PMID- 36483469
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221210
IS  - 2296-2360 (Print)
IS  - 2296-2360 (Electronic)
IS  - 2296-2360 (Linking)
VI  - 10
DP  - 2022
TI  - Case Report: Everolimus reduced bone turnover markers but showed no clinical 
      benefit in a patient with severe progressive osseous heteroplasia.
PG  - 936780
LID - 10.3389/fped.2022.936780 [doi]
LID - 936780
AB  - BACKGROUND: Progressive osseous heteroplasia (POH) is an ultrarare genetic 
      disorder characterized by an inactivating mutation in the GNAS gene that causes 
      heterotopic ossification. Inhibition of the mammalian target of the rapamycin 
      (mTOR) signalling pathway has been proposed as a therapy for progressive bone 
      fibrodysplasia and non-genetic forms of bone heteroplasia. Herein, we describe 
      the impact of using Everolimus as a rescue therapy for an identical twin girl 
      exhibiting an aggressive clinical phenotype of POH. METHODS: Clinical evaluation 
      of the progression of the disease during Everolimus treatment was performed 
      periodically. Cytokine markers involved in bone metabolism and protein markers 
      related to bone activity were analyzed to explore bone turnover activity. 
      RESULTS: The patient received Everolimus therapy for 36 weeks. During treatment, 
      no clinical improvement of the disease was perceived. Analysis of biochemical 
      parameters, namely, beta-CTX (r (2) = -0.576, P-value = 0.016) and PNIP (r 
      (2) = -0.598, P-value = 0.011), indicated that bone turnover activity was 
      significantly reduced. Additionally, bone metabolism-related biomarkers showed 
      only a significant positive correlation with PTH levels. CONCLUSIONS: Everolimus 
      treatment did not modify the clinical progression of the disease in an aggressive 
      form of POH, although an impact on the protein markers studied was observed.
CI  - (c) 2022 Cebey-Lopez, Curras-Tuala, Gomez-Rial, Rivero-Calle, Pardo-Seco, 
      Mendez-Gallart, Pischedda, Gomez-Carballa, Barral-Arca, Justicia-Grande, 
      Viz-Lasheras, Rodriguez-Tenreiro, Gomez, Salas and Martinon-Torres.
FAU - Cebey-Lopez, M
AU  - Cebey-Lopez M
AD  - Genetics, Vaccines, Infectious Diseases and Pediatrics Research Group (GENVIP), 
      Health Research Institute of Santiago de Compostela (IDIS), Santiago de 
      Compostela, Spain.
AD  - Translational Pediatrics and Infectious Diseases, Department of Pediatrics, 
      Hospital Clinico Universitario de Santiago de Compostela, Santiago de Compostela, 
      Spain.
FAU - Curras-Tuala, M J
AU  - Curras-Tuala MJ
AD  - Genetics, Vaccines, Infectious Diseases and Pediatrics Research Group (GENVIP), 
      Health Research Institute of Santiago de Compostela (IDIS), Santiago de 
      Compostela, Spain.
AD  - Translational Pediatrics and Infectious Diseases, Department of Pediatrics, 
      Hospital Clinico Universitario de Santiago de Compostela, Santiago de Compostela, 
      Spain.
FAU - Gomez-Rial, J
AU  - Gomez-Rial J
AD  - Genetics, Vaccines, Infectious Diseases and Pediatrics Research Group (GENVIP), 
      Health Research Institute of Santiago de Compostela (IDIS), Santiago de 
      Compostela, Spain.
AD  - Translational Pediatrics and Infectious Diseases, Department of Pediatrics, 
      Hospital Clinico Universitario de Santiago de Compostela, Santiago de Compostela, 
      Spain.
AD  - Servicio de inmunologia, Servicio de Analisis Clinicos. Hospital Clinico 
      Universitario (SERGAS), Santiago de Compostela, Spain.
FAU - Rivero-Calle, I
AU  - Rivero-Calle I
AD  - Genetics, Vaccines, Infectious Diseases and Pediatrics Research Group (GENVIP), 
      Health Research Institute of Santiago de Compostela (IDIS), Santiago de 
      Compostela, Spain.
AD  - Translational Pediatrics and Infectious Diseases, Department of Pediatrics, 
      Hospital Clinico Universitario de Santiago de Compostela, Santiago de Compostela, 
      Spain.
FAU - Pardo-Seco, J
AU  - Pardo-Seco J
AD  - Genetics, Vaccines, Infectious Diseases and Pediatrics Research Group (GENVIP), 
      Health Research Institute of Santiago de Compostela (IDIS), Santiago de 
      Compostela, Spain.
AD  - Translational Pediatrics and Infectious Diseases, Department of Pediatrics, 
      Hospital Clinico Universitario de Santiago de Compostela, Santiago de Compostela, 
      Spain.
FAU - Mendez-Gallart, R
AU  - Mendez-Gallart R
AD  - Pediatric Surgery, Hospital Clinico Universitario de Santiago, Santiago de 
      Compostela, Spain.
FAU - Pischedda, S
AU  - Pischedda S
AD  - Genetics, Vaccines, Infectious Diseases and Pediatrics Research Group (GENVIP), 
      Health Research Institute of Santiago de Compostela (IDIS), Santiago de 
      Compostela, Spain.
AD  - Translational Pediatrics and Infectious Diseases, Department of Pediatrics, 
      Hospital Clinico Universitario de Santiago de Compostela, Santiago de Compostela, 
      Spain.
FAU - Gomez-Carballa, A
AU  - Gomez-Carballa A
AD  - Genetics, Vaccines, Infectious Diseases and Pediatrics Research Group (GENVIP), 
      Health Research Institute of Santiago de Compostela (IDIS), Santiago de 
      Compostela, Spain.
AD  - Translational Pediatrics and Infectious Diseases, Department of Pediatrics, 
      Hospital Clinico Universitario de Santiago de Compostela, Santiago de Compostela, 
      Spain.
FAU - Barral-Arca, R
AU  - Barral-Arca R
AD  - Genetics, Vaccines, Infectious Diseases and Pediatrics Research Group (GENVIP), 
      Health Research Institute of Santiago de Compostela (IDIS), Santiago de 
      Compostela, Spain.
AD  - Translational Pediatrics and Infectious Diseases, Department of Pediatrics, 
      Hospital Clinico Universitario de Santiago de Compostela, Santiago de Compostela, 
      Spain.
FAU - Justicia-Grande, A
AU  - Justicia-Grande A
AD  - Genetics, Vaccines, Infectious Diseases and Pediatrics Research Group (GENVIP), 
      Health Research Institute of Santiago de Compostela (IDIS), Santiago de 
      Compostela, Spain.
AD  - Translational Pediatrics and Infectious Diseases, Department of Pediatrics, 
      Hospital Clinico Universitario de Santiago de Compostela, Santiago de Compostela, 
      Spain.
FAU - Viz-Lasheras, S
AU  - Viz-Lasheras S
AD  - Genetics, Vaccines, Infectious Diseases and Pediatrics Research Group (GENVIP), 
      Health Research Institute of Santiago de Compostela (IDIS), Santiago de 
      Compostela, Spain.
AD  - Translational Pediatrics and Infectious Diseases, Department of Pediatrics, 
      Hospital Clinico Universitario de Santiago de Compostela, Santiago de Compostela, 
      Spain.
FAU - Rodriguez-Tenreiro, C
AU  - Rodriguez-Tenreiro C
AD  - Genetics, Vaccines, Infectious Diseases and Pediatrics Research Group (GENVIP), 
      Health Research Institute of Santiago de Compostela (IDIS), Santiago de 
      Compostela, Spain.
AD  - Translational Pediatrics and Infectious Diseases, Department of Pediatrics, 
      Hospital Clinico Universitario de Santiago de Compostela, Santiago de Compostela, 
      Spain.
FAU - Gomez, R
AU  - Gomez R
AD  - Musculoskeletal Pathology Group, Institute IDIS, Santiago University Clinical 
      Hospital (SERGAS), Santiago de Compostela, Spain.
FAU - Salas, A
AU  - Salas A
AD  - Genetics, Vaccines, Infectious Diseases and Pediatrics Research Group (GENVIP), 
      Health Research Institute of Santiago de Compostela (IDIS), Santiago de 
      Compostela, Spain.
AD  - Unidade de Xenetica, Instituto de Ciencias Forenses (INCIFOR), Facultade de 
      Medicina, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
AD  - GenPoB Research Group, Instituto de Investigacion Sanitaria, Hospital Clinico 
      Universitario de Santiago (SERGAS), Santiago de Compostela, Spain.
FAU - Martinon-Torres, F
AU  - Martinon-Torres F
AD  - Genetics, Vaccines, Infectious Diseases and Pediatrics Research Group (GENVIP), 
      Health Research Institute of Santiago de Compostela (IDIS), Santiago de 
      Compostela, Spain.
AD  - Translational Pediatrics and Infectious Diseases, Department of Pediatrics, 
      Hospital Clinico Universitario de Santiago de Compostela, Santiago de Compostela, 
      Spain.
LA  - eng
PT  - Case Reports
DEP - 20221122
PL  - Switzerland
TA  - Front Pediatr
JT  - Frontiers in pediatrics
JID - 101615492
PMC - PMC9723155
OTO - NOTNLM
OT  - Everolimus
OT  - bone metabolism
OT  - bone turnover
OT  - mTOR
OT  - progressive osseous heteroplasia
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/12/10 06:00
MHDA- 2022/12/10 06:01
PMCR- 2022/11/22
CRDT- 2022/12/09 04:02
PHST- 2022/05/05 00:00 [received]
PHST- 2022/10/24 00:00 [accepted]
PHST- 2022/12/09 04:02 [entrez]
PHST- 2022/12/10 06:00 [pubmed]
PHST- 2022/12/10 06:01 [medline]
PHST- 2022/11/22 00:00 [pmc-release]
AID - 10.3389/fped.2022.936780 [doi]
PST - epublish
SO  - Front Pediatr. 2022 Nov 22;10:936780. doi: 10.3389/fped.2022.936780. eCollection 
      2022.