Multiple assessment methodologies in determining the antibiofilm actions of sodium hypochlorite mixed with clodronate or etidronate in endodontic irrigation.

This study aimed to use multiple methodologies, including a novel usage of scanning electron microscopy (SEM), to evaluate the antimicrobial actions of sodium hypochlorite (NaOCl) admixed with clodronate or etidronate in root canal irrigation. The study also examined the usefulness of colony counting as a biofilm assessment methodology. Seven day Enterococcus faecalis biofilms were grown on hydroxyapatite discs. The discs were disinfected with 0.26 M clodronate-5% NaOCl, 0.26 M etidronate-5% NaOCl, 5% NaOCl, or treated with phosphate buffered saline (PBS). Assessments were performed using colony counting, SEM and the XTT reduction assay. The XTT assessment used the same groups but with 2.5% NaOCl. For colony counting, bacteria were removed from the discs by vortex mixing, followed by plating. The discs were subsequently fixed for SEM imagining and evaluators scored the SEM micrographs for remaining bacteria. Antibiofilm actions were assessed with the Kruskal-Wallis and Dunn's multiple comparison tests. SEM micrographs and the XTT assay revealed no differences between the NaOCl controls and the clodronate or etidronate mixtures with NaOCl (P > 0.05). It was concluded that the chelator mixtures with NaOCl had antibiofilm actions comparable to NaOCl. Furthermore, vortex mixing incompletely removed biofilm from HA discs in the PBS controls and hence colony counting using E. faecalis biofilms on hydroxyapatite discs could not be used for intergroup comparisons involving PBS. Additionally, colony counting could not be used for comparisons between the NaOCl treatment groups because the removal of bacteria from the substrate by vortex mixing was affected by the irrigant type.

Clinical utility of clodronate in the prevention and management of osteoporosis in patients intolerant of oral bisphosphonates.

Bisphosphonates have a long history in the treatment of osteoporosis and bone-related disease. This review focuses on the use of a specific nonaminobisphosphonate, clodronate, which appears to be much better tolerated than other bisphosphonates and free of high-risk contraindications. Specifically, this paper reviews its use in the prevention of osteoporosis in postmenopausal women, taking into account its tolerability profile and recent safety issues arising regarding the use of bisphosphonates.

Assessment of metalloproteinase inhibitors clodronate and doxycycline in the neutralization of hemorrhage and coagulopathy induced by Bothrops asper snake venom.

Snake venom metalloproteinases (SVMPs) play a prominent role in the local and systemic manifestations of viperid snakebite envenomations. Thus, the possibility of using metalloproteinase inhibitors in the treatment of these envenomations is a promising therapeutic alternative. This study assessed the ability of two metalloproteinase inhibitors, the biphosphonate clodronate and the tetracycline doxycycline, to inhibit proteolytic, hemorrhagic, coagulant and defibrinogenating effects of Bothrops asper venom. Both compounds were able to inhibit these activities, at concentrations in the mM range, when incubated with venom prior to testing. However, when inhibition of hemorrhage was assessed in assays involving independent injection of venom and drug, inhibition was poor, even when these compounds were injected immediately after envenomation. These findings support the concept that the effectiveness of compounds, such as clodronate and doxycycline, whose inhibitory action on SVMPs is based on zinc chelation alone, is limited, and stress the view that more specific molecules are required for an effective inhibition of SVMPs in vivo.

Cost-effectiveness of oral clodronate compared with oral ibandronate, intravenous zoledronate or intravenous pamidronate in breast cancer patients.

This study aimed to identify the effects of different bisphosphonates in reducing skeletal-related events, and to determine whether there are any differences in their cost-effectiveness, taking into account their efficacy, safety profile and administration routes. A systematic literature search of databases, such as PubMed and the Cochrane Controlled Trials Register, supplemented by the latest congress abstracts from meetings of the European Hematology Association and the American Society of Clinical Oncology was conducted up to November 2006. Important references in reviews published by peer-reviewed journals were also taken into consideration. Our base-case cost-effectiveness analysis for Germany and the UK showed cost savings for oral clodronate therapy compared with other bisphosphonate therapies. In Germany, costs per patient of treatment with oral clodronate were euro1092.38, euro2360.40 and euro2500.29 less than with oral ibandronate, intravenous pamidronate and intravenous zoledronate, respectively. The UK results were similar, the costs per patient of treatment with oral clodronate being euro841.79, euro2989.99 and euro3669.19 less than with oral ibandronate, intravenous pamidronate and intravenous zoledronate, respectively.

An assessment of the interaction between human neutrophils, hydroxyapatite and dichloromethylene bisphosphonate in vitro: an electron microscopic and chemiluminescence study.

The potentially destructive effects of neutrophils, following particulate stimulus such as by hydroxyapatite (HA) crystals, may be pertinent to the progression of some inflammatory diseases, including rheumatoid arthritis. This study was designed to examine the interaction between pure hydroxyapatite particles and human neutrophil granulocytes by transmission electron microscopy and chemiluminescence (CL). The influence of dichloromethylene bisphosphonate (clodronate) in this model was investigated. Neutrophils convincingly phagocytosed HA particles within 15 min and a high CL response was elicited by the zymosan stimulated CL reaction. Clodronate alone appeared to have little effect on the cell morphology or CL. When HA was combined with clodronate, phagocytosis was more rapid, and the zymosan-stimulated CL was 50% of that of the HA group. The results demonstrate neutrophil phagocytosis of HA particles and subsequent cellular activation, which may play a role in the pathogenesis of tissue damage and suggest that the anti-inflammatory role of clodronate should be further investigated.