HypophosphatasiaNCT04018287
Circulating miRNAs and Bone Microstructure in Adults With Hypophosphatasia
An observational study of Hypophosphatasia and Bone Diseases, Metabolic, run by Medical University of Vienna at 1 site in Austria.
Trial summary
The aim of the study is to accomplish a complete bone status of patients with HPP using new approaches to assess bone quality. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Hypophosphatasia, Bone Diseases, Metabolic, Bone
- What is being tested?
- HR-pQCT scans, BMD measurements, bone specific circulating microRNAs (miRNAs)
- How many people
- 60 participants
- Where
- 1 siteAustria
- Study dates
- 1 Aug 2017to 1 Jun 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
The aim of the study is to accomplish a complete bone status of patients with HPP using new approaches to assess bone quality.
Read the detailed description
Hypophosphatasia (HPP) is a hereditary disease of bone metabolism that is not yet curable. Clinical phenotype is variable and reaches from demineralization of bone, deformation of the skeleton, microsomia and gait abnormality to breathing difficulties. Symptoms of the adult form are low-traumatic fractures, hip or thigh pain and arthropathy. Cause of the disease is a mutation in the ALPL-gene (1p36.1-p34) coding for the tissue-nonspecific isoenzyme of alkaline phosphatase (TNAP) in liver, bone and kidney. This leads to a low activity of alkaline phosphatase (AP) and elevated levels of phosphoethanolamine (PEA) in urine.
HPP is a very rare disease with a prevalence of ~1/100 000. The Medical Department II of the St. Vincent Hospital Vienna, Department of the Medical University of Vienna and the Sigmund Freud University Vienna is a department that is specialized on bone diseases and, as a member of "Orphanet", also on In particular, (i) bone microstructure as a main component of bone strength and (ii) circulating microRNAs (miRNAs) as promising biomarkers for bone diseases will be analyzed in patients with HPP and age-, and gender-matched healthy controls.
Microstructural deteriorations of cortical and trabecular bone as well as volumetric bone density (vBMD) in radius and tibia in patients with HPP will be compared to healthy individuals using HR-pQCT (High resolution peripheral quantitative computer tomography, Scanco Medical, Brütisellen). HR-pQCT is a high-resolution, non-invasive technique to measure cortical and trabecular bone mircostructures as well as vBMD at a high resolution level (82µm).
Micro-RNAs (miRNAs) are short, non-coding RNA molecules of which some have been identified as bone specific (e.g. miR-31, miR-335, miR-155, miR-29b, miR-188, miR-550a). They play a significant role in bone metabolism controlling synthesis and function of osteoblasts as well as osteoclasts.
In recent studies we could show that these microRNAs can be detected in serum and that their serum concentration correlates with the risk for osteoporotic fractures. Data for patients with HPP do not exist yet. miRNAs will be measured by qPCR (quantitative polymerase chain reaction) in serum of patients with HPP and respective controls.
In addition, measurements of areal BMD (aBMD) by DXA (Dual Energy X-ray Absorptiometry) and DXL (Dual X-ray and Laser) will be performed. Vitamin D and established bone turnover markers including PINP (N-terminal propeptide of type I collagen), CTX (collagen type 1 cross-linked C-telopeptid) and sclerostin will be analyzed. Moreover, body composition will be determined.
- Conditions
- Hypophosphatasia, Bone Diseases, Metabolic, Bone
- Being tested
- HR-pQCT scans, BMD measurements, bone specific circulating microRNAs (miRNAs)
- Keywords
- microRNAs, bone microstructure
- Medical subject headings
- Hypophosphatasia, Bone Diseases, Metabolic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| HPP-Group | 1. genetical verified hypophosphatasia
2. age >18 years
3. written informed consent
4. complete serological and radiological examinations Receives: 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 Receives: Other: HR-pQCT scans, BMD measurements, bone specific circulating microRNAs (miRNAs) |
What is being measured
The primary outcome is the main question the study is designed to answer.
HR-pQCT
non-invasively measurement of trabecular and cortical bone microstructure
Measured: Assessment once after Inclusion is completed.
microRNA pattern
bone specific circulating microRNAs (miRNAs) in the serum of adult patients
Measured: Assessment once after Inclusion is completed
Secondary outcomes (2)
DXA Scanning
measurement of areal bone mineral density (aBMD) at the lumbar spine, radius, total body and hip by DXA • measurement of aBMD at the calcaneus by DXL
Measured: Assessment once after Inclusion is completed.
Bone Turnover Markers (BTMs)
serological analysis of established BTMs including PINP, CTX and sclerostin
Measured: Assessment once after Inclusion is completed.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2019
- Study start1 Aug 2017
- Primary completion1 Mar 2023 (estimated)
- Study completion1 Jun 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypophosphatasiaStudies of the same condition, open and under way.
- More trials run by Medical University of ViennaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University of Vienna
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Christian Muschitz, Medical University of Vienna
- Investigators
- Roland Kocijan, Principal investigator, Vinforce Study Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04018287
- Sponsor's protocol ID
- HPP-study
- Status last verified
- Jan 2023
- First submitted
- 13 Jun 2019
- Last updated
- 26 Jan 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 39930630
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Circulating miRNAs and Bone Microstructure in Adults With Hypophosphatasia
- ClinicalTrials.gov ID
- NCT04018287
- Acronym / sponsor ID
- HPP-study
- Conditions
- Hypophosphatasia, Bone Diseases, Metabolic, Bone
- Keywords
- microRNAs, bone microstructure
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Medical University of ViennaUniversity, hospital or other
- Study start
- 1 Aug 2017 (actual)
- Primary completion
- 1 Mar 2023 (estimated)
- Study completion
- 1 Jun 2023 (estimated)
- First posted
- 12 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of the study is to accomplish a complete bone status of patients with HPP using new approaches to assess bone quality.
Detailed description
Hypophosphatasia (HPP) is a hereditary disease of bone metabolism that is not yet curable. Clinical phenotype is variable and reaches from demineralization of bone, deformation of the skeleton, microsomia and gait abnormality to breathing difficulties. Symptoms of the adult form are low-traumatic fractures, hip or thigh pain and arthropathy. Cause of the disease is a mutation in the ALPL-gene (1p36.1-p34) coding for the tissue-nonspecific isoenzyme of alkaline phosphatase (TNAP) in liver, bone and kidney. This leads to a low activity of alkaline phosphatase (AP) and elevated levels of phosphoethanolamine (PEA) in urine.
HPP is a very rare disease with a prevalence of ~1/100 000. The Medical Department II of the St. Vincent Hospital Vienna, Department of the Medical University of Vienna and the Sigmund Freud University Vienna is a department that is specialized on bone diseases and, as a member of "Orphanet", also on In particular, (i) bone microstructure as a main component of bone strength and (ii) circulating microRNAs (miRNAs) as promising biomarkers for bone diseases will be analyzed in patients with HPP and age-, and gender-matched healthy controls.
Microstructural deteriorations of cortical and trabecular bone as well as volumetric bone density (vBMD) in radius and tibia in patients with HPP will be compared to healthy individuals using HR-pQCT (High resolution peripheral quantitative computer tomography, Scanco Medical, Brütisellen). HR-pQCT is a high-resolution, non-invasive technique to measure cortical and trabecular bone mircostructures as well as vBMD at a high resolution level (82µm).
Micro-RNAs (miRNAs) are short, non-coding RNA molecules of which some have been identified as bone specific (e.g. miR-31, miR-335, miR-155, miR-29b, miR-188, miR-550a). They play a significant role in bone metabolism controlling synthesis and function of osteoblasts as well as osteoclasts.
In recent studies we could show that these microRNAs can be detected in serum and that their serum concentration correlates with the risk for osteoporotic fractures. Data for patients with HPP do not exist yet. miRNAs will be measured by qPCR (quantitative polymerase chain reaction) in serum of patients with HPP and respective controls.
In addition, measurements of areal BMD (aBMD) by DXA (Dual Energy X-ray Absorptiometry) and DXL (Dual X-ray and Laser) will be performed. Vitamin D and established bone turnover markers including PINP (N-terminal propeptide of type I collagen), CTX (collagen type 1 cross-linked C-telopeptid) and sclerostin will be analyzed. Moreover, body composition will be determined.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HPP-Group | – | Other: HR-pQCT scans, BMD measurements, bone specific circulating microRNAs (miRNAs)1. genetical verified hypophosphatasia 2. age >18 years 3. written informed consent 4. complete serological and radiological examinations |
| Control-Group | – | Other: HR-pQCT scans, BMD measurements, bone specific circulating microRNAs (miRNAs)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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (8 listed)
- genetically verified hypophosphatasia
- age >18 years
- written informed consent
- complete serological and radiological examinations
- healthy men and women without any history of musculoskeletal diseases
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HR-pQCT scans, BMD measurements, bone specific circulating microRNAs (miRNAs)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. | Other | Control-Group, HPP-Group |
Primary outcome
HR-pQCT
Time frame: Assessment once after Inclusion is completed.
non-invasively measurement of trabecular and cortical bone microstructure
microRNA pattern
Time frame: Assessment once after Inclusion is completed
bone specific circulating microRNAs (miRNAs) in the serum of adult patients
2 secondary outcomes
DXA Scanning
Time frame: Assessment once after Inclusion is completed.
Bone Turnover Markers (BTMs)
Time frame: Assessment once after Inclusion is completed.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2023.
- Derived from this study: PubMed 39930630Haschka 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roland Kocijan principal investigator
Vinforce Study Group
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hypophosphatasia and Bone Diseases, Metabolic, run by Medical University of Vienna at 1 site in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 26 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
HR-pQCT (time frame: Assessment once after Inclusion is completed.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04018287, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jan 2023.