This trial was conducted to investigate the long-term effects of proton pump inhibitor (PPI) coadministration on the efficacy of weekly risedronate treatment for osteoporosis. Ninety-six women over 50 years old with low bone mineral density (BMD) participated in this trial. Subjects were randomly divided into 2 groups: a 17.5？mg dose of sodium risedronate was administered weekly, with or without a daily 10？mg dose of sodium rabeprazole ( and 47 in the BP + PPI and BP groups, resp.). The following biomarkers were measured at the baseline and every 3 months: bone-specific alkaline phosphatase, N-terminal telopeptide of type I collagen corrected for creatinine, parathyroid hormone, BMD of the lumbar spine, and physical parameters evaluated according to the SF-36v2 Health Survey. Statistical comparisons of these parameters were performed after 6, 12, 18, and 24 months. The Δ values of improvement in physical functioning after 12 months and bodily pain after 6 and 12 months in the BP + PPI group were significantly larger than those in the BP group. These results suggest that PPI does not adversely affect bone metabolism. Alternatively, approved bone formation by concomitant PPI treatment may have had favorable effects on the improvement of bodily pain and physical functions. 1. Introduction Various types of therapeutic products for osteoporosis have been developed. Among them, bisphosphonate (BP) is currently the most commonly prescribed drug for the treatment of osteoporosis. This compound can selectively inhibit osteoclast-mediated bone resorption, thereby resulting in an increase in bone mineral density (BMD). Pyridinyl BP risedronate ([1-hydroxy-2-(3-pyridinyl)-ethylidene] bis[phosphonic acid] monosodium salt) in the risedronate group is effective for the treatment of postmenopausal osteoporosis and reduces the risk of vertebral fracture within the first year of treatment [1, 2]. Gastrointestinal medicine is occasionally used to prevent upper gastrointestinal (GI) tract adverse events for the prolonged administration of risedronate. It is reported that the infusion of ranitidine, which is a histamine H2-receptor antagonist that inhibits stomach acid production, increases the gastric pH and doubles the bioavailability of 4-amino-1-hydroxybutylidene-1,1-bisphosphonate monosodium [3]. Hence, it is expected that risedronate administered in combination with a proton pump inhibitor (PPI) may be more effective than the administration of risedronate alone in inhibiting bone resorption and treating osteoporosis as well as preventing GI tract adverse events.
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