Pharmacology of bisphosphonates in pain

Tzschentke, Thomas

doi:10.1111/bph.14799

Cited by 25 publications

(21 citation statements)

References 150 publications

(214 reference statements)

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“…The ability of clodronate to reduce pain in OA could be due to the modulation of multiple pain generators not only in the intra-articular environment [ 32 ]. In chronic pain conditions, clodronate blocks the release of ATP at the vesicular level by interfering with the purinergic chemical transmission [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

“…The inhibition of osteoclast activity by BPs not only reduces bone turnover but also leads to a reduction in extracellular acidity. This latter mechanism reduces the activation of primary nociceptive bone afferents mediated by the ion channels ASICs (acid-sensing ion channels) and TRPV1 (transient receptor potential cation channel subfamily V member 1) sensitive to extracellular acidity [ 32 , 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

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The Rationale for the Intra-Articular Administration of Clodronate in Osteoarthritis

Moretti

Paoletta

Liguori

et al. 2021

IJMS

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Background: Several pharmacological therapeutic approaches have been proposed to manage osteoarthritis (OA), including intra-articular (IA) injections. Although the discovery of clodronate, a bisphosphonate, dates back to the 1960s and the effects of its IA administration have been investigated for decades in animal models, mechanisms of action of this drug are not quite clear, particularly in OA. This scoping review is an overview of the biological as well as the clinical role of clodronic acid in OA. Method: A scoping review based on the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) model was performed to characterize the mechanisms of action of IA clodronate in OA and to evaluate its efficacy from a clinical point of view. Results: Several effects of clodronate have been observed in animal models of OA, including depletion of synovial lining cells that results in reduced production of chemokines (IL-1, TNF- α), growth factors (TGF-β, BMP 2/4), and metalloproteases (MMP 2/3/9); prevention of cartilage damage, synovial hyperplasia, and proteoglycans loss; reduction in joint inflammation, joint swelling, and osteophyte formation. From a clinical perspective, patients with knee OA treated with IA clodronate experienced improvements in pain and joint mobility. Conclusion: Clodronate appears to have different mechanisms of action interfering with the pathogenic processes contributing to OA development and progression. This intervention demonstrated positive effects for patients affected by knee OA.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Rationale for the Intra-Articular Administration of Clodronate in Osteoarthritis

Moretti

Paoletta

Liguori

et al. 2021

IJMS

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“…Bisphosphonates are agents that are often used to treat pain as a symptom [67]. They act by inhibiting farnesyl diphosphate synthase in phagocytic cells, e.g.…”

Section: Bisphosphonatesmentioning

confidence: 99%

“…They act by inhibiting farnesyl diphosphate synthase in phagocytic cells, e.g. osteoclasts, macrophages and microglia, thereby decrease extracellular acidification and consequently reduce ASIC-and TRPV1-mediated activation of nociceptive primary afferents located in bone [67]. Other effects of bisphosphonates unrelated to farnesyl diphosphate synthase inhibition that have been suggested are interactions with purinergic receptors, e.g.…”

Section: Bisphosphonatesmentioning

confidence: 99%

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Bone Cancer Pain, Mechanism and Treatment

Sliepen¹

2021

Recent Advances in Bone Tumours and Osteoarthritis

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The world health organization (WHO) has predicted a global amount of 19 million cancer cases by 2025. Breast, prostate and lung cancer are common cancer types and show metastasis in 60 to 84% of the cases, with 75 to 90% experiencing life-altering cancer-induced bone pain (CIBP), characterized by continuous, dull progressive pain with movement-induced incident peaks and random breakthrough spikes. Therefore, it is the most difficult pain condition to treat. CIBP is a unique type of pain with neuropathic and nociceptive components. Briefly, an invading tumor cell disturbs the healthy balance of the bone resulting in an acidic microenvironment, activating sensory fibers in the bone. The invaded tumor cell and adjacent stromal cells secrete mediators initiating an immune response with transcriptional signaling, resulting in increased cytokines and growth factors. Sensory nerve fibers are damaged and start to sprout, causing ectopic firing, and as tumors grow in size they activate mechanoreceptors. Aside from bisphosphonates and antibody therapy, CIBP is treated by a range of NSAIDs to strong opioids, but remains undertreated in one-third of cases. This chapter discusses the accompanying CIBP of bone tumors, the mechanism of action and current treatments.

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