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

NCT04159675 · Status: RECRUITING · Type: OBSERVATIONAL · Enrollment: 20

Last updated 2026-04-16

No results posted yet for this study

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

Interventions

BIOLOGICAL

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

Sponsors & Collaborators

  • Hospices Civils de Lyon

    lead OTHER

Principal Investigators

  • Federico DI ROCCO, MD · Hospices Civils de Lyon Centre de référence des craniosténoses et malformations cranio-faciales Service de neurochirurgie Pédiatrique

Eligibility

Min Age
4 Months
Max Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2020-09-04
Primary Completion
2029-04-04
Completion
2029-04-04

Countries

  • France

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT04159675 on ClinicalTrials.gov