Characterisation of adult onset hypophosphatasia v1.0
Research type
Research Study
Full title
Characterisation of adult onset hypophosphatasia
IRAS ID
202179
Contact name
Richard Eastell
Contact email
Sponsor organisation
Sheffield Teaching Hospitals
Duration of Study in the UK
1 years, 9 months, 30 days
Research summary
Summary of Research
Hypophosphatasia (HPP) is an inherited condition which causes a defect in bone calcification, leading to weak bones. Early childhood forms are severe and easily recognised, and there is now a drug treatment which is very effective in children. Adult forms are milder, often missed by doctors or confused with osteoporosis. This is important because the usual osteoporosis treatments may be harmful in HPP, and increase the risk of broken bones. One of the reasons it is missed is a lack of research describing the typical features of HPP, so doctors don’t recognise the signs, and don’t know when or how to test for it.
Our aim is to establish clear criteria (from clinical history, examination and blood tests) to identify people with HPP. The results will also determine if there should be a trial of drug treatment for adults with HPP.
We have previously collected blood samples from 2000 patients referred to osteoporosis clinics in Sheffield and Oxford. We will test these samples for possible signs of HPP, and invite people with possible HPP and people with normal blood tests (a control group) to come for more detailed tests and an assessment with a doctor. We will use the information to investigate which symptoms and blood tests are the best way to identify HPP.Summary of Results
Patients with hypophosphatasia (HPP) were younger, more likely to have had breaks of the bones (fractures) in their feet (metatarsals) or in their femur. They were less likely to have fractures in their spine when compared to patients with low bone mineral density (BMD).
The HPP group had lower alkaline phosphatase (ALP - used to diagnose disorders in the bone), higher pyridoxal 5′ -phosphate (PLP - related to the presence and severity of HPP), and lower vitamin D (necessary for strong bones and muscles). The low-BMD group had lower C-terminal telopeptide (CTX) and tartrate-resistant acid phosphatase 5b (TRACP5b) - both measures of bone breakdown. However 62% of the low BMD group were taking bisphosphonates to reduce bone loss.
Dual energy x-ray absorptiometry (DXA) showed that the HPP group had higher hip and spine BMD compared with the low BMD group. No differences were found between the two groups when physical functioning tests were performed.In summary, the SHADES study showed that low ALP and high PLP measurements, younger age, fractures in the metatarsals and/or femur without low BMD could be used to help clinicians recognize which adult patients should be further evaluated for HPP.
REC name
North West - Greater Manchester East Research Ethics Committee
REC reference
16/NW/0385
Date of REC Opinion
21 Jun 2016
REC opinion
Further Information Favourable Opinion