Influence on the bone mineral density and bone metabolism marker after the interruption and reinitiation of monthly minodronate therapy in postmenopausal women with osteoporosis

OBJECTIVES: The purpose of this study was to investigate the influences of interruption and reinitiation of monthly minodronate therapy on the bone mineral density (BMD) and bone metabolism markers in postmenopausal women with osteoporosis. METHODS: Study patients were included if they had been administered monthly minodronate therapy for ≥6 months, interrupted the therapy, and reinitiated the therapy for ≥12 months. The BMD and bone metabolism markers were assessed at 4 time points: initiation, interruption, reinitiation and 1 year after reinitiation of therapy. RESULTS: A total of 23 patients were enrolled. The mean monthly minodronate treatment period was 23.8 ± 12.9 months following a mean interruption period of 11.9 ± 5.4 months. Once increased by monthly minodronate treatment for 2 years on average, the BMD of lumbar spine and radius did not significantly decrease even after an interruption for 1 year on average. However, the BMD of the femoral neck did decrease after interruption. The BMD of the lumbar spine and radius increased further after 1 year of monthly minodronate retreatment. The BMD of the femoral neck did not change. Once decreased after the treatment for an average of 2 years followed by an interruption for 1 year, bone metabolism markers increased gradually but did not recover to baseline levels. A potent suppressive effect on bone resorption was noted. The change rate was greater for the bone formation marker procollagen 1 N-terminal propeptide. CONCLUSIONS: Monthly minodronate treatment increases BMD and reduces bone metabolism markers. The effect lessens after treatment interruptions, and can be restored by retreatment.

Comparison of effectiveness and safety of ibandronate and minodronate combined with eldecalcitol in primary osteoporosis of women: A 1-year follow-up study

OBJECTIVES: This is an open labeled and retrospective cohort study which compared the effectiveness and safety of ibandronate (IBN) and minodronate (MIN) combined with eldecalcitol (ELD) in primary osteoporosis of women. METHODS: One hundred and forty-eight primary osteoporotic women were classified into 3 groups; 1) intravenous IBN combined with oral ELD (IBN + ELD group, N = 50; 81.8 ± 6.2 years), 2) oral MIN combined with oral ELD (MIN + ELD group, N = 50; 77.2 ± 6.9 years) and 3) oral ELD alone (ELD group, N = 48; 75.0 ± 8.3 years). For statistical analysis, L-BMD, H-BMD, serum corrected Ca, serum iP, intact-PTH, TRACP-5b, BAP, serum Hcy, eGFR and urine Ca/Cr ratio were measured until 12 months after the start of therapy. RESULTS: L-BMD values increased significantly in both IBN + ELD and MIN + ELD group, however, H-BMD increased significantly in the IBN + ELD group only. TRACP-5b values decreased rapidly during the first 6 months in both IBN + ELD and MIN + ELD group. However, BAP value in the IBN + ELD group decreased more gradually compared with that in the MIN + ELD group. Both serum Ca value and urine Ca/Cr ratio tended to increase, and the eGFR value decreased significantly in each group. CONCLUSIONS: IBN combined with ELD administration can act more effectively to increase BMD compared with MIN combined with ELD administration. Differences of decreasing rate in TRACP-5b and BAP value may lead to differences of increased rate of BMD in the IBN + ELD and MIN + ELD group. Because many cases of osteoporosis are elderly persons associated with chronic kidney disease, monitoring of kidney function and concentration of Ca in blood and urine is essential.

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.

Monthly minodronate inhibits bone resorption to a greater extent than does monthly risedronate

As a bisphosphonate, minodronate (MIN) is one of the strongest inhibitors of bone resorption. However, there have been no reports directly comparing the antiresorptive effects of monthly MIN with those of monthly risedronate (RIS). We enrolled 30 cases of osteoporosis (OP; 16 in the MIN group [mean age: 68.2 years] and 14 in the RIS group [mean age: 68.1 years]) to investigate the early effects of treatment by monthly MIN or RIS over a 4-month period using bone turnover marker values. Only female patients were enrolled to avoid gender bias. Urinary cross-linked N-telopeptide of type I collagen (NTX) before treatment and at 1, 2, and 4 months of therapy, as well as serum bone alkaline phosphatase and alkaline phosphatase before treatment and at 4 months afterwards, were evaluated. All bone turnover marker values were significantly decreased at 4 months in both groups. The changes in urinary NTX at the study end point for RIS and MIN were -30.1% and -63.1%, respectively. From 2 months of treatment, the antiresorptive effects on urinary NTX by MIN were significantly higher than those by RIS, indicating that MIN more immediately and strongly inhibited bone absorption. Thus, monthly MIN seems to suppress bone resorption faster and more strongly than RIS in OP treatment.