Simulated effects of early menopausal bone mineral density preservation on long-term fracture risk: a feasibility study.

Prevention of early menopausal bone loss may reduce the future burden of osteoporosis. In this modelling exercise, an osteoporosis prevention strategy involving 5-year infusions of zoledronic acid, beginning early in menopause, reduced long-term fracture risk and the proportion of aging women with femoral neck densitometric osteoporosis. This strategy warrants further evaluation. INTRODUCTION: Preventing early menopausal bone loss may substantially reduce the future burden of osteoporosis. We modelled the effects of infrequent zoledronic acid infusions on long-term fracture risk. METHODS: Data from the Canadian Multicentre Osteoporosis Study (CaMos) were used to determine the expected natural history of femoral neck areal bone mineral density (BMD) and fracture risk (using FRAX®) from ages 50-80 for women with no antiresorptive drug exposures. We modelled the effects of three infusions of zoledronic acid (at ages 50, 55, 60) on long-term fracture risk, assuming this intervention would preserve BMD until age 65 years, followed by losses mirroring early menopausal BMD loss. RESULTS: At age 65, untreated women and zoledronic acid recipients had expected mean (SD) femoral neck T-scores of - 1.5(1.0) and - 0.8(1.0), 10-year major osteoporotic fracture (MOF) risks of 9.8%(5.0) and 8.0%(3.7) and hip fracture risks of 1.7%(2.4) and 0.8%(1.2), respectively. At age 80, untreated women and zoledronic acid recipients had expected femoral neck T-scores of - 1.9(0.9) and - 1.4(0.9), MOF risks of 17.9%(8.2) and 14.9%(6.4) and hip fracture risks of 6.3%(6.2) and 4.4%(4.5), respectively. The expected proportion of women with femoral neck T-score ≤ - 2.5 was 14.9% for untreated women and 3.8% for zoledronic acid recipients at age 65, increasing to 28.1% and 12.0%, respectively, at age 80. Numbers-needed-to-treat to prevent one case of densitometric osteoporosis were 9 at age 65 and 5 at age 80. CONCLUSION: Infrequent infusions of zoledronic acid, initiated early in menopause, are expected to reduce long-term fracture risk and result in a substantial reduction in the proportion of women with densitometric osteoporosis after age 65.

Osteoporotic vertebral fractures redux.

Osteoporosis remains an important cause of morbidity and mortality especially in the elderly. This fact is largely due to fractures of the proximal femur and spine. As recently recognized, vertebral fractures are as much a threat to health and longevity as fractures of the proximal femur. In recent decades, the development of tools to evaluate fracture risk as well as medications to treat osteoporosis has altered the management of people who are at fracture risk. At the same time identification and management procedures concerning spinal fracturing are not very clear. Besides there is not even clear consensus about what exactly constitutes a vertebral fracture, particularly those of minor degree. While height loss is a simple and valuable tool to detect vertebral fractures, it is neither sensitive nor specific enough to replace radiographs. Some 65% of fractures cause no symptoms. Often vertebral fractures are misdiagnosed, especially if they have occurred silently and if the opportunity for diagnosis arises fortuitously. It is to the patient's benefit that radiologists report and physicians identify vertebral fractures evident on a chest or other radiograph, no matter how incidental to the immediate clinical indication for the examination. Technological evolution now allows dual-energy x-ray absorptiometry machines to be used to take spine images while doing a densitometry. The images are adequate, even if not of high radiographic quality, and, more important, the patient undergoes a smaller radiation dose than with conventional spinal radiographs. Such technology may promote fracture recognition. The recognition of vertebral fractures, as well as the prevention and treatment of further fractures, will likely do much to reduce both the burden of osteoporosis-related morbidity and mortality, as well as fracture-related costs to healthcare systems.

Premenopausal ovariectomy-related bone loss: a randomized, double-blind, one-year trial of conjugated estrogen or medroxyprogesterone acetate.

The purpose of this study was to contrast the effects of conventional estrogen treatment with medroxyprogesterone on cancellous and cortical bone change in the first year following premenopausal ovariectomy. This 1-year double-blind randomized therapy trial was stratified by osteoporosis family history and performed in an academic medical center and community hospitals. Premenopausal women 45 +/- 5 years old, postovariectomy for benign diseases were provided 600 mg/day of calcium and randomized to daily therapy with conjugated equine estrogen (CEE, 0.6 mg) or medroxyprogesterone (MPA, 10 mg). The primary outcome variable was spinal quantitative computed tomography (QCT) bone density change over 1 year with additional outcomes of dual-energy X-ray absorptiometry (DXA) of proximal femur (FN), whole body (WB), and spine segment (WBS) and N-telopeptide, bone-specific alkaline phosphatase, and other bone marker, hormonal, and weight changes. Results in the 33 women completing the study, whose initial bone densities were normal (QCT 133 mg/cm3, femoral neck 0.94 g/cm2, whole body DXA 1.13 g/cm2), showed annual QCT loss during CEE therapy of -11.5 mg/cm3 (p < 0.0007) and MPA bone loss of -19.7 mg/cm3 (p < 0.0001). Losses were marginally greater on MPA than CEE (p = 0.04). Extremely high postovariectomy (5 days) and pretreatment resorption markers (> 3 SD above premenopausal normal levels) were significantly related to bone loss. Across the year, resorption decreased during CEE but increased on MPA treatment. Significant DXA bone losses were prevented by CEE treatment (-1.4% FN, -.4% WB, and -1.5% WBS, all NS). However, DXA bone loss was not prevented by MPA treatment (-5% FN, -2.8% WB, and -6.1% WBS, all p < 0.03). Average weight gain was significant (+ 3.2 +/- 4.0 kg) and greater on CEE than MPA (+ 4.7 vs. + 2.0 kg, p = 0.049). In conclusion, CEE therapy did not prevent significant 8% cancellous spinal bone loss in the first year following premenopausal ovariectomy, despite supplementation with 600 mg/day of calcium, good control of vasomotor symptoms, and nearly 5 kg of gain in weight. Significant DXA bone loss, however, was prevented by CEE, but not by MPA therapy. These unexpected results were statistically related to high bone resorption following ovariectomy, which CEE suppressed but MPA did not. Bone formation markers increased during MPA therapy but were unchanged during CEE therapy.

Cyclic medroxyprogesterone treatment increases bone density: a controlled trial in active women with menstrual cycle disturbances.

OBJECTIVE: Bone loss occurs in young women who experience amenorrhea or ovulatory disturbances. The purpose of this study was to determine whether bone loss could be prevented by simulating a more normal hormonal pattern, using treatment with cyclic medroxyprogesterone, with or without calcium supplementation, in physically active women with disturbed menstruation. DESIGN: This study was a 1-year randomized, double-blind, placebo-controlled trial. Women who were stratified by menstrual cycle disturbance were randomized into four groups. The outcome variable was the change in spinal bone density measured by dual energy techniques. SETTING: A large metropolitan area. PARTICIPANTS: Sixty-one healthy, normal-weight physically active premenopausal women aged 21 to 45 years who experienced amenorrhea, oligomenorrhea, anovulation, or short luteal phase cycles completed the study. INTERVENTION: Therapies were cyclic medroxyprogesterone (10 mg/day for 10 days per month) and calcium carbonate (1,000 mg/day of calcium) in four groups: (A) (n = 16) cyclic medroxyprogesterone plus calcium carbonate; (B) (n = 16) cyclic medroxyprogesterone with calcium placebo; (C) (n = 15) placebo medroxyprogesterone with active calcium; or (D) (n = 14) both medroxyprogesterone and calcium placebos. RESULTS: The initial bone density (mean = 1.12 g/cm2) did not differ by group (P = 0.85). The 1-year bone density change was strongly related to treatment with medroxyprogesterone (P = 0.0001) and weakly to calcium (P = 0.072) treatment. Bone density increased significantly (+1.7% +/- 0.5%, +/- SEM, P = 0.004) in the medroxyprogesterone-treated groups (A and B), did not change in the calcium-treated group (C) (-0.7% +/- 0.6%, P = 0.28), and decreased on both placebos (D) (-2.0% +/- 0.6%, P = 0.005). CONCLUSIONS: Cyclic medroxyprogesterone increased spinal bone density in physically active women experiencing amenorrhea or ovulatory disturbances. POTENTIAL CLINICAL SIGNIFICANCE: Amenorrhea, oligomenorrhea, anovulation, and short luteal phase cycles are common in premenopausal women and associated with spinal bone loss occurring at a stage of life when bone density would normally be stable or increasing. This controlled trial shows a significant gain in bone in women in the cyclic medroxyprogesterone intervention group, whereas those subjects in the placebo group lost bone. Calcium supplementation appeared to be helpful but did not reach statistical significance. The implications of these findings for the prevention of osteoporosis warrant further investigation.

A follow-up study of 48 patients with Reiter's syndrome.

A follow-up study of 48 patients with Reiter's syndrome was carried out in an attempt to clarify the clinical course of the disease. The mean age at the onset of Reiter's syndrome was 27.1 years (range 15 to 52 years) and when seen at follow-up 32.5 years (range 19 to 58 years). The average time from the onset of the first attack of peripheral arthritis to the time of follow-up was six and a half years (range 0.5 to 27 years). Only three patients had diarrhea prior to the onset of Reiter's syndrome. At follow-up 22 per cent of the patients were asymptomatic, 24 per cent had recurrent minor symptoms, 24 per cent had recurrent moderate symptoms, and 30 per cent had recurrent major symptoms. However, even in the last group, all patients were in functional classes 1 or 2 between the flares of disease. No patients in the series were in functional class 3 or 4, and 30 per cent were in class 1.

Computerized tomography versus perfusion lung scanning in canine radiation lung injury.

Computerized tomographic (CT) measurements of lung density were obtained before and serially after thoracic irradiation in dogs to detect the alterations caused by radiation therapy. Fourteen mongrel dogs were given either 2000 cGy (Group A, 10 dogs, right lower zone irradiation), 1000 cGy (Group B, 2 dogs, right lower zone irradiation), or 500 cGy (Group C, 2 dogs, right lung irradiation) in one fraction. Once before and bi-weekly after irradiation, the anesthetized dogs had thoracic CT scans. CT numbers for the irradiated area were compared to their preirradiation control values. Macro-aggregated albumin (MAA) perfusion lung scans were also obtained before and at weekly intervals after irradiation and were evaluated visually and quantitatively for abnormalities. When both these tests were abnormal, or at the end of the scheduled study, the dogs were sacrificed to confirm radiation lung injury histologically. Our results showed that CT numbers (as a measure of tissue density) were higher with higher doses of radiation. Among all the techniques used, only the quantitative assessment of macro-aggregated albumin perfusion scan detected abnormalities in all the dogs given 2000 cGy. Their abnormalities correlated well with the presence of radiation lung damage histologically, however, the applicability of these methods in the detection of early injury has to be further evaluated.

Detecting bone marrow metastases at the time of examining the liver with radiocolloid.

In a prospective study of 200 different consecutive patients with cancer, the bone marrow of the lumbar spine and pelvis has been examined at the time of obtaining a radiocolloid examination of liver and spleen. The images were examined "blind" by three observers who all agreed about the findings in 177 (89%) of the patients. Agreement by any two was considered to be definitive. The radiocolloid marrow examinations in this selected population had an accuracy of 0.97, sensitivity of 0.80, and specificity of 0.98 in diagnosing metastatic disease when validated by all other available evidence, or follow-up. Of the patients thus examined, 16 (8%) had abnormal marrow scan findings reflecting metastatic disease, eight (4%) at the time radiographs were normal, and two at the time bone scintigraphy was normal. Excluding patients with bowel cancer, in whom the detection rate was zero, 16 (12.4%) marrow examinations were abnormal. As a result we now obtain "saturated" images of the marrow incidental to radiocolloid examinations of the liver and spleen in patients with cancer other than that of the bowel.

Correction for out-of-focal-plane blurring in a simulated multiplane tomographic scanner.

A technique has been developed to remove out-of-focal-plane blurring from coronal and axial images made using a multiplane tomographic scanner. The technique uses a combined smoothing and differential operator that is applied to the axial images. It has been tested using computer-simulated images, with favorable results. The usefulness of the technique in a real system has yet to be determined.

The effect of contrast lymphangiography on localization of 67Ga-citrate.

Oily lymphangiographic contrast material introduced prior to total-body 67Ga-citrate scanning may be responsible for accumulation of the radionuclide within the lungs. The possibility of false-positive examinations suggests caution in the interpretation of the scan which evidences this finding. When possible, gallium scintiscans should be scheduled prior to contrast lymphangiography.

Interactive three-dimensional region of interest analysis of HMPAO SPECT brain studies.

An interactive computer program has been developed to align a three-dimensional region of interest (ROI) model to technetium-99m-hexamethylpropylenamine oxime (99mTc-HMPAO) single-photon emission computed tomography (SPECT) studies of the brain. The ROI model subdivides the human brain into fourteen discrete regions. A study was performed to determine normal ranges for HMPAO uptake in the ROIs defined by the model, and to assess the relative interobserver variability using the fitting program. HMPAO SPECT studies of twelve normal volunteers were independently analyzed by four observers. Small but significant differences between operators occurred primarily because of difficulty in defining the angle of the orbitomeatal plane on sagittal SPECT images. Despite this difficulty, the program and model have proven useful in defining ranges for normal cerebral perfusion in a healthy adult population. A study of a small group of patients with Alzheimer's dementia suggests that this procedure may be of use in the diagnosis of this disease.

The role of bone scintigraphy in the evaluation of talar dome fractures.

We undertook a retrospective study of 122 patients with ankle pain to determine the accuracy of bone scintigraphy using 99mTc-methylene diphosphonate (MDP) for detection of osteochondral talar dome fractures (OCTDF). Plain radiographs, which were available in 97 patients, had not revealed any abnormality in the talar dome. Bone scintigraphy was followed by CT, which was considered to be the reference test in diagnosing OCTDF. Analysis of our data showed that when the bone scan findings in the two highest confidence categories (high and moderate probability) were accepted as abnormal, the sensitivity and the specificity of the test were 0.94 and 0.76, respectively. Although CT is mandatory to establish the stage of OCTDF, it cannot be used routinely due to its high cost. Bone scintigraphy appears to be a good screening procedure that will identify patients who are likely to benefit from further radiographic studies such as CT. These findings are subject to further confirmation in a prospective study.

The scintigraphic investigation of sacroiliac disease.

Bone scintigraphs obtained with both Technetium-99m polyphosphate and Technetium-99m pyrophosphate have been abnormal at the sacroiliac joints of 44 patients with definite ankylosing spondylitis (AS). Because of the normal registration of the sacroiliac joints on bone scintigraphy, it has been necessary to develop a profile-scan technique to quantify the abnormality that proves to be significantly different from the normal finding. In 17 patients with a strong clinical suspicion of AS but normal radiographs, the sacroiliac joints have frequently been abnormal. This finding is meaningful because there is a common occurence in this group of the histocompatibility antigen HL A-B27, known to be a marker of AS. We also note the frequency of abnormal sacroiliac scinitigrams in 26 patients with rheumatoid arthritis and in a group of other diseases-Crohn's disease, uveitis, psoriasis, ulcerative colitis, and Reiter's disease-all of which share some of the manifestations of AS.

Scintigraphic findings in ankylosing spondylitis.

A prospective study of bone scintigraphic findings has been carried out in 63 patients, firmly diagnosed as having ankylosing spondylitis. In addition to abnormal uptake of the radiotracer at the sacroiliac joints, a peripheral arthropathy has been a common finding, particularly in the proximal joints, occurring in up to 50% of patients. Increased uptake of radiotracer in the spine has also been found both diffusely and focally. Focal increases have been noted at the apophyseal joints in 40% of patients and in three patients with a sterile intervertebral diskitis, an unusual complication of this disease only diagnosed in two patients after bone scintigraphy.

Iatrogenic alterations in radionuclide biodistributions.

The biodistribution of radiotracers used in diagnostic imaging is grossly and recognizably altered by a wide variety of drugs and other treatment modalities, such as surgery and radiotherapy. Knowledge of such altered biodistribution is important both in making diagnostic inferences from scans and in dosimetric considerations.

Imaging of diffuse lung diseases. Past, present, and future.

For many years the plain chest radiograph was the only imaging modality used in the assessment of patients who had diffuse lung disease. Presently, high resolution computed tomography (CT) and lung scintigraphy play a major role in the assessment of these patients. Use of magnetic resonance (MR) imaging in the assessment of the lung parenchyma has been limited by poor signal-to-noise ratio and physiologic motion. Recent improvements in technique, however, have allowed assessment of patients with diffuse lung disease. It is likely that MR imaging will play an increasing role in the assessment of these patients in the near future.

Localization of gallium-67 citrate in salivary glands following radiation therapy.

Gallium-67 citrate was found to localize in the salivary glands of eight patients after therapeutic doses of radiation to a treatment field including the glands. In two patients, autopsy evidence to the effect that no primary disease was present to explain such uptake was obtained. In another two patients the abnormal uptake was not observed on follow-up. The recognition that radiation sialadenitis is a potential cause of false-positive gallium scintiscans is important in their interpretation.

Spinal bone mineral density in premenopausal vegetarian and nonvegetarian women: cross-sectional and prospective comparisons.

OBJECTIVE: To compare spinal bone mineral density (BMD) and 1-year BMD change between premenopausal vegetarian and nonvegetarian women. DESIGN: Cross-sectional comparison of spinal BMD at baseline and prospective comparison of a subsample. SETTING: A western Canadian metropolitan area. SUBJECTS/SAMPLES: Healthy vegetarian (n = 15 lacto-ovo-vegetarian, n = 8 vegan) and nonvegetarian (n = 22) women aged 20 to 40 years, with regular menstrual cycles and stable body weight completed baseline measurements. Twenty of these women (6 lacto-ovo-vegetarian, 5 vegan, 9 nonvegetarian) participated in repeat measurements at approximately 13 months. STATISTICAL ANALYSES PERFORMED: Descriptive statistics, independent sample and paired t tests, 1-way analysis of variance, correlation analysis, and stepwise multiple regression were used to compare groups and to assess associations with BMD. RESULTS: At baseline, subjects were 27.2 +/- 5.1 years old. Vegetarians had lower body mass index (21.1 +/- 2.3 vs 22.7 +/- 1.9, P < .05) and percent body fat (24.0 +/- 5.5% vs 27.4 +/- 5.1%, P < .05); they also tended to have lower BMD (1.148 +/- 0.111 g/cm2 vs 1.216 +/- 0.132 g/cm2, P = .06), although this was not apparent with weight as a covariate (P = .14). Baseline BMD was predicted by vitamin B-12 intake and total body fat (R2 = .24, P = .001). Participants in the follow-up differed only in their being older than nonparticipants. Over 1 year, mean BMD increased significantly (1.1%): by diet group, nonvegetarians' BMD increased but vegetarians' BMD was unchanged. No other monitored variables were associated with BMD change. APPLICATIONS/CONCLUSIONS: Vegetarian women should be aware of links between low BMD and low body weight/body fat, and should maintain adequate intakes of nutrients believed to affect BMD.

Radionuclide angiography in juvenile angiofibroma of the nasopharynx.

Radionuclide angiography was performed by intravenous injection of 99mTc-pertechnetate and recorded by serial gamma camera scintiphotographs. Its usefulness as a prebiopsy or preoperative procedure is demonstrated by two case reports of angiofibroma of the nasopharynx and it was also found to be useful for radiation therapy follow-up assessment. Radionuclide angiography offers a convenient and safe method to assess the vascularity of a mass and by this technique the surgeon may be alerted to the possibility of severe postbiopsy hemorrhage and also the occasional dramatic complications of radiological carotid angiography can be avoided.