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Summary: We addressed the question whether the response of osteoporotic patients to bisphosphonate treatment is reduced with time. Bisphosphonate-treated women with postmenopausal or glucocorticoid-induced osteoporosis showed adequate and consistent changes of bone markers to subsequently administered intravenous pamidronate. Response of osteoporotic patients to bisphosphonates is not impaired during their long-term administration. Introduction: Inadequate response to bisphosphonate treatment has been described in patients with Paget's disease of bone but has not been addressed in osteoporosis although treatment failure is a clinically relevant problem. Methods: Twenty one women with postmenopausal osteoporosis (PMO) aged 68 ± 8.2 years and 14 women with glucocorticoid-induced osteoporosis (GIOP) aged 65 ± 10 years were treated with tri-monthly intravenous infusions of 45 mg of pamidronate for 1 year. All patients had been previously treated with bisphosphonates (alendronate, risedronate, pamidronate) for a mean period of 6.2 years (range, 1.3-14 years). Blood samples were taken for measurement of the bone resorption marker C-terminal crosslinking telopeptide of type I collagen (CTX-I) on days 1 and 4 and of the bone formation marker procollagen type I N propeptide, (P1NP) on day 1 of every tri-monthly treatment course. Results: With each treatment course there was a significant decrease in serum CTX-I on day 4 and an increase to baseline values 3 months after each infusion in both PMO (mean values, day 1: 291.33 ± 160.78 pg/ml vs. day 4: 131 ± 91.7 pg/ml, p < 0.001) and GIOP (day 1: 219.3 ± 114.8 pg/ml vs. day 4: 98.8 ± 51.6 pg/ml, p < 0.001). Serum P1NP remained stable during the whole year of treatment. Conclusions: Long-term bisphosphonate treatment of women with either PMO or GIOP does not impair the response to subsequently administered intravenous pamidronate suggesting that inadequate response to long-term bisphosphonate treatment is not responsible for treatment failure. [ABSTRACT FROM AUTHOR]