Pharmacodynamics of bisphosphonates in arthritis

Goff, Benoît Le; Heymann, Dominique

doi:10.1586/ecp.11.40

Cited by 9 publications

(5 citation statements)

References 64 publications

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“…As bisphosphonates have been ascribed to possess antiinflammatory, chondro-protective, and anti-catabolic effects they have been suggested to be promising drugs for the treatment of arthritis. While recent reports have concluded that bisphosphonates do not have any significant clinical effects on either disease activity or pain in osteoarthritis 8 and rheumatoid arthritis 9 , there has been little attempt to distinguish clinical efficacy based on bisphosphonate type. Interestingly, while the nitrogen-containing bisphosphonates risedronate, alendronate and zoledronate are generally ineffective 8,9 , the non-nitrogen containing bisphosphonate clodronate appears to be have some limited effects in reducing pain associated with both osteoarthritis 10,11 and rheumatoid arthritis 12,13 .…”

Section: Discussionmentioning

confidence: 99%

Clodronate exerts an anabolic effect on articular chondrocytes mediated through the purinergic receptor pathway

Rosa

Collavino

Lakhani

et al. 2014

Osteoarthritis and Cartilage

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Section: Discussionmentioning

confidence: 99%

Clodronate exerts an anabolic effect on articular chondrocytes mediated through the purinergic receptor pathway

Rosa

Collavino

Lakhani

et al. 2014

Osteoarthritis and Cartilage

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“…Clodronate is a first-generation bisphosphonate-family compound that is now used in the clinic to prevent or actively inhibit the development of bone metastases and treat inflammatory diseases such as autoimmune rheumatoid arthritis and osteoarthritis ( 140 ). With experimental encapsulation of clodronate into liposomes, researchers developed an efficient reagent that selectively depleted MPs when successfully applied in several immunological studies ( 141 ).…”

Section: Targeting Tams In B-cell Lymphoma Patientsmentioning

confidence: 99%

The Role of Macrophage/B-Cell Interactions in the Pathophysiology of B-Cell Lymphomas

2018

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Macrophages (MPs) are heterogeneous, multifunctional, myeloid-derived leukocytes that are part of the innate immune system, playing wide-ranging critical roles in basic biological activities, including maintenance of tissue homeostasis involving clearance of microbial pathogens. Tumor-associated MPs (TAMs) are MPs with defined specific M2 phenotypes now known to play central roles in the pathophysiology of a wide spectrum of malignant neoplasms. Also, TAMs are often intrinsic cellular components of the essential tumor microenvironment (TME). In concert with lymphoid-lineage B and T cells at various developmental stages, TAMs can mediate enhanced tumor progression, often leading to poor clinical prognosis, at least partly through secretion of chemokines, cytokines, and various active proteases shown to stimulate tumor growth, angiogenesis, metastasis, and immunosuppression. Researchers recently showed that TAMs express certain key checkpoint-associated proteins [e.g., programmed cell death protein 1 (PD-1), programmed cell death-ligand 1 (PD-L1)] that appear to be involved in T-cell activation and that these proteins are targets of other specific checkpoint-blocking immunotherapies (anti-PD-1/PD-L1) currently part of new therapeutic paradigms for chemotherapy-resistant neoplasms. Although much is known about the wide spectrum and flexibility of MPs under many normal and neoplastic conditions, relatively little is known about the increasingly important interactions between MPs and B-lymphoid cells, particularly in the TME in patients with aggressive B-cell non-Hodgkin lymphoma (NHL-B). Normal and neoplastic lymphoid and myeloid cell/MP lineages appear to share many primitive cellular characteristics as well as transcriptional factor interactions in human and animal ontogenic studies. Such cells are capable of ectopic transcription factor-induced lineage reprogramming or transdifferentiation from early myeloid/monocytic lineages to later induce B-cell lymphomagenesis in experimental in vivo murine systems. Close cellular interactions between endogenous clonal neoplastic B cells and related aberrant myeloid precursor cells/MPs appear to be important interactive components of aggressive NHL-B that we discuss herein in the larger context of the putative role of B-cell/MP cellular lineage interactions involved in NHL-B pathophysiology during ensuing lymphoma development.

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“…BPs may be used in rheumatoid arthritis or in other inflammatory autoimmune joint diseases due to their effects on osteoclasts, which play a key role in the bone loss process that accompanies the joint damage in arthritis. 52 The anti-inflammatory effects of clodronate may add further beneficial effects in the treatment of inflammatory joint diseases. in a study in 163 patients with rheumatoid or psoriatic arthritis starting steroid therapy, 45 who were randomised to receive i.m clodronate 100 mg/week plus calcium and vitamin d or calci-Minerva Medica august 2018 these trials, the dosing regimen of oral clodronate used was greater (1600 mg/day) compared to that usually prescribed for the management of postmenopausal osteoporosis (800 mg/day), being doubled.…”

Section: Effects Of Clodronate In Other Forms Of Secondary Osteoporosismentioning

confidence: 99%

Clodronate in the management of different musculoskeletal conditions

Frediani¹,

Giusti²,

Bianchi³

et al. 2018

Minerva Med

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inTrOdUcTiOn: clodronic acid is a non-nitrogen-containing bisphosphonate largely used from some decades in the prevention and treatment of postmenopausal and secondary osteoporosis. in addition to antiresorptive activity, clodronate has shown anti-inflammatory and analgesic properties, and modulatory effects on bone and cartilage metabolism. evidence acQUiSiTiOn: a literature review has been conducted to characterize the mechanism of action of clodronate and to retrieve available evidence about the use of clodronate in primary and secondary osteoporosis, and its potential role in other musculoskeletal conditions and orthopedic surgery. EVIDENCE SYNTHESIS: The efficacy and safety of the available clodronate formulations (oral, intravenous and intramuscular) in the prevention and treatment of postmenopausal and secondary osteoporosis, including corticosteroidinduced osteoporosis and bone mass loss secondary to endocrine, gastrointestinal and neoplastic diseases, have been demonstrated in a variety of clinical trials. The analgesic, anti-inflammatory, bone-and chondro-modulating properties of clodronate have allowed to expand its use in other musculoskeletal conditions to those currently approved. clodronate has proven to be beneficial in the treatment of osteoarthritis of the knee and of the hand, in the management of complex regional pain syndrome, and in the peri-and postoperative phase in subjects undergoing arthroplasty. cOncLUSiOnS: The analysis of the available literature has shown that clodronate has relevant musculoskeletal effects beyond the antiresorptive activity. Further research is needed to better position clodronate therapy in the management of these conditions and to define the optimal formulation and dose regimen in any of the tested new indications.

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Pharmacodynamics of bisphosphonates in arthritis

Cited by 9 publications

References 64 publications

Clodronate exerts an anabolic effect on articular chondrocytes mediated through the purinergic receptor pathway

Clodronate exerts an anabolic effect on articular chondrocytes mediated through the purinergic receptor pathway

The Role of Macrophage/B-Cell Interactions in the Pathophysiology of B-Cell Lymphomas

Clodronate in the management of different musculoskeletal conditions

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