Bisphosphonate associated osteonecrosis of the jaw (BP-ONJ) is one of the main side effects of bisphosphonate therapy (BPT). To date, there is no effective therapy of the BP-ONJ. Nitrogen-containing bisphosphonates (N-BPs) are particularly able to inhibit pyrophosphate synthase (FPPS) in the mevalonate pathway (MVP). Consequent of decreased synthesis of the metabolite Geranylgeraniol (GGOH) is believed to largely account for the development of BP-ONJ. Negative effect of N-BPs could be shown, resulting in decreased viability and migration capacity of different cell types of hard and soft tissues such as osteoblasts, fibroblast und endothelial cells. Aim of our in vitro study was to demonstrate that the mevalonate pathway metabolite GGOH could reverse the negative biological effect of N-BPs. Biological effect of GGOH on bisphosphonate-treated human umbilicord vein endothelial cells (HUVEC), fibroblast and osteogenic cells was analyzed by a viability test and measuring the migration capacity in a scratch wound assay as well as a migration assay using Boyden chambers. The morphological cell architecture of the treated cells was analyzed by phallacidin staining. GGOH cell-treatment can rescue the negative effect of bisphosphonates. These results underline the hypothesis that systemic or local treatment with GGOH could lead to new therapeutic strategies for BP-ONJ.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.oraloncology.2010.12.003 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Comparative cardiovascular safety of romosozumab versus bisphosphonates in Japanese patients with osteoporosis: a new-user, active comparator design with instrumental variable analyses.
J Bone Miner Res
January 2025
Department of Clinical Epidemiology, Graduate School of Medicine, Fukushima Medical University, Fukushima-city, Fukushima, Japan.
This study analyzed the association of romosozumab, a human monoclonal antibody with bone-forming and bone resorption-inhibiting effects, and bisphosphonates with the development of cardiovascular disease among patients with osteoporosis. A new-user design was employed to address selection bias, and instrumental variable analysis was used to address confounding by indication. Japanese patients aged ≥40 years, diagnosed with osteoporosis or experienced a fragility fracture, were admitted to medical facilities covered by a commercial administrative claims database, and newly prescribed romosozumab or bisphosphonates after the commercialization of romosozumab in Japan (March 4, 2019) were included based on verification of a 180-day washout period.
View Article and Find Full Text PDFEldecalcitol Add-On to Risedronate Reduces Bone Loss from Aromatase Inhibitors in Postmenopausal Breast Cancer Patients.
J Clin Endocrinol Metab
January 2025
Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.
Context: Aromatase inhibitors (AIs) cause bone loss and increase fracture risk in women with hormone receptor-positive early-stage breast cancer (HR+EBC). Bone antiresorptive agents are recommended for patients at risk of fragility fractures. Eldecalcitol, combined with bisphosphonate, increases bone mineral density (BMD) in primary osteoporosis.
View Article and Find Full Text PDFImportance: Fragility fractures result in significant morbidity.
Objective: To review evidence on osteoporosis screening to inform the US Preventive Services Task Force.
Data Sources: PubMed, Embase, Cochrane Library, and trial registries through January 9, 2024; references, experts, and literature surveillance through July 31, 2024.
Medication related osteonecrosis (MRONJ) in the management of CTIBL in breast and prostate cancer patients. Joint report by SIPMO AND SIOMMMS.
J Bone Oncol
February 2025
Unit of Oral Medicine and Dentistry for Frail Patients, Department of Rehabilitation, Fragility, and Continuity of Care, Regional Center for Research and Care of MRONJ, University Hospital Palermo, Palermo, PA, Italy.
Background: Low-doses of bone modifying agents (LD-BMAs) compared to those used to treat bone metastases are used in breast or prostate cancer patients on adjuvant endocrine therapy to prevent Cancer Treatment Induced Bone Loss (CTIBL). Their use is associated with an increased risk of developing Medication-Related Osteonecrosis of the Jaw (MRONJ). However, there is not clarity about strategies aimed to minimize the MRONJ risk in cancer patients at different conditions as low- vs high-doses of BMA.
View Article and Find Full Text PDFIn silico evaluation of bisphosphonates identifies leading candidates for SARS-CoV-2 RdRp inhibition.
J Mol Graph Model
January 2025
School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA 6027, Australia; Department of Health Sciences, University of York, York, YO10 5DD, UK. Electronic address:
The novel coronavirus disease (COVID-19) pandemic has resulted in 777 million confirmed cases and over 7 million deaths worldwide, with insufficient treatment options. Innumerable efforts are being made around the world for faster identification of therapeutic agents to treat the deadly disease. Post Acute Sequelae of SARS-CoV-2 infection or COVID-19 (PASC), also called Long COVID, is still being understood and lacks treatment options as well.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!