THU181 Evaluation Of Bone Mineral Density In A Cohort Of Children With ACH Participating In The PROPEL 2 Study Of Infigratinib
Notice bibliographique
Résumé
Abstract Disclosure: R. Savarirayan: Advisory Board Member; Self; Ascendis Pharma, BioMarin, QED Therapeutics, Sanofi, Sanofi. Consulting Fee; Self; BioMarin. Grant Recipient; Self; Ascendis Pharma, BioMarin, QED Therapeutics, Therachon. Research Investigator; Self; Ascendis Pharma, BioMarin, QED Therapeutics, Therachon. J. De Bergua: None. P. Arundel: None. J. Salles: None. A. Leiva-Gea: None. M. Irving: Advisory Board Member; Self; Ascendis Pharma, BioMarin, QED Therapeutics, Sanofi, Therachon/Pfizer. Speaker; Self; BioMarin, QED Therapeutics. V. Saraff: None. H. McDevitt: None. M. Salcedo: None. M.P. Nicolino: None. V. Cormier-Daire: Advisory Board Member; Self; BioMarin. P. Kannu: Advisory Board Member; Self; Novartis, Ipsen. Grant Recipient; Self; CIHR. M. Skae: None. M. Bober: Advisory Board Member; Self; Biomarin. Consulting Fee; Self; Ascendis Pharma, Biomarin, Pfizer, QED Therapeutics. Grant Recipient; Self; Ascendis Pharma, BioMarin, Pfizer, QED Therapeutics. Research Investigator; Self; Ascendis Pharma, BioMarin, Pfizer, QED Therapeutics. J. Phillips III: None. T. Candler: None. P. Harmatz: Consulting Fee; Self; Audentes, Aeglea, Homology, JCR, Denali, Inventiva, Paradigm, Capsida, Chiesi, Avrobio. Grant Recipient; Self; BioMarin, Inventiva. Research Investigator; Self; BioMarin, Shire/Takeda, QED Therapeutics, RegenXbio, Denali, Ascendis, Amicus, Allievex, JCR, Orphazyme, Idorsia, Sangamo. H. Saal: Advisory Board Member; Self; Alexion. Grant Recipient; Self; Alexion, BioMarin, Pfizer, QED Therapeutics. Research Investigator; Self; Alexion, BioMarin, Pfizer, QED Therapeutics. J. Hoover-Fong: Consulting Fee; Self; Pfizer/Therachon, BioMarin, QED Therapeutics, Sanofi, Ascendis Pharma. Grant Recipient; Self; Pfizer/Therachon, BioMarin, Ascendis Pharma. Research Investigator; Self; Pfizer/Therachon, BioMarin, Ascendis Pharma. E. Muslimova: Employee; Self; QED Therapeutics. Stock Owner; Self; QED Therapeutics. T. Cho: Employee; Self; QED Therapeutics. Stock Owner; Self; QED Therapeutics. R. Weng: Employee; Self; QED Therapeutics. Stock Owner; Self; QED Therapeutics. D. Rogoff: Employee; Self; QED Therapeutics. Stock Owner; Self; QED Therapeutics. Background: Achondroplasia (ACH) is the most common form of short-limbed skeletal dysplasias and is caused by an activating pathogenic variant of the fibroblast growth factor receptor 3 (FGFR3) gene. People with ACH are at risk for several significant co-morbidities, including foramen magnum stenosis, obstructive sleep apnea, chronic otitis media with conductive hearing loss, spinal stenosis, and a propensity towards obesity. Decreased bone mass has been observed previously in gain-of-function mutation Fgfr3 mice, and adults with ACH can have a decrease in bone mineral density (BMD). Here we describe baseline BMD of a cohort of children with ACH participating in PROPEL 2, a proof-of-concept study evaluating preliminary efficacy and safety of infigratinib, an oral FGFR-1-3 tyrosine kinase inhibitor in development for ACH. Methods: Dual energy X-ray absorptiometry (DXA) scans of the spine (L1-4) were collected at baseline in children participating in PROPEL 2 using a Hologic or GE Lunar scanner following a pre-specified image acquisition procedure. Images were evaluated by a single reviewer. Results are expressed as z-score for age and sex based on average-height children. Results: 52 children (mean±SD age: 7.97±1.9 years; 29 female; mean±SD height z-score: -5.4±1) were included in this analysis. BMD of the lumbar spine was -0.96±0.9 SDS (min -4.1; max 0.7 SDS). No statistical difference was found between males and females. 85% of children (n=44) had a BMD <0 SDS, from which 21 (40%) had a BMD between -2 and < -1 SDS, 18 (35%) presented a BMD between -1 and 0, and 5 (10%) presented a BMD < -2 SDS. Eight children (15%) had a BMD >0 SDS. No correlations were observed between BMD and age, height z-score or BMI. Conclusion: Our findings show that lumbar spine BMD is lower in children with ACH compared with normative data from children of average height. Low BMD in the context of short stature is difficult to interpret, raising the question of the degree to which low bone status can be attributed to smaller bone size relative to age. Even though our findings do not take into account children’s height, no correlation between BMD and baseline height z-score was identified in this cohort, suggesting that the findings may not be solely attributable to overall height. These findings reinforce the need to better understand how to circumvent this limitation in children with skeletal dysplasias in order to improve DXA interpretation and avoid misdiagnoses. Presentation: Thursday, June 15, 2023
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».