title: Supplementation of L-arginine prevents glucocorticoid-induced reduction of bone growth and bone turnover abnormalities in a growing rat model.
abstract: The present study was designed to evaluate the effects of glucocorticoid (GC) treatment on bone turnover and bone mineral density in the growing rat. Because of the recent evidence that nitric oxide (NO) can counteract prednisolone-induced bone loss in mature rats, we examined the effect on bone of the NO donor L: -arginine in young male rats, in which bone mass is increased by the same biological mechanism as in children and adolescents. Thirty-six 10-week-old Sprague-Dawley male rats were assigned to six groups of six animals each, and treated for 4 weeks with either vehicle (once a week subcutaneous injection of 100 microl of sesame oil); prednisolone sodium succinate, 5 mg/kg, 5 days per week by intramuscular injection (i.m.); L-arginine, 10 mg/kg intraperitoneally (i.p.) once a day; N(G)-nitro-L-arginine methylester (L-NAME), 50 mg/kg subcutaneously once a day; prednisolone sodium succinate 5 mg/kg, 5 days per week i.m. +L-arginine 10 mg/kg i.p. once a day; or prednisolone sodium succinate, 5 mg/kg, 5 days per week i.m. +L-NAME 50 mg/kg subcutaneously once a day. Serum calcium, alkaline phosphatase (ALP), osteocalcin, and the C-terminal telopeptides of type I collagen (RatLaps) were measured at baseline conditions and after 2 and 4 weeks. Prior to treatment, and after 2 and 4 weeks, the whole body, vertebral, pelvic, and femoral bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) scanning. Prednisolone and prednisolone+L-NAME treated rats had significantly lower ALP and osteocalcin levels than controls at 2 and 4 weeks, and significantly higher levels of Rat-Laps than controls at 4 weeks. Prednisolone, L-NAME, and prednisolone+L-NAME produced a significant inhibition of bone accumulation and bone growth at all sites measured. Supplementation with L-arginine appeared to prevent the inhibition of bone growth and increase in bone resorption induced by prednisolone. These data would suggest, for the first time, that supplementation with an NO donor could be considered as a treatment for steroid-induced osteoporosis in the developing skeleton.
authors.affiliation: Department of Internal Medicine OVE, Via Plebiscito 628, 95124, Catania, Italy.
authors.forename: Pietra
authors.initials: P
authors.lastname: Pennisi
authors.forename: Maria Antonia
authors.initials: MA
authors.lastname: D'Alcamo
authors.forename: Concetta
authors.initials: C
authors.lastname: Leonetti
authors.forename: Anna
authors.initials: A
authors.lastname: Clementi
authors.forename: Vincenza Maria
authors.initials: VM
authors.lastname: Cutuli
authors.forename: Stefania
authors.initials: S
authors.lastname: Riccobene
authors.forename: Natalia
authors.initials: N
authors.lastname: Parisi
authors.forename: Carmelo Erio
authors.initials: CE
authors.lastname: Fiore
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects*; D001846:Bone Development / Q000187:drug effects*; D002118:Calcium / Q000097:blood; D003094:Collagen / Q000097:blood; D024042:Collagen Type I; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology; D015675:Osteocalcin / Q000097:blood; D010455:Peptides / Q000097:blood; D011239:Prednisolone / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D024042:Collagen Type I; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D009569:Nitric Oxide; D003094:Collagen; D001120:Arginine; D011239:Prednisolone; D000469:Alkaline Phosphatase; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester