Hypophosphatemic Rickets
Conditions
Brief summary
Fibroblast growth factor 23 (FGF23) is the cornerstone of phosphate / calcium / vitamin D metabolism: it is synthesized mainly by osteocytes and acts as a Phosphating agent, inhibitor of dihydroxyvitamin D, and inhibitor of synthesis and secretion of Parathyroid hormone (PTH) in most tissues. The specific role of FGF23 on bone has yet to be demonstrated. In some diseases such as hypophosphatemic rickets (HR), the direct role of FGF23 on bone has not yet been studied to our knowledge, whereas these genetic hypophosphatemias are secondary to overexpression of FGF23, whether an activating mutation of FGF23 or inhibitory mutations of its inhibitors (Dentin matrix acidic phosphoprotein 1 (DMP1) and Phosphate-regulating neutral endopeptidase, X-linked (PHEX)). However, patients with X-linked hypophosphatemic rickets (XLH) have higher circulating FGF23 levels than healthy controls and these levels are higher in treated patients. Management of XLH consists primarily of correcting the native vitamin D defect by prescribing active vitamin D analogs as well as phosphate supplementation to improve bone mineralization and decrease dental complications, growth, and bone deformities. Recently, a new therapeutic option has been developed for XLH, burosumab, a human monoclonal antibody that binds and inhibits FGF23 activity. The use of burosumab is currently authorized in France in some pediatric patients with severe forms of XLH. Independently of the indirect bone effects of phosphate correction and vitamin D levels, the direct role of burosumab on bone cells has never been studied. The objective of this project is to study the osteoclastic biology of patients with HR compared to control patients, and to evaluate the direct impact of the treatments used in this pathology on human osteoclasts.
Interventions
OTHERblood sample
25 mL blood sample will be collected on citrate tubes for osteoclastic analysis.
Sponsors
Hospices Civils de Lyon
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
Inclusion criteria
hypophosphatemic rickets patients: Inclusion Criteria: * children from 2 yars-old to 18 years old and adults * patients with HR followed in the center of calcium and phosphorus metabolism rare diseases in Lyon- * Patients and parent / holder of parental authority who have been informed of the study and do not object to participate
Exclusion criteria
* Patient being treated with oral corticosteroid or having received more than 3 months of corticosteroid treatment before surgery. * Patients under tutorship or curatorship * Pregnant and / or breastfeeding woman * Patient deprived of liberty Controls patients: Inclusion Criteria: * children from 2 years-old to 18 years old and adults * patients with normal renal function (Schwartz glomerular filtration rate (GFR) \>90 ml/min/1.73m²) * Patients and parent / holder of parental authority who have been informed of the study and do not object to participate
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| number of osteoclastic cells obtained after at the end of differentiation | 1 day | The analysis of osteoclastic differentiation will be obtained from the bone cells from patients with burosumab and/or 1-25 (OH) vitamin D |
Countries
France
Outcome results
None listed