Effects of intraperitoneal administration of hexasodium N,N,N′,N′-ethylenediaminetetramethylenephosphonate on rat bone metabolism

• Published in: Fundamental and applied toxicology 1990-04, Vol.14 (3), p.491-501
• Main Authors: Moore, Nel C., Chipman, James K.
• Format: Article
• Language: English
• Subjects: Acid Phosphatase - blood; Alkaline Phosphatase - blood; Animals; Biological and medical sciences; Bone and Bones - drug effects; Bone and Bones - metabolism; Bone Resorption - metabolism; Chemical and industrial products toxicology. Toxic occupational diseases; DNA - metabolism; Male; Medical sciences; Organophosphorus Compounds - administration & dosage; Organophosphorus Compounds - pharmacology; Rats; Rats, Inbred Strains; Thymidine - metabolism; Toxicology; Various organic compounds
• ISSN: 0272-0590; 1095-6832
• DOI: 10.1016/0272-0590(90)90253-G

The influence of hexasodium N,N,N′,N′-ethylenediaminetetramethylenephosphonate (EDITEMP.Na 6) on biochemical parameters in bone has been studied to help explain recently reported histological and pathological changes in bone induced by this agent. A single, intraperitoneal (ip) injection of EDITEMP.Na 6 (350 μmol/kg on Day 0) significantly decreased the activity of serum alkaline phosphatase (Alp) in mature male Wistar rats for up to 10 days following the injection. However, in immature rats the initial EDITEMP.Na 6-induced reduction of serum Alp activity preceded a steady increase in serum Alp activity, which was significantly elevated between Days 6 and 13. This increase coincided with a significant increase in bone Alp activity (an indicator of bone formation) on Day 8. Diaphyseal acid phosphatase (Acp) activity (an indicator of bone resorption) was significantly reduced, on Days 4 and 8 but not on Day 1, following treatment with EDITEMP.Na 6. Repeated exposure of immature male Wistar rats to EDITEMP.Na 6 (70 μmol/kg/day, ip for 7 days) also led to a significant and persistent increase in serum and bone Alp activities and a reduction in diaphyseal Acp activity. The data are in accord with published histomorphological evidence of reduced bone resorption and suggest delayed mineralization of osteoid tissue laid down during the treatment with EDITEMP.Na 6. There were only transient and limited changes in bone DNA content and [ 3H]thymidine incorporation throughout the studies, indicating the absence of marked cytotoxicity or altered bone cell proliferation associated with EDITEMP.Na 6-induced changes in phosphatase enzyme activities.