Nuclear medicine of bone

Bone scintigraphy using 99mTc-labeled phosphorous compounds was found to be the most frequently ordered nuclear medicine examination in a nationwide survey in Japan, and has been used for the detection of lesions and the evaluation of disease progression and response to therapy in various skeletal diseases. In this article, we review improvement of the diagnostic sensitivity and specificity for bone metastasis of not only nuclear medicine techniques, such as planar imaging, SPECT, early flow phase imaging and quantification of bone scintigraphy, and bone marrow scintigraphy but also such recently developed methods as bone mineral measurement, and bone metabolic marker assays. In addition, radionuclide therapy of intractable bone pain due to bone metastasis is also addressed.     

Nuclear medicine imaging of bone infections

The inflammation and infection of bone include a wide range of processes that can result in a reduction of function or in the complete inability of patients. Apart from the inflammation, infection is sustained by pyogenic microorganisms and results mostly in massive destruction of bones and joints. The treatment of osteomyelitis requires long and expensive medical therapies and, sometimes, surgical resection for debridement of necrotic bone or to consolidate or substitute the compromised bones and joints. Radiographs and bone cultures are the mainstays for the diagnosis but often are useless in the diagnosis of activity or relapse of infection in the lengthy management of these patients. Imaging with radiopharmaceuticals, computed tomography and magnetic resonance are also used to study secondary and chronic infections and their diffusion to soft or deep tissues. The diagnosis is quite easy in acute osteomyelitis of long bones when the structure of bone is still intact. But most cases of osteomyelitis are subacute or chronic at the onset or become chronic during their evolution because of the frequent resistance to antibiotics. In chronic osteomyelitis the structure of bones is altered by fractures, surgical interventions and as a result of bone reabsorption produced by the infection. Metallic implants and prostheses produce artefacts both in computed tomography and magnetic resonance images, and radionuclide studies should be essential in these cases. Vertebral osteomyelitis is a specific entity that can be correctly diagnosed by computed tomography or magnetic resonance imaging at the onset of symptoms but only with radionuclide imaging is it possible to assess the activity of the disease after surgical stabilization or medical therapy. The lack of comparative studies showing the accuracy of each radiopharmaceutical for the study of bone infection does not allow the best nuclear medicine techniques to be chosen in an evidence-based manner. To this end we performed a meta-analysis of peer reviewed articles published between 1984 and 2004 describing the use of nuclear medicine imaging for the study of the most frequent causes of bone infections, including prosthetic joint, peripheric post-traumatic bone infections, vertebral and sternal infections. Guidelines for the choice of the optimal radiopharmaceuticals to be used in each clinical condition and for different aims is provided.     

Nuclear medicine studies of the heart

Nuclear imaging techniques are well established diagnostic tools in clinical cardiology, providing noninvasive information about myocardial perfusion, function and metabolism. The cost-effectiveness of radionuclide imaging in the diagnostic work-up of patients with coronary artery disease has been demonstrated. Additionally, the documented prognostic value of scintigraphic parameters is of clinical importance to guide decision making. Advances in technology, new radiotracers and new applications contribute to continuous growth in the field of nuclear cardiology. Multi-headed gamma camera systems lead to higher spatial resolution and sensitivity of cardiac single photon emission tomography (SPECT), and they also provide the opportunity for attenuation correction or electrocardiographic gating of SPECT images. Objective quantitative values of perfusion, function and metabolism are derived from scintigraphic data by use of improved software and hardware. With the latest developments in tracer technology, imaging of myocardial necrosis, receptor systems and autonomic innervation has become a reality and will lead to new clinical applications in the future. Received 12 December 1997; Revision received 16 February 1998; Accepted 18 February 1998     

Quantitative radionuclide scanning in metabolic bone disease

A simple method of quantifying skeletal uptake of 99Tcm-methylene diphosphonate, using a rectilinear scanner and a simultaneously image standard, is described. The pattern of quantified uptake in ten regions of the skeleton, the sacro-iliac joints and kidneys in 57 controls and 54 patients with various metabolic bone disease is presented. This method distinguishes patients with primary hyperparathyroidism and osteomalacia from controls with a sensitivity adequate for clinical purposes. In primary hyperparathyroidism the increased skull uptake of tracer correlated well with levels of serum alkaline phosphatase, plasma parathyroid hormone, urinary hydroxyproline excretion and the degree of intracortical resorption in the metacarpal bones. The skull uptake in oestoporosis was normal or moderately elevated and correlated well with bone mass density measurements of the radius. Patients with osteomalacia also showed the greatest increase in tracer uptake in the skull. Patients with thyrotoxicosis differed from most other patients by showing moderately increased uptake in shafts of long bones. We propose our method of quantitative bone uptake as a useful noninvasive test to detect metabolic bone disease and to monitor responses to therapy of bone disease.     

Nuclear medicine imaging of inflammatory bowel disease

With the availability of indium-labeled white blood cells, radionuclide imaging studies have a definite role in the diagnosis and staging of patients with inflammatory bowel disease. The In-111 white blood cell study is particularly helpful in evaluating recurrent disease in patients with severe intercurrent diseases and in screening patients without the need for barium examinations.     

Semi-quantitative interpretation of the bone scan in metabolic bone disease

Certain easily recognisable features are commonly seen in the bone scans of patients with metabolic bone disorders. Seven such features have been numerically graded by three independent observers in the scans of 100 patients with metabolic bone disease and of 50 control subjects. The total score for each patient is defined as the metabolic index. The mean metabolic index for each group of patients with metabolic bone disease is significantly greater than that for the control group (P<0.001).     

The pathology of metabolic bone disease

The skeletal manifestations of the diverse group of metabolic bone diseases are mediated through the altered function of osteoblasts and osteoclasts and abnormal rates of mineralization. Appropriate understanding of their pathologic conditions requires familiarity with the normal anatomy and physiology of the skeleton. The accurate identification of metabolic bone disease frequently demands histologic confirmation and sophisticated analysis of undecalcified bone specimens labeled with tetracycline by histomorphometric techniques. These procedures allow the assessment of many morphologic features that characterize specific disease states. The most common types of metabolic bone diseases are acquired disorders; nonetheless, rare forms frequently are genetically based and cause intrinsic alterations in the bone-cell populations.     

Recognition of cortical bone resorption in metabolic bone disease in vivo

This is an outline of radiologic assessment of cortical bone resorption for improved diagnosis of metabolic bone diseases by simple radiographic means: microradioscopy and morphometry. The methodology permits separate assessment of endosteal, intracortical, and periosteal resorption and an evaluation of both the quantity and the quality of cortical bone.     

Nuclear medicine in diagnosis and therapy of bone and joint diseases

Concerning bone and joint diseases therapy of rheumatic synovitis (= radiosynoviorthesis) was introduced in 1952 before clinically relevant diagnostic procedures were developed. Radionuclides of Sr and later on 99mTc phosphonates then started the wide use of bone scintigraphy since > 30 years. The diagnostic methods have an excellent sensitivity for detection of local abnormalities of bone metabolism, the specificity of such studies, however, is low. Modifications of the technique (3-phase-bone-scintigraphy, pinhole collimators, ROI-technique), increasing knowledge of pathological scan patterns and introduction of other radionuclide studies (67Ga, 201Tl, inflammation scans with 99mTc-leukocytes or 99mTc-HIG) as well as 18FDG-PET have increased the specificity significantly in recent years and improvements of imaging systems (SPECT) also increased the accuracy of diagnostic methods in diseases of bone and joints. Therapy of such diseases has made considerable progress: inflamed, swollen joints can effectively be treated with 90Y-, 186Re, 169Er-colloids or with 165Dy-particles by radiosynoviorthesis. Severe pain due to disseminated bone metastases of cancer or polyarthritis can be controlled by radionuclide therapy with 89Sr, 153Sm-EDTMP, 186Re- or 188Re-HEDP and possibly 117mSn-DTPA with an acceptable risk of myelodepression. Possibilities, technical details and limitations of radionuclide applications for diagnostic and therapeutic purposes must be considered if optimal benefit for individual patients should be achieved. Overall Nuclear Medicine can become an essential element in management of bone and joint diseases. The relationship of Nuclear Medicine to bone and joint pathology is peculiar: In 1952 treatment of rheumatic synovitis by radiosynoviorthesis with 198Au Colloid was started by Fellinger and Schmid before diagnostic approaches to bone pathology existed. Bone scintigraphy was introduced only in 1961 using 85Sr but obviously the unfavourable radiation characteristics of this radionuclide limited it's broad application and 87mSr did not improve this situation. Only when 99mTc phosphonates were developed by Subramanian the importance of bone scintigraphy became apparent: The excellent imaging properties of these radiotracers showed, that abnormal bone metabolism could be visualized even before morphological alterations in the skeleton become visible on radiographies or even CT-scans. Moreover, proposals made earlier to use 32P or 89Sr for palliation of pain in patients with disseminated skeletal metastases were picked up again and led also to other radiopharmaceuticals (186Re-HEDP, 153Sm-EDTMP, 117mSn-DTPA) which are applied today for the same purpose with very good success. Therefore Nuclear Medicine today has a broad program for diagnostic and therapeutic approaches to diseases of bone and joints. In bone scanning the high sensitivity led to inclusion of this method for routine staging and re-staging programs in a variety of cancer forms which have a trend to develop bone metastases (e.g. breast, lung, prostate, melanoma) but the low specificity of abnormal patterns on such scans can impair the diagnostic value of the technique. To increase specificity and to define inflammatory lesions, radiotracers used for "inflammation scanning" were introduced such as labeled granulocytes, 99mTc Human Immunoglobulin and others but also a simple modification of bone scanning--triple phase bone scintigraphy--was used. Recently the excellent properties of 18F for PET of the skeleton were rediscovered again and emission CT scanning--possibly with overlay with transmission CT or MRT pictures--can enhance the diagnostic impact of radionuclide bone studies.     

Nuclear medicine methods for the determination of bone mineral content

Osteoporosis is becoming recognized as a major social and economical health problem. Bone mineral content (BMC) depends on many hormonal and metabolic factors. The pathophysiological mechanism of the loss of bone mass is still unclear. For preventive diagnosis and treatment of osteoporosis, quantitative technology is required that will measure BMC with high precision and reproducibility. Nuclear medical methods permit the BMC of the appendicular skeleton to be measured by single photon absorptiometry. Whole-body BMC, as well as spine and femur BMC, can be measured by dual photon absorptiometry. The results from both procedures are reasonably precise and correlate well with the ash weight of isolated bone. The radiation exposure level in both SPA and DPA is low. SPA and DPA may be used for cost-effective screening of high-risk patients to predict the likelihood of future fractures and control osteoporosis therapy.     

Nutritional and metabolic bone disease in a zoological population

The radiologic survey technique used at the National Zoological Park has disclosed many cases of nutritional and metabolic bone disease of various types. This communication discusses calcium deficiency states seen in lion cubs associated with a meat diet, the increased need for calcium noted in egg-laying lizards, problems found in New World monkeys, antelopes (due to selenium and/or vitamin E deficiency), hypervitaminosis D, and lead poisoning noted in young primates. In all of these diagnoses, the use of routine radiographic studies has been extremely helpful, first in detecting that a bone or soft tissue abnormality is present, and then in the differential diagnosis of the etiology of this abnormality. As more is learned of the necessary nutriments for exotic species kept in captivity, it is expected that the nutritional disturbances described in this article will be seen with decreasing frequency.