Neridronate

개요Neridronic acid was launched in Italy as intravenous or intramuscular injection for the treatment of osteogenesis imperfecta. It is the first drug launched worldwide for this “orphan disease” characterized by a fragility of the bone. Sufferers risk frequent fractures commencing during infancy, eventually leading to bone deformation and a severe deterioration of the quality of life and life expectancy. Neridronic acid is structurally related to the second generation of bisphosphonates characterized by an amino terminal group and can be synthesized by treating E-aminocaproic acid with phosphoric acid and phosphorous trichloride. Bisphosphonates, synthetic analogs of the endogenous mineral deposition inhibitor pyrophosphate, are extremely potent inhibitors of bone resorption and increase bone mineral density, possibly by inhibiting the activity of osteoclasts and promoting the death of these bone-eroding cells. In vitro, neridronic acid was a poor inhibitor of phagocytosis, but significantly and dose dependently inhibited 8glucuronidase release and superoxide anion production in the rat peritoneal macrophage, two parameters that may have a part in bone resorption. In a clinical study on patients with osteogenesis imperfecta, neridronic acid increased remarkably bone mass in young growing individuals. In adults the changes were less important but still significant.