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

NCT04181164 | Unknown

• 1 other identifier: HvH-BABS-Study
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Hypophosphatasia (HPP)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Correlation between BMSi and fracture prevalence in the HPP-Group and the Control-Group.

  1. October 2019 - 31.July 2020

• Evaluation of differences in bone microarchitecture between the HPP- and Control-Group by high resolution peripheral quantitative computed tomography (HRpQCT).

  1. October 2019 - 31.July 2020

• 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)

  1. October 2019 - 31.July 2020

Study Arms (2)

HPP-Group

Adults with hypophosphatasia.

Other: Microindentation; Other: High resolution peripheral quantitative computed tomography (HRpQCT); Biological: Biochemical analysis of different bone markers.

Control-Group

Healthy control subjects.

Other: Microindentation; Other: High resolution peripheral quantitative computed tomography (HRpQCT); Biological: Biochemical analysis of different bone markers.

Interventions

Microindentation OTHER

Microindentation is a new technology directly measuring bone strength by a minimal invasive technique.

Control-Group; HPP-Group

High resolution peripheral quantitative computed tomography (HRpQCT) OTHER

HRpQCT scan can assess the cross-sectional geometry of the bone and is an appropriate investigation to evaluate bone quality.

Control-Group; HPP-Group

Biochemical analysis of different bone markers. BIOLOGICAL

Measurement of different bone markers by biochemical analysis of blood samples.

Control-Group; HPP-Group

Eligibility Criteria

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

Study Population

Adults, diagnosed with HPP (genetic verified) (n=15), matched 1:1 in case of gender, age (± 5 years), BMI (± 3 kg/m2), postmenopausal status (± 2 years) with healthy controls.

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• Hvidovre University Hospital: lead
• Odense University Hospital: collaborator

Study Sites (1)

Hvidovre University Hospital

Hvidovre, Capital Region, 2650, Denmark

Location

Related 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.

  PMID: 27840302 BACKGROUND

MeSH Terms

Conditions

Hypophosphatasia

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

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, MD

Study Record Dates

• First Submitted: November 18, 2019
• First Posted: November 29, 2019
• Study Start: October 1, 2019
• Primary Completion: September 30, 2021
• Study Completion: December 30, 2021
• Last Updated: September 1, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)