35 ± 1.09 17 1.34 ± 1.55 15 1.33 ± 1.03 12 −0.27 (−0.84, 0.62) 0.3079 −0.07 (−0.72, 0.96) 0.8075 Osteoid surface/bone surface, % 6.38 ± 3.54 17 8.69 ± 8.62 15 9.21 ± 7.60 12 0.24 (−3.37, 5.94) 0.8651 0.59 (−1.60, 5.21) 0.6902 Bone formation rate/bone surface (double + half single tetracycline label), μm3/μm2/day 0.0072 ± 0.0055 16 0.0059 ± 0.0076 13 0.0070 ± 0.0043 11 −0.0017 (−0.0058, 0.0013) 0.1476 −0.0001
(−0.0038, 0.0046) 0.9214 Eroded (resorption) surface/bone surface, % 1.57 ± 0.94 17 1.21 ± 0.49 15 1.81 ± 0.80 12 −0.21 (−0.93, Selleckchem Tariquidar 0.25) 0.4168 0.30 (−0.54, 0.92) 0.3190 Activation frequency (double + half single tetracycline label), per year 0.09 ± 0.07 16 0.08 ± 0.11 13 0.09 ± 0.06 11 −0.02 (−0.07, 0.02) 0.2010 0.01 (−0.04, 0.06) 0.7854 Bone mineralization parameters Osteoid thickness, μm 5.8 ± 0.9 17 5.2 ± 0.8 15 5.3 ± 0.6 12 −0.6 (−1.1, 0.0) 0.0337 −0.3 (−1.0, 0.2) 0.2221 Osteoid volume/bone volume, % 0.81 ± 0.63 17 0.99 ± 1.22 15 0.97 ± 0.96 12 −0.08 (−0.43, 0.49) 0.6101 0.00 (−0.31, 0.56) 1.000 Mineral apposition rate, μm/day 0.47 ± 0.11 16 0.45 ± 0.16 13 0.50 ± 0.15 11 −0.04 (−0.14, 0.08) 0.3913 0.03 (−0.10, 0.14) 0.5870 Mineralization lag time (double + half single tetracycline label), days 91.8 ± 85.0
16 108.0 ± 91.3 13 131.7 ± 172.7 11 16.3 SC79 (−24.1, 68.0) 0.4560 7.9 (−39.0, 53.7) 0.6930 a P value from Wilcoxon rank sum test Discussion Risedronate 5 mg IR daily significantly reduces
the incidence of major fragility fractures in women with postmenopausal osteoporosis and of vertebral fractures in subjects receiving glucocorticoids [11–14]. Fracture risk reduction occurs within Selleck CA4P months of beginning therapy and appears to persist with treatment for at least 17-DMAG (Alvespimycin) HCl 7 years [15–17]. Weekly and monthly IR dosing forms of risedronate were developed to make dosing more convenient and acceptable and in the hope of improving persistence with treatment [18, 19]. However, all of these regimens, like other oral bisphosphonate dosing schedules, require dosing at least 30 min before food or drink. Even taking oral bisphosphonates with tap water or bottled water can decrease bioavailability [20]. None of the current oral bisphosphonate dosing schemes solves the possible detrimental effect of poor compliance with dosing instructions on bisphosphonate absorption and clinical effectiveness. That the impact of poor compliance can be important was demonstrated by the significant blunting of the BMD response to risedronate IR given between meals compared to being taken before breakfast [21]. The unique risedronate weekly DR formulation, consisting of both the addition of a chelating agent and the enteric coating, promotes disintegration of the tablet in the small intestine. This formulation obviates the food effect and minimizes the concern about poor compliance.