Clinical trial NCT04159675: Burosumab and 1-25 (OH) Vitamin D on Human Osteoblasts
Official title: Effect of Burosumab and 1-25 (OH) Vitamin D on Human Osteoblasts from Patients Requiring Craniosynostosis Surgery for Idiopathic Reason or Due to Hypophosphatemic Rickets (HR)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Craniosynostoses
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2019-11-12
Enrollment: 20
Sex: ALL
Minimum age (years): 4
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: patients with craniosynostosis, idiopathic (control patients) or due to HR

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.


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.

Primary outcomes:
measure: Number of osteoblastic cells obtained at the end of differentiation
timeFrame: Day 0
Secondary outcomes:
Other outcomes:
Locations:
city: Bron
country: France
facility: Centre de référence des craniosténoses et malformations cranio-faciales Service de neurochirurgie Pédiatrique
Study officials:
affiliation: Hospices Civils de Lyon Centre de référence des craniosténoses et malformations cranio-faciales Service de neurochirurgie Pédiatrique
name: Federico DI ROCCO, MD
role: PRINCIPAL_INVESTIGATOR
References: