Combined treatment with minodronate and vitamin C increases bone mineral density and strength in vitamin C-deficient rats

OBJECTIVES: Reduced bone quality caused by vitamin C deficiency in older persons may lead to incidental fragility fractures during bisphosphonate treatment, although bisphosphonate increases bone mineral density (BMD). This study aimed to evaluate the effects of minodronate and ascorbic acid (Aa) on BMD, bone quality, and bone strength in Aa-deficient osteogenic disorder Shionogi (ODS) rats. METHODS: Six-month-old ODS rats were divided into four groups (n = 20 per group): (1) Aa supplementation (Aa(+)); (2) Aa-deficient (Aa(−)); (3) Aa supplementation and minodronate administration (Aa(+) + Mino); and (4) Aa-deficient and minodronate administration (Aa(−) + Mino). BMD, bone strength, bone histomorphometry, and bone quality determined using Fourier transform infrared spectroscopy imaging (FTIRI) were evaluated after 4 and 8 weeks. RESULTS: BMD was significantly higher in the Aa(+) + Mino group than in the Aa(−) group (p < 0.05). Bone strength was significantly higher in the Aa(+) and Aa(+) + Mino groups than in the Aa(−) group (p < 0.05). Furthermore, bone strength was significantly higher in the Aa(+) + Mino group than in the Aa(−) + Mino group (p < 0.05). Minodronate treatment irrespective of Aa supplementation significantly decreased bone resorption compared with the Aa(+) and Aa(−) groups (p < 0.05). No significant differences in the parameters evaluated by FTIRI were observed between the groups. CONCLUSIONS: Aa supplementation improved bone strength in ODS rats. Combined treatment with minodronate and Aa, but not minodronate alone, improved bone strength and increased BMD. Aa is required for bone health because it is essential for osteoblast differentiation.