Comparison of the effects of 12 months of monthly minodronate monotherapy and monthly minodronate combination therapy with vitamin K2 or eldecalcitol in patients with primary osteoporosis.

The aim of this observational, nonrandomized study was to compare the effects of 12 months of monthly minodronate (MIN; 50 mg/month) monotherapy and MIN combination therapy with vitamin K2 (VK; 45 mg/day) or eldecalcitol (ELD; 0.75 μg/day) in treatment-naïve patients with primary osteoporosis. Patients (n = 193; 178 postmenopausal women and 15 men; mean age 71.6 years) were treated with (1) MIN monotherapy (n = 63), (2) MIN plus VK combination therapy (n = 50), or (3) MIN plus ELD combination therapy (n = 80) for 12 months. Changes in bone mineral density (BMD) and the levels of serum bone turnover markers were monitored. No significant difference was observed in baseline BMD among the three groups. After 12 months, BMD increased by 2.93, 4.65, and 6.55 % in the lumbar spine, 0.66, 2.57, and 3.42 % in the total hip, and 0.05, 2.06, and 3.58 % in the femoral neck in groups 1, 2, and 3, respectively. The BMD increase induced by MIN plus ELD combination therapy was significantly greater than that induced by MIN monotherapy in the lumbar spine (P = 0.0002), total hip (P = 0.003), and femoral neck (P = 0.004), and also that induced by MIN plus VK combination therapy in the lumbar spine (P = 0.03). MIN plus ELD combination therapy compared with MIN monotherapy resulted in a greater decrease in serum procollagen type I N-terminal propeptide levels (-37.4 % vs -54.6 %; P = 0.001) and tartrate-resistant acid phosphatase isoform 5b levels (-41.1 % vs -52.9 %; P = 0.009) at 3 months, and a greater decrease in procollagen type I N-terminal propeptide levels (-64.3 % vs -50.3 %; P = 0.03) and a decrease in intact parathyroid hormone levels (-12.3 % vs 14.0 %; P = 0.01) at 12 months. Combination therapy with MIN and VK or ELD for 12 months showed additive effects in decreasing the levels of bone turnover markers compared with MIN monotherapy, whereas MIN plus ELD combination therapy resulted in the highest BMD increase compared with MIN monotherapy and MIN plus VK combination therapy.