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

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Hypophosphatemic Rickets Avitaminosis Bone Diseases Bone Diseases, Metabolic Calcium Metabolism Disorders Deficiency Diseases Hypophosphatemia Malnutrition Metabolic Diseases Musculoskeletal Diseases Nutrition Disorders Nutritional and Metabolic Diseases Phosphorus Metabolism Disorders Rickets Rickets, Hypophosphatemic Vitamin D Deficiency

Age range

2 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Hôpital Femme mère enfant, Bron, France

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

blood sample

Other

25 mL blood sample will be collected on citrate tubes for osteoclastic analysis.

Primary outcomes

number of osteoclastic cells obtained after at the end of differentiation

Time frame: 1 day

The analysis of osteoclastic differentiation will be obtained from the bone cells from patients with burosumab and/or 1-25 (OH) vitamin D

Sponsors and collaborators

Lead sponsor

Hospices Civils de Lyon

Other

Registry information

Official study title

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

Acronym: HYPO-CLASTE

Important dates

Study start: 2021
Primary completion: 2021
Study completion: 2021
First posted: Dec 3, 2019
Registry last updated: Oct 6, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed