Evaluation of Bone Architecture and Bone Strength in Adults With Hypophosphatasia (HPP)

Hypophosphatasia (HPP) Clinical Trial

— BABS  

Official title:

Evaluation of Bone Architecture and Bone Strength in Adults With Hypophosphatasia (HPP)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04181164
• Other study ID #: HvH-BABS-Study
• Status: Active, not recruiting
• Start date: October 1, 2019
• Est. completion date: December 30, 2021

Study information

• Verified date: August 2021
• Source: Hvidovre University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The study aims to evaluate the bone architecture and bone strength in adults with Hypophosphatasia (HPP).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 30
• Est. completion date: December 30, 2021
• Est. primary completion date: September 30, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria HPP-Group:

• Genetically verified HPP

• Age: = 18 years

• Persistently low levels of alkaline phosphatase (ALP) = 35 U/L (normal range 35-105 U/L)

• At least one of the following symptoms: a) dental manifestations; b) musculoskeletal pain; c) history of fracture(s)

• Submitted informed consent

Inclusion Criteria Control-Group:

• No ALP measurements = 45 U/l and = 50% of all ALP measurements, registered in the electronical clinical journal = 55 U/l

• Normal parathyroid hormone (PTH) and Pyridoxal-5´-phosphate (PLP)

• Vitamin D3 = 25 nmol/L

• Submitted informed consent

Exclusion criteria HPP-Group:

• Pregnancy

• Skin infection or severe skin affection in the measurement area of microindentation

• Known allergy to Lidocain

• Former or current medical treatment influencing bone metabolism (oral corticosteroid > 12 weeks, former or current anti-osteoporosis treatment at any time (regardless drug holiday), all kind of sex steroids (excluding oral contraception), anti-convulsants)

• Current malignant disorders

Exclusion Criteria Control-Group:

• Family history of a genetic metabolic bone disease (HPP, Osteogenesis imperfecta)

• Rickets in childhood

• Former or current Osteoporosis

• Former or current Osteomalacia

• Known diabetes

• Former or current medical treatment influencing bone metabolism (oral corticosteroid > 12 weeks, former or current anti-osteoporosis treatment at any time (regardless drug holiday), all kind of sex steroids (excluding oral contraception), anti- convulsants)

• Skin infection or severe skin affection in the measurement area of microindentation

• Chronic liver or gallbladder disease

• Current malignant disorders

• Former or current thyrotoxicosis (T4 over normal range = 6 months)

• Cushing disease

• Pregnancy

Related Conditions & MeSH terms

• Hypophosphatasia
• Hypophosphatasia (HPP)

Intervention

Other:
• Microindentation
Microindentation is a new technology directly measuring bone strength by a minimal invasive technique.
• High resolution peripheral quantitative computed tomography (HRpQCT)
HRpQCT scan can assess the cross-sectional geometry of the bone and is an appropriate investigation to evaluate bone quality.

Biological:
• Biochemical analysis of different bone markers.
Measurement of different bone markers by biochemical analysis of blood samples.

Locations

Country	Name	City	State
Denmark	Hvidovre University Hospital	Hvidovre	Capital Region

Sponsors (2)

Lead Sponsor	Collaborator
Hvidovre University Hospital	Odense University Hospital

Country where clinical trial is conducted

Denmark, 

References & Publications (1)

Herrera S, Diez-Perez A. Clinical experience with microindentation in vivo in humans. Bone. 2017 Feb;95:175-182. doi: 10.1016/j.bone.2016.11.003. Epub 2016 Nov 11. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Differences in Bone Mineral Strength Index (BMSi) between the two groups, assessed by microindentation (OsteoProbe®).	Differences in BMSi between the HPP- and Control-Group will be evaluated by microindentation (OsteoProbe®).; Microindentation is a technology directly measuring bone strength by a minimal invasive technique. By applying a standardized pressure with a probe, which at the same time measures the indentation depth in the tibia bone, a measure of bone strength is obtained and calculated as Bone Mineral Strength Index (BMSi) [1].	1. October 2019 - 31.July 2020
Secondary	Correlation between BMSi and fracture prevalence in the HPP-Group and the Control-Group.	BMSi will be evaluated by microindentation (described above). In addition, information about the occurrence of fractures in the HPP- and Control-Group will be obtained by data from the Danish National Patient Register and a structured clinical interview.	1. October 2019 - 31.July 2020
Secondary	Evaluation of differences in bone microarchitecture between the HPP- and Control-Group by high resolution peripheral quantitative computed tomography (HRpQCT).	To asses differences in bone architecture between the two groups, the non-dominant distal radius and non-dominant distal tibia will be examined by HRpQCT, which will provide data about total, trabecular and cortical BMD, trabecular thickness, cortical thickness, trabecular number, stiffness and finite element failure load of the radius and tibia.	1. October 2019 - 31.July 2020
Secondary	Evaluation of differences in bone homeostasis between the two groups by biochemical analysis of different bone markers (P1NP, CTx, BALP, Trab-5, Sclerostin, Osteocalcin and FGF23)	Blood samples will be collected for biochemical analysis of different bone markers (P1NP, CTx, BALP, Trab-5, Sclerostin, Osteocalcin and FGF23).; BALP = Bone specific alkaline phosphatase CTx = Carboxy-terminal collagen crosslinks FGF-23 = Fibroblast growth factor 23 P1NP = Procollagen type 1 amino-terminal propeptide Trab-5 = Tartrate-resistant acid phosphatase-5	1. October 2019 - 31.July 2020