Aromatase Inhibitors in the Treatment of Short Stature.
Abstract
Reports published in the 1990s of men with estrogen deficiency caused by defective aromatase or estrogen resistance due to a defective estrogen receptor α confirmed the crucial role of estrogen in bone maturation, closure of the epiphyses and cessation of statural growth. Based on these findings, it became reasonable to postulate that selective inhibition of estrogen synthesis with aromatase inhibitors could increase adult height by delaying bone maturation and prolonging the period of growth in males. To date, aromatase inhibitors have been employed in rare pediatric conditions associated with s...
Source: Endocrine Development - December 21, 2015 Category: Endocrinology Authors: Hero M Tags: Endocr Dev Source Type: research
Gene Therapy for Rare Central Nervous System Diseases Comes to Age.
Abstract
Gene therapy for rare inherited neurologic diseases has entered the clinics. One strategy relies upon the replacement of brain microglia using hematopoietic stem cell gene therapy with lentiviral vectors. Therapeutic success using this approach has been obtained in X-linked adrenoleukodystrophy and metachromatic leukodystrophy. The other strategy relies upon the intracerebral administration of adeno-associated virus vectors encoding lysosomal enzymes. Therapeutic trials are ongoing in Batten's disease, metachromatic leukodystrophy, and Sanfilippo type A and B diseases.
PMID: 26684481 [Pub...
Source: Endocrine Development - December 21, 2015 Category: Endocrinology Authors: Aubourg P Tags: Endocr Dev Source Type: research
Novel Therapeutic Targets and Drug Candidates for Modifying Disease Progression in Adrenoleukodystrophy.
Abstract
X-linked adrenoleukodystrophy (X-ALD) is the most frequent inherited monogenic demyelinating disease. It is often lethal and currently lacks a satisfactory therapy. The disease is caused by loss of function of the ABCD1 gene, a peroxisomal ATP-binding cassette transporter, resulting in the accumulation of very-long-chain fatty acids (VLCFA) in organs and plasma. Recent findings on pathomechanisms of the peroxisomal neurometabolic disease X-ALD have provided important clues on therapeutic targets. Here we describe the impact of chronic redox imbalance caused by the excess VLCFA on mitochondrial bio...
Source: Endocrine Development - December 21, 2015 Category: Endocrinology Authors: Pujol A Tags: Endocr Dev Source Type: research
Voyages of Discovery.
Abstract
The metabolism of calcium and bone is controlled by five principal hormones: parathyroid hormone, 1,25-dihydroxyvitamin D, calcitonin, parathyroid hormone-related peptide and fibroblast growth factor 23, some of which have been known for several decades and some of which have only more recently been identified. The stories of the discovery of these hormones have constituted a series of complex journeys that have been undertaken over the past century or so, none of which has yet been completed. The complexities of bone and calcium metabolism have been and remain, to many people, somewhat mysterious...
Source: Endocrine Development - July 5, 2015 Category: Endocrinology Authors: Allgrove J Tags: Endocr Dev Source Type: research
Physiology of Calcium, Phosphate, Magnesium and Vitamin D.
Abstract
The physiology of calcium and the other minerals involved in its metabolism is complex and intimately linked to the physiology of bone. Five principal humoral factors are involved in maintaining plasma concentrations of calcium, magnesium and phosphate and in coordinating the balance between their content in bone. The transmembrane transport of these elements is dependent on a series of complex mechanisms that are partly controlled by these hormones. The plasma concentration of calcium is initially sensed by a calcium-sensing receptor, which then sets up a cascade of events that initially determin...
Source: Endocrine Development - July 5, 2015 Category: Endocrinology Authors: Allgrove J Tags: Endocr Dev Source Type: research
Physiology of Bone.
Abstract
Bone serves three main physiological functions: its mechanical nature provides support for locomotion and offers protection to vulnerable internal organs, it forms a reservoir for the storage of calcium and phosphate in the body, and it provides an environment for bone marrow production and haematopoietic cell development. The traditional view of bone as a passive tissue that responds to hormonal and dietary influences has changed over the past half century to one of bone as a dynamic adaptive tissue that responds to mechanical demands. This chapter gathers together some recent advances in bone ph...
Source: Endocrine Development - July 5, 2015 Category: Endocrinology Authors: Grabowski P Tags: Endocr Dev Source Type: research
Radiology of Osteogenesis Imperfecta, Rickets and Other Bony Fragility States.
Abstract
This section gives an overview of radiological findings in bony fragility states, with a special focus on osteogenesis imperfecta (OI) and rickets. Conventional radiological assessment of bone density is inaccurate and imprecise and only reliably detects severe osteopaenia. However, other aspects of bone structure and morphology can be assessed, and it is possible to distinguish between osteopaenic and osteomalacic states. OI is a heterogeneous group of disorders of type 1 collagen formation and processing that are characterised by varying degrees of bony fragility, with presentations varying from...
Source: Endocrine Development - July 5, 2015 Category: Endocrinology Authors: Calder AD Tags: Endocr Dev Source Type: research
Bone Densitometry: Current Status and Future Perspective.
We describe bone densitometry measurement techniques that are currently available and consider the strengths and limitations of each technique, with particular emphasis on paediatric scanning. Magnetic resonance imaging is reviewed, as it is one of the newer technologies applied to assessment of the growing skeleton. The role of dual-energy X-ray absorptiometry and quantitative computed tomography in the clinical assessment of bone health in children is considered, and their current diagnostic application is reviewed. © 2015 S. Karger AG, Basel.
PMID: 26138836 [PubMed - in process] (Source: Endocrine Development)
Source: Endocrine Development - July 5, 2015 Category: Endocrinology Authors: Crabtree N, Ward K Tags: Endocr Dev Source Type: research
A Practical Approach to Hypocalcaemia in Children.
Abstract
Hypocalcaemia is one of the commonest disorders of mineral metabolism seen in children and may be a consequence of several different aetiologies. These include a lack of secretion or function of parathyroid hormone, disorders of vitamin D metabolism and abnormal function of the calcium-sensing receptor. A practical approach to the investigation, diagnosis and subsequent management of hypocalcaemic disorders is presented. © 2015 S. Karger AG, Basel.
PMID: 26138837 [PubMed - in process] (Source: Endocrine Development)
Source: Endocrine Development - July 5, 2015 Category: Endocrinology Authors: Shaw NJ Tags: Endocr Dev Source Type: research
Approach to the Child with Hypercalcaemia.
Abstract
Hypercalcaemia is rare in children. In adulthood, the causes are most frequently malignancy and primary hyperparathyroidism. In children, however, the aetiologies are diverse and age specific, and many have an underlying genetic basis. Hypercalcaemia is a serious condition that frequently leads to end-organ damage. In order to provide the most appropriate treatment, a key part of the management pathway is to establish the correct diagnosis promptly. When considering a practical approach to hypercalcaemia in children, it is helpful to consider the causes of hypercalcaemia according to the accompany...
Source: Endocrine Development - July 5, 2015 Category: Endocrinology Authors: Davies JH Tags: Endocr Dev Source Type: research
A Practical Approach to Vitamin D Deficiency and Rickets.
Abstract
Rickets is a condition in which there is failure of the normal mineralisation (osteomalacia) of growing bone. Whilst osteomalacia may be present in adults, rickets cannot occur. It is generally caused by a lack of mineral supply, which can either occur as a result of the deficiency of calcium (calciopaenic rickets, now known as parathyroid hormone-dependent rickets) or of phosphate (phosphopaenic rickets, now called FGF23-dependent rickets). Renal disorders may also interfere with the process of mineralisation and cause rickets. Only parathyroid hormone-dependent rickets and distal renal tubular d...
Source: Endocrine Development - July 5, 2015 Category: Endocrinology Authors: Allgrove J, Shaw NJ Tags: Endocr Dev Source Type: research
A Practical Clinical Approach to Paediatric Phosphate Disorders.
Abstract
Phosphate metabolism is critical to multiple systems and cellular functions. Disruption of any point in the pathways of phosphate metabolism may cause serum phosphate abnormalities and resultant acute or chronic clinical conditions. The study of phosphate disorders has revealed a wealth of information regarding normal phosphate physiology. Careful evaluation of affected patients based on pathophysiologic assessments will usually identify the aetiology of hypophosphataemia or hyperphosphataemia, which is important to guide appropriate therapy. Because of the relative importance of chronic hypophosp...
Source: Endocrine Development - July 5, 2015 Category: Endocrinology Authors: Imel EA, Carpenter TO Tags: Endocr Dev Source Type: research
Primary Osteoporosis.
Abstract
Primary osteoporosis in childhood encompasses a range of bone fragility conditions that typically have a genetic origin. Understanding of the pathophysiology and genetics of primary osteoporosis has increased dramatically over the past 10 years. The clinical manifestations and consequences of the disease range from mild to severe, with the degree of growth retardation and bony deformity reflecting the severity and the underlying pathology. In children, primary osteoporosis is most commonly caused by one of the forms of osteogenesis imperfecta, which comprises a group of disorders characterised by ...
Source: Endocrine Development - July 5, 2015 Category: Endocrinology Authors: Arundel P, Bishop N Tags: Endocr Dev Source Type: research
Osteoporosis in Children with Chronic Disease.
Abstract
Serious illness in children and its therapy can cause osteoporosis, manifesting as vertebral and nonvertebral fractures, pain, skeletal deformity and temporary or even permanent loss of ambulation. In contrast to adults, skeletal growth in children offers tremendous potential to recover bone mineral density and to reshape fractured vertebral bodies, even without bone-targeted therapy, provided that bone health threats are transient and residual growth is sufficient. Here, we outline the principles of bone strength development and the risk factors for osteoporosis due to various paediatric systemic...
Source: Endocrine Development - July 5, 2015 Category: Endocrinology Authors: Högler W, Ward L Tags: Endocr Dev Source Type: research
Genetics of Osteoporosis in Children.
Abstract
In the pathogenesis of paediatric osteoporosis, genetic causes may play an important role. The most prevalent monogenic cause of paediatric osteoporosis is osteogenesis imperfecta, a disorder characterised primarily by liability to fractures. With regard to diagnosis or exclusion of a monogenic cause of paediatric osteoporosis, clinical practice has changed rapidly in recent years. This is largely due to the discovery of many new genetic causes in patients with a clear clinical diagnosis of osteogenesis imperfecta but also due to the identification of genetic causes in patients with isolated or no...
Source: Endocrine Development - July 5, 2015 Category: Endocrinology Authors: van Dijk FS Tags: Endocr Dev Source Type: research
