Abstract
Limited data are available on the safety and efficacy of anti-resorptive agents, particularly once-monthly bisphosphonates, for use in osteoporotic patients with chronic kidney disease (CKD). We conducted a post hoc analysis of data from a 12-month, randomized, double-blind, phase III study to evaluate the safety and efficacy of once-monthly risedronate (RIS-OM) 75 mg tablets in Japanese osteoporosis patients with mild-to-moderate CKD. Patients who received RIS-OM 75 mg were stratified by baseline estimated glomerular filtration rate (eGFR; ≥ 90, ≥ 60 to < 90, or ≥ 30 to < 60 mL/min/1.73 m2). Safety endpoints were incidence of adverse events (AEs) and percent change from baseline in eGFR, serum creatinine, calcium, and phosphorus. Efficacy endpoints were percent change from baseline in lumbar spine bone mineral density (BMD) and bone turnover markers (BTMs). In 420 patients included (age 67.7 ± 6.7 years, women 98.8%), the incidence of all AEs, gastrointestinal disorders, acute phase reaction, non-vertebral fractures, and renal and urinary disorders was not significantly different among subgroups. Interaction between subgroups and time was significant for eGFR (p = 0.010) and serum creatinine (p = 0.001) but considered to be regression to the mean and clinically insignificant. BMD significantly increased while BTMs significantly decreased from baseline with a similar degree of change among the subgroups. In conclusion, RIS-OM 75 mg showed consistent safety and efficacy in suppressing bone turnover and increasing BMD in Japanese primary osteoporosis patients with mild-to-moderate CKD. These results should, however, be interpreted with caution because the number of patients with moderate CKD was limited.
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References
Qaseem A, Forciea MA, McLean RM, Denberg TD (2017) Treatment of low bone density or osteoporosis to prevent fractures in men and women: a clinical practice guideline update from the American College of Physicians. Ann Intern Med 166:818–839
Compston J, Cooper A, Cooper C, Gittoes N, Gregson C, Harvey N, Hope S, Kanis JA, McCloskey EV, Poole KES, Reid DM, Selby P, Thompson F, Thurston A, Vine N (2017) UK clinical guideline for the prevention and treatment of osteoporosis. Arch Osteoporos 12:43
Japan Osteoporosis Society (2015) Guideline for prevention and treatment of osteoporosis (written in Japanese). https://www.josteo.com/ja/guideline/. Accessed 6 Nov 2017
Camacho PM, Petak SM, Binkley N, Clarke BL, Harris ST, Hurley DL, Kleerekoper M, Lewiecki EM, Miller PD, Narula HS, Pessah-Pollack R, Tangpricha V, Wimalawansa SJ, Watts NB (2016) American Association of Clinical Endocrinologists and American College of Endocrinology clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis—2016. Endocr Pract 22:1–42
Rossini M, Bianchi G, Di Munno O, Giannini S, Minisola S, Sinigaglia L, Adami S (2006) Determinants of adherence to osteoporosis treatment in clinical practice. Osteoporos Int 17:914–921
Cook PF, Emiliozzi S, McCabe MM (2007) Telephone counseling to improve osteoporosis treatment adherence: an effectiveness study in community practice settings. Am J Med Qual 22:445–456
Briesacher BA, Andrade SE, Harrold LR, Fouayzi H, Yood RA (2010) Adoption of once-monthly oral bisphosphonates and the impact on adherence. Am J Med 123:275–280
Kishimoto H, Maehara M (2015) Compliance and persistence with daily, weekly, and monthly bisphosphonates for osteoporosis in Japan: analysis of data from the CISA. Arch Osteoporos 10:231
Ohta H, Solanki J (2015) Incorporating bazedoxifene into the treatment paradigm for postmenopausal osteoporosis in Japan. Osteoporos Int 26:849–863
Lima GA, Paranhos Neto Fde P, Pereira GR, Gomes CP, Farias ML (2014) Osteoporosis management in patient with renal function impairment. Arq Bras Endocrinol Metabol 58:530–539
Nickolas TL, McMahon DJ, Shane E (2006) Relationship between moderate to severe kidney disease and hip fracture in the United States. J Am Soc Nephrol 17:3223–3232
Japanese Society of Nephrology (2014) Evidence-based clinical practice guideline for CKD 2013. Clin Exp Nephrol 18:346–423
Miller PD, Jamal SA, Evenepoel P, Eastell R, Boonen S (2013) Renal safety in patients treated with bisphosphonates for osteoporosis: a review. J Bone Miner Res 28:2049–2059
Miller PD (2011) The kidney and bisphosphonates. Bone 49:77–81
Bock O, Boerst H, Thomasius FE, Degner C, Stephan-Oelkers M, Valentine SM, Felsenberg D (2007) Common musculoskeletal adverse effects of oral treatment with once weekly alendronate and risedronate in patients with osteoporosis and ways for their prevention. J Musculoskelet Neuronal Interact 7:144–148
Reid IR, Gamble GD, Mesenbrink P, Lakatos P, Black DM (2010) Characterization of and risk factors for the acute-phase response after zoledronic acid. J Clin Endocrinol Metab 95:4380–4387
Miller PD, McClung MR, Macovei L, Stakkestad JA, Luckey M, Bonvoisin B, Reginster JY, Recker RR, Hughes C, Lewiecki EM, Felsenberg D, Delmas PD, Kendler DL, Bolognese MA, Mairon N, Cooper C (2005) Monthly oral ibandronate therapy in postmenopausal osteoporosis: 1-year results from the MOBILE study. J Bone Miner Res 20:1315–1322
Delmas PD, McClung MR, Zanchetta JR, Racewicz A, Roux C, Benhamou CL, Man Z, Eusebio RA, Beary JF, Burgio DE, Matzkin E, Boonen S (2008) Efficacy and safety of risedronate 150 mg once a month in the treatment of postmenopausal osteoporosis. Bone 42:36–42
Hagino H, Kishimoto H, Ohishi H, Horii S, Nakamura T (2014) Efficacy, tolerability and safety of once-monthly administration of 75 mg risedronate in Japanese patients with involutional osteoporosis: a comparison with a 2.5 mg once-daily dosage regimen. Bone 59:44–52
Wilson LM, Rebholz CM, Jirru E, Liu MC, Zhang A, Gayleard J, Chu Y, Robinson KA (2017) Benefits and harms of osteoporosis medications in patients with chronic kidney disease: a systematic review and meta-analysis. Ann Int Med 166:649–658
Jamal SA, Bauer DC, Ensrud KE, Cauley JA, Hochberg M, Ishani A, Cummings SR (2007) Alendronate treatment in women with normal to severely impaired renal function: an analysis of the fracture intervention trial. J Bone Miner Res 22:503–508
Miller PD, Roux C, Boonen S, Barton IP, Dunlap LE, Burgio DE (2005) Safety and efficacy of risedronate in patients with age-related reduced renal function as estimated by the Cockcroft and Gault method: a pooled analysis of nine clinical trials. J Bone Miner Res 20:2105–2115
Shigematsu T, Muraoka R, Sugimoto T, Nishizawa Y (2017) Risedronate therapy in patients with mild-to-moderate chronic kidney disease with osteoporosis: post hoc analysis of data from the risedronate phase III clinical trials. BMC Nephrol 18:66
Uyama Y, Shibata T, Nagai N, Hanaoka H, Toyoshima S, Mori K (2005) Successful bridging strategy based on ICH E5 guideline for drugs approved in Japan. Clin Pharmacol Ther 78:102–113
Ogura Y, Gonsho A, Cyong JC, Orimo H (2004) Clinical trial of risedronate in Japanese volunteers: single and multiple oral dose studies. J Bone Miner Metab 22:111–119
Orimo H, Hayashi Y, Fukunaga M, Sone T, Fujiwara S, Shiraki M, Kushida K, Miyamoto S, Soen S, Nishimura J, Oh-Hashi Y, Hosoi T, Gorai I, Tanaka H, Igai T, Kishimoto H (2001) Diagnostic criteria for primary osteoporosis: year 2000 revision. J Bone Miner Metab 19:331–337
Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, Yamagata K, Tomino Y, Yokoyama H, Hishida A (2009) Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis 53:982–992
KDIGO (2012) Clinical practice guideline for the evaluation and management of chronic kidney disease. Chapter 1: definition and classification of CKD. Kidney Int Suppl 3:19–62
Satterthwaite FE (1946) An approximate distribution of estimates of variance components. Biom Bull 2:110–114
Mitchell DY, St Peter JV, Eusebio RA, Pallone KA, Kelly SC, Russell DA, Nesbitt JD, Thompson GA, Powell JH (2000) Effect of renal function on risedronate pharmacokinetics after a single oral dose. Br J Clin Pharmacol 49:215–222
Bertoldo F, Pancheri S, Zenari S, Boldini S, Giovanazzi B, Zanatta M, Valenti MT, Dalle Carbonare L, Lo Cascio V (2010) Serum 25-hydroxyvitamin D levels modulate the acute-phase response associated with the first nitrogen-containing bisphosphonate infusion. J Bone Miner Res 25:447–454
Barnett AG, van der Pols JC, Dobson AJ (2005) Regression to the mean: what it is and how to deal with it. Int J Epidemiol 34:215–220
Wheater G, Elshahaly M, Tuck SP, Datta HK, van Laar JM (2013) The clinical utility of bone marker measurements in osteoporosis. J Transl Med 11:201
Yamada S, Inaba M, Kurajoh M, Shidara K, Imanishi Y, Ishimura E, Nishizawa Y (2008) Utility of serum tartrate-resistant acid phosphatase (TRACP5b) as a bone resorption marker in patients with chronic kidney disease: independence from renal dysfunction. Clin Endocrinol 69:189–196
Fahrleitner-Pammer A, Herberth J, Browning SR, Obermayer-Pietsch B, Wirnsberger G, Holzer H, Dobnig H, Malluche HH (2008) Bone markers predict cardiovascular events in chronic kidney disease. J Bone Miner Res 23:1850–1858
Imai E, Horio M, Watanabe T, Iseki K, Yamagata K, Hara S, Ura N, Kiyohara Y, Moriyama T, Ando Y, Fujimoto S, Konta T, Yokoyama H, Makino H, Hishida A, Matsuo S (2009) Prevalence of chronic kidney disease in the Japanese general population. Clin Exp Nephrol 13:621–630
Acknowledgements
This study was supported by the Joint Development Program of EA Pharma Co., Ltd. and Takeda Pharmaceutical Co., Ltd. Medical writing services were provided by Mami Hirano, MS, of Cactus Communications, and funded by EA Pharma Co., Ltd. Support for statistical analysis was provided by Ryoichi Muraoka, DVM, of Asklep, and funded by EA Pharma Co., Ltd.
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TSu, DI (guarantor), TSh, and YN designed the study. MM designed the study and contributed to the conduct of the study and data acquisition and interpretation. IO was responsible for statistical analysis and data interpretation. All authors critically reviewed the paper for intellectual content and approved the final version. All authors agree to be accountable for the work and to ensure that any questions related to the accuracy and integrity of the paper will be investigated and properly resolved.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Informed consent was obtained from all individual participants included in the study.
Conflict of interest
Dr. Toshitsugu Sugimoto has received research grants from Eli Lilly Japan, Taisho Toyama Pharmaceutical, Chugai Pharmaceutical, Daiichi-Sankyo Co., Astellas Pharma, and Eisai, as well as consulting fee from Asahi-Kasei Pharma Co. Dr. Daisuke Inoue reports personal fees from EA Pharma and grants from Astellas Pharma, Asahi-Kasei Pharma, Chugai Pharmaceutical, Daiichi-Sankyo Co., EA Pharma, Eli Lilly Japan, Eisai, Pfizer, Ono Pharmaceutical, Taisho Toyama Pharmaceutical, Takeda Pharmaceutical, and Teijin Pharma, outside the submitted work. Mr. Masayuki Maehara and Mr. Ichiro Oikawa are full-time employees of EA Pharma. Dr. Takashi Shigematsu has received consultant fees from EA pharma and Takeda pharmaceutical. Dr. Yoshiki Nishizawa has no conflicts of interest to disclose.
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774_2018_977_MOESM1_ESM.tif
Percent change from baseline in a eGFR, b serum creatinine, c serum calcium, d serum phosphorus in the overall population (mean ± SD). *Significantly (p < 0.05) different from baseline. Ca calcium, Cre creatinine, eGFR estimated glomerular filtration rate, P phosphorus, SD standard deviation (TIF 2571 KB)
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Sugimoto, T., Inoue, D., Maehara, M. et al. Efficacy and safety of once-monthly risedronate in osteoporosis subjects with mild-to-moderate chronic kidney disease: a post hoc subgroup analysis of a phase III trial in Japan. J Bone Miner Metab 37, 730–740 (2019). https://doi.org/10.1007/s00774-018-0977-1
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DOI: https://doi.org/10.1007/s00774-018-0977-1