Nicotinamide treatment in a murine model of familial tumoral calcinosis reduces serum Fgf23 and raises heart calcium

Austin M. Reilly, Amie K. Gray, Sharon Moe, Shoji Ichikawa

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Mutations in the GALNT3 gene result in familial tumoral calcinosis, characterized by persistent hyperphosphatemia and ectopic calcific masses in soft tissues. Since calcific masses often recur after surgical removal, a more permanent solution to the problem is required. Nicotinamide is reported to lower serum phosphate by decreasing sodium-dependent phosphate co-transporters in the gut and kidney. However, its effectiveness in tumoral calcinosis remains unknown. In this study, we investigated nicotinamide as a potential therapy for tumoral calcinosis, using a murine model of the disease- Galnt3 knockout mice. Initially, five different doses of nicotinamide were given to normal heterozygous mice intraperitoneally or orally. Treatment had no effect on serum phosphate levels, but serum levels of a phosphaturic hormone, fibroblast growth factor 23 (Fgf23), decreased in a dose-dependent manner. Subsequently, high-dose nicotinamide (40. mM) was tested in Galnt3 knockout mice fed a high phosphate diet. The radiographic data pre- and post-treatment showed that nicotinamide did not reverse the calcification. However, the treatment retarded calcification growth after 4. weeks, while in the untreated animals, calcifications increased in size. The therapy did not affect serum phosphate levels, but intact Fgf23 decreased in the treated mice. The treated mice also had increased calcium in the heart. In summary, nicotinamide did not alter serum phosphate levels, likely due to compensatory decrease in Fgf23 to counteract the phosphate lowering effect of nicotinamide. Although increased calcium accumulation in the heart is a concern, the therapy appears to slow down the progression of ectopic calcifications.

Original languageEnglish
Pages (from-to)139-144
Number of pages6
JournalBone
Volume67
DOIs
StatePublished - 2014

Fingerprint

Calcinosis
Niacinamide
Calcium
Phosphates
Serum
Knockout Mice
Phosphate Transport Proteins
Hyperphosphatemia
Symporters
fibroblast growth factor 23
Therapeutics
Hormones
Diet
Kidney
Mutation
Growth

Keywords

  • Calcification
  • Fgf23
  • Nicotinamide
  • Phosphate
  • Tumoral calcinosis

ASJC Scopus subject areas

  • Physiology
  • Endocrinology, Diabetes and Metabolism
  • Histology
  • Medicine(all)

Cite this

Nicotinamide treatment in a murine model of familial tumoral calcinosis reduces serum Fgf23 and raises heart calcium. / Reilly, Austin M.; Gray, Amie K.; Moe, Sharon; Ichikawa, Shoji.

In: Bone, Vol. 67, 2014, p. 139-144.

Research output: Contribution to journalArticle

Reilly, Austin M. ; Gray, Amie K. ; Moe, Sharon ; Ichikawa, Shoji. / Nicotinamide treatment in a murine model of familial tumoral calcinosis reduces serum Fgf23 and raises heart calcium. In: Bone. 2014 ; Vol. 67. pp. 139-144.
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