title: Reduction of plasma taurine level in children affected by osteogenesis imperfecta during bisphosphonate therapy.
abstract: Osteogenesis imperfecta (OI) is a heritable disease of connective tissue characterized by increased bone fragility. To date, bisphosphonates seem to be the most promising therapy, at least for children. In the last decade experimental and clinical studies indicate that several amino acids are implicated in bone mineralization. Particularly, taurine is localized in matrices of the bone and can regulate osteoblast metabolism with antiosteopenic effect. To investigate a possible interaction between pharmacological effects of bisphosphonates and amino acids involved in bone metabolism, we performed plasma and urine amino acids analysis in children affected by OI before and during treatment with bisphosphonates. Fourteen prepubertal children with moderate to severe types of OI, 8 males and 6 females, aged from 2 to 11 years (mean (SD) 6.9+/-2.53) were enrolled in the study. Patients were treated with neridronate infusion (1mg/kg/body weight) every three months. Plasma and urine specimens for amino acid analysis were kept at baseline (T0) and three months after each infusion of four consecutive cycles (T1-T4). A significant decrease in respect to the pre-treatment levels (T0) was observed after the fourth infusion for taurine (p<0.01). In addition, urinary excretion of this amino acid showed a significant decrease after the fourth infusion. No significant correlations were found between plasma level or urinary excretion of hydroxyproline, taurine, arginine and lysine in respect to bone mineral density. The progressive reduction of plasma taurine found in our patients treated with bisphosphonates could be implicated in the action mechanism of this drug in OI and possibly in other disorders of bone metabolism. This knowledge could provide new opportunities to improve treatment with bisphosphonates and address novel strategies for the therapeutic approach to bone disorders.
authors.affiliation: Department of Pediatrics, University "La Sapienza" Roma, Viale Regina Elena 324, 00161 Rome, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: D'Eufemia
authors.forename: Roberto
authors.initials: R
authors.lastname: Finocchiaro
authors.forename: Anna
authors.initials: A
authors.lastname: Zambrano
authors.forename: Martina
authors.initials: M
authors.lastname: Tetti
authors.forename: Valentina
authors.initials: V
authors.lastname: Ferrucci
authors.forename: Mauro
authors.initials: M
authors.lastname: Celli
mesh_terms: D000596:Amino Acids / Q000097:blood / Q000652:urine; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004164:Diphosphonates / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D010013:Osteogenesis Imperfecta / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D013654:Taurine / Q000097:blood* / Q000652:urine
chemical_list: D000596:Amino Acids; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D013654:Taurine; C053389:6-amino-1-hydroxyhexane-1,1-diphosphonate