Burosumab and 1-25 (OH) Vitamin D on Human Osteoclasts (HYPO-CLASTE)

Effect of Burosumab and 1-25 (OH) Vitamin D on Human Osteoclasts From Patients With Hypophosphatemic Rickets (HR)

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.

Study Overview

• Status: Completed
• Conditions: Hypophosphatemic Rickets
• Intervention / Treatment: Other: blood sample

• Study Type: Observational
• Enrollment (Actual): 52

Contacts and Locations

Study Locations

• France
  • Bron, France, 69677
    • Hopital Femme Mere Enfant
  • Lyon, France
    • Hôpital Edouard Herriot
  • Paris, France
    • Hôpital Bicêtre Paris Saclay

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

patients with hypophosphatemic rickets and controls patients without hypophosphatemic rickets

Description

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

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
• Patient treated with immunosuppressive drugs
• Patient with inflammatory disease

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
hypophosphatemic rickets patients; 30 hypophosphatemic rickets patients older than 2 years will be included in this study	Other: blood sample; 25 mL blood sample will be collected on citrate tubes for osteoclastic analysis.
controls patients; 10 controls patients from pediatric nephrology unit without hypophosphatemic rickets, older than 2 years will be included in this study	Other: blood sample; 25 mL blood sample will be collected on citrate tubes for osteoclastic analysis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of osteoclastic cells obtained after at the end of differentiation	The analysis of osteoclastic differentiation will be obtained from the bone cells from patients with burosumab and/or 1-25 (OH) vitamin D	1 day

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2021
• Primary Completion (Actual): October 27, 2021
• Study Completion (Actual): October 27, 2021

Study Registration Dates

• First Submitted: November 28, 2019
• First Submitted That Met QC Criteria: November 28, 2019
• First Posted (Actual): December 3, 2019

Study Record Updates

• Last Update Posted (Actual): October 6, 2022
• Last Update Submitted That Met QC Criteria: October 5, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Kidney Diseases; Urologic Diseases; Nutrition Disorders; Genetic Diseases, Inborn; Musculoskeletal Diseases; Avitaminosis; Deficiency Diseases; Malnutrition; Bone Diseases; Metabolism, Inborn Errors; Bone Diseases, Metabolic; Renal Tubular Transport, Inborn Errors; Calcium Metabolism Disorders; Metal Metabolism, Inborn Errors; Phosphorus Metabolism Disorders; Vitamin D Deficiency; Hypophosphatemia, Familial; Hypophosphatemia; Rickets; Familial Hypophosphatemic Rickets; Rickets, Hypophosphatemic
• Other Study ID Numbers: 69HCL19_0725; 2019-A02914-53 (Other Identifier: ID-RCB)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No