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 this issue of Seminars in Musculoskeletal Radiology 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 azotaemic osteodystrophy (metabolic bone disease associated with chronic renal failure). Paget's disease does, however, disrupt bone turnover (becomes increased) and has distinctive and diagnostic radiologic features so it is included as an article in this issue, and is mentioned in other articles as well (e.g., nuclear medicine imaging). The epicenter of Paget's disease is in Rochdale, in the Northwest corner of England and only a few miles from Manchester, so it is a relatively common disease in the area, whereas it is extremely rare in other parts of the world (e.g., the Middle and Far East).

The mineralization of bone matrix (osteoid) depends on the adequate supply of vitamin D in the form of its active metabolite 1,25 dihydroxyvitamin D (1,25(OH)₂), calcium, phosphorus and alkaline phosphatase, and on a normal pH in the body environment. If for any reason there is a deficiency of these substances, or if there is a severe systemic acidosis, then the mineralization of bone will be defective. This leads to a qualitative abnormality of bone, with reduction in the mineral to osteoid ratio, resulting in rickets in children and osteomalacia in adults. In the immature skeleton, the radiographic abnormalities predominate at the growing ends of bones where endochondral ossification is taking place, giving the classic radiographic appearances of rickets. In the mature skeleton, the defective mineralization of osteoid is evident radiographically as Looser's zones (i.e., pseudofractures, Milkman's fractures), which are pathognomonic of osteomalacia. However, a number of different diseases, such as vitamin D deficiency, hypophosphataemia (e.g., x-linked hypophosphataemic rickets), hypophosphatasia, and chronic renal failure, can cause rickets and osteomalacia, but the radiologic abnormalities found are similar, irrespective of the cause.

Fish oil, a rich source of vitamin D, was long recognized as a popular cure for "chronic rheumatism" (osteomalacia) in adults, and limb deformities (rickets) in children. The occurrence of rickets increased during the industrial revolution, largely through the lack of sunlight that accompanied the growth of industrial towns and cities, and the associated air pollution. The importance of adequate exposure to sunlight and ultraviolet light was recognized only later. Physiologic doses (400 IU per day) of vitamin D were found to cure some forms of rickets, but not others (chronic renal failure, X-linked hypophosphataemia) in which very large pharmacologic (up to 300,000 IU per day) doses were required for effect. This increased therapeutic requirement for vitamin D led to the terms "refractory rickets" and "vitamin D resistant rickets." There was therefore confusion between these conditions that had similar clinical and radiologic features, but clearly different courses of progression and responses to the therapies of the time. The unravelling of the structure and function of vitamin D and its metabolites during the twentieth century has explained the causes for this confusion and the variability in response to therapy. The metabolism and effects of vitamin D are covered by Berry, Davies, and Mee in the first article of this issue. Despite the increased knowledge and understanding of vitamin D metabolism and effective treatment to prevent deficiency, rickets is still prevalent, even in the Western world, and the reasons for this are discussed by Mughal in the next article. Imaging plays an important role in the identification of "oncogenic" rickets and osteomalacia, and in the localization of the tumor responsible for the disorder. The characteristic clinical, metabolic and imaging findings of this uncommon, but fascinating, entity are reviewed by Edmister and Sundaram in the third article, as is the radiologist's role in evaluation and diagnosis. Also included in the review are new insights into the pathophysiology of oncogenic osteomalacia.

Primary hyperparathyroidism is the third most common endocrine disorder (after diabetes and thyroid disorders) and, in the past, imaging played an important role in the diagnosis, but this has now changed. With auto-analysers for serum biochemistry routinely providing the measurement of serum calcium, phosphorus and alkaline phosphatase, more patients with primary hyperparathyroidism have come to diagnosis, many with mild and often asymptomatic disease. Few patients now present clinically with overt metabolic bone disease. As a consequence, the classical radiologic features (e.g., sub-periosteal erosions, chondrcalcinosis, bone cysts, nephrocalcinosis, renal stones) are now less frequently present, and may be seen in only about 5 to 10 % of patients. Because the skeletal abnormalities are so well recognized, albeit now uncommonly, I have chosen not to include a review on hyperparathyroidism. In contrast, osteoporosis (a quantitative abnormality of bone [too little bone]) is the most common of the metabolic bone disorders, affecting 1 in 3 women and 1 in 12 men during their lifetime. The low trauma fractures that occur are associated with considerable morbidity and mortality, with resultant significant socio-economic impacts for society and healthcare systems. Over the past 10 to 15 years, the number and efficacy of therapies available has increased (e.g., hormone replacement therapy [HRT], selective oestrogen modulators [SERMS], bisphosphonates), and the methods of bone densitometry that enable those at risk of osteoporosis to be identified before fractures occur have improved. The remainder of this issue covers these important aspects of the diagnosis and treatment of osteoporosis. These include the radiographic features and differential diagnoses, the importance, relevance, and definition of vertebral fractures and the principles, strengths, limitations, and technical developments in currently available methods of bone densitometry (i.e., dual energy X-ray absorptiometry [DXA], quantitative computed tomography [QCT], quantitative ultrasound [QUS]). Because of the recognized pitfalls of bone densitometry in children, a review by van Rijn and van Kuijk is dedicated to this important topic. There is currently research activity in the challenging field of imaging bone structure by high resolution CT and magnetic resonance imaging (MRI) to obtain histomorphometric measurements noninvasively, and to relate these parameters to the assessment of bone strength and quality. There is much interest generally in the radiographic community of vertebroplasty, and Deramond and Mathis, in the final article of this issue, cover the execution of this procedure for treatment of some patients with osteoporotic vertebral fracture.

I thank the editors for inviting me to be the guest editor for this and the following issue (Imaging in Metabolic Bone Disease, Part 2) of Seminars in Musculoskeletal Radiology. I am most grateful to all the expert contributors, 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.