Clinical trial NCT04181164: Evaluation of Bone Architecture and Bone Strength in Adults With Hypophosphatasia (HPP)
Official title: Evaluation of Bone Architecture and Bone Strength in Adults With Hypophosphatasia (HPP)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Hypophosphatasia (HPP)
Lead sponsor: Hvidovre University Hospital
Sponsor class: OTHER
Collaborators: name: Odense University Hospital
First posted: 2019-11-29
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
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.

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


Eligibility criteria: 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

Primary outcomes:
measure: Differences in Bone Mineral Strength Index (BMSi) between the two groups, assessed by microindentation (OsteoProbe®).
timeFrame: 1. October 2019 - 31.July 2020
Secondary outcomes:
measure: Correlation between BMSi and fracture prevalence in the HPP-Group and the Control-Group.
timeFrame: 1. October 2019 - 31.July 2020
measure: Evaluation of differences in bone microarchitecture between the HPP- and Control-Group by high resolution peripheral quantitative computed tomography (HRpQCT).
timeFrame: 1. October 2019 - 31.July 2020
measure: 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)
timeFrame: 1. October 2019 - 31.July 2020
Other outcomes:
Locations:
city: Hvidovre
country: Denmark
facility: Hvidovre University Hospital
state: Capital Region
Study officials:
References:
citation: 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.