Intermittent Therapy with 1,25 Vitamin D and Calcitonin Prevents Cyclosporin-Induced Alveolar Bone Loss in Rats

• Published in: Calcified tissue international 2010-09, Vol.87 (3), p.236-245
• Main Authors: Spolidorio, Luís C., Herrera, Bruno S., Coimbra, Leila S., Spolidorio, Denise M. P., Muscará, Marcelo N., Rossa, C.
• Format: Article
• Language: English
• Subjects: Acid Phosphatase - blood; Administration, Oral; Alveolar Bone Loss - blood; Alveolar Bone Loss - chemically induced; Alveolar Bone Loss - prevention & control; Animals; Biochemistry; Biomarkers; Biomedical and Life Sciences; Bone density; Bone Density Conservation Agents - administration & dosage; Bone Density Conservation Agents - therapeutic use; Calcitonin - administration & dosage; Calcitonin - therapeutic use; Calcitriol - administration & dosage; Calcitriol - therapeutic use; Cell Biology; Cell Count; Cyclosporine - adverse effects; Cytokines; Drug Administration Schedule; Drug therapy; Endocrinology; Hormones; Immune system; Interleukins - blood; Isoenzymes - blood; Life Sciences; Male; Mandibular Diseases - chemically induced; Mandibular Diseases - prevention & control; Orthopedics; Osteoclasts - cytology; Rats; Rats, Wistar; Rodents; Side effects; Tartrate-Resistant Acid Phosphatase; Tumor Necrosis Factor-alpha - blood; Vitamin D
• ISSN: 0171-967X; 1432-0827
• DOI: 10.1007/s00223-010-9380-1

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 μg/kg, p.o.; in weeks 1, 3, 5, and 7) plus calcitonin (2 μg/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)-1β, IL-6, and tumor necrosis factor alpha (TNF-α) 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-1β, IL-6, and TNF-α 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.