Circulating miRNAs and Bone Microstructure in Adults With Hypophosphatasia

NCT04018287 | Unknown

• 1 other identifier: HPP-study
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the study is to accomplish a complete bone status of patients with HPP using new approaches to assess bone quality.

Conditions

Hypophosphatasia; Bone Diseases, Metabolic; Bone

Keywords

microRNAs, bone microstructure

Outcome Measures

Primary Outcomes (2)

• HR-pQCT

  non-invasively measurement of trabecular and cortical bone microstructure

  Assessment once after Inclusion is completed.

• microRNA pattern

  bone specific circulating microRNAs (miRNAs) in the serum of adult patients

  Assessment once after Inclusion is completed

Secondary Outcomes (2)

• DXA Scanning

  Assessment once after Inclusion is completed.

• Bone Turnover Markers (BTMs)

  Assessment once after Inclusion is completed.

Other Outcomes (1)

• Patient Characteristics

  Assessment once after Inclusion is completed.

Study Arms (2)

HPP-Group

1. genetical verified hypophosphatasia 2. age \>18 years 3. written informed consent 4. complete serological and radiological examinations

Other: HR-pQCT scans, BMD measurements, bone specific circulating microRNAs (miRNAs)

Control-Group

1. healthy men and women without any history of musculoskeletal diseases 2. Alkaline phosphatase (AP) in reference range 3. written informed consent 4. complete serological and radiological examinations

Other: HR-pQCT scans, BMD measurements, bone specific circulating microRNAs (miRNAs)

Interventions

HR-pQCT scans, BMD measurements, bone specific circulating microRNAs (miRNAs) OTHER

HR-pQCT scans (XtremeCT, SCANCO Medical, Brütisellen, Switzerland) will be performed in all patients with HPP and all CTRL at the ultradistal radius and the distal tibia, using the manufacturer's standard protocol. Volumetric bone Mineral density (vBMD) will be carried out. The peripheral trabecular density adjacent to the cortex and the central medullary trabecular density will be automatically evaluated. Bone microstructure including trabecular bone volume fraction, trabecular number, trabecular thickness inhomogeneity of the network, cortical thickness and cortical porosity will be analyzed. Measurements will be carried out by two well-trained physicians and performed with the latest available software (software version 6.0). Daily crosscalibrations with standardized control phantoms (Moehrendorf, Germany) will be conducted for validation.

Control-Group; HPP-Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

30 adult patients with genetical verified childhood-onset hypophophatasia. All data will be compared to a healthy, age- and gender-matched control Group (CTRL, n=30), recruited from the general population. Healthy controls will be matched by age and gender. All subjects will be recruited from the general population to avoid bias. The number of female and male subjects will be equal in both groups. Postmenopausal status will be taken into account.

You may qualify if:

• genetically verified hypophosphatasia
• age \>18 years
• written informed consent
• complete serological and radiological examinations
• healthy men and women without any history of musculoskeletal diseases
• written informed consent
• Alkaline phosphatase (AP) in reference range
• complete serological and radiological examinations

You may not qualify if:

• inflammatory diseases
• other genetic disorders affecting bone such as osteogenesis imperfecta, Ehlers-Danlos-syndrome and fibrous dysplasia
• diabetes mellitus type 1 and 2
• COPD
• chronic kidney and liver dysfunction
• systemic glucocorticoid use and glucocorticoid induced osteoporosis
• eating disorders
• HIV-infections and any malignancy including plasmacytosis and lymphoma.

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Medical University Vienna; St. Vincent Hospital

Vienna, 1060, Austria

Location

Related Publications (1)

• Haschka J, Messner Z, Feurstein J, Hadzimuratovic B, Zwerina J, Diendorfer AB, Pultar M, Hackl M, Kuzma M, Payer J, Resch H, Kocijan R. Circulating Micro-RNAs in Patients With Hypophosphatasia: Results of the First Micro-RNA Analysis in HPP. J Clin Endocrinol Metab. 2025 Sep 16;110(10):2741-2751. doi: 10.1210/clinem/dgaf080.

  PMID: 39930630 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Plasma/Serum Samples

MeSH Terms

Conditions

Hypophosphatasia; Bone Diseases, Metabolic

Interventions

MicroRNAs

Condition Hierarchy (Ancestors)

Metal Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Bone Diseases; Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

RNA, Antisense; Antisense Elements (Genetics); Nucleic Acids, Nucleotides, and Nucleosides; RNA; Nucleic Acids; RNA, Small Untranslated; RNA, Untranslated

Study Officials

• Roland Kocijan

  Vinforce Study Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Ass. Prof. Dr. Christian Muschitz

Study Record Dates

• First Submitted: June 13, 2019
• First Posted: July 12, 2019
• Study Start: August 1, 2017
• Primary Completion: March 1, 2023
• Study Completion: June 1, 2023
• Last Updated: January 26, 2023

Record last verified: 2023-01

Locations

AU (1)