Intermittent therapy with 1,25 vitamin D and calcitonin prevents cyclosporin-induced alveolar bone loss in rats.
Bone loss associated with cyclosporin A (CsA) therapy can result in serious morbidity to patients. Intermittent administration of 1,25 Vitamin D and calcitonin reduces osteopenia in a murine model of postmenopausal osteoporosis. The purpose of this study was to evaluate the effects of this therapeutic approach on CsA-induced alveolar bone loss in rats. Forty male Wistar rats were allocated to four experimental groups according to the treatment received during 8 weeks: (1) CsA (10 mg/kg/day, s.c.); (2) 1,25 Vitamin D (2 microg/kg, p.o.; in weeks 1, 3, 5, and 7) plus calcitonin (2 microg/kg, i.p.; in weeks 2, 4, 6, and 8); (3) CsA concurrently with intermittent 1,25 Vitamin D and calcitonin administration; and (4) the control treatment group (vehicle). At the end of the 8-week treatment period, serum concentrations of bone-specific alkaline phosphatase, tartrate-resistant acid phosphatase (TRAP-5b), osteocalcin, interleukin (IL)-1 beta, IL-6, and tumor necrosis factor alpha (TNF-alpha) were measured and an analysis of bone volume, bone surface, number of osteoblasts, and osteoclasts was performed. CsA administration resulted in significant alveolar bone resorption, as assessed by a lower bone volume and an increased number of osteoclasts, and increased serum bone-specific alkaline phosphatase, TRAP-5b, IL-1 beta, IL-6, and TNF-alpha concentrations. The intermittent administration of calcitriol and calcitonin prevented the CsA-induced osteopenic changes and the increased serum concentrations of TRAP-5b and inflammatory cytokines. Intermittent calcitriol/calcitonin therapy prevents CsA-induced alveolar bone loss in rats and normalizes the production of associated inflammatory mediators.
Department of Physiology and Pathology, Faculdade de Odontologia de Araraquara, UNESP-University Estadual Paulista, Rua Humaitá, 1380, Araraquara, São Paulo, Brazil. lcs@foar.unesp.br
Luís C
LC
Spolidorio
Bruno S
BS
Herrera
Leila S
LS
Coimbra
Denise M P
DM
Spolidorio
Marcelo N
MN
Muscará
C
C
Rossa
D000135:Acid Phosphatase / Q000097:blood; D000284:Administration, Oral; D016301:Alveolar Bone Loss / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002116:Calcitonin / Q000008:administration & dosage / Q000627:therapeutic use*; D002117:Calcitriol / Q000008:administration & dosage / Q000627:therapeutic use*; D002452:Cell Count; D016572:Cyclosporine / Q000009:adverse effects; D004334:Drug Administration Schedule; D007378:Interleukins / Q000097:blood; D007527:Isoenzymes / Q000097:blood; D008297:Male; D008336:Mandibular Diseases / Q000139:chemically induced / Q000517:prevention & control*; D010010:Osteoclasts / Q000166:cytology; D051381:Rats; D017208:Rats, Wistar; D000071681:Tartrate-Resistant Acid Phosphatase; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D050071:Bone Density Conservation Agents; D007378:Interleukins; D007527:Isoenzymes; D014409:Tumor Necrosis Factor-alpha; D016572:Cyclosporine; D002116:Calcitonin; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D002117:Calcitriol