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Biomedical subjects

Ignac Fogelman

Publications and source records attributed to Ignac Fogelman.

At least 19 recordsLinked to original sources
PubMed2007

The impact of vitamin D status on changes in bone mineral density during treatment with bisphosphonates and after discontinuation following long-term use in post-menopausal osteoporosis.

BACKGROUND: It is still unclear whether addition of calcium/vitamin D supplements leads to an incremental benefit in patients taking bisphosphonates and whether achievement of serum level of 25 (OH) vitamin D of at least 70 nmol/L has an impact on the skeletal response to bisphosphonates. Moreover the maintenance of BMD after bisphosphonates withdrawal with the continuation of calcium/vitamin D supplements only, remains uncertain. The aims were to assess the impact of vitamin D status on changes in bone mineral density (BMD) in firstly patients with post-menopausal osteoporosis on bisphosphonates and secondly following discontinuation of bisphosphonates after long-term use. METHODS: Two patient groups were recruited. The first study population comprised of 112 women treated with a bisphosphonate. The second study population consisted of 35 women who had been on bisphosphonates for > 5 years in whom the treatment agent was discontinued. Baseline BMD, changes in BMD following treatment, duration of treatment, serum 25 (OH) vitamin D, parathyroid hormone (PTH), urine C-terminal telopeptides of type 1 collagen (CTX) were obtained on the study participants. RESULTS: In the first study group, subjects with serum vitamin D concentrations (> 70 nmol/L) had a significantly lower serum PTH level (mean [SEM] 41 2 ng/L). PTH concentrations of 41 ng/L or less was associated with a significantly higher increase in BMD at the hip following treatment with bisphosphonates compared to patients with PTH > 41 ng/L (2.5% [0.9] v/s -0.2% [0.9], P = 0.04). In the second study group, discontinuation of bisphosphonate for 15 months after long-term treatment did not result in significant bone loss at the lumbar spine and total hip, although a trend towards gradual decline in BMD at the femoral neck was observed. CONCLUSION: the data suggest that optimal serum 25 (OH) vitamin D concentration may lead to further reduction in bone loss at the hip in patients on bisphosphonates. A prospective controlled trial is needed to evaluate whether the response to bisphosphonates is influenced by vitamin D status. BMD is preserved at the lumbar spine and total hip following discontinuation of bisphosphonate for a short period following long-term treatment, although a gradual loss occurs at the femoral neck.

Aged↗
PubMed2006

FDG-PET and CT patterns of bone metastases and their relationship to previously administered anti-cancer therapy.

PURPOSE: To assess (18)F-fluorodeoxyglucose (FDG) uptake in bone metastases in patients with and without previous treatment, and compare positive positron emission tomography (PET) with osteolytic or osteoblastic changes on computed tomography (CT). METHODS: One hundred and thirty-one FDG-PET/CT studies were reviewed for bone metastases. A total of 294 lesions were found in 76 patients, 81 in untreated patients and 213 in previously treated patients. PET was assessed for abnormal FDG uptake localised by PET/CT to the skeleton. CT was evaluated for bone metastases and for blastic or lytic pattern. The relationship between the presence and pattern of bone metastases on PET and CT, and prior treatment was statistically analysed using the chi-square test. RESULTS: PET identified 174 (59%) metastases, while CT detected 280 (95%). FDG-avid metastases included 74/81 (91%) untreated and 100/213 (47%) treated lesions (p<0.001). On CT there were 76/81 (94%) untreated and 204/213 (96%) treated metastases (p NS). In untreated patients, 85% of lesions were seen on both PET and CT (26 blastic, 43 lytic). In treated patients, 53% of lesions were seen only on CT (95 blastic, 18 lytic). Of the osteoblastic metastases, 65/174 (37%) were PET positive and 98/120 (82%), PET negative (p<0.001). CONCLUSION: The results of the present study indicate that when imaging bone metastases, prior treatment can alter the relationship between PET and CT findings. Most untreated bone metastases are PET positive and lytic on CT, while in previously treated patients most lesions are PET negative and blastic on CT. PET and CT therefore appear to be complementary in the assessment of bone metastases.

Adult↗
PubMed2006

The role of fluorodeoxyglucose, 18F-dihydroxyphenylalanine, 18F-choline, and 18F-fluoride in bone imaging with emphasis on prostate and breast.

Diagnostic imaging has played a major role in the evaluation of patients with bone metastases. The imaging modalities have included bone scintigraphy, computed tomography, magnetic resonance imaging, and most recently PET/CT, which can be performed with different tracers, including fluorodeoxyglucose (FDG), 18F-fluoride, 18F-choline (FCH), and 18F-DOPA (dihydroxyphenylalanine). For most tumors the sensitivity of FDG in detecting bone metastases is similar to bone scintigraphy; additionally it can be used to monitor the response to chemotherapy and hormonal therapy. 18F-Fluoride may provide a more sensitive "conventional" bone scan and is superior for FDG nonavid tumors, but, nevertheless, FDG in "early disease" often has clear advantages over 18F-fluoride. Although more data need to be obtained, it appears that FCH is highly efficient in preoperative management regarding N and M staging of prostate cancer once metastatic disease is strongly suspected or documented. For neuroendocrine tumors and in particular in medullary thyroid cancer, DOPA is similar to 18F-fluoride in providing high quality information regarding the skeleton. Nevertheless, prospective studies with large patient groups will be essential to define the exact diagnostic role of FCH and DOPA PET in different clinical settings.

Bone Neoplasms↗
PubMed2006

Theoretical model for the interpretation of BMD scans in patients stopping strontium ranelate treatment.

UNLABELLED: Strontium ranelate is a new treatment for osteoporosis that results in large increases in BMD, much of which is an artefact caused by high bone strontium content. We used clinical trial data and a model of long-term strontium kinetics to estimate the effect of past strontium treatment on future BMD measurements. INTRODUCTION: The oral administration of strontium ranelate causes a clinically significant overestimation of BMD because of the high attenuation of X-rays by strontium atoms in bone. As more patients are treated with strontium ranelate, questions will arise about the correct interpretation of their future BMD measurements. We performed a theoretical study to calculate the long-term effect of strontium treatment on BMD and establish the duration of past treatment for which the remaining bone strontium content (BSC) has a negligible effect on BMD. MATERIALS AND METHODS: The BMD changes measured at the spine and hip during strontium ranelate treatment were interpolated from clinical trial data. The long-term retention of strontium in bone was estimated using the International Commission on Radiological Protection (ICRP) strontium retention function modified for use in postmenopausal women. Estimates of the strontium BMD artefact after treatment has stopped were performed on the assumption that the BSC effect accounts for 75% of the total measured BMD change at 3 years. RESULTS: If 75% of the BMD changes are explained by BSC, in the average patient, 3-year treatment leads to a spine BMD artefact of 11.2%, decreasing to 3.8% 10 years after stopping treatment. The BMD artefacts at the total hip and femoral neck sites are smaller by factors of 0.65 and 0.53, respectively. If pre- and post-therapy BMD measurements are available, these predictions can be tailored to the individual patient. On average, 6-month treatment is required for the spine BMD artefact to exceed 3%, the figure adopted as the maximum BMD change caused by bone strontium that has a negligible effect on scan interpretation. Ten years after stopping treatment, 28 months of treatment are required for the residual BMD artefact to still exceed the 3% threshold. CONCLUSIONS: Strontium ranelate treatment lasting for >6 months can affect BMD measurements for many years afterward.

Bone Density↗
PubMed2006

Validation of a blood-sampling method for the measurement of 99mTc-methylene diphosphonate skeletal plasma clearance.

UNLABELLED: Quantitative studies of bone using (99m)Tc-methylene diphosphonate (MDP) reflect bone remodeling. The simplest method of evaluating (99m)Tc-MDP kinetics involves taking multiple blood samples and measuring total clearance (K(total)) from the area under the plasma curve (AUC) and deriving bone clearance (K(bone)) by subtracting glomerular filtration rate (GFR) from K(total). However, the accuracy of the AUC method is uncertain because of assumptions that the terminal exponential is reached by 2 h and that the rate constant k(4), representing the backflow of tracer from bone to plasma, is negligibly small. The aim of this study was to validate the accuracy of the AUC method by comparing K(bone) values obtained by that method with those obtained by gamma-camera imaging. METHODS: Seventy-one patients were injected with 600 MBq of (99m)Tc-MDP. For the first 22 patients, whole-body images were acquired at 15 min and at 1, 2, 3, and 4 h after injection, whereas the remaining 49 were imaged at 15 min and at 1 and 3 h. Two-minute static images of the thighs were acquired immediately before each whole-body scan. Multiple blood samples were taken between 5 min and 4 h, and free (99m)Tc-MDP was measured using ultrafiltration. Two gamma-camera methods were used to evaluate K(bone): the Patlak plot method and the Brenner method, which is based on measuring soft-tissue uptake in the thighs. The soft-tissue data were also used to measure k(4). RESULTS: The soft-tissue data gave a k(4) value of 0.0003 min(-1) (95% confidence interval, 0-0.0008 min(-1)). The mean (+/-SD) (99m)Tc-MDP K(bone) was 56.0 +/- 32.4 mL x min(-1) with the AUC method, 49.5 +/- 32.1 mL x min(-1) with the Patlak method, and 42.8 +/- 32.0 mL x min(-1) with the Brenner method. Correcting the AUC values of K(total) by factors of 0.95 and 0.90 gave K(bone) values in agreement with the Patlak and Brenner methods, respectively. CONCLUSION: Values of k(4) are too small to affect values of K(bone) measured using the AUC method. Correcting K(total) by factors in the range of 0.90-0.95 corrects for the error in the terminal exponential and brings K(bone) values measured using the AUC method into agreement with the gamma-camera results.

Adult↗
PubMed2006

Bone scintigraphy predicts outcome of steroid injection for plantar fasciitis.

UNLABELLED: Plantar fasciitis is a common cause of foot pain and may be disabling. Although localized injection is painful, anesthetics or corticosteroids can relieve symptoms well. Bone scintigraphy can confirm the diagnosis. We hypothesized that blood-pool abnormalities could provide prognostic information on the response to such injections. METHODS: We devised scintigraphic criteria that graded the blood-pool abnormalities as being localized to the plantar enthesis, being localized to half the length of the aponeurosis, or involving the whole aponeurosis. We evaluated 24 patients with an established diagnosis of plantar fasciitis, 8 of whom had bilateral disease, leading to a total of 32 feet injected. RESULTS: After injection, pain was relieved either completely or nearly completely in 20 feet. The other 12 feet had short-term or no improvement, with persistent pain and loss of function at 4-5 wk after injection. Of the 20 feet responding to injection, 14 had focal hyperemia on blood-pool images and 6 had minimal extension into the proximal third of the plantar soft tissues. No patient with diffuse hyperemia in the plantar fascia had a response (5/12 feet). On the delayed images of the 20 responders, mild inferior calcaneal uptake was seen in 8 feet, moderate uptake in 6, and severe uptake in 6. These groups did not significantly differ (P > 0.05). The blood-pool studies had good reproducibility, with a kappa-value of 0.64. CONCLUSION: Critical evaluation of plantar blood-pool images provides prognostic information on the response to localized injection into the enthesis. Reporting such studies is simple and reproducible.

Adult↗
PubMed2005

Fracture prediction by bone density measurements at sites other than the fracture site: the contribution of BMD correlation.

It is widely believed that the most reliable BMD measurement for predicting fracture risk at any given skeletal site is one made at the fracture site itself. This study examines the hypothesis that the ability of BMD measurements at other distant sites in the skeleton remote from the fracture site to predict fracture risk is due to their correlation with the BMD measurements at the fracture site. We refer to this assumption as the correlation hypothesis. We show that the correlation hypothesis predicts the relationship betadist = rbetafrac, where beta is the gradient of the exponential relationship between fracture risk and Z-score, betafrac is the beta-value for the fracture site, betadist the beta-value for the distant BMD site, and r is the correlation coefficient between the Z-scores at the two sites. In practice it is important to consider the effect of BMD measurement errors on the (r, beta) relationship. We show that the effect of errors at the distant site is to reduce betadist and r in a way that preserves their original relationship. When errors at the fracture site are taken into account the effect on the (r, beta) plot is for the point representing the fracture site to fall below the extrapolation of the straight-line relationship predicted for the points representing the distant BMD sites. We tested the correlation hypothesis by using data from the Study of Osteoporotic Fractures to examine the (r, beta) plots for hip, spine and forearm fractures. For the hip the data are consistent with a straight-line relationship and suggest that measurements made at other sites provide no additional information about fracture risk over and above that provided by hip BMD itself. For spine and forearm fractures the data show that distant sites do provide additional information about fracture risk in a way that is quantitatively consistent with the BMD measurement errors reported in cadaver studies. It is clear that random BMD errors at the fracture site cause loss of information about fracture risk and that some of this lost information is recoverable from measurements made at other sites in the skeleton. Overall, this study points to BMD correlation as an important factor in explaining the ability of measurements made at distant sites to predict fracture risk.

Absorptiometry, Photon↗
PubMed2005

Positron emission tomography and bone metastases.

The use of 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in the evaluation and management of patients with malignancy continues to increase. However, its role in the identification of bone metastases is far from clear. FDG has the advantage of demonstrating all metastatic sites, and in the skeleton it is assumed that its uptake is directly into tumor cells. It is probable that for breast and lung carcinoma, FDG-PET has similar sensitivity, although poorer specificity, when compared with the isotope bone scan, although there is conflicting evidence, with several articles suggesting that it is less sensitive than conventional imaging in breast cancer. There is convincing evidence that for prostate cancer, FDG-PET is less sensitive than the bone scan and this may be tumor specific. There is very little data relating to lymphoma, but FDG-PET seems to perform better than the bone scan. There is an increasing body of evidence relating to the valuable role of FDG-PET in myeloma, where it is clearly better than the bone scan, presumably because FDG is identifying marrow-based disease at an early stage. There are, however, several other important variables that should be considered. The morphology of the metastasis itself appears to be relevant. At least in breast cancer, different patterns of FDG uptake have been shown in sclerotic, lytic, or lesions with a mixed pattern, Furthermore, the precise localization of a metastasis in the skeleton may be important with regard to the extent of the metabolic response induced. Previous treatment is highly relevant and it has been found that although the majority of untreated bone metastases are positive on PET scans and have a lytic pattern on computed tomography (CT), after treatment, incongruent CT-positive/PET-negative lesions are significantly more prevalent and generally are blastic, which presumably reflects a direct effect of treatment. Finally, the aggressiveness of the tumor itself may be relevant. The most important question, however, is irrespective of whether a lesion is seen on x-ray, CT, or bone scan and irrespective of lytic of blastic morphology: if the FDG-PET study is negative, what is the clinical relevance of that lesion?

Bone Neoplasms↗
PubMed2005

Bone mineral density and its relationship to prolactin levels in patients taking antipsychotic treatment.

Antipsychotic treatment is frequently associated with elevated prolactin levels. Raised prolactin levels have been linked with osteoporosis. The objective of this study is to determine whether patients taking antipsychotics show reduced bone mineral density (BMD), and whether this is associated with prolactin levels. BMD (standardized as z scores) was compared using dual x-ray absorptiometry of the lumbar spine and hip in patients taking antipsychotics (n = 102, mean age: 46.0, SD: 13.1, 47% male, median treatment duration: 3.0 years) to matched reference controls. Levels of prolactin, markers of bone metabolism, and risk factors for osteoporosis were measured. Mean BMD was not significantly reduced, other than the total spine score for black males (mean z score: -0.88, P = 0.00001). BMD was correlated with body mass index but there was no correlation with prolactin. BMD was not correlated with prolactin levels and showed no clinically significant reduction. The low BMD in black males warrants further investigation.

Adult↗
PubMed2005

Where now for the management of osteoporosis?

Osteoporosis is a metabolic bone disorder, leading to bone fragility and fracture. Recent guidance from the National Institute for Clinical Excellence (NICE) emphasizes the importance of secondary prevention of fragility fractures in postmenopausal women. What impact can the expanding range of treatments make on the growing and costly burden of osteoporosis?

Calcium↗
PubMed2004

Dissociation between global markers of bone formation and direct measurement of spinal bone formation in osteoporosis.

UNLABELLED: Regional bone metabolism measured using 18F-fluoride PET was assessed in 72 postmenopausal women classified as normal, osteopenic, or osteoporotic. Lower values of regional bone formation activity at the lumbar spine were seen in osteoporotic women, whereas global markers of bone formation were significantly increased. INTRODUCTION: Evaluations of global bone remodeling have revealed that increased bone turnover is a feature of patients with osteoporosis. The noninvasive functional imaging technique of 18F-fluoride positron emission tomography (PET) allows the direct quantitative assessment of bone metabolism at specific sites in the skeleton, including the clinically important site of the lumbar spine. MATERIALS AND METHODS: The aim of this study was to compare regional skeletal kinetics in 72 postmenopausal women (mean age, 61 years) classified as normal, osteopenic, or osteoporotic according to their BMD T score at the lumbar spine. Each woman had a dynamic PET scan of the lumbar spine after injection of 90 MBq 18F-fluoride ion and measurements of biochemical markers of bone formation and resorption. The arterial plasma input function was derived using aorta arterial activity from the PET image. Time-activity curves were obtained by placing regions of interest over the lumbar vertebrae. A three-compartmental model was used to calculate bone blood flow (K1) and the net plasma clearance of tracer to bone mineral (Ki), reflecting regional osteoblastic activity (ml/minutes/ml). Rate constants k2, k3, and k4, which describe transport between plasma, the extracellular fluid (ECF) compartment, and the bone mineral compartment, were also measured. RESULTS: The net uptake of fluoride to the bone mineral compartment (Ki) was significantly lower in the osteoporotic group compared with both the osteopenic and normal groups, with a mean difference of 0.005 ml/minutes/ml (16.7%). The fraction of the tracer in the extravascular tissue space that underwent specific binding to bone mineral (k3/k2 + k3) was also significantly reduced in the women classified as osteoporotic. In contrast, levels of bone-specific alkaline phosphatase (BSALP) were significantly higher in the osteoporotic group compared with the normal and osteopenic groups by 35% and 27%, respectively. A significant negative correlation (r = -0.41) was observed between levels of BSALP and the fraction of the tracer that underwent specific binding to bone mineral. CONCLUSION: Lower values of Ki, a measurement of regional bone formation activity, were seen in women classified as osteoporotic, whereas levels of BSALP, a measure of global bone formation, were significantly increased. These findings are suggestive of increased global skeletal bone turnover in women with postmenopausal osteoporosis but with relatively reduced regional bone formation at the predominantly trabecular site of the lumbar spine.

Absorptiometry, Photon↗
PubMed2004

A comparison of the effects of raloxifene and conjugated equine estrogen on bone and lipids in healthy postmenopausal women.

BACKGROUND: Although many studies have assessed the effects of estrogen and raloxifene hydrochloride on bone mineral density and serum lipid concentrations, there are few direct comparative data. METHODS: Randomized placebo-controlled trial for 3 years, intention-to-treat analysis. Six hundred nineteen postmenopausal women with prior hysterectomy (mean age, 53.0 years) were studied in 38 centers in Europe, North America, Australasia, and South Africa. They were randomized to 60 mg/d or 150 mg/d of raloxifene, 0.625 mg/d of conjugated equine estrogen (CEE), or placebo. Bone density of the lumbar spine and proximal femur, biochemical markers of bone turnover, and fasting serum lipid concentrations were assessed for 3 years. RESULTS: Compared with baseline, bone density in the lumbar spine progressively declined by 2.0% in the placebo group (P <.05), was stable in the 2 raloxifene groups, and increased 4.6% in the subjects receiving CEE (P <.001). Effects in both raloxifene groups were different from those observed in the CEE and placebo groups (P <.001). Bone density in the total hip showed similar results. Conjugated equine estrogen produced significantly greater depression of serum osteocalcin, bone-specific alkaline phosphatase, and urine C-telopeptide, compared with raloxifene. Each of the active treatments caused comparable depression of low-density lipoprotein cholesterol below placebo levels (P <.001 at most time points). Raloxifene did not affect high-density lipoprotein cholesterol, whereas CEE increased it by 13.4% compared with placebo at 3 years (P <.001). Triglyceride concentrations increased 24.6% in the CEE group at 3 years (P <.003), a significantly greater change than in the raloxifene groups, which were 4.9% and 8.0% above baseline (P < or =.002) but not different from placebo. Urinary incontinence was reported in 11 women receiving CEE, but in only 1 or 2 in each of the other groups (P < or =.01 compared with the other groups). Hernias occurred less frequently in those receiving 150 mg/d of raloxifene or CEE (P =.03 vs placebo). CONCLUSIONS: Raloxifene and CEE have beneficial effects on bone density and bone turnover, although effects of CEE are more marked. Raloxifene and CEE produce different patterns of lipid responses and have distinct adverse effect profiles.

Alkaline Phosphatase↗
PubMed2004

An evaluation of the United Kingdom National Osteoporosis Society position statement on the use of peripheral dual-energy X-ray absorptiometry.

A recent position statement issued by the UK National Osteoporosis Society recommends a triage approach to the use of peripheral dual-energy X-ray absorptiometry (pDXA) devices. Patients with a forearm T-score greater than -1 or less than -2.5 are regarded as normal or osteoporotic, respectively, while those with a T-score between -1 and -2.5 are sent for further assessment with spine and hip DXA. We have evaluated the NOS pDXA algorithm by comparing it with the alternative strategies of relying on forearm BMD alone, or performing spine and hip DXA in every patient. The evaluation was carried out using a mathematical model, and the predictions were compared with in vivo data obtained in patients referred for investigation by their general practitioner. In the model the population distribution of spine, hip, and forearm BMD was described by a trivariant Gaussian function. Relative risks of fracture were taken from a meta-analysis. The three strategies were compared using receiver operating characteristic (ROC) curves in which the percentage of future fracture cases identified was plotted against the percentage of the whole population found to have osteoporosis. ROC curves plotted for the discrimination of hip, vertebral, and Colles fracture risk and the risk of a fracture at any skeletal site were similar for all three strategies, with the curves for the NOS pDXA algorithm nearly identical to those for spine and hip DXA. For the case of hip fracture, vertebral fracture, or a fracture at any site, forearm BMD was slightly inferior to the NOS algorithm, but the reverse was true for Colles fracture. The small difference between the ROC curves suggests that forearm BMD used alone can reproduce clinical decision-making with the NOS pDXA algorithm provided that a T-score threshold of T=-2.1 is used for the diagnosis of osteoporosis, instead of the conventional figure of T=-2.5. Results from the in vivo study were in good agreement with the predictions of the model, although some differences were observed that were explained by inaccuracies in the forearm reference data. We conclude that use of forearm BMD alone with a modified T-score threshold of -2.1 would save the need for spine and hip DXA scans and identify only slightly fewer fracture cases for treatment.

Absorptiometry, Photon↗