the future.

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Alteration of macrophage viability, differentiation, and function by bisphosphonates

Abstract: BPs directly acted on macrophage by reducing macrophage survival, inducing morphological alterations, impairing differentiation from monocytes to macrophages, and affecting macrophage function at both mRNA and activity levels.

Cited by 36 publications

References 36 publications

Overview: Systemic Inflammatory Response Derived From Lung Injury Caused by SARS-CoV-2 Infection Explains Severe Outcomes in COVID-19

Overview: Systemic Inflammatory Response Derived From Lung Injury Caused by SARS-CoV-2 Infection Explains Severe Outcomes in COVID-19

The effect of pamidronate delivery in bisphosphonate-naïve patients on neutrophil chemotaxis and oxidative burst

Pathogenesis and multidisciplinary management of medication-related osteonecrosis of the jaw

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