Lanthanum carbonate stimulates bone formation in a rat model of renal insufficiency with low bone turnover
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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.
KeywordsHyperphosphatemia FGF-23 Osteoblast Osteocyte Osteoclast
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).
- 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.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
- 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
- 8.Tonelli M, Pannu N, Manns B (2010) Oral phosphate binders in patients with kidney failure. N Engl J Med 362:1312–1324Google Scholar
- 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
- 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
- 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.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