Endocrine development最新文献

As many as 50% of children will sustain a fracture before 18 years of age, and up to 20% will have two or more fractures. A small proportion of children who experience multiple fractures have osteoporosis, either from a genetic bone disorder (primary osteoporosis) or secondary to another underlying medical condition (secondary osteoporosis). Fracture history, together with bone mineral density assessment and vertebral radiographs, help clinicians to identify children with osteoporosis. Its aetiology can usually be determined through the combination of a detailed medical history and physical examination, laboratory investigations to assess mineral homeostasis, evaluation of secondary causes of osteoporosis and genetic studies to identify the underlying cause of the disorder. Transiliac bone biopsy with histology and histomorphometry should not be overlooked as valuable tools for the investigation of a child with osteoporosis of uncertain aetiology. Optimal management of osteoporosis requires a multidisciplinary team to address physical activity, nutrition, pubertal progression, the management of any underlying medical condition, pharmacotherapy (bisphosphonates) and orthopaedic surgery. This chapter outlines an approach to the evaluation and treatment of children with recurrent fractures and describes three common scenarios involving infants, children with chronic illness and children without chronic illness.

Inflicted non-accidental skeletal injuries form a small but important part of the spectrum of child abuse, with the majority of skeletal injuries occurring in children under 2 years of age. Radiology plays a vital role in the detection and evaluation of these skeletal injuries. A thorough detailed radiological evaluation should be undertaken to investigate a child appropriately for a suspected inflicted non-accidental injury to accurately detect and possibly date any injuries and also to exclude normal variants of growth that may mimic fractures. In some cases, the survey may diagnose an underlying metabolic or genetic disorder of the bone that may predispose the child to fracturing. While radiology plays an important role in the dating of injuries, the dating of fractures from radiological appearances is difficult and imprecise. Any fracture may be the result of an inflicted injury or accidental event. Therefore, it is important that all fractures identified are correlated with any relevant clinical history. Certain injuries, such as rib and metaphyseal fractures, require a more specific method of causation and therefore carry a higher degree of suspicion of being the result of an inflicted injury compared with other fracture types, which are relatively non-specific in their mechanisms of causation, such as skull and clavicular fractures. In all cases, correlation with clinical history is mandatory.

Classification is a natural human trait that enables us to put what may otherwise be very complex subjects into some order. However, classification should be seen not as an end in itself but rather as a means to help us understand certain topics. In the case of medicine, classification helps to provide information about the causes underlying many of the conditions encountered and, in some cases, provides a rationale for developing new treatments. This chapter aims to provide a helpful (if complex) classification of diseases of bone and calcium and, where known, to describe the underlying genetic mechanisms.

Conditions related to abnormalities of calcium and bone metabolism are large in number and are characterised by hypocalcaemia, hypercalcaemia, primary and secondary osteoporosis, rickets resulting from both vitamin D and phosphate metabolism disorders, and a series of miscellaneous conditions. Included in this chapter is a series of cases drawn from our clinics and from colleagues who have presented these clinical problems at the recent Advanced Courses in Paediatric Bone and Calcium Metabolism run by the British Paediatric and Adolescent Bone group. This series of cases is not fully comprehensive but is designed to cover the major aspects of bone- and calcium-related disorders.

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 and a daunting task to understand. This book is designed to try to unravel those mysteries and present them in an interesting and comprehensible manner.

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 accompanying levels of parathyroid hormone (PTH), indicating whether the causes are PTH dependent or PTH independent. This chapter reviews the recent advances in this area and presents a practical approach to the investigation and subsequent management of this condition.

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 non-syndromal osteoporosis with fractures. In this chapter, known monogenic causes of syndromal and non-syndromal osteoporosis in children will be described. Furthermore, we will discuss when to refer for clinical genetic evaluation as well as the current and future merits of genetic evaluation of children with osteoporosis.

In this chapter, we discuss the concept of what determines bone strength and fracture risk and how this can be quantified using current technologies. 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.

This chapter deals with a few of the important childhood bone disorders associated with high bone mass as well as conditions associated with fragility fractures and limb deformities that have not been addressed in previous chapters. A couple of skeletal dysplasias that can sometimes be confused with rickets are also dealt with in this chapter.

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 physiology and molecular cell biology and discusses the potential application of the functional adaptation of bone to loading to enhance bone strength during childhood and adolescence.