Acute effects of calcitriol and phosphate salts on mineral metabolism in children with hypophosphatemic rickets

Bettinelli, Alberto; Bianchi, Maria Luisa; Mazzucchi, Elisabetta; Gandolini, Giorgio; Appiani, Aldo Claris

doi:10.1016/s0022-3476(05)82149-3

Cited by 24 publications

(11 citation statements)

References 33 publications

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“…In contrast to calcipenic rickets, parathyroid hormone (PTH) levels are usually at the upper limit of the normal range or even slightly elevated. Circulating levels of 1,25(OH) 2 vitamin D are low or inappropriately normal in the setting of hypophosphataemia 6,[62][63][64] .…”

Section: Biochemical Characteristicsmentioning

confidence: 99%

Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia

et al. 2019

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X-linked hypophosphataemia (XLH) is an X-linked dominant disorder caused by mutations in PHEX (located at Xp22.1), which encodes a cell-surface-bound protein-cleavage enzyme (phosphate-regulating neutral endopeptidase PHEX), predominantly expressed in osteoblasts, osteocytes and teeth (odontoblasts and cementoblasts). XLH is the most common cause of inherited phosphate wasting, with an incidence of 3.9 per 100,000 live births and a prevalence ranging from 1.7 per 100,000 children to 4.8 per 100,000 persons (children and adults) 1-3. Although the pathogenesis of XLH is not fully understood, animal studies indicate that loss of Phex function results in enhanced secretion of the phosphaturic hormone fibroblast growth factor 23 (FGF23), with osteocytes being the primary source of FGF23 production 4. These effects explain most of the characteristic features of the disease, including renal phosphate wasting with consequent hypophosphataemia, diminished synthesis of active vitamin D (1,25(OH) 2 vitamin D), rickets, osteomalacia, odontomalacia and disproportionate short stature 4-6. Patients usually develop clinical symptoms during the first or second year of life. Early treatment with oral phosphate supplementation and active vitamin D heals rickets, limits dental abscess formation and prevents progressive growth failure, but in a substantial proportion of patients treatment is unsuccessful and/or associated with adverse effects (for example, hyper parathyroidism and nephrocalcinosis) 7,8. Up to two-thirds of children with XLH require lower limb surgery 9-12. Conventional therapy further stimulates FGF23 levels and thereby renal phosphate wasting, resulting in a vicious circle, which might limit its efficacy 6,13-15. Adult patients with XLH are at risk of complications such as early osteoarthritis, enthesopathies, spinal stenosis, pseudofractures and hearing loss, which might limit quality of life 16-18. In 2018, burosumab, a fully human monoclonal IgG1 antibody neutralizing FGF23, was approved by health authorities for the treatment of patients with

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Section: Biochemical Characteristicsmentioning

confidence: 99%

Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia

et al. 2019

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“…X ‐LINKED HYPOPHOSPHATEMIA (XLH) IS an inherited disorder characterized by severe hypophosphatemia, rachitic bone disease, and growth retardation mainly caused by renal defects in phosphate reabsorption and vitamin D metabolism (1–2) . The combination of large amounts of phosphate salts and supraphysiological doses of active vitamin D has allowed adequate bone matrix mineralization and healing of rickets (3–5) . However, this form of therapy still has several problems to be solved.…”

Section: Introductionmentioning

confidence: 99%

“…(1)(2) The combination of large amounts of phosphate salts and supraphysiological doses of active vitamin D has allowed adequate bone matrix mineralization and healing of rickets. (3)(4)(5) However, this form of therapy still has several problems to be solved. For example, secondary hyperparathyroidism may develop from oral phosphate administration and the risk of nephrocalcinosis with hypercal-ciuria may be increased by high-dose active vitamin D administration.…”

Section: Introductionmentioning

confidence: 99%

The Effects of Bone Marrow Transplantation on X-linked Hypophosphatemic Mice

Miyamura

Tanaka

Inoue

et al. 2000

Journal of Bone and Mineral Research

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The genes responsible for X-linked hypophosphatemic (XLH) vitamin D-resistant rickets and the murine homolog, hypophosphatemic mice (Hyp), were identified as PHEX and Phex (phosphate-regulating gene with homology to endopeptidases on the X chromosome), respectively. However, the mechanism by which inactivating mutations of PHEX cause XLH remains unknown. We investigated the mechanisms by syngeneic bone marrow transplantation (

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“…The effect of Pi on hyperparathyroidism has also been attributed to secondary alterations in calcitriol concentrations (Silver et al ., 1986; Portale et al ., 1989). In a study by Bettinelli et al . (1991), no significant changes in calcium concentrations were observed in patients with XLH after an oral Pi load, whereas a significant decrease in S‐1,25(OH) 2 D concentration with an increase in S‐PTH concentration was noticed; these could be prevented when oral Pi was combined with calcitriol.…”

Section: Discussionmentioning

confidence: 99%

Prolonged high‐dose phosphate treatment: a risk factor for tertiary hyperparathyroidism in X‐linked hypophosphatemic rickets

Mäkitie

Kooh

Sochett

2003

Clinical Endocrinology

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Acute effects of calcitriol and phosphate salts on mineral metabolism in children with hypophosphatemic rickets

Cited by 24 publications

References 33 publications

Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia

Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia

The Effects of Bone Marrow Transplantation on X-linked Hypophosphatemic Mice

Prolonged high‐dose phosphate treatment: a risk factor for tertiary hyperparathyroidism in X‐linked hypophosphatemic rickets

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