Combination Therapy of High-calcium and Bisphosphonate for Rats' Steroid-induced Osteoporosis

Objectives: Bisphosphonate is one of the therapeutics for steroid-induced osteoporosis, and so is high-calcium diet. But there is no information about their combination therapy on mandible. We evaluated combination therapy of Bisphosphonate and high-calcium diet on steroid-induced osteoporosis. Methods: Fifty Wistar rats were divided into: 6-weeks control (C6), steroid (St), 9-weeks control (C9), steroid{high-calcium diet (StHC), and steroid{high- calcium diet with Bisphosphonate (StHCBP) groups. St, StHC, and StHCBP were administered with steroid (Prednine^®, Shionogi Pharmaceutical, Japan) (30mg/kg/2 days) for the first 6 weeks, and C6 and St were sacrificed. Then StHC was treated with high-calcium diet, and StHCBP was treated with high-calcium diet with HEBP (Didronel^®, Sumitomo Pharmaceutical, Japan) (5mg/kg/day) for the following 3 weeks. We evaluated all mandibles with two dimensional densitometry (PDS-15), three dimensional peripheral Quantitative Computed Tomography (pQCT), and analysis of Ca, P, Mg, and Zn elements with a sequential plasma spectrometer (ICPS-8000). Results: By PDS-15, no difference is observed among all groups, but by pQCT, all bone parameters in St were lower than those of C6 except trabecular bone density (TrBD, mg/cm³) (p<0.05). All bone parameters in StHC and StHCBP were higher than those of C9 except trabecular bone mineral content (TrBMC,mg/mm) in StHCBP, and trabecular cross-sectional area (TrCSA, mm²) in StHCBP (p<0.05). TrBMC and cortical bone density (CtBD, mg/cm³) in StHCBP were higher than those in StHC(p<0.05). Stress-strain index to the reference axis X and Z (xSSI and zSSI) in StHCBP were higher than those in StHC (p<0.01). Ca (mg/mg), P (mg/mg), and Mg (μg/mg) in StHCBP were higher than those in StHC(p<0.05). Conclusions: Our findings suggest that combination therapy of high-calcium diet and bisphosphonate improves steroid-induced osteoporosis of mandibular better than High-calcium diet or Bisphosphonate single.