Effect of high doses of oral risedronate (20 mg/day) on serum parathyroid hormone levels and urinary collagen cross-link excretion in postmenopausal women with spinal osteoporosis

The present study describes the biological effects of rise-dronate, a pyrid inyl bisphosphonate, on bone and assesses the safety and tolerability of ri sedronate when given at high doses, with or without calcium, to postmenopau sal women with spinal osteoporosis. This single-center descriptive, double- blind, placebo-controlled, randomized, parallel group study included 32 pos tmenopausal white women with at least one radiographically confirmed verteb ral compression fracture. Patients were randomized to one of four different dose regimen groups: (i) R-P, risedronate 20 mg/day for 14 days, followed by placebo for 42 days; (ii) R-CP-P, risedronate 20 mg/day for 14 days, fol lowed by elemental calcium 1000 mg/day and placebo for 14 days, then by pla cebo for 28 days; (iii) R-CP-R-CP, risedronate 20 mg/day for 7 days, follow ed by elemental calcium 1000 mg/day and placebo for 21 days, then risedrona te 20 mg/day for 7 days, and finally elemental calcium 1000 mg/day and plac ebo for 21 days; and (iv) P, placebo for 56 days. The biological response w as investigated by measuring serum calcium, parathyroid hormone (PTH), and 2 h urinary pyridinoline/creatinine (Pyr/Cr) and deoxypyridinoline/creatini ne (DPyr/Cr) ratios at baseline and at days 3, 7, 14, 21, 28, 35, 42, 49, 5 6, and 84. Overall, there were no consistent trends observed between the ac tive group and placebo for serum calcium. In groups R-P, R-CP-P, and R-CP-R -CP, mean serum PTH levels were elevated above baseline values for the enti re 56 day treatment period and remained elevated, although to a lesser exte nt, at the day 84 follow-up visit. The effect of calcium supplementation on PTH was variable. Urinary Pyr/Cr and DPyr/Cr ratios were decreased from ba seline over the entire study period in all groups receiving risedronate. Th e maximum observed percent decreases from baseline for Pyr/Cr and DPyr/Cr w ere -46.9% and -58.8%, respectively, at day 49 in the R-CPR-CP group. In co nclusion, risedronate given orally at a dose of 20 mg/day, continuously for 7 or 14 days, resulted in the expected biological response in osteoporotic women. The time course of changes in PTH levels following cessation of dos ing was unaffected by calcium supplementation. There was no evidence of a P TH-mediated rebound in bone resorption following cessation of therapy. Furt hermore, based on collagen cross-link data, patients did not show an excess ive reduction in bone turnover. (C) 2001 by Elsevier Science Inc. All right s reserved.