Successful Treatment of Hyperphosphatemic Tumoral Calcinosis with Long-Term Acetazolamide

Yamaguchi, Toru; Sugimoto, Takemi; Imai, Yohsuke; Fukase, Masaaki; Fujita, Takeshi; Chihara, Kazuo

doi:10.1016/8756-3282(95)00019-a

Cited by 49 publications

(31 citation statements)

References 5 publications

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“…Previously described therapies include dietary phosphate restriction, phosphate binders, and drugs that are thought to be phosphaturic, but these treatments are only limited to single case reports or anecdotes [14–16]. One of those drugs is nicotinamide (also known as niacinamide), which reduces phosphate (re)absorption by decreasing activity of sodium-dependent phosphate co-transporters in both intestine [17, 18] and kidney [19, 20].…”

Section: Introductionmentioning

confidence: 99%

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

Reilly

Gray

Moe

et al. 2014

Bone

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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; however, 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 four 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.

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Section: Introductionmentioning

confidence: 99%

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

Reilly

Gray

Moe

et al. 2014

Bone

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“…Pathogenesis of the disease is unclear, but an inherited error of inorganic phosphate and vitamin D metabolism is the most probable hypothesis 6–116 12…”

Section: Discussionmentioning

confidence: 99%

“…Diets restricted in calcium and phosphate along with phosphate binding antacids have been used in some cases 5 6 11 12. This modality may be successful in hyperphosphataemic patients 10 11. Complete surgical excision of the mass is the optimal treatment 5 6 12 14 27 28…”

Section: Discussionmentioning

confidence: 99%

“…In some cases, calcific mass may recur despite the complete surgical resections 11 23. We prescribed sevelamer to the patient and recommended her to be followed as an outpatient.…”

Section: Discussionmentioning

confidence: 99%

“…However, genetic disorders, recurrent soft-tissue micro traumas and renal-failure are considered 3. An inborn error in vitamin D and inorganic phosphate metabolism is the most probable hypothesis in the pathogenesis of idiopathic tumoural calcinosis 5–11…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A rare disorder: tumoral calcinosis and cirrhosis

Allameh

Ghadiri‐Anari²,

Gharabaghi³

et al. 2011

Case Reports

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Phenotypic and Genotypic Characterization and Treatment of a Cohort With Familial Tumoral Calcinosis/Hyperostosis-Hyperphosphatemia Syndrome

Ramnitz

Gourh

Goldbach‐Mansky

et al. 2016

Journal of Bone and Mineral Research

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Familial tumoral calcinosis (FTC)/hyperostosis-hyperphosphatemia syndrome (HHS) is a rare disorder caused by mutations in the genes encoding fibroblast growth factor-23 (FGF23), N-acetylgalactosaminyltransferase 3 (GALNT3), or KLOTHO. The result is functional deficiency of, or resistance to, intact FGF23 (iFGF23), causing hyperphosphatemia, increased renal tubular reabsorption of phosphorus (TRP), elevated or inappropriately normal 1,25-dihydroxyvitamin D3 (1,25D), ectopic calcifications and/or diaphyseal hyperostosis. Eight subjects with FTC/HHS were studied and treated. Clinical manifestations varied, even within families, ranging from asymptomatic to large, disabling calcifications. All subjects had hyperphosphatemia, increased TRP, and elevated or inappropriately normal 1,25D. C-terminal FGF23 was markedly elevated while iFGF23 was comparatively low, consistent with increased FGF23 cleavage. Radiographs ranged from diaphyseal hyperostosis to massive calcification. Two subjects with severe calcifications also had overwhelming systemic inflammation and elevated C-reactive protein (CRP). GALNT3 mutations were identified in 7 subjects; no causative mutation was found in the eighth. Biopsies from 4 subjects showed ectopic calcification and chronic inflammation, with areas of heterotopic ossification observed in 1 subject. Treatment with low phosphate diet, phosphate binders, and phosphaturia-inducing therapies was prescribed with variable response. One subject experienced complete resolution of a calcific mass after 13 months of medical treatment. In the 2 subjects with systemic inflammation, interleukin-1 (IL-1) antagonists significantly decreased CRP levels with resolution of calcinosis cutis and peri-lesional inflammation in one subject and improvement of overall well-being in both subjects. This cohort expands the phenotype and genotype of FTC/HHS and demonstrates the range of clinical manifestations despite similar biochemical profiles and genetic mutations. Overwhelming systemic inflammation has not been described previously in FTC/HHS; the response to IL-1 antagonists suggests that anti-inflammatory drugs may be useful adjuvants. In addition, this is the first description of heterotopic ossification reported in FTC/HHS, possibly mediated by the adjacent inflammation.

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Successful Treatment of Hyperphosphatemic Tumoral Calcinosis with Long-Term Acetazolamide

Cited by 49 publications

References 5 publications

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

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

A rare disorder: tumoral calcinosis and cirrhosis

Phenotypic and Genotypic Characterization and Treatment of a Cohort With Familial Tumoral Calcinosis/Hyperostosis-Hyperphosphatemia Syndrome

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