Clodronate news of efficacy in osteoporosis

Abstract

SummaryClodronate belongs to Bisphosphonates family and it has been studied especially for osteoporosis treatment, Paget's disease, osteolytic metastases, hypercalcemia malignancy and some childhood skeletal diseases. Besides the osteoporosis treatment, it has been successfully used for treating tumoral osteolysis and for bone localization of multiple myeloma, hypercalcemia malignancy, primary hyperparathyroidism, Paget's disease and algodystrophy. Filipponi study showed a statistically significant reduction of the incidence of vertebral fractures after 4 years of treatment with clodronate, intravenously administered at a dose of 200 mg every three weeks. Frediani study, published in 2003 on BONE, proved the clodronate efficacy in the prevention of fractures caused by glucocorticoid-induced osteoporosis (GIO). Clodronate doses of 800 mg/day per os and 100 mg i.m./week are substantially equivalent, because the oral absorption is about 1,9%. A higher efficacy on BMD was documented in various works, especially in cohorts of patients with a greater fracture risk, using higher doses (1600 mg per os). This has led to the hypothesis of using clodronate 200 mg i.m. formulation. Clodronate is an osteoporosis drug that can be assumed in different doses (100 mg i.m./week, clodronate 200 mg i.m. every 2 weeks) considering the risk band, identified by algorithms (FRAX o DeFRA), by BMD and by the presence of at least one risk factor. That means that it is possible to envisage a differentiated use of clodronate adapting the doses to the fracture risk and to the severity of pain symptoms, thus promoting a greater adherence to the therapy. To conclude clodronate is helpful in reducing fracture risk, is safe, well tolerated, and has a good rate cost/effectiveness in patients with fracture risk over 7% established with FRAX.

Phytochemical Analysis, Antioxidant and Bone Anabolic Effects of Blainvillea acmella (L.) Philipson

“…Clodronate is the earliest group of non-nitrogen bisphosphonates that have been widely used in the clinical treatment for bone-related diseases by enhancing bone inhibition ( Koch et al, 2011 ; Frediani and Bertoldi, 2015 ; Nardi et al, 2016 ; Pherwani and Sathaye, 2020 ). Bisphosphonates reacted with osteoblast cells and altered bone metabolism by stimulating bone formation ( Corrado et al, 2017 ).…”

Involvement of VNUT-exocytosis in transient receptor potential vanilloid 4-dependent ATP release from gastrointestinal epithelium

“…It is thought that although VNUT is an essential component for vesicular ATP release in many cells, vesicular ATP release is not apparently necessary for maintaining life. Moreover, although the VNUT inhibitors identified thus far are toxic, clodronate has been used worldwide for the treatment of osteoporosis by intravenous or oral administration and has been shown to be analgesic in nature and safe without any severe adverse events including autonomic nervous system [ 30 – 32 ]. Therefore, VNUT inhibitors may be effective against pain [ 6 ].…”

Microglial Depletion with Clodronate Liposomes Increases Proinflammatory Cytokine Levels, Induces Astrocyte Activation, and Damages Blood Vessel Integrity

“…Clodronate, a member of the bisphosphonate family, is best known as an effective clinical therapy for osteometabolic disorders such as osteoporosis, arthritis, and osteo-articular pain [1–4]. When liposome-encapsulated clodronate (clodronate liposomes or Clo-Lip) is injected into an organ, it is phagocytosed by mononuclear phagocytes and then digested by lysosomal enzymes.…”