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

NCT ID: NCT04159675

Last Updated: 2025-01-06

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 20 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-09-04
• Study Completion Date: 2026-04-04

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

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

control patients

Patients with idiopathic craniosynostosis

osteoblast biology study

Intervention Type: 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

Patients with craniosynostosis due to HR

osteoblast biology study

Intervention Type: BIOLOGICAL

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

Interventions

osteoblast biology study

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

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

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

• Minimum Eligible Age: 4 Months
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospices Civils de Lyon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Federico DI ROCCO, MD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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

Bron, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Federico DI ROCCO, MD

Role: CONTACT

federico.dirocco@chu-lyon.fr

04 72 35 75 72 ext. +33

Justine BACCHETTA, MD

Role: CONTACT

justine.bacchetta@chu-lyon.fr

0427856178 ext. +33

Facility Contacts

Federico DI ROCCO, MD

Role: primary

federico.dirocco@chu-lyon.fr

Justine BACCHETTA, MD

Role: backup

justine.bacchetta@chu-lyon.fr

Federico DI ROCCO, MD

Role: backup

Justine BACCHETTA, MD

Role: backup

Aurélia BERTHOLET-THOMAS, MD

Role: backup

Other Identifiers

2019-A02762-55

Identifier Type: OTHER

Identifier Source: secondary_id

69HCL19_0773

Identifier Type: -

Identifier Source: org_study_id