Endocrine Abstracts

Hypophosphatasia (HPP), a heritable metabolic bone disease, results from low alkaline phosphatase (TNSALP) activity. Inorganic pyrophosphate (PPi), an inhibitor of mineralization, and pyridoxal 5′-phosphate (PLP), are substrates that accumulate in HPP. There is no approved therapy. ENB-0040, a bone-targeted, recombinant, human TNSALP improves skeletal mineralization in affected infants and children with HPP.Objective: Evaluate substrate levels and ...

Introduction: The role of dietary protein in maintaining bone health is controversial. Traditionally the acidifying effect of high dietary protein (HP) has been thought to promote calcium loss from bone and hence hypercalciuria and so was considered harmful compared to a normal protein (NP) diet. However more recently the anabolic effect of increased dietary protein and its effect in increasing calcium absorption have been appreciated. There are no long term prospective clinic...

Insulin-like factor 3 (INSL3) is a testis-specific, Leydig cell derived hormone, which we recently demonstrated to play a role in bone metabolism. Young men with mutations in the gene for the INSL3 receptor (Relaxin family peptide 2, RXFP2) are at risk of reduced bone mass and osteoporosis. Consistent with the human phenotype, bone analyses of Rxfp2−/− mice showed decreased bone volume, alterations of the trabecular bone, reduced mineralizing surface, bo...

Heart failure (HF) has been associated with bone loss and an increased risk of fragility fractures. Indeed, most of literature data on fractures were based on an historical and clinical approach focused on the identification of peripheral fractures, whereas the risk of vertebral fractures in this clinical setting is still unclear. In this study, we aimed at evaluating the prevalence of radiological vertebral fractures in 791 consecutive elderly and hospitalized patients (372 f...

Pseudohypoparathyroidism (PHP) type I includes two major subtypes, Ia and Ib. About 70% of Ia patients, characterized by Albright hereditary osteodystrophy and multihormone resistance (PTH/TSH/GHRH/gonadotropins), carry point mutations in GNAS exons encoding Gsα. About 60% of Ib patients, with hormone resistance limited to PTH and TSH, have methylation defects within GNAS locus (sporadic or genetic-based). Recently, methylation defects were detected in pts with Ia phenoty...

The majority of patients affected with pseudohypoparathyroidism type 1b (PHP-1b) display loss of imprinting (LOI) encompassing the GNAS locus responsible for decreased Gsa expression in target tissues and PTH resistance. In other imprinting disorders like Silver-Russell, Wiedemann-Beckwith syndromes or transient neonatal diabetes mellitus due to LOI of the imprinted 11p15 and 6q24 regions respectively, we and others have shown that the LOI may spread over to other imprinted lo...