Imaging in Metabolic Bone Disease

Metabolic bone disease can result from genetic, endocrine, nutritional, and biochemical disorders that affect bone as a tissue. As a result, all the bones of the skeleton are affected to some degree and show histological changes typical of each form of metabolic bone disease, although abnormalities may not be evident on imaging. All the diseases included in Part 1 (Semin Mulsculoskel Radiol 2002; 6.3) and Part 2 (this issue) of "Imaging in Metabolic Bone Disease" conform to this definition, except for Paget's disease, which may be monostotic or polyostotic, but does not generally affect all bones, and tumoral calcinosis, which shares some features (e.g. metastatic calcification) with azotemic osteodystrophy (metabolic bone disease associated with chronic renal failure). The article on drug-induced skeletal disorders mainly covers the osteoporotic and ricketic/osteomalcic syndromes that arise as complications of treatments given for other conditions, but for completeness, also covers other drug-induced bone disorders.

Paget's disease does disrupt bone turnover (becomes increased), and has distinctive and diagnostic radiological features, so it is included as a separate article, and is mentioned in others (e.g., nuclear medicine imaging). The epicenter of Paget's disease is in Rochdale, in the Northwest of England and only a few miles from Manchester, so it is a relatively common disease in these parts, whereas it is extremely rare in other parts of the world, such as the Middle and Far East. The second section of this issue covers the less common forms of metabolic bone diseases. These conditions may show radiological features that are diagnostic of them. In addition, there have been major developments in the genetic and biochemical understanding of these disorders. These aspects are covered in the following articles, all of which have been written by experts in the field.

The first article covers pseudo-hypoparathyroidism (PHP), which was the first hormone resistance syndrome to be recognized in humans. The original description was given by Fuller Albright and colleagues in 1942. They described a 28-year-old woman who presented with hypocalcaemic fits; had a mental age of 7 years; and had a short stocky build, round face, brachydactyly, and ectopic calcification. Her biochemical abnormalities seemed typical of hypoparathyroidism, but the biochemical response to parathyroid hormone was abnormal, indicating an end-organ resistance to parathyroid hormone (PTH). The constellation of physical features is now known as Albright's Hereditary Osteodystrophy (AHO). Ten years later, Albright presented another patient with AHO, but with no biochemical abnormality. Because of the resemblance to PHP, the condition was named pseudo-pseudo-hypoparathyroidism (PPHP). Over the ensuing years, other AHO and PPHP patients have been described; much more is known about the genetic and biochemical basis for the disorders, and these are reviewed in detail. PHP and PPHP are not interchangeable terms, although within different members of the same family, they can be etiologically linked. A number of drugs may have metabolic effects on, and result in abnormal changes in, the musculoskeletal system. These medications may affect the developing fetus, infant, child, or adult, and may manifest as drug-induced embryopathies, osteoporosis, osteomalacia and/or rickets, or be associated with proliferative bone changes. Not uncommonly, the radiologist may be the first clinician to identify the metabolic manifestations of these medications, so the second article in this issue is a thorough review of this topic.

Osteopetrosis is a rare, inherited, sclerosing dysplasia of bone, caused by defective function of the osteoclasts, and having very characteristic dense, and abnormally modelled, bones on radiographs. At first, the disease was divided into the severe infantile recessive and the more benign, autosomal dominant types. However, clinical differences and progress in genetic understanding have now enabled identification of two distinct autosomal dominant types. Classification continues to evolve as genetic features are established, and treatment of the severe recessive disease by bone marrow transplantation offers therapeutic opportunity in a condition that is otherwise fatal. Idiopathic hyperphosphatasia is another rare, autosomal recessive bone disorder, characterised by excessive bone resorption and bone formation. The radiographic appearances include widening of the diaphyses, vertebral osteoporosis, acetabular protrusion and thickening of the skull vault. There is considerable variability in phenotype-with some cases diagnosed in infancy and others later in childhood. There have been important developments in the understanding of the genetic basis for this disorder that are described in the article in detail, as are the approaches to treatment.

Nuclear medicine (NM) is an important imaging tool in metabolic bone disorders because it is sensitive to identification of bone abnormalities, sometimes before radiographic features are evident (Looser's zones in osteomalacia). Isotope scans can show the extent of the bone involvement (e.g., Paget's disease), and help in localizing overactive parathyroid tissue. It therefore seemed desirable to have an article covering this imaging modality, and its application to the diagnosis and management of metabolic bone disorders.

Although not always strictly associated with metabolic bone disease, it seemed appropriate to include an article on tumoral calcinosis in this issue of Seminars. Tumoral calcinosis (TC) can give very dramatic radiographic appearances, with large calcified soft tissue masses, particularly around the large joints. The various theories proposed to explain the cause of TC are described in detail. However, an inborn error of renal handling of phosphorus is generally accepted as the primary cause, resulting in hyperphosphataemia. This condition must be differentiated from the metastatic calcification that may occur in association with chronic renal impairment with secondary hyperparathyoidism.

Animals are not immune from developing metabolic bone diseases, particularly when taken out of their natural habitats to zoos and other non-native environments. I was impressed some years ago when I saw florid osteomalacia in a lizard that was kept in a zoo. I thought it would be fun to conclude the issue with an article on metabolic bone disorders and their causes in animals.

I thank the editors for entrusting me to be the guest editor for the two issues on "Imaging in Metabolic Bone Disease"; I am most grateful to all the experts-drawn from many and varied medical and scientific disciplines-who have been willing to contribute their knowledge and experience. They have enabled the journal to fulfil its objective of providing topical reviews of clinical and technical advances, and innovations in the field of metabolic bone diseases.