Hypophosphatasia (HPP)
Conditions
Brief summary
The study aims to evaluate the bone architecture and bone strength in adults with Hypophosphatasia (HPP).
Interventions
OTHERMicroindentation
Microindentation is a new technology directly measuring bone strength by a minimal invasive technique.
OTHERHigh 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.
BIOLOGICALBiochemical analysis of different bone markers.
Measurement of different bone markers by biochemical analysis of blood samples.
Sponsors
Odense University Hospital
Hvidovre University Hospital
Study design
Observational model
CASE_CONTROL
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Differences in Bone Mineral Strength Index (BMSi) between the two groups, assessed by microindentation (OsteoProbe®). | 1. October 2019 - 31.July 2020 | 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) \[1\]. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation between BMSi and fracture prevalence in the HPP-Group and the Control-Group. | 1. October 2019 - 31.July 2020 | 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. |
| 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 | 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. |
| 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 | 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 |
Countries
Denmark
Outcome results
None listed