Advertisement

Journal of Bone and Mineral Metabolism

, Volume 32, Issue 5, pp 484–493 | Cite as

Lanthanum carbonate stimulates bone formation in a rat model of renal insufficiency with low bone turnover

  • Toshio Fumoto
  • Masako Ito
  • Kyoji Ikeda
Original Article
  • 485 Downloads

Abstract

Control of phosphate is important in the management of chronic kidney disease with mineral and bone disorder (CKD-MBD), for which lanthanum carbonate, a non-calcium phosphate-binding agent, has recently been introduced; however, it remains to be determined whether it has any beneficial or deleterious effect on bone remodeling. In the present study, the effects of lanthanum carbonate were examined in an animal model that mimics low turnover bone disease in CKD, i.e., thyroparathyroidectomized (TPTX) and 5/6 nephrectomized (NX) rats undergoing a constant infusion of parathyroid hormone (PTH) and thyroxine injections (TPTX-PTH-5/6NX). Bone histomorphometry at the second lumbar vertebra and tibial metaphysis revealed that both bone formation and resorption were markedly suppressed in the TPTX-PTH-5/6NX model compared with the sham-operated control group, and treatment with lanthanum carbonate was associated with the stimulation of bone formation but not an acceleration of bone resorption. Lanthanum treatment caused a robust stimulation of bone formation with an activation of osteoblasts on the endosteal surface of femoral diaphysis, leading to an increase in cortical bone volume. Thus, lanthanum carbonate has the potential to stimulate bone formation in cases of CKD-MBD with suppressed bone turnover.

Keywords

Hyperphosphatemia FGF-23 Osteoblast Osteocyte Osteoclast 

Notes

Acknowledgments

We thank members of our Department (NCGG) for discussion and Mr. Tsuyoshi Makino, Hisashi Uchiyama and Yasuhide Kanada, and Ms. Hatsumi Ikuma (Japan SLC Inc., Shizuoka, Japan) for the surgical procedures. Pacific Edit reviewed the manuscript before submission.

Conflict of interest

This study was carried out with a research Grant from Bayer Yakuhin Ltd (Osaka, Japan).

References

  1. 1.
    Imai E, Horio M, Watanabe T, Iseki K, Yamagata K et al (2009) Prevalence of chronic kidney disease in the Japanese general population. Clin Exp Nephrol 13:621–630PubMedCrossRefGoogle Scholar
  2. 2.
    Kidney disease: improving global outcomes CKDMBDWG (2009) KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int Suppl S1–130Google Scholar
  3. 3.
    Palmer SC, Hayen A, Macaskill P, Pellegrini F, Craig JC et al (2011) Serum levels of phosphorus, parathyroid hormone, and calcium and risks of death and cardiovascular disease in individuals with chronic kidney disease: a systematic review and meta-analysis. JAMA 305:1119–1127Google Scholar
  4. 4.
    Gutierrez OM, Mannstadt M, Isakova T, Rauh-Hain JA, Tamez H et al (2008) Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med 359:584–592PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    White KE, Larsson TE, Econs MJ (2006) The roles of specific genes implicated as circulating factors involved in normal and disordered phosphate homeostasis: frizzled related protein-4, matrix extracellular phosphoglycoprotein, and fibroblast growth factor 23. Endocr Rev 27:221–241PubMedCrossRefGoogle Scholar
  6. 6.
    Fukumoto S, Martin TJ (2009) Bone as an endocrine organ. Trends Endocrinol Metab 20:230–236PubMedCrossRefGoogle Scholar
  7. 7.
    Quarles LD (2003) Evidence for a bone-kidney axis regulating phosphate homeostasis. J Clin Invest 112:642–646PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Tonelli M, Pannu N, Manns B (2010) Oral phosphate binders in patients with kidney failure. N Engl J Med 362:1312–1324Google Scholar
  9. 9.
    Malluche HH, Siami GA, Swanepoel C, Wang GH, Mawad H et al (2008) Improvements in renal osteodystrophy in patients treated with lanthanum carbonate for two years. Clin Nephrol 70:284–295PubMedGoogle Scholar
  10. 10.
    Shigematsu T, Tokumoto A, Nakaoka A, Arisaka H (2011) Effect of lanthanum carbonate treatment on bone in Japanese dialysis patients with hyperphosphatemia. Ther Apher Dial 15:176–184Google Scholar
  11. 11.
    Behets GJ, Dams G, Vercauteren SR, Damment SJ, Bouillon R et al (2004) Does the phosphate binder lanthanum carbonate affect bone in rats with chronic renal failure? J Am Soc Nephrol 15:2219–2228PubMedCrossRefGoogle Scholar
  12. 12.
    Damment S, Secker R, Shen V, Lorenzo V, Rodriguez M (2011) Long-term treatment with lanthanum carbonate reduces mineral and bone abnormalities in rats with chronic renal failure. Nephrol Dial Transpl 26:1803–1812CrossRefGoogle Scholar
  13. 13.
    Iwasaki-Ishizuka Y, Yamato H, Nii-Kono T, Kurokawa K, Fukagawa M (2005) Downregulation of parathyroid hormone receptor gene expression and osteoblastic dysfunction associated with skeletal resistance to parathyroid hormone in a rat model of renal failure with low turnover bone. Nephrol Dial Transpl 20:1904–1911CrossRefGoogle Scholar
  14. 14.
    Ito M, Nakayama K, Konaka A, Sakata K, Ikeda K et al (2006) Effects of a prostaglandin EP4 agonist, ONO-4819, and risedronate on trabecular microstructure and bone strength in mature ovariectomized rats. Bone 39:453–459PubMedCrossRefGoogle Scholar
  15. 15.
    Bouxsein ML, Boyd SK, Christiansen BA, Guldberg RE, Jepsen KJ et al (2010) Guidelines for assessment of bone microstructure in rodents using micro-computed tomography. J Bone Miner Res 25:1468–1486PubMedCrossRefGoogle Scholar
  16. 16.
    Dempster DW, Compston JE, Drezner MK, Glorieux FH, Kanis JA et al (2013) Standardized nomenclature, symbols, and units for bone histomorphometry: a 2012 update of the report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res 28:2–17PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Parfitt AM (1984) The cellular basis of bone remodeling: the quantum concept reexamined in light of recent advances in the cell biology of bone. Calcif Tissue Int 36:S37–S45PubMedCrossRefGoogle Scholar
  18. 18.
    Malluche HH, Monier-Faugere MC (2006) Renal osteodystrophy: what’s in a name? Presentation of a clinically useful new model to interpret bone histologic findings. Clin Nephrol 65:235–242PubMedCrossRefGoogle Scholar
  19. 19.
    Ball AM, Gillen DL, Sherrard D, Weiss NS, Emerson SS et al (2002) Risk of hip fracture among dialysis and renal transplant recipients. JAMA 288:3014–3018PubMedCrossRefGoogle Scholar
  20. 20.
    Karsenty G (2006) Convergence between bone and energy homeostases: leptin regulation of bone mass. Cell Metab 4:341–348PubMedCrossRefGoogle Scholar
  21. 21.
    Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA et al (2001) Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 344:1434–1441PubMedCrossRefGoogle Scholar
  22. 22.
    Rodriguez-Ortiz ME, Lopez I, Munoz-Castaneda JR, Martinez-Moreno JM, Ramirez AP et al (2012) Calcium deficiency reduces circulating levels of FGF23. J Am Soc Nephrol 23:1190–1197PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    O’Brien CA, Plotkin LI, Galli C, Goellner JJ, Gortazar AR et al (2008) Control of bone mass and remodeling by PTH receptor signaling in osteocytes. PLoS One 3:e2942PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Yajima A, Inaba M, Tominaga Y, Nishizawa Y, Ikeda K et al (2010) Increased osteocyte death and mineralization inside bone after parathyroidectomy in patients with secondary hyperparathyroidism. J Bone Miner Res 25:2374–2381PubMedCrossRefGoogle Scholar
  25. 25.
    Paszty C, Turner CH, Robinson MK (2010) Sclerostin: a gem from the genome leads to bone-building antibodies. J Bone Miner Res 25:1897–1904Google Scholar
  26. 26.
    Qing H, Ardeshirpour L, Pajevic PD, Dusevich V, Jahn K et al (2012) Demonstration of osteocytic perilacunar/canalicular remodeling in mice during lactation. J Bone Miner Res 27:1018–1029Google Scholar

Copyright information

© The Japanese Society for Bone and Mineral Research and Springer Japan 2013

Authors and Affiliations

  1. 1.Department of Bone and Joint DiseaseNational Center for Geriatrics and GerontologyObuJapan
  2. 2.Medical Work-Life-Balance CenterNagasaki University HospitalNagasakiJapan

Personalised recommendations