Biomedical subjects
Publications and source records attributed to I Fogelman.
The bone scan has well-recognized appearances in metabolic bone diseases, with its main clinical value found in focal conditions or the focal complications of disease. In clinical practice, the bone scan is most widely used to detect fractures in osteoporosis and pseudofractures in osteomalacia and to evaluate Paget's disease.
PURPOSE: To determine whether intermittent cyclical etidronate therapy can prevent early postmenopausal bone loss. PATIENTS AND METHOD: This was a 2-year outpatient, randomized, double-blind, placebo-controlled clinical trial. The subjects were 152 women within 1 to 10 years of the onset of menopause and bone mineral density (BMD) between 0 and -2 SD of normal values for a 50 year old woman. The women were stratified according to years since the menopause (1 to 3 years: n = 43; 4 to 6 years: n = 53; 7 to 10 years: n = 56). Measurements of lumbar spine, proximal femur and total body BMD were performed at baseline, 12 and 24 months by dual x-ray absorptiometry. Biochemical markers of bone resorption and bone formation were measured on the same visits. RESULTS: One hundred thirty-five subjects completed the study. Mean percentage change in lumbar spine BMD (and SEM) at 2 years was +2.14 (0.47)% in the etidronate group and -1.72 (0.41)% in the placebo group. Results for lumbar spine BMD in the treated and control groups stratified according to years since the menopause were: 1 to 3 years: +1.73 (0.84)% and -3.30 (0.70)%; 4 to 6 years: +1.37 (0.88)% and -1.80 (0.61)%; 7 to 10 years: +3.42 (0.61)% and -0.38 (0.70)%. The effect of both treatment group and menopausal stratum were highly statistically significant for lumbar spine and total body BMD. Treatment group, but not stratum, was significant for BMD in the proximal femur. Markers of bone resorption and bone formation were significantly decreased by etidronate therapy. CONCLUSIONS: Cyclical etidronate prevents bone loss in the total skeleton and at the clinically relevant sites (spine and proximal femur) even in the early postmenopausal years. Hence, it appears to be an effective and safe nonhormonal therapy in postmenopausal women with normal or low BMD.
We assessed the value of bone scintigraphy combined with X-ray registration for the diagnosis and management of wrist pain in 65 patients. Studies were reported independently by two observers before and after registration. Registration improved localization of scan abnormalities in 53% (observer 1) and 61% (observer 2). In these patients, the bone scan contributed to the diagnosis independently of the X-ray in 37% and the management was altered in 31%. The value of the bone scan in the early diagnosis and management of wrist pain is increased when it is registered with X-rays.
A case of osteoid osteoma in a young man is presented which evaded diagnosis for 9 years, and was eventually localized to the palmar aspect of the third carpometacarpal joint using the technique of registration bone scan to provide accurate localization. The lesion was removed with complete relief of pain.
One hundred and fourteen patients with painful bone metastases participated in this randomised, dose-controlled study of the efficacy and safety of 153Sm-ethylenediaminetetramethylenephosphonate (EDTMP), a systemically administered radiopharmaceutical. Fifty-five patients received single doses of 0.5 mCi/kg and 59 patients received single doses of 1.0 mCi/kg. Treatment with 153-Sm-EDTMP produced improvement from baseline in all patient-rated efficacy assessments, including degree of pain, level of daytime discomfort, quality of sleep and pain relief. During the first 4 weeks after dose administration, when the patients evaluated efficacy daily, there were statistically significant changes from baseline with the 1.0 mCi/kg dose but not with the 0.5 mCi/kg dose. The difference between doses in visual analogue pain scores was statistically significant at week 4 (P = 0.0476). Among subsets of patients examined, female patients with breast cancer receiving 1.0 mCi/kg had the most noticeable improvement. The physicians judged that approximately half of the patients in each dose group were experiencing some degree of pain relief by week 2. This value increased to 55% for the 0.5 mCi/kg group and 70% for the 1.0 mCi/kg group at week 4. More patients in the higher dose group (54%) than in the lower dose group (44%) completed the 16-week study. A predictable level of dose-related marrow suppression was the only toxicity associated with 153Sm-EDTMP treatment. Values for platelets and WBCs reached nadirs at 3 or 4 weeks with both doses and recovered by 8 weeks. Even at their lowest point, the values were generally higher than those associated with infectious or haemorrhagic complications. Myelotoxicity was no greater in female patients than in male patients. Long-term follow-up revealed longer survival among breast cancer patients who had received the higher dose than among those who had received the lower dose. The results suggest that the 1.0 mCi/kg dose of 153Sm-EDTMP is safe and effective for the treatment of painful bone metastases.
Bone SPECT has acquired a useful role in the evaluation of acute and chronic back pain. Spinal pain is also a characteristic of chronic ankylosing spondylitis. The authors investigated the bone SPECT appearances of the lower thoracic and lumbar spine in 28 symptomatic patients with established ankylosing spondylitis, half of whom had complete ankylosis of the sacroiliac and one third complete ankylosis of the intervertebral joints. SPECT abnormalities were identified in 89%. Facetal joint uptake was found in 16 (57%) patients, of whom 7 (25%) had three or more, and 2 (7%) had seven or more active sites. The only other common site of uptake was in the vertebral body, in which 15 patients (54%) showed increased uptake with three or more sites found in 3 (11%) patients. The authors conclude that SPECT abnormalities in the lower thoracic and lumbar spine are frequently found in patients with ankylosing spondylitis, with the most common sites of abnormality in the facetal joints or vertebral body. Multiple sites of uptake in the facetal joints maybe striking in such patients and has not been previously described.
OBJECTIVES: To measure the long term effects of dance training and the contribution of the timing and duration of any menstrual disruption on bone mineral density (BMD). DESIGN: Measurement of BMD in 57 premenopausal, previously professionally dance trained women and the relationship to menstrual and training history. MAIN OUTCOME MEASURES: Bone density measurements at lumbar spine and femoral neck by dual energy x-ray absorptiometry. RESULTS: The average Z score for BMD at the lumbar spine in the amenorrhoeic dancers was significantly below that for the normal population. The average Z score for BMD at the femoral neck in the eumenorrhoeic dancers was significantly above that for the normal population. There was a significant difference between the average Z score for BMD at both the lumbar spine and femoral neck between the amenorrhoeic and eumenorrhoeic dancers. Significant negative relationships were found between BMD at the lumbar spine and (1) age at menarche, (2) duration of amenorrhoea, (3) BMD at the femoral neck, and (4) the variable of ideal minus lowest weight, which was independent of amenorrhoea. No significant relationships were found between duration of oral contraceptive pill usage and BMD at either the lumbar spine or the femoral neck in eumenorrhoeic or amenorrhoeic dancers. In order to quantify the effect of a combination of these significant factors, a model of BMD was constructed using multiple regression incorporating the variables duration of amenorrhoea, age at menarche, and ideal minus lowest body weight. In this model R2 was 33.6%, in other words 33.6% of the total variation in the Z score for BMD at the lumbar spine could be accounted for by these factors. CONCLUSION: Professional female dancers with a history of delayed menarche and amenorrhoea have been identified as another group of premenopausal women potentially at risk of developing osteoporosis because of a decrease in BMD at the lumbar spine. The femoral neck in dancers with a history of amenorrhoea was partially protected from loss of BMD by virtue of being the major weight bearing site in previous dance training, and in eumenorrhoeic dancers BMD was significantly increased at this site.
Over the past decade, growing awareness of the impact of osteoporosis on the elderly population and the consequent costs of healthcare have stimulated development of new treatments to prevent fractures, together with new imaging technologies to assist in diagnosis. With its ability to perform high-precision measurements of bone mineral density (BMD) in the spine and hip, dual X-ray absorptiometry (DXA) is well suited to meet this latter need. However, there is continuing interest in smaller, less expensive, systems for assessing the peripheral skeleton. These include peripheral DXA scanning of the distal forearm and a variety of devices for performing quantitative ultrasound (QUS) measurements of broad-band ultrasonic attenuation (BUA) and speed of sound (SOS) in bone. Pivotal to all these developments is the demonstration in prospective studies that new technologies can reliably identify patients at risk of osteoporotic fractures. Whether DXA technology can meet the anticipated need for wider provision of diagnostic services is uncertain at present. The likely alternative is bone ultrasound. Although QUS technology is substantially cheaper than DXA and has proved its ability to predict fracture risk in the elderly, it is less precise, there is a lack of appropriate phantoms for quality control and there are doubts about how to interpret results in younger women.
UNLABELLED: Paget's disease of bone is common in the elderly and is associated with increased osteoblastic and osteoclastic activity at affected sites in the skeleton. It is not known whether this high metabolic activity is associated with increased glycolysis and, hence, uptake of [18F]FDG. The appearances of Paget's disease with [18F]FDG PET have not been described and it is not known whether Paget's may cause false-positive studies in those undergoing oncological staging or whether [18F]FDG PET can reliably differentiate benign pagetic change from osteosarcoma that may complicate Paget's disease. We reviewed [18F]FDG PET scans in patients with uncomplicated Paget's disease and documented its appearances. METHODS: Eighteen patients with established Paget's disease and typical radiological features had 99mTc-MDP bone scans and [18F]FDG PET scans performed. Serum alkaline phosphatase (ALP) was also measured. RESULTS: All patients showed high uptake of MDP in affected bones. Of the 18 patients only six showed any uptake of [18F]FDG. This occurred in some but not all bones shown to be involved on MDP bone scans. Three patients demonstrated low-grade uptake and three showed marked accumulation of [18F]FDG. The [18F]FDG-positive group had higher serum ALP levels than the [18F]FDG-negative patients (p < 0.05). CONCLUSION: Paget's disease of bone is not associated with abnormal [18F]FDG uptake in the majority of patients and, therefore, there is potential for discriminating between benign Paget's disease and associated Paget's sarcoma. However, low-grade uptake may be seen in patients with more active disease as measured by ALP. Rarely, marked uptake of [18F]FDG may be seen and Paget's disease should be included as a possible cause of false-positive scans in elderly patients who are being assessed for metastatic disease.
We report two cases, with magnetic resonance imaging correlation, of acute lateral collateral ligament tear of the knee following trauma with findings on bone scintigraphy with single-photon emission tomography (SPET). The typical bone scan features are presented. In addition, the advantages of the use of SPET in the detection of associated lesions are discussed.
Nineteen patients with angina were recruited in this study for comparison of two 1-day protocols (stress-4h rest and rest-4-h stress) and a 2-day protocol of technetium-99m tetrofosmin single-photon emission tomography (SPET). All of them underwent coronary angiography before or after the study. Exercise stress-rest study and rest-stress study were performed on two consecutive days. Delayed imaging was performed before the rest injection on the 2nd day. The stress study on the 1st day and rest study on the 2nd day were considered as a 2-day protocol. The 1-day stress-rest protocol had a sensitivity of 100% (18/18) and an accuracy of 100% (19/19) in diagnosing ischaemic heart disease. The 1-day rest-stress protocol had a sensitivity of 94.4% (17/18) and an accuracy of 94.7% (18/19). These differences were not statistically significant (P=0.5 for sensitivity and accuracy). There was also no statistically significant difference between the two protocols in the diagnosis of ischaemic heart disease in individual artery territories. For the left descending artery, sensitivity was 88.2% (15/17) vs 76.5% (13/17) (P=0.48) for the stress-rest and rest-stress studies respectively. For the left circumflex artery, sensitivity was 90% (9/10) vs 80% (8/10) (P=1) and specificity was 66.7% (6/9) vs 77.8% (7/9) (P=1) respectively. For the right coronary artery, the sensitivity was 100% (16/16) vs 94% (15/16) (P=1) respectively, while the specificity was 33.3% (1/3) in both studies. Three hundred and forty-two myocardial segments were analysed. The stress-rest and 2-day protocols showed no statistically significant difference in the overall identification of segments with reversible ischaemia (48/141 segments vs 48/141 segments) or in respect of individual artery territories. There was also no significant difference in the identification of reversible ischaemic segments between the rest-stress and 2-day protocols (48/141 segments vs 34/135 segments, P=0.14). Abdominal activity was seen in 36 studies and interpretation was affected in five of them. Five patients with 24-h delayed images were evaluated and 24 segments with washout were identified. It is concluded that 99mTc-tetrofosmin is a valuable new tracer in the investigation of ischaemic heart disease. The 1-day stress-rest protocol is as good as the 1-day rest-stress protocol in diagnosing coronary heart disease. The 1-day protocols and the 2-day protocol display no difference in identifying segments with reversible ischaemia.
We report a study to assess whether supine lateral dual-energy X-ray absorptiometry (DXA) scans of the lumbar spine provide better data for monitoring response to treatment than alternative measurement sites such as the posteroanterior (PA) spine, hip and total body. The study population was 152 women enrolled in a placebo-controlled clinical trial of cyclical etidronate therapy. All subjects were 1-10 years after the menopause with bone mineral density (BMD) between 0 and -2 SD of age-matched normal women. Paired PA and lateral spine, left hip and total-body DXA scans were performed at baseline, 1 year and 2 years on a Hologic QDR-2000. One hundred and thirty-one subjects completed the study. Mean percentage change from baseline at 2 years in the treated (n = 61) and control (n = 70) groups was calculated for vertebral body, width-adjusted (WA) vertebral body, mid-vertebral body and WA mid-vertebral body BMD measurement on the lateral scans and compared with the percentage changes in PA spine, femoral neck, trochanter, Ward's triangle and total-body BMD. The long-term precision for each BMD measurement site was obtained by linear regression analysis in subjects taking placebo. Overall treatment effect, defined as the difference in the percentage change in BMD in the two treatment groups at 2 years, was divided by long-term precision to give an index of the ability of each site to monitor response to treatment. Results (and standard errors) normalized to the ratio of treatment effect/ precision for PA spine BMD were as follows: PA spine, 1.00; vertebral body, 0.89 (0.14); WA vertebral body, 0.78 (0.14); mid-vertebral body, 0.65 (0.14); WA mid-vertebral body, 0.60 (0.13); femoral neck, 0.35 (0.15); trochanter, 0.45 (0.15); Ward's triangle, 0.59 (0.22); total body, 0.52 (0.19). Although treatment effect was larger for lateral than for PA spine BMD, this advantage was offset by the greater precision errors. PA spine BMD remains the optimum measurement for longitudinal studies in recently postmenopausal women.
The use of positron-emission tomography in clinical practice is increasing, particularly with the use of 18-fluoro-2-deoxyglucose (FDG) for oncological studies. As in other imaging modalities, it is important to be aware of normal variants and benign diseases that may mimic more serious pathology. Uptake of FDG in a number of sites may be variable. Uptake of FDG may be seen normally in the skeletal muscle after exercise or under tension, in the myocardium, in parts of the gastrointestinal tract, especially the stomach and cecum, and in the urinary tract. Some causes of increased physiological uptake are avoidable, and measures can be taken to minimize accumulation, thus aiding study interpretation. Inflammatory lesions may cause an increase in FDG uptake, but not usually to the same degree as malignancy. Benign disease such as Paget's disease of bone, sarcoidosis, and tuberculosis may cause uptake that occasionally mimics that of malignancy. Typical examples of a number of physiological and benign variants are described and illustrated.
Patients with a wide variety of rheumatological conditions can be usefully investigated by nuclear medicine techniques and particularly by bone scintigraphy. This aspect of nuclear medicine work is increasing and the trend can be expected to continue. The principal conditions that can be imaged are sports medicine injuries, osteomyelitis, avascular necrosis, reflex sympathetic dystrophy syndrome, enthesopathies and bio-mechanical stress lesions, inflammatory arthropathies, metabolic bone disease and miscellaneous bone conditions such as costo-chondritis. Single photon emission tomography (SPECT) has provided new indications for bone scintigraphy such as the evaluation of spondylolysis and facet syndrome in the spine and of meniscal tears and ligamental lesions.
Osteoporosis is a common disease with a strong genetic component, characterized by reduced bone mass and increased fracture risk. Current evidence suggests that the inheritance of bone mass is under polygenic control but the genes responsible are poorly defined. Type I collagen is the major protein of bone encoded by the COLIA1 and COLIA2 genes. While these are strong candidates for the genetic regulation of bone mass, no abnormality of either gene has so far been defined in osteoporosis. In this study, we describe a novel G-->T polymorphism in a regulatory region of COLIA1 at a recognition site for the transcription factor Sp1(7) that is significantly related to bone mass and osteoporotic fracture. G/T heterozygotes at the polymorphic Sp1 site (Ss) had significantly lower bone mineral density (BMD) than G/G homozygotes (SS) in two populations of British women and BMD was lower still in T/T homozygotes (ss). The unfavourable Ss and ss genotypes were over-represented in patients with severe osteoporosis and vertebral fractures (54%), as compared with controls (27%), equivalent to a relative risk of 2.97 (95% confidence interval 1.63-9.56) for vertebral fracture in individuals who carry the 's' allele. While the mechanisms that underlie this association remain to be defined, the COLIA1 Sp1 polymorphism appears to be an important marker for low bone mass and vertebral fracture, raising the possibility that genotyping at this site may be of value in identifying women who are at risk of osteoporosis.
Lumbar facet disease is sometimes implicated in low back pain. Identification is difficult and this may account for a variable response. Single photon emission computerized tomography (SPECT) is a scanning technique which enables localization of facet joint pathology. We determined whether recognition of facet disease by this method improved the response to corticosteroid injection treatment. Fifty-eight patients with low back pain and displaying accepted clinical criteria for facet joint disease were evaluated by SPECT. Twenty-two had facetal uptake of isotope. These and the tender facet joints of 36 scan-negative patients were injected with 40 mg methylprednisolone and 1 ml 1% lignocaine under X-ray control. Pain was assessed by a blind observer using the McGill questionnaire (MGQ), Present Pain Intensity score (PPI) and a Visual Analogue Scale (VAS). VAS, PPI and MGQ were reduced in the scan-positive patients at 1 month (P = 0.05, P = 0.0005, P = 0.005) and MGQ at 3 months (P = 0.01), whilst scan-negative patients were unchanged. The percentage of scan-positive patients who reported improvement was 95% at 1 month and 79% at 3 months, significantly greater than the control group (P = 0.0005, P = 0.01). Within 6 months, pain improvement in the SPECT-positive group was no longer statistically significant. Tenderness did not correlate with increased uptake on SPECT scan. Osteoarthritis of the facets was more common in the SPECT-positive patients (P < 0.001), but did not correspond with sites of increased uptake on SPECT scan. These results suggest that SPECT can enhance the identification of back pain sufferers likely to obtain short-term benefit from facet joint injection.
To define the phenotype of patients with benign joint hypermobility syndrome (BJHS), we studied 58 consecutive patients (mean age 37 yr) presenting to a rheumatology clinic and 30 controls. Patients underwent rheumatological and ophthalmic examination, hypermobility scoring, echocardiography, measurement of bone mineral density (BMD), and skin thickness, elasticity and light transmissibility. The median hypermobility score was 5/9 Beighton and 31/56 Contompasis. Eighteen (31%) patients complained of significant arthralgia. Six (10%) patients and two (7%) controls had mitral valve prolapse (MVP) (chi(2) = 0.27, P = NS). Neither MVP nor aortic diameters showed a correlation with hypermobility score. There was no significant reduction in BMD. There was a significant correlation between hypermobility and light transmissibility of the skin (r = 0.71, P < 0.0001 Contompasis; r = 0.47, P < 0.05 Beighton) and skin stretchiness (r = 0.49, P < 0.05 Contompasis; r = 0.39, P < 0.05 Beighton). On ophthalmic examination, 14 (41%) patients had upper eyelid laxity. Thus, patients with BJHS do not have an increased prevalence of significant cardiac, bone, skin or eye abnormalities, helping differentiate BJHS from other more serious hereditary disorders of connective tissue.
Bone single photon emission tomography (SPET) of the knees has been shown to be of diagnostic value for the investigation of knee pain. This study compared bone SPET with magnetic resonance imaging (MRI) for the diagnosis of knee disorders. Thirty-six patients were studied with modalities, performed an average of 4 months apart (range 0-10 months). There was agreement on the presence or absence and nature of pathology in 24 (67%) patients. In a further three patients, there was an abnormal SPET with equivocal change for the same pathology on MRI. Equivocal change on both modalities for the same pathology were found in one patient. Three patients had abnormalities on MRI with normal SPET, with the remaining patients having equivocal or non-specific changes on one modality only. In the majority of patients, there was agreement on the presence or absence of pathology and the nature of pathology with both modalities. Significant pathology detected on MRI was also identified by bone SPET. This initial study suggests that further work should be undertaken to evaluate the role of bone SPET as a screening test for the evaluation of knee disorders and its role in relation to MRI is justified.