Nationwide survey of fibroblast growth factor 23 (FGF23)-related hypophosphatemic diseases in Japan: prevalence, biochemical data and treatment

Abstract

FIBROBLAST GROWTH FACTOR 23 (FGF23) is a hormone produced by bone and reduces serum phosphate by inhibiting proximal tubular phosphate reabsorption and intestinal phosphate absorption through decreasing serum 1,25-dihydroxyvitamin D [1]. It has been shown that excessive actions of FGF23 cause several kinds of FGF23-related hypophosphatemic Abstract. A nationwide epidemiologic survey of fibroblast growth factor 23 (FGF23)-related hypophosphatemic diseases was conducted in 2010 to clarify the prevalence and the clinical presentations of the disorders. A questionnaire inquiring the experience of patients with these diseases was sent to randomly selected hospitals throughout Japan. The estimated annual incidence of the diseases was 117 cases (95% CI 75 -160), 55 males (95% CI 30 -81) and 62 females (95% CI 40 -84). Tumor-induced osteomalacia (TIO) and X-linked hypophosphatemic rickets (XLH) were the most prevalent causes of acquired and genetic FGF23-related hypophosphatemic diseases, respectively. The estimated incidence of XLH was about 1 in 20,000. We have also collected clinical data of the patients by a secondary survey. These patients showed FGF23 levels of above 30 pg/mL by intact assay in the presence of hypophosphatemia. While complete resection of responsible tumors improved biochemical abnormalities in patients with TIO, treatment with phosphate and/or active vitamin D 3 did not normalize serum phosphate and tubular maximum transport of phosphate in patients with XLH. Our results suggest that there is no racial difference in the incidence of XLH. While FGF23 measurement is useful for the diagnosis of FGF23-related hypophosphatemic diseases, the better management is necessary especially for patients with genetic hypophosphatemic rickets caused by excessive actions of FGF23.

Nonremission and Recurrent Tumor-Induced Osteomalacia: A Retrospective Study

“…The result of our cohort may provide convincing evidence for this predicament. We found that the disease was equally prevalent in women and men, which is consistent with previous reports, (1,4,11) but our results suggest that the refractory risk in women is twofold to threefold higher than that in men. To our knowledge, this finding is difficult to explain.…”

“…Its incidence or prevalence is still unclear, and only one Japanese study reported an estimated annual incidence of 117 cases nationally. (1) As the most prevalent cause of acquired hypophosphatemic osteomalacia, TIO is not as common as other common FGF23-related hypophosphatemic diseases, such as X-linked hypophosphatemia, which requires long-term drug therapy and is curable by tumor resection. Hence, comprehending the prognosis of surgical treatment and finding predictors are of great importance.…”

X-Linked Hypophosphatemia: Uniquely Mild Disease Associated With PHEX 3′-UTR Mutation c.*231A>G (A Retrospective Case–Control Study)

“…X‐linked hypophosphatemia (XLH, OMIM #307800), the most common genetic rickets or osteomalacia, is due to loss‐of‐function mutations of PHEX : “phosphate‐regulating endopeptidase homolog, X‐linked” . Consequently, circulating levels of the phosphatonin fibroblast growth factor 23 (FGF23) increase and affected individuals manifest hypophosphatemia from renal wasting of inorganic phosphate (Pi), diminished kidney synthesis of 1,25‐dihydroxyvitamin D (1,25(OH) 2 D), and decreased intestinal absorption of calcium (Ca) and Pi . XLH accounts for >80% of heritable hypophosphatemic bone disease and occurs in ~1 per 20,000 births .…”

Incidence rate and characteristics of symptomatic vitamin D deficiency in children: a nationwide survey in Japan

“…The selection rate was 100% for hospitals with 500 beds or more and medical university hospitals, whereas it was 5% for hospitals with 99 beds or less at random. We previously estimated the incidence of X-linked hypophosphatemic rickets in Japan in a similar survey [14].…”