Endocrine Abstracts

Asfotase alfa (AA, STRENSIQ, Alexion Pharmaceuticals, Inc.) is the first FDA-Approved treatment for patients with hypophosphatasia, the result of a mutation in the tissue-nonspecific alkaline phosphatase (ALPL) gene. Because it contains the ALP active site, AA is able to catalyse the substrate as the antibody-conjugated ALP would within an assay. Therefore, AA present in a patient’s sample may generate a false positive or a false negative result. We investigated ...

One of the most significant health measures implemented during the COVID-19 pandemic has been extended periods of lockdown. Vitamin D is essential for many biological functions including pregnancy and bone health and modulate the immune system. Many studies also suggested a beneficial effect of replenished stores of vitamin D (25(OH)D >50 nmol/l) against severe and long term COVID-19 and self-supplementation is recommended by the government. Here we report on the vitamin D...

Sclerostin (SOST) and Dickkopf-related protein 1 (DKK1) are antagonists of Wnt signalling, inhibiting osteoblast activity and indirectly stimulating osteoclast activity. SOST and DKK1 antibody therapy leads to increases in bone mass and bone formation. However, reported associations between plasma SOST and DKK1 concentrations and measures of bone mass and turnover are conflicting. This study in healthy older men and women (n =379; median 74.1 [IQR 71.5-77.0]y) investi...

Fibroblast growth factor 23 (FGF-23) is a phosphatonin produced by osteocytes in response to serum phosphate concentration. Immunoassays are widely employed to detect C-terminal fragments of FGF-23 (cFGF-23). Quantitative assays for intact FGF-23 (iFGF-23) measurement are also available. Causes of increased FGF-23 include Tumour Induced Osteomalacia (TIO), X-linked hypophosphataemic rickets (XLH) and end stage renal disease (ESRD). We observed that some individuals, with no id...

Introduction: In CKD, net effects of declining kidney function and increasing FGF23 (and PTH) concentrations on vitamin D catabolism and iron metabolism are not clear.Objectives: Compare the Biomedica to the Immutopics’ immunoassay for measurement of cFGF23. Determine the relationship between iron status; vitamin D and intact FGF23 (iFGF23) and c-terminal (cFGF23) concentrations in blood.Method: Samples from routine care and a...

Burosumab has become available as a treatment for children with X-linked hypophosphatemia (XLH) and is a recombinant fully human IgG1 against FGF23. By binding to the active FGF23, burosumab inhibits its effect and symptoms (growth retardation, rickets, enthesiopathy, low phosphate) may improve, however, not in all children. Concomitantly paediatricians are keen to measure FGF23, in treated children, to avoid overtreatment with burosumab, associated with potential calcificatio...

Background: 25-hydroxyvitamin D (25(OH)D) is metabolised into two forms of metabolites: 1,25-dihydroxyvitamin D (1,25(OH)2D) by the actions of 1α hydroxylase, and 24,25-dihydroxyvitamin D (24,25(OH)2D) by 24-hydroxylase. Studies suggest the production of 1,25(OH)2D is 24,25(OH)2D dependent. Genetic mutations of CYP24A1 gene resulting in reduced or total loss of 24-hydroxylase function are associated with hypercalcaemic condition...

Introduction: British Army recruits suffer from musculoskeletal injuries (MSI) during initial training. Up to 10% suffer skeletal stress fracture (SFx) resulting in lost training days and medical attrition. There is evidence to suggest that vitamin D deficiency is prevalent in the army. Our aim was to determine vitamin D metabolites (VDM) in recruits upon starting training, and health outcomes after a 14-week training programme.Methods: ...

Zoledronate in the Prevention of Paget’s disease (ZiPP) trial (ClinicalTrials.gov ID:NCT03859895) is a multi-centre, double-blind, placebo-controlled, randomised trial of Zoledronic acid (ZA) in sequestosome1 (SQSTM1) mutation carriers. SQSTM1 mutation has high penetrance and is associated with the early onset of Paget’s disease of bone. Participants with the SQSTM1 genotype received either a single dose of IV 5mg ZA (Aclasta, Novartis); intervention group n...

Hypomorphic CYP24A1 protein coding mutations causing inappropriate 1,25(OH)2D concentrations are associated with idiopathic infantile hypercalcemia and adult-onset hypercalciuria and nephrolithiasis. It is unclear why some cases present with CYP24A1-mediated abnormal calcium handling lack protein-coding CYP24A1 mutations. Non-coding region mutations, e.g. the 3’ UTR, impacting messenger RNA (mRNA) structure have rarely been studied in...