SHORT COMMUNICATION Long-term treatment of osteoporotic women with bisphosphonates does not impair the response to subsequently administered intravenous pamidronate M. P. Yavropoulou & N. A. T. Hamdy & S. E. Papapoulos Received: 18 December 2012 / Accepted: 28 January 2013 # International Osteoporosis Foundation and National Osteoporosis Foundation 2013 Abstract Summary We addressed the question whether the response of osteoporotic patients to bisphosphonate treatment is re- duced with time. Bisphosphonate-treated women with post- menopausal or glucocorticoid-induced osteoporosis showed adequate and consistent changes of bone markers to subse- quently administered intravenous pamidronate. Response of osteoporotic patients to bisphosphonates is not impaired during their long-term administration. Introduction Inadequate response to bisphosphonate treat- ment 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 osteo- porosis (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 mea- surement of the bone resorption marker C-terminal crosslinking telopeptide of type I collagen (CTX-I) on days1 and 4 and of the bone formation marker procollagen type I N propeptide, (P1NP) on day1 of every tri-monthly treatment course. Results With each treatment course there was a significant decrease in serum CTX-I on day4 and an increase to baseline values 3 months after each infusion in both PMO (mean values, day1: 291.33±160.78 pg/ml vs. day4: 131± 91.7 pg/ml, p <0.001) and GIOP (day1: 219.3±114.8 pg/ml vs. day4: 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 treat- ment is not responsible for treatment failure. Keywords Bisphosphonates . Bone turnover . Osteoporosis . Pamidronate . Treatment failure Introduction Due to their efficacy and favourable safety profile, bisphosphonates are considered the mainstay of treatment of osteoporosis. However, treatment failure represents a clinical- ly relevant but difficult to characterize problem mainly due to inability of existing parameters to define inadequate therapeu- tic responses. The subject was recently reviewed by an advi- sory committee of the International Osteoporosis Foundation (IOF) that recommended criteria for diagnosing treatment failures in clinical practice [1]. Inadequate responses to treat- ment with oral bisphosphonates are generally attributed to poor persistence with their long-term administration [2, 3]. In studies of patients with Paget’ s disease, impaired response or acquired resistance to consecutive treatments with bisphosphonate for recurrent disease has been reported for etidronate and pamidronate [4–7], but this has not been con- sidered as a cause of treatment failure in osteoporosis. Due to the specific action of bisphosphonates to reduce bone resorption and turnover, biochemical markers of bone turnover are commonly used to define responses to treatment in Paget’ s disease and osteoporosis. Longitudinal studies with oral or intravenous bisphosphonates have shown that the average values of bone turnover markers, after an initial M. P. Yavropoulou : N. A. T. Hamdy : S. E. Papapoulos (*) Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands e-mail: m.v.iken@lumc.nl Osteoporos Int DOI 10.1007/s00198-013-2301-1