title: Olpadronate prevents the bone loss induced by cyclosporine in the rat.
abstract: The aim of the present in vivo experimental study was to investigate changes in bone turnover and bone mineral density (BMD) induced by cyclosporine (CsA) administration. The effectiveness of olpadronate (OPD) in preventing bone loss associated with CsA treatment was also evaluated. Forty male Sprague-Dawley rats (approximately 5 months old) were treated as follows: Group I: CsA+OPD vehicles (control); Group II: CsA 15 mg/kg + OPD vehicle; Group III: CsA 15 mg/kg + 4 ug OPD/100g rat; Group IV: CsA 15 mg/kg + 8 ug OPD/100g rat; Group V: CsA 15 mg/kg + 16 ug OPD/100g rat. CsA was administered by daily oral gavage and OPD by intraperitoneal injection once a week. Serum bone-alkaline phosphatase (b-ALP) and urinary deoxypyridinoline (DPyr) were measured on days 0, 14 and 30. Total skeleton, femur, lumbar spine, proximal, and middle tibia BMDs were measured on days 0 and 30. No significant differences were found between the CsA and the control groups as regards serum bALP levels, on days 14 and 30. CsA+OPD treated rats presented a transient increment in serum b-ALP on day 14 and a significantly lower level on day 30 compared to the control and CsA groups (P < 0.05). On days 14 and 30, DPyr excretion increased in the CsA group compared to control animals (P < 0.05). The three studied doses of OPD induced a significant decrease in DPyr excretion in the CsA group on days 14 and 30 (P < 0.05). Group V (receiving the highest dose of OPD) presented a significantly lower level of DPyr compared to the other two OPD-treated groups (P < 0.05). On day 30, the CsA group presented a significant reduction in proximal tibia, spine and whole femur BMDs (P < 0.05) compared to controls. On day 30, OPD treatment increased BMD of all the studied areas in CsA rats. Proximal tibia BMD of group V reached significantly higher values than the other studied OPD groups (P < 0.05). In summary, this study suggests that CsA-induced high bone resorption and trabecular bone loss is prevented by cotreatment with OPD. Moreover, it encourages the possible use of OPD to treat patients receiving CsA as immunosuppressive therapy.
authors.affiliation: Sección Osteopatías Médicas, Hospital de Clínicas José de San Martín, Facultad de Medicina, Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina.
authors.forename: Susana N
authors.initials: SN
authors.lastname: Zeni
authors.forename: S
authors.initials: S
authors.lastname: Gregorio
authors.forename: A C
authors.initials: AC
authors.lastname: Gomez
authors.forename: J
authors.initials: J
authors.lastname: Somoza
authors.forename: C
authors.initials: C
authors.lastname: Mautalen
mesh_terms: D015502:Absorptiometry, Photon; D000284:Administration, Oral; D000469:Alkaline Phosphatase / Q000097:blood; D000596:Amino Acids / Q000652:urine; D000818:Animals; D015519:Bone Density; D001862:Bone Resorption / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects*; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
chemical_list: D000596:Amino Acids; D004164:Diphosphonates; D007166:Immunosuppressive Agents; D016572:Cyclosporine; C055774:olpadronic acid; C036020:deoxypyridinoline; D000469:Alkaline Phosphatase