Drugs & Aging

, Volume 29, Issue 2, pp 133–142 | Cite as

RETRACTED ARTICLE: Three-year Experience with Alendronate Treatment in Postmenopausal Osteoporotic Japanese Women with or without Renal Dysfunction

A Retrospective Study
  • Jun IwamotoEmail author
  • Yoshihiro Sato
  • Mitsuyoshi Uzawa
  • Tsuyoshi Takeda
  • Hideo Matsumoto
Original Research Article


Background and Objective: Chronic kidney disease is associated with an increased risk of fragility fractures. A retrospective study was conducted to compare outcomes after 3 years of alendronate treatment in postmenopausal osteoporotic Japanese women with or without renal dysfunction (RD).

Methods: One hundred and thirty-five postmenopausal osteoporotic Japanese women (mean age at baseline: 68 years) who had been treated with alendronate in our outpatient clinic for more than 3 years were analysed. The lumbar spine bone mineral density (BMD) of patients was measured using dual energy x-ray absorptiometry, and urinary levels of cross-linked N-terminal telopeptides of type I collagen (NTX) and serum levels of alkaline phosphatase (ALP) were monitored during the 3-year treatment period. The incidence of osteoporotic fractures was also assessed.

Results: Twenty-six women had RD with an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2. The urinary NTX and serum ALP levels significantly decreased and the lumbar spine BMD significantly increased, compared with the baseline values, in a manner that was similar among women with or without RD. However, the incidence of non-vertebral fractures, but not that of vertebral fractures, was significantly higher among women with RD than among women without RD.

Conclusions: Alendronate treatment appeared to have a similar effect on surrogate markers in postmenopausal osteoporotic Japanese women with or without RD. However, further studies are needed to confirm that RD may increase the risk of non-vertebral fractures in patients treated with alendronate.


Bone Mineral Density Vertebral Fracture Renal Dysfunction Alendronate Lumbar Spine Bone Mineral Density 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors report no funding sources or conflict of interest in this work.


  1. 1.
    Black DM, Cummings SR, Karpf DB, et al. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet 1996; 348: 1535–41CrossRefGoogle Scholar
  2. 2.
    Cummings SR, Black DM, Thompson DE, et al. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. JAMA 1998; 280: 2077–82CrossRefGoogle Scholar
  3. 3.
    Wells GA, Cranney A, Peterson J, et al. Alendronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev 2008; 23(1): CD001155Google Scholar
  4. 4.
    Kushida K, Shiraki M, Nakamura T, et al. The efficacy of alendronate in reducing the risk of vertebral fracture in Japanese patients with osteoporosis: a randomized, double-blind, active-controlled, double-dummy trial. Curr Ther Res Clin Exp 2002; 63: 606–20CrossRefGoogle Scholar
  5. 5.
    Kushida K, Shiraki M, Nakamura T, et al. Alendronate reduced vertebral fracture risk in postmenopausal Japanese women with osteoporosis: a 3-year follow-up study. J Bone Miner Metab 2004; 22: 462–8CrossRefGoogle Scholar
  6. 6.
    Shiraki M, Kushida K, Fukunaga M, et al. A double-masked multicenter comparative study between alendronate and alfacalcidol in Japanese patients with osteoporosis. Osteoporos Int 1999; 10: 183–92CrossRefGoogle Scholar
  7. 7.
    Uchida S, Taniguchi T, Shimizu T, et al. Therapeutic effects of alendronate 35 mg once weekly and 5 mg once daily in Japanese patients with osteoporosis: a double-blind, randomized study. J Bone Miner Metab 2005; 23: 382–8CrossRefGoogle Scholar
  8. 8.
    Iwamoto J, Miyata A, Sato Y, et al. Five-year alendronate treatment outcome in older postmenopausal Japanese women with osteoporosis or osteopenia and clinical risk factors for fractures. Ther Clin Risk Manag 2009; 5: 773–9CrossRefGoogle Scholar
  9. 9.
    Iwamoto J, Sato Y, Uzawa M, et al. Seven years’ experience with alendronate in postmenopausal Japanese women with osteoporosis. Ther Clin Risk Manag 2010; 6: 201–6CrossRefGoogle Scholar
  10. 10.
    Fried LF, Biggs ML, Shlipak MG, et al. Association of kidney function with incident hip fracture in older adults. J Am Soc Nephrol 2007; 18: 282–6CrossRefGoogle Scholar
  11. 11.
    Nickolas TL, McMahon DJ, Shane E. Relationship between moderate to severe kidney disease and hip fracture in the United States. J Am Soc Nephrol 2006; 17: 3223–32CrossRefGoogle Scholar
  12. 12.
    Nickolas TL, Leonard MB, Shane E. Chronic kidney disease and bone fracture: a growing concern. Kidney Int 2008; 74: 721–31CrossRefGoogle Scholar
  13. 13.
    West SL, Lok CE, Jamal SA. Fracture risk assessment in chronic kidney disease, prospective testing under real world environments (FRACTURE): a prospective study. BMC Nephrol 2010; 11: 17CrossRefGoogle Scholar
  14. 14.
    Kinsella S, Chavrimootoo S, Molloy MG, et al. Moderate chronic kidney disease in women is associated with fracture occurrence independently of osteoporosis. Nephron Clin Pract 2010; 116: c256–62CrossRefGoogle Scholar
  15. 15.
    Pitts TO, Piraino BH, Mitro R, et al. Hyperparathyroidism and 1,25-dihydroxyvitamin D deficiency in mild, moderate, and severe renal failure. J Clin Endocrinol Metab 1988; 67: 876–81CrossRefGoogle Scholar
  16. 16.
    Jamal SA, Bauer DC, Ensrud KE, et al. Alendronate treatment in women with normal to severely impaired renal function: an analysis of the Fracture Intervention Trial. J Bone Miner Res 2007; 22: 503–8CrossRefGoogle Scholar
  17. 17.
    Vervoort G, Willems HL, Wetzels FM, et al. Assessment of glomerular filtration rate in healthy subjects and normoalbuminuric diabetic patients: validity of a new (MDRD) prediction equation. Nephrol Dial Transplant 2002; 17: 1909–13CrossRefGoogle Scholar
  18. 18.
    Orimo H, Sugioka Y, Fukunaga M, et al. Diagnostic criteria of primary osteoporosis. J Bone Miner Metab 1998; 16: 139–50CrossRefGoogle Scholar
  19. 19.
    Orimo H, Hayashi Y, Fukunaga M, et al. Diagnostic criteria for primary osteoporosis: year 2000 revision. J Bone Miner Metab 2001; 19: 331–7CrossRefGoogle Scholar
  20. 20.
    Matsuo S, Imai E, Horio M, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kid Dis 2009; 53: 982–92CrossRefGoogle Scholar
  21. 21.
    Coresh J, Astor BC, Greene T, et al. Prevalence of chronic kidney disease and decreased kidney function in the adult US population. Am J Kid Dis 2003; 41: 1–12CrossRefGoogle Scholar
  22. 22.
    Iwamoto J, Takeda T, Sato Y, et al. Early changes in urinary cross-linked N-terminal telopeptides of type I collagen level correlate with one-year response of lumbar bone mineral density to alendronate in Japanese postmenopausal women with osteoporosis. J Bone Miner Metab 2005; 23: 238–42CrossRefGoogle Scholar
  23. 23.
    Nishizawa Y, Nakamura T, Ohta H, et al. Guidelines for the use of biochemical markers of bone turnover in osteoporosis (2004). J Bone Miner Metab 2005; 23: 97–104CrossRefGoogle Scholar
  24. 24.
    Ruggiero SL, Dodson TB, Assael LA, et al. American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws: 2009 update. J Oral Maxillofac Surg 2009; 67: 2–12CrossRefGoogle Scholar
  25. 25.
    Lo JC, O’Ryan FS, Gordon NP, et al. Prevalence of osteonecrosis of the jaw in patients with oral bisphosphonate exposure. J Oral Maxillofac Surg 2010; 68: 243–53CrossRefGoogle Scholar
  26. 26.
    Lenart BA, Lorich DG, Lane JM. Atypical fractures of the femoral diaphysis in postmenopausal women taking alendronate. N Engl J Med 2008; 358: 1304–6CrossRefGoogle Scholar
  27. 27.
    Rizzoli R, Akesson K, Bouxsein M, et al. Subtrochanteric fractures after long-term treatment with bisphosphonates: a European Society on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis, and International Osteoporosis Foundation Working Group report. Osteoporos Int 2011; 22: 373–90CrossRefGoogle Scholar
  28. 28.
    Giusti A, Hamdy NA, Papapoulos SE. Atypical fractures of the femur and bisphosphonate therapy: a systematic review of case/case series studies. Bone 2010; 47: 169–80CrossRefGoogle Scholar
  29. 29.
    Giusti A, Hamdy NA, Dekkers OM, et al. Atypical fractures and bisphosphonate therapy: a cohort study of patients with femoral fracture with radiographic adjudication of fracture site and features. Bone 2011 May 1; 48(5): 966–71CrossRefGoogle Scholar
  30. 30.
    Shane E, Burr D, Ebeling PR, et al. Atypical subtrochanteric and diaphyseal femoral fractures: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 2010; 25: 2267–94CrossRefGoogle Scholar
  31. 31.
    Pazianas M, Compston J, Huang CL. Atrial fibrillation and bisphosphonate therapy. J Bone Miner Res 2010; 25: 2–10CrossRefGoogle Scholar
  32. 32.
    Heckbert SR, Li G, Cummings SR, et al. Use of alendronate and risk of incident atrial fibrillation in women. Arch Intern Med 2008; 168: 826–31CrossRefGoogle Scholar
  33. 33.
    Pazianas M, Cooper C, Ebetino FH, et al. Long-term treatment with bisphosphonates and their safety in postmenopausal osteoporosis. Ther Clin Risk Manag 2010; 6: 325–43PubMedPubMedCentralGoogle Scholar
  34. 34.
    Vestergaard P, Schwartz K, Pinholt EM, et al. Risk of atrial fibrillation associated with use of bisphosphonates and other drugs against osteoporosis: a cohort study. Calcif Tissue Int 2010; 86: 335–42CrossRefGoogle Scholar
  35. 35.
    Lim SK, Kung AW, Sompongse S, et al. Vitamin D inadequacy in postmenopausal women in Eastern Asia. Curr Med Res Opin 2008; 24: 99–106CrossRefGoogle Scholar
  36. 36.
    Lips P, Duong T, Oleksik A, et al. A global study of vitamin D status and parathyroid function in postmenopausal women with osteoporosis: baseline data from the multiple outcomes of raloxifene evaluation clinical trial. J Clin Endocrinol Metab 2001; 86: 1212–21CrossRefGoogle Scholar
  37. 37.
    Malabanan AO, Holick MF. Vitamin D and bone health in postmenopausal women. J Womens Health (Larchmt) 2003; 12: 151–6CrossRefGoogle Scholar
  38. 38.
    Bischoff HA, Borchers M, Guadt F, et al. In situ detection of 1,25-dihydroxyvitamin D3 receptor in human skeletal muscle tissue. Histochem J 2001; 33: 19–24CrossRefGoogle Scholar
  39. 39.
    Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC, et al. Effect of vitamin D on falls: a meta-analysis. JAMA 2004; 291: 1999–2006CrossRefGoogle Scholar
  40. 40.
    Bischoff-Ferrari HA, Willett WC, Wong JB, et al. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA 2005; 293: 2257–64CrossRefGoogle Scholar
  41. 41.
    Bonjour JP, Rizzoli R, Caverzasio J. Phosphate homeostasis, 1, 25-dihydroxyvitamin-D3, and hyperparathyroidism in early chronic failure. Trends Endocrinol Metab 1992; 3: 301–5CrossRefGoogle Scholar
  42. 42.
    Reichel H, Deibert B, Schmidt-Gayk H, et al. Calcium metabolism in early chronic renal failure: implications for the pathogenesis of hyperparathyroidism. Nephrol Dial Transplant 1991; 6: 162–9CrossRefGoogle Scholar
  43. 43.
    Hochberg MC, Thompson DE, Black DM, et al. Effect of alendronate on the age-specific incidence of symptomatic osteoporotic fractures. J Bone Miner Res 2005; 20: 971–6CrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2012

Authors and Affiliations

  • Jun Iwamoto
    • 1
    Email author
  • Yoshihiro Sato
    • 2
  • Mitsuyoshi Uzawa
    • 3
  • Tsuyoshi Takeda
    • 1
  • Hideo Matsumoto
    • 1
  1. 1.Institute for Integrated Sports MedicineKeio University School of MedicineShinjuku-ku, TokyoJapan
  2. 2.Department of NeurologyMitate HospitalFukuokaJapan
  3. 3.Department of Orthopaedic SurgeryKeiyu Orthopaedic HospitalGunmaJapan

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