NDLI: Mineralizing Enthesopathy Is a Common Feature of Renal Phosphate-Wasting Disorders Attributed to FGF23 and Is Exacerbated by Standard Therapy in Hyp Mice

Content Provider	PubMed Central
Author	Karaplis, Andrew C. Bai, Xiuying Jean-pierre, Falet Macica, Carolyn M.
Copyright Year	2012
Abstract	We have previously confirmed a paradoxical mineralizing enthesopathy as a hallmark of X-linked hypophosphatemia. X-linked hypophosphatemia is the most common of the phosphate-wasting disorders mediated by elevated fibroblast growth factor 23 (FGF23) and occurs as a consequence of inactivating mutations of the PHEX gene product. Despite childhood management of the disease, these complications of tendon and ligament insertion sites account for a great deal of the disease's morbidity into adulthood. It is unclear whether the enthesopathy occurs in other forms of renal phosphate-wasting disorders attributable to high FGF23 levels. Here we describe two patients with autosomal recessive hypophosphatemic rickets due to the Met1Val mutation in dentin matrix acidic phosphoprotein 1 (DMP1). In addition to the biochemical and skeletal features of long-standing rickets with elevated FGF23 levels, these individuals exhibited severe, debilitating, generalized mineralized enthesopathy. These data suggest that enthesophytes are a feature common to FGF23-mediated phosphate-wasting disorders. To address this possibility, we examined a murine model of FGF23 overexpression using a transgene encoding the secreted form of human FGF23 (R176Q) cDNA (FGF23-TG mice). We report that FGF23-TG mice display a similar mineralizing enthesopathy of the Achilles and plantar facial insertions. In addition, we examined the impact of standard therapy for phosphate-wasting disorders on enthesophyte progression. We report that fibrochondrocyte hyperplasia persisted in Hyp mice treated with oral phosphate and calcitriol. In addition, treatment had the untoward effect of further exacerbating the mineralization of fibrochondrocytes that define the bone spur of the Achilles insertion. These studies support the need for newer interventions targeted at limiting the actions of FGF23 and minimizing both the toxicities and potential morbidities associated with standard therapy.
Related Links	http://dx.doi.org/10.1210/en.2012-1551
Ending Page	5917
Page Count	12
Starting Page	5906
File Format	PDF
ISSN	00137227
e-ISSN	19457170
Journal	Endocrinology
Issue Number	12
Volume Number	153
Language	English
Publisher	Endocrine Society
Publisher Date	2012-12-01
Access Restriction	Open
Rights Holder	Endocrine Society
Subject Keyword	Endocrinology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Endocrinology

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