A Clinician's Guide to X-Linked Hypophosphatemia

Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520-8064, USA.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research (Impact Factor: 6.59). 07/2011; 26(7):1381-8. DOI: 10.1002/jbmr.340
Source: PubMed

ABSTRACT X-linked hypophosphatemia (XLH) is the prototypic disorder of renal phosphate wasting, and the most common form of heritable rickets. Physicians, patients, and support groups have all expressed concerns about the dearth of information about this disease and the lack of treatment guidelines, which frequently lead to missed diagnoses or mismanagement. This perspective addresses the recommendation by conferees for the dissemination of concise and accessible treatment guidelines for clinicians arising from the Advances in Rare Bone Diseases Scientific Conference held at the NIH in October 2008. We briefly review the clinical and pathophysiologic features of the disorder and offer this guide in response to the conference recommendation, based on our collective accumulated experience in the management of this complex disorder.

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    ABSTRACT: Hereditary hypophosphatemic rickets (HHR) is a rare disorder of renal phosphate wasting and the most common form of heritable rickets. Here, we report a case of an active 25-year-old male with HHR showing atraumatic bilateral femoral neck pseudarthrosis after 4 years of consecutive knee pain. A conservative therapy was administered, taking into account both the risks of surgical treatment and the little impairment even in the sport activities which the patient experienced.
    01/2014; 2014:312712. DOI:10.1155/2014/312712
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    ABSTRACT: The classification of the various forms of hypophosphatemic rickets has been rationalized by the discovery of the central role that fibroblast growth factor 23 (FGF23) plays in the pathogenesis of a number of genetic and acquired forms of the disease. Although the details of the interaction of FGF23 with other osteoblast/osteocyte-derived proteins remain unclear at present, the measurement of circulating levels of FGF23 appears to be a useful biochemical test in determining the various causes of hypophosphatemic rickets. Furthermore, animal studies suggest that agents interfering in the action of FGF23 might play important roles in the future management of the FGF23-mediated forms of rickets. Phase 1 and phase 2 trials in humans with X-linked hypophosphatemic rickets are currently under way.
    Calcified Tissue International 11/2012; 91(5). DOI:10.1007/s00223-012-9651-0 · 2.75 Impact Factor
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    ABSTRACT: Patients with X-linked hypophosphatemia (XLH) develop enthesophytes and osteophytes secondary to articular cartilage degeneration and together are the primary cause of morbidity in adult patients so afflicted. We have previously characterized the enthesopathy in Hyp mice, a murine model of XLH. We now extend these studies to the synovial joint in order to characterize potential cellular changes in articular cartilage that may predispose patients to the osteoarthropathy of XLH. We report that, despite highly elevated levels of alkaline phosphatase activity throughout articular cartilage, there is a complete loss in the mineralized zone of articular cartilage as assessed by von Kossa staining of mineral and as quantified by EPIC-microCT analysis and evidence of vascular invasion. We also identify the downregulation of extracellular matrix (ECM) factors identified as regulators of terminally differentiated mineralizing articular chondrocytes. There is also a striking increase in the histochemical staining of sulfated proteoglycans, a change that may reflect the loss of a transitional tissue that reduces mechanical stress at the interface between cartilage and subchondral bone. The failure of mineralizing articular chondrocytes to develop in the hypophosphatemic state suggests that phosphate may be a key regulator of chondrocyte mineralization. Accordingly, we find that the appropriate zonal arrangement and phenotypic markers of articular cartilage are significantly reestablished by phosphate-replacement therapy. Given the turnover and maintenance of articular cartilage ECM, the identification of early and abnormal cellular changes unique to XLH will undoubtedly aid in a more effective management of this disease to minimize the onset of degenerative osteoarthropathy.
    Calcified Tissue International 06/2011; 89(2):151-62. DOI:10.1007/s00223-011-9502-4 · 2.75 Impact Factor


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