Burosumab and 1-25 (OH) Vitamin D on Human Osteoblasts

NCT04159675 | Recruiting

• 2 other identifiers: 69HCL19_07732019-A02762-55
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

FGF23 is the cornerstone of phosphate / calcium / vitamin D metabolism: it is synthesized mainly by osteocytes and acts as a phosphaturizing agent, inhibitor of dihydroxyvitamin D, and inhibitor of synthesis and secretion of PTH in most tissues. The specific role of FGF23 on bone has yet to be demonstrated. In osteoblasts, overexpression of FGF23 in vitro suppresses not only osteoblastic differentiation but also the synthesis of the mineralized matrix independently of its systemic action on phosphate metabolism. In osteoblasts, FGF23 also regulates the secretion of osteopontin by directly suppressing transcription of alkaline phosphatase. 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 (DMP1 and 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 osteoblastic biology of patients with RH compared to control patients, and to evaluate the direct impact of the treatments used in this pathology on human osteoblasts.

Conditions

Craniosynostoses

Outcome Measures

Primary Outcomes (1)

• Number of osteoblastic cells obtained at the end of differentiation

  The analysis of osteoblastic differentiation obtained from the bone cells from patients with burosumab and/or 1-25 (OH) vitamin D (HR patients vs idiopathic craniosynostosis)

  Day 0

Study Arms (2)

control patients

Patients with idiopathic craniosynostosis

Biological: osteoblast biology study

HR patients

Patients with craniosynostosis due to HR

Biological: osteoblast biology study

Interventions

osteoblast biology study BIOLOGICAL

Describe the in-vitro action of burosumab and vitamin D on human osteoblastogenesis from osteoblasts from patients with craniosynostosis due to HR

HR patients; control patients

Eligibility Criteria

• Age: 4 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

patients with craniosynostosis, idiopathic (control patients) or due to HR

You may qualify if:

• Children from 4 months-old to 18 years-old
• Patients requiring craniosynostosis surgery followed by reference centers for rare diseases of calcium and phosphate metabolism / craniofacial malformations
• Patients and parent / holder of parental authority who have been informed of the study and do not object to participate

You may not qualify if:

• Patient being treated with oral corticosteroid or having received more than 3 months of corticosteroid treatment before surgery.

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

Centre de référence des craniosténoses et malformations cranio-faciales Service de neurochirurgie Pédiatrique

Bron, 69500, France

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

pieces of bone skull (considered as biological waste) during surgery

MeSH Terms

Conditions

Craniosynostoses

Condition Hierarchy (Ancestors)

Synostosis; Dysostoses; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Federico DI ROCCO, MD

  Hospices Civils de Lyon Centre de référence des craniosténoses et malformations cranio-faciales Service de neurochirurgie Pédiatrique

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Federico DI ROCCO, MD

CONTACT

04 72 35 75 72; federico.dirocco@chu-lyon.fr

Justine BACCHETTA, MD

CONTACT

0427856178; justine.bacchetta@chu-lyon.fr

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2019
• First Posted: November 12, 2019
• Study Start: September 4, 2020
• Primary Completion (Estimated): April 4, 2029
• Study Completion (Estimated): April 4, 2029
• Last Updated: April 16, 2026

Record last verified: 2026-04

Locations

FR (1)