Abstract
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.
References
Diez-Perez A, Adachi JD, Agnusdei D, Bilezikian JP, Compston JE, Cummings SR, Eastell R, Eriksen EF, Gonzalez-Macias J, Liberman UA, Wahl DA, Seeman E, Kanis JA, Cooper C, The IOF CSA Inadequate Responders Working Group (2012) Treatment failure in osteoporosis. Osteoporos Int 23(12):2769–74. doi:10.1007/s00198-012-2093-8
Adami S, Isaia G, Minisola S, Sinigaglia L, Gentilella R, Agnusdei D, Iori N, Nuti R, ICARO Study Group (2006) Fracture incidence and characterization in patients on osteoporosis treatment: the ICARO study. J Bone Miner Res 21:1565–1570
Díez-Pérez A, Olmos JM, Nogués X, Sosa M, Díaz-Curiel M, Pérez-Castrillón JL, Pérez-Cano R, Muñoz-Torres M, Torrijos A, Jodar E, Del Rio L, Caeiro-Rey JR, Farrerons J, Vila J, Arnaud C, González-Macías J (2012) Risk factors for prediction of inadequate response to antiresorptives. J Bone Miner Res 27:817–824
Altman RD (1985) Long-term follow-up of therapy with intermittent etidronate disodium in Paget’s disease of bone. Am J Med 79:583–590
Gutteridge DH, Ward LC, Stewart GO, Retallack RW, Will RK, Prince RL, Criddle A, Bhagat CI, Stuckey BG, Price RI, Kent GN, Faulkner DL, Geelhoed E, Gan SK, Vasikaran S (1999) Paget’s disease: acquired resistance to one aminobisphosphonate with retained response to another. J Bone Miner Res 14:79–84
Trombetti A, Arlot M, Thevenon J, Uebelhart B, Meunier PJ (1999) Effect of multiple intravenous pamidronate courses in Paget’s disease of bone. Rev Rhum Engl Ed 66:467–476
Papapoulos SE, Eekhoff EM, Zwinderman AH (2006) Acquired resistance to bisphosphonates in Paget's disease of bone. J Bone Miner Res 21(Suppl 2):P88–91
Bone HG, Hosking D, Devogelaer JP, Tucci JR, Emkey RD, Tonino RP, Rodriguez-Portales JA, Downs RW, Gupta J, Santora AC, Liberman UA, Alendronate Phase III Osteoporosis Treatment Study Group (2004) Ten years' experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med 350:1189–99
Mellström DD, Sörensen OH, Goemaere S, Roux C, Johnson TD, Chines AA (2004) Seven years of treatment with risedronate in women with postmenopausal osteoporosis. Calcif Tissue Int 75:462–8
Black DM, Reid IR, Boonen S, Bucci-Rechtweg C, Cauley JA, Cosman F, Cummings SR, Hue TF, Lippuner K, Lakatos P, Leung PC, Man Z, Martinez RL, Tan M, Ruzycky ME, Su G, Eastell R (2012) The effect of 3 versus 6 years of zoledronic acid treatment of osteoporosis: a randomized extension to the HORIZON-Pivotal Fracture Trial (PFT). J Bone Miner Res 27:243–54
Miller PD, Recker RR, Reginster JY, Riis BJ, Czerwinski E, Masanauskaite D, Kenwright A, Lorenc R, Stakkestad JA, Lakatos P (2012) Efficacy of monthly oral ibandronate is sustained over 5 years: the MOBILE long-term extension study. Osteoporos Int 23:1747–56
Iba K, Takada J, Hatakeyama N, Ozasa Y, Wada T, Yamashita T (2008) Changes in urinary NTX levels in patients with primary osteoporosis undergoing long-term bisphosphonate treatment. J Orthop Sci 13:438–41
van Beek ER, Cohen LH, Leroy IM, Ebetino FH, Löwik CW, Papapoulos SE (2003) Differentiating the mechanisms of antiresorptive action of nitrogen containing bisphosphonates. Bone 33:805–11
Cauza E, Etemad M, Winkler F, Hanusch-Enserer U, Partsch G, Noske H, Dunky A (2004) Pamidronate increases bone mineral density in women with postmenopausal or steroid-induced osteoporosis. J Clin Pharm Ther 29:431–6
Hernández MV, Peris P, Monegal A, Reyes R, Muxi A, Gifre L, Guañabens N (2010) Effects of intravenous pamidronate on renal function, bone mineral metabolism and bone mass in patients with severe osteoporosis. Am J Med Sci 339:225–9
Makras P, Hamdy NAT, Zwinderman AH, Ballieux BEPB, Papapoulos SE (2009) Bisphosphonate dose and incidence of fractures in postmenopausal osteoporosis. Bone 44:766–71
McClung M, Recker R, Miller P, Fiske D, Minkoff J, Kriegman A, Zhou W, Adera M, Davis J (2007) Intravenous zoledronic acid 5 mg in the treatment of postmenopausal women with low bone density previously treated with alendronate. Bone 41:122–8
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Yavropoulou, M.P., Hamdy, N.A.T. & Papapoulos, S.E. Long-term treatment of osteoporotic women with bisphosphonates does not impair the response to subsequently administered intravenous pamidronate. Osteoporos Int 24, 2353–2357 (2013). https://doi.org/10.1007/s00198-013-2301-1
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DOI: https://doi.org/10.1007/s00198-013-2301-1