Skip to main content

Advertisement

SpringerLink
Log in

Effects of raloxifene on bone metabolism in postmenopausal women on chronic hemodialysis

  • Original Article
  • Published:
Clinical and Experimental Nephrology Aims and scope Submit manuscript

Abstract

Background

Postmenopausal women with end-stage renal failure are at an increased risk of fracture because of the effects of secondary hyperparathyroidism and postmenopausal osteoporosis. In the present study, we investigated the feasibility of using raloxifene to prevent fractures in postmenopausal women with end-stage renal failure on hemodialysis.

Methods

This study was conducted using a multicenter, single-arm, prospective design. Raloxifene was administered to postmenopausal women aged ≥50 years who were on maintenance hemodialysis and met any of the following criteria after a 24-week run-in period: an alkaline phosphatase level (bone formation marker) of ≥6.18 µkat/L (≥370 U/L), a bone-specific alkaline phosphatase (BAP; bone formation marker) level of ≥0.59 µkat/L (≥35.4 U/L), or a bone-derived tartrate-resistant acid phosphatase (TRACP-5b; bone resorption marker) level of ≥4.2 U/L.

Results

A total of 48 individuals were eligible for study inclusion. Of them, 30 individuals participated in this study. The BAP levels were significantly decreased at week 4, but returned to the baseline levels at week 24. Similarly, the TRACP-5b levels were significantly decreased at week 4, but returned to the baseline levels at week 24. The serum calcium value decreased consistently after the start of raloxifene therapy. The intact parathyroid hormone (iPTH) levels were likely increased at week 4. The ratio of BAP to iPTH levels and the ratio of TRACP-5b to iPTH levels both showed significant decreases over time. During the raloxifene therapy, no thrombosis or other drug-related adverse events developed.

Conclusion

The study results indicated that raloxifene can transiently reduce the levels of bone metabolism markers and might be useful for preventing fractures in postmenopausal women with end-stage renal failure, although raloxifene use over the long term may not have adequate efficacy in the absence of appropriate concomitant active vitamin D therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Atsumi K, Kushida K, Yamazaki K, Shimizu S, Ohmura A, Inoue T. Risk factors for vertebral fractures in renal osteodystrophy. Am J Kidney Dis. 1999;33:287–93.

    Article  CAS  PubMed  Google Scholar 

  2. Alem AM, Sherrard DJ, Gillen DL, Weiss NS, Beresford SA, Heckbert SR, Wong C, Stehman-Breen C. Increased risk of hip fracture among patients with end-stage renal disease. Kidney Int. 2000;58:396–9.

    Article  CAS  PubMed  Google Scholar 

  3. Arneson TJ, Li S, Liu J, Kilpatrick RD, Newsome BB, St Peter WL. Trends in hip fracture rates in US hemodialysis patients, 1993–2010. Am J Kidney Dis. 2013;62:747–54.

    Article  PubMed  Google Scholar 

  4. Jadoul M, Albert JM, Akiba T, Akizawa T, Arab L, Bragg-Gresham JL, Mason N, Prutz KG, Young EW, Pisoni RL. Incidence and risk factors for hip or other bone fractures among hemodialysis patients in the dialysis outcomes and practice patterns study. Kidney Int. 2006;7:1358–66.

    Article  Google Scholar 

  5. Fukagawa M, Yokoyama K, Koiwa F, Taniguchi M, Shoji T, Kazama JJ, Komaba H, Ando R, Kakuta T, Fujii H, Nakayama M, Shibagaki Y, Fukumoto S, Fujii N, Hattori M, Ashida A, Iseki K, Shigematsu T, Tsukamoto Y, Tsubakihara Y, Tomo T, Hirakata H, Akizawa T, CKD-MBD Guideline Working Group; Japanese Society for Dialysis Therapy. Clinical practice guideline for the management of chronic kidney disease-mineral and bone disorder. Ther Apher Dial. 2013;17:247–88.

    Article  PubMed  Google Scholar 

  6. National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis. 2003;42(4 Suppl 3):S1–201.

    Google Scholar 

  7. Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int Suppl. 2009;113:S1–130.

    Google Scholar 

  8. Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK, Christiansen C, Delmas PD, Zanchetta JR, Stakkestad J, Glüer CC, Krueger K, Cohen FJ, Eckert S, Ensrud KE, Avioli LV, Lips P, Cummings SR. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple outcomes of raloxifene evaluation (MORE) investigators. JAMA. 1999;282:637–45.

    Article  CAS  PubMed  Google Scholar 

  9. Hernández E, Valera R, Alonzo E, Bajares-Lilue M, Carlini R, Capriles F, Martinis R, Bellorin-Font E, Weisinger JR. Effects of raloxifene on bone metabolism and serum lipids in postmenopausal women on chronic hemodialysis. Kidney Int. 2003;63:2269–74.

    Article  PubMed  Google Scholar 

  10. Eriguchi R, Umakoshi J, Miura S, Sato Y. Raloxifene ameliorates progressive bone loss in postmenopausal dialysis patients with controlled parathyroid hormone levels. Clin Nephrol. 2009;72:423–9.

    Article  CAS  PubMed  Google Scholar 

  11. Tanaka M, Itoh K, Matsushita K, Matsushita K, Moriishi M, Kawanishi H, Fukagawa M. Effects of raloxifene on bone mineral metabolism in postmenopausal Japanese women on hemodialysis. Ther Apher Dial. 2011;15(Suppl 1):62–6.

    Article  CAS  PubMed  Google Scholar 

  12. Saito O, Saito T, Asakura S, Sugase T, Ito C, Ando Y, Muto S, Kusano E. The effects of raloxifene on bone turnover markers and bone mineral density in women on maintenance hemodialysis. Clin Exp Nephrol. 2011;15:126–31.

    Article  CAS  PubMed  Google Scholar 

  13. Guideline Working Group, Japanese Society for Dialysis Therapy. Clinical practice guideline for the management of secondary hyperparathyroidism in chronic dialysis patients. Ther Apher Dial. 2008;12:514–25.

    Article  Google Scholar 

  14. Payne RB, Little AJ, Williams RB, Milner JR. Interpretation of serum calcium in patients with abnormal serum proteins. Br Med J. 1973;4:643–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499–502.

    CAS  PubMed  Google Scholar 

  16. NIH Consensus Development Panel on Osteoporosis Prevention. Diagnosis, and therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA. 2001;285:785–95.

    Article  Google Scholar 

  17. Ureña P, Bernard-Poenaru O, Ostertag A, Baudoin C, Cohen-Solal M, Cantor T, de Vernejoul MC. Bone mineral density, biochemical markers and skeletal fractures in haemodialysis patients. Nephrol Dial Transpl. 2003;18:2325–31.

    Article  Google Scholar 

  18. Delmas PD, Eastell R, Garnero P, Seibel MJ, Stepan J, Committee of Scientific Advisors of the International Osteoporosis Foundation. The use of biochemical markers of bone turnover in osteoporosis. Committee of Scientific Advisors of the International Osteoporosis Foundation. Osteoporos Int. 2000;11(Suppl 6):S2–17.

    Article  PubMed  Google Scholar 

  19. Fletcher S, Jones RG, Rayner HC, Harnden P, Hordon LD, Aaron JE, Oldroyd B, Brownjohn AM, Turney JH, Smith MA. Assessment of renal osteodystrophy in dialysis patients: use of bone alkaline phosphatase, bone mineral density and parathyroid ultrasound in comparison with bone histology. Nephron. 1997;75:412–9.

    Article  CAS  PubMed  Google Scholar 

  20. Chu P, Chao TY, Lin YF, Janckila AJ, Yam LT. Correlation between histomorphometric parameters of bone resorption and serum type 5b tartrate-resistant acid phosphatase in uremic patients on maintenance hemodialysis. Am J Kidney Dis. 2003;41:1052–9.

    Article  CAS  PubMed  Google Scholar 

  21. Hamano T, Tomida K, Mikami S, Matsui I, Fujii N, Imai E, Rakugi H, Isaka Y. Usefulness of bone resorption markers in hemodialysis patients. Bone. 2009;45(Suppl 1):S19–25.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Katsuyuki Nagatoya and Toru Inoue report receiving Grant support from Chugai Pharmaceutical Co., Ltd.

Conflict of interest

The other authors report no conflict of interest.

Author information

Authors and Affiliations

  1. Blood Purification Center, Osaka Medical College Hospital, Takatsuki, Japan

    Katsuyuki Nagatoya

  2. Department of Laboratory Medicine, Osaka Rosai Hospital, 1179-3 Nagasone-cho, Sakai, Osaka, 591-8025, Japan

    Katsuyuki Nagatoya

  3. Nishimoto Clinic, Hirakata, Japan

    Kazuhiko Nishimoto

  4. Arisawa General Hospital, Hirakata, Japan

    Nobuhisa Shibahara

  5. Department of Nephrology, Takatsuki General Hospital, Takatsuki, Japan

    Toshikazu Takahashi

  6. Kanehara Clinic, Takatsuki, Japan

    Hironori Kanehara

  7. Sanko Clinic, Ibaraki, Japan

    Nobuyuki Ueno

  8. Sanko Fuzoku Clinic, Takatsuki, Japan

    Hideaki Yasuda

  9. Okada Clinic, Osaka, Japan

    Shigeki Okada

  10. Kamo Hospital, Kyoto, Japan

    Haruhiko Ueda

  11. Sanko Clinic, Takatsuki, Japan

    Kei Hirai

  12. Department of Internal Medicine, General Hospital Higashikouri, Hirakata, Japan

    Toru Inoue

Authors
  1. Katsuyuki Nagatoya
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kazuhiko Nishimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nobuhisa Shibahara
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Toshikazu Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hironori Kanehara
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nobuyuki Ueno
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hideaki Yasuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Shigeki Okada
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Haruhiko Ueda
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Kei Hirai
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Toru Inoue
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

Hokusetsu Renal Osteodystrophy Study Group

Corresponding author

Correspondence to Katsuyuki Nagatoya.

Electronic supplementary material

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nagatoya, K., Nishimoto, K., Shibahara, N. et al. Effects of raloxifene on bone metabolism in postmenopausal women on chronic hemodialysis. Clin Exp Nephrol 19, 939–946 (2015). https://doi.org/10.1007/s10157-014-1065-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10157-014-1065-z

Keywords

Search

Navigation