Anorexia nervosa, osteoporosis and circulating leptin: the missing link.

UNLABELLED: Methods: Leptin levels were measured in 103 consecutive women with anorexia nervosa. Results: Spine BMD and Z-score values were found to be significantly lower in the low tertile compared with the highest tertile. Duration of amenorrhea and leptin level accounted for 27% of the variance in lumbar spine BMD. INTRODUCTION: The purpose of this study was to assess leptin levels and other biological variables in a population of anorexia nervosa patients. METHODS: Leptin levels were measured consecutively in 103 women with anorexia nervosa (AN) with a mean age of 24.9 +/- 7.4 years. Osteodensitometry was also performed by dual energy X-ray absorptiometry (DXA). RESULTS: Spine bone mineral density (BMD) and Z-score values were found to be significantly lower in the low tertile compared with the highest tertile. Duration of amenorrhea and leptin level accounted for 27% of the variance in lumbar spine BMD. The mean leptin level was 3.9 +/- 4.6 ng/mL (normal values, 3.5-11 ng/mL). The distribution of leptin values was not a Gaussian distribution, and a log-transformed was therefore performed. A significant correlation was found between leptin level and spinal BMD (r = 0.3; p = 0.002); significant correlations were observed for both femoral neck and total hip BMDs. When leptin level values were divided into tertiles, spine BMD and Z-score values were found to be significantly lower in the lower tertile (p = 0.04 and p = 0.02) compared with the highest tertile. For femoral neck BMDs, the T-score was slightly lower between low and high tertile, but the difference was not statistically significant (p = 0.07). When multivariate analyses were performed, two independent factors which could possibly account for the variance in spinal BMDs were found. Duration of amenorrhea and leptin level accounted for 27% of the variance (p < 0.0001). CONCLUSION: The mechanisms underlying bone loss in AN patients remain unclear and complex, involving hypoestrogenia as well as nutritional factors such as insulin-like growth factor and leptin.

Ligament fibre recruitment of the elbow joint during gravity-loaded passive motion: an experimental study.

BACKGROUND: Knowledge of elbow collateral ligament length during passive motion is essential in understanding ligament physiology and pathology, such as tightness and instability. METHODS: Five anatomical unembalmed specimens were passively placed in six flexion positions together with three forearm rotations, using equipment with gravity as motion force. These 18 positions were recorded using CT-scan. Three-dimensional data of ligament insertions were obtained through anatomical millimetre sections. Ligament length was measured in each position. FINDINGS: In neutral rotation, the lateral collateral ligament was long between 0 degrees and 30 degrees as well as at 90 degrees, and short between about 60 degrees and 120 degrees of flexion. In pronation, it was long at about 0 degrees and between 60 degrees and 120 degrees, short at about 30 degrees of flexion. In supination, it was long at about 30 degrees and 90 degrees and short between 120 degrees and 150 degrees of flexion. In any forearm rotation, the highest length of the anterior bundle of the ulnar collateral ligament was measured at about 90 degrees, its smallest length between 120 degrees and 150 degrees of flexion, position at which the posterior bundle length was greatest. INTERPRETATION: At 60 degrees of flexion, the collateral ligaments were slackened in any forearm rotations. Forearm rotation plays an indirect role in the posterolateral stability of elbow as it changes length of the lateral collateral ligament. This ligament can be tested passively at 90 degrees of flexion in supination, the anterior bundle of the ulnar collateral ligament between 0 degrees and 30 degrees in neutral rotation and the posterior bundle between 120 degrees and 150 degrees in neutral rotation.

Thyrotoxicosis revealing metastases of unrecognized thyroid cancer: a report on two cases.

We report two cases of thyrotoxicosis-revealing functional metastases of a follicular carcinoma that extended to the bones, liver and kidneys in one case and to the lungs in the other. Both patients had undergone surgical intervention for a thyroid nodule more than 15 years before the diagnosis of thyrotoxicosis and metastatic dissemination. In both the cases, the carcinoma was not recognized by the pathologist after the first surgical intervention, but was finally diagnosed several years later due to the occurrence of thyrotoxicosis. Iodine-131 therapy was effective at suppressing the thyrotoxicosis in both the patients. The effectiveness on the metastatic extension was very different for each patient: in the first case, the patient died a few years later without any control of the metastatic tissue. For the second patient, the metastases disappeared a few months after radioiodine treatment, with the patient still in remission more than 10 years later. The physiopathology and the evolution of these two cases are discussed with the data available in the literature.

[131 iodine for the treatment of benign goiters]. / L'iode 131 comme traitement des goitres bénins.

INTRODUCTION: In order to evaluate the efficacy of 131 Iodine on goitre volume and on thyroid function, we studied a cohort of patients exhibiting a multinodular and toxic or non toxic goitre. METHODS: This retrospective study was conducted at the Marc Linquette clinic in Lille, in collaboration with the department of nuclear medicine. Thirty-eight patients treated with 131 Iodine were included from 1995 to 2001. Clinical examination and serum analyses including TSH, free T4 and T3, anti-thyroid peroxidase and anti-thyroglobulin antibodies and TSH-receptor antibodies measurements were conducted on inclusion and then at 3, 6, 12 and 72 months. The activity of 131 Iodine corresponded to a standard dose or was calculated according to Marinelli's method. We excluded patients who had not undergone assessment at the above-mentioned time schedules. RESULTS: The treatment was indicated in 30 patients presenting with a non compressive but toxic goitre, in 5 patients with a toxic compressive goitre and in 3 patients with a compressive but non-toxic goitre. Surgery had been excluded for all these patients because of their age, their cardiac status or because they had refused surgery after failure with prior partial thyroidectomy or medical treatment. Among the toxic goitres, TSH levels were low and T3 and T4 increased in 17 patients. In the 18 others, hyperthyroidism was manifested by an isolated decrease of TSH. The thyroid volume before treatment, assessed in 20 patients, was of 18 to 135 cm3 (mean: 53 cm3). Treatment consisted in administration of radioactivity of 3 to 30 mCi in 30 patients and standard activity of 20 to 25 mCi in 8. Functional efficacy with reduction in hyperthyroidism was noted after 3 months, and corrected in nearly all patients after 1 year, and morphological efficacy, with a mean decrease of 33.5% in the size of the goitres. No supplementary surgery was required, notably for the initially compressed goitres. Immediate and long term tolerance was satisfactory. CONCLUSION: Metabolic 131Iodine radiotherapy is effective for the functional and morphological treatment of goitres with good tolerance and few side effects. 131 Iodine is a reasonable alternative in cases with absolute or relative contraindication for surgery.

Relationship between computed tomographic image analysis and histomorphometry for microarchitectural characterization of human calcaneus.

The present study aimed to characterize the relationships between several variables reflecting bone microarchitecture assessed by both computed tomographic (CT) image analysis and histomorphometry (conventional CT system) at the calcaneus. A total of 24 cadaveric specimens were studied. The mean age at death was 78 +/- 10 years (range, 53-93 years). A total of 15 sagittal sections (1 mm in width and spaced 2 mm apart) were selected for CT analysis; 6 undecalcified sections (7 microm) were analyzed for histomorphometry. The histomorphometric analysis was performed on a Leica Quantimet Q570 image analyzer. Features measured by both methods were: bone volume/tissue volume (BV/TV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), trabecular number (Tb.N), interconnectivity index (ICI), number of nodes (N Nd), number of terminus (N Tm), node-to-node strut count (NNS), node-to-terminus strut count (NTS), terminus-to-terminus strut count (TTS), marrow space star volume (SV), Euler number (EN), and fractal dimension (FD). The coefficient of correlations' values (simple linear regression) between histomorphometry and CT image analysis varied according to the parameters selected. R values were high for BV/TV, Tb.N, and Tb.Sp (range, 0.69-0.90; P < 0.01). R values were less significant for some variables also obtained from the binary image: SV (0.5, P < 0.05) and EN (0.43, P < 0.05). Finally R values were also significant for (two) variables obtained from skeletonized images, i.e., N Nd (0.4, P < 0.05) and N Tm (0.61, P < 0.01). Other correlations were not statistically significant. Moreover, for some variables the relationships between the two methods (CT analysis and histomorphometry) seemed best-described by using nonlinear models. For example, a logarithmic model was more appropriate for SV (r = 0.71, P < 0.01), N Nd (r = 0.52, P < 0.01). Finally the relationship between apparent (App) N Tm and N Tm was most satisfying when using an exponential model (r = 0.64, P < 0.01). In conclusion, trabecular bone structure measures determined on CT images show highly significant correlations with those determined using histomorphometry. The level of correlation varies according to the type of method used for characterizing bone structure, however, and the strongest correlations were found for the most basic features (Parfitt's parameters). Finally, for some variables, nonlinear models seem more appropriate.

Does quantitative ultrasound of bone reflect more bone mineral density than bone microarchitecture?

Relationships among quantitative ultrasound of bone (QUS), bone mineral density (BMD) and bone microarchitecture have been poorly investigated in human calcaneus.Twenty-four specimens, from 12 men and 12 women (mean age 78 +/- 10 years; range 53-93), removed from cadavers were studied. The feet were axially sectioned above the ankle. Two variables were measured for QUS (Achilles, Lunar): broadband ultrasound attenuation (BUA) and speed of sound (SOS). A third variable, the stiffness index (SI), which is a combination of both BUA and SOS, was also calculated. BMD (a lateral view) was measured on a QDR 2000 densitometer (Hologic). Bone microarchitecture was assessed by computed tomography (CT) using a conventional CT-system. Fifteen sagittal sections (1 mm in width and 2 mm apart) were selected for CT. Methods used for characterizing bone microarchitecture consisted in structural (trabecular network characterization) and a fractal analyses. The relationships between QUS and bone microarchitecture were assessed by simple linear regression analysis with and without adjustment for BMD (partial correlation) and by backward stepwise regression analysis. Strong relationships were found between BMD and QUS. Adjusted r(2) values were 0.545 for SOS and 0.717 for SI. Two microarchitectural variables were also significantly correlated with both SOS and SI: apparent trabecular separation (App Tr Sp) and trabecular bone pattern factor (App TBPF). After adjustment for BMD few correlations between QUS and microarchitectural variables were always significant. Adjusted squared semipartial coefficients of correlation (rsp2) values between SOS and bone microarchitecture were 6%, 6.8%, 13.2% and 4.6% for App BV/TV, App Tr Sp, App TBPF and fractal dimension (FD), respectively. For SI, corresponding figures were 3.7%, 4.1%, 5.2% and 3.2%. Backward stepwise regression analysis using BMD and microarchitecture showed a slight increase of r(2) values that varied from 8.4% for SI to 17.8% for SOS, compared with BMD alone. The current study suggests that although BMD is a major determinant of acoustic properties of human calcaneus, significant density independent relationships with bone microarchitecture should also be taken into account.

Quantitative ultrasound of bone in male osteoporosis.

Quantitative ultrasound (QUS) measurement, a different approach to bone fragility assessment, has already been attempted in women with osteoporosis but rarely in men. In order to test its value and ability to identify osteoporotic men, a case-control prospective study was conducted using the Lunar Achilles, a device that measures attenuation and velocity parameters. Broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (SI), a composite parameter, were assessed through the heel of 66 osteoporotic patients, and compared with the results in 35 controls. Patients had sustained a low-trauma fracture and/or had a lumbar and/or femoral bone mineral density (BMD) more than 2.5 SD below the young male reference value. As expected, all QUS parameters were statistically lower in patients, as were the dual-energy X-ray absorptiometry (DXA) measurements at the hip and lumbar spine. The two methods were compared for their ability to predict the risk of osteoporotic fractures. The odds ratios (ORs), with their 95% confidence limits, for fractures per 1 SD decrease were significant, especially for SOS and SI (OR = 2.3 [1.4-3.6] and 2.1 [1.3-3.3] respectively) and to a lesser extent for BUA (1.6 [1.0-2.4]). Our study suggests that QUS is associated with a history of low-trauma fracture in men; sensitivity is, however, less than when results are compared with BMD measurements (OR = 2.8 [1.6-5.0] and 3.4 [1.6-7.0] for lumbar spine and hip, respectively). Prospective studies are required before QUS can be recommended for clinical use in male osteoporosis.

Computed tomography image analysis of the calcaneus in male osteoporosis.

The present study aimed to characterize bone microarchitecture assessed by computed tomography (CT) at the calcaneus in male subjects suffering from osteoporosis. Seventy-nine subjects were assessed (45 with osteoporosis and 34 control subjects matched for age). Osteoporosis was defined according to the World Health Organization classification either at the lumbar spine or at the femoral neck. Thirty-three subjects (73%) had a past history of low-energy fracture mainly represented by vertebral fractures (24/33). Nine axial sections (1 mm in width and 2 mm apart) were selected for each subject. Bone microarchitecture analysis was performed using structural (binary and skeletonized images but also skeletonization from gray levels) and fractal analyses. Bone densitometry by dual-energy X-ray absorptiometry (DXA) at the calcaneus was also performed in 73 cases. Bone mineral density (BMD) was decreased in osteoporotic patients compared with controls both at the lumbar spine and hip and also at the calcaneus (p<0.01). Also 14 microarchitectural features among 25 measured were significantly different between the two groups (p<0.01). The odds ratio for fracture per 1 control group standard deviation decrease were also significant for 13 structural features but also for BMD at the calcaneus. The odds ratios after adjustment for BMD at the calcaneus were significant for the following features (p<0.05): number of valleys, 2.8 (1.2-6.9); trabecular partition, 3.3 (1.3-7.9); apparent trabecular spacing, 1.8 (1.0-3.1); trabecular bone pattern factor, 2.2 (1.1-4.3); Euler number, 3.0 (1.1-8.7); node-to-terminus strut count, 3.3 (1.4-7.8); terminus-to-terminus strut count, 2.9 (1.2-6.9); and fractal dimension, 3.7 (1.5-9.7). Few and weak correlations were found between BMD at the calcaneus measured with DXA and features obtained from CT, suggesting that these two methods give different information about bone status. In conclusion, male osteoporosis is a disease characterized by decreased bone mass but also by microarchitectural deterioration of bone tissue which is partly independent of BMD.

Vitamin D deficiency and severe hyperparathyroidism.

The typical manifestations of severe hypercalcemia with osteitis fibrosa cystica have become exceedingly rare. We describe the case of a woman hospitalized for a tibial tumor with functional impotence, leading to a diagnosis of primary hyperparathyroidism (HPT I) associated with profound vitamin D deficiency. This 31-year-old woman was admitted, after two pregnancies complicated by the HELLP syndrome. Preoperative laboratory values were as follows: calcemia 4.05 mmol/l (2.2-2.6); urinary calcium 30 mmol/24 h (1.25-7.5); parathormone (PTH) 1 195 pg/ml (10-60); and 25 OH-vitamin D 13 nmol/l (22-120). Specific MIBI uptake by the tibial lesion oriented the diagnosis towards a brown tumor. After surgical excision of a parathyroid adenoma and the brown tumor (associated with tibial fracture), calcemia fell to 1.55 mmol/l and normalized after three months. Urinary calcium fell to 0.1 mmol/24 h and remained low during the 2 years following surgery. Vitamin D levels rapidly normalized on supplementation (87 nmol/l). PTH levels fell markedly after surgery but remained higher than normal till 2 years after surgery despite normalization of calcemia three months after. Bone repair, estimated by means of bone densitometry, improved from preoperative Z-score values of - 6.54, - 5.20 and - 3.50 in the left femoral neck, right femoral neck and lumbar spine, respectively, to - 0.20, - 1.55 and - 0.28, respectively, one year after surgery. In conclusion, this case illustrates: 1) the severe osseous expression of HPT probably related to vitamin D deficiency; 2) specific MIBI uptake by the bone lesion, orientating the diagnosis towards a brown tumor; 3) the consequences of vitamin D deficiency on postoperative outcome, with transient severe initial hypocalcemia related to bone calcium avidity; 4) a possible link between HPT and the HELLP syndrome.

Comparative efficacy and safety study of etidronate and alendronate in postmenopausal osteoporosis. effect of adding hormone replacement therapy.

OBJECTIVES: To compare the efficacy and safety of etidronate and alendronate in patients with postmenopausal osteoporosis and to assess the efficacy of either bisphosphonate in combination with hormone replacement therapy (HRT). PATIENTS AND METHODS: In this pragmatic study, the main efficacy criterion was the mean annual change in bone mineral density (BMD). Patients who had a past or current history of etidronate or alendronate treatment for postmenopausal osteoporosis with at least 18 months follow-up and an evaluation in 1999 were eligible. Recruitment was in an outpatient clinic with a special focus on metabolic bone diseases. Osteoporosis was defined as at least one low-energy fracture or as a lumbar spine or femoral neck BMD decrease to at least 2.5 SD below the mean in young women. HRT was not an exclusion criterion provided treatment duration was longer than 1 year. Etidronate was given cyclically (14-day courses in a dosage of 400 mg/d separated by 76-day intervals with calcium and vitamin D supplementation) and alendronate was given daily in a dosage of 10 mg/d. RESULTS: Of the 99 patients who met our inclusion criteria, 53 received etidronate (including 23 on HRT) and 46 alendronate (18 on HRT). Repeat BMD measurements were obtained in 88 patients, including 11 who stopped their bisphosphonate therapy within the first year of use because of adverse events. Lumbar spine BMD (mean +/- SD) increased significantly both in the etidronate group (+2.1% +/- 0.7%/year) and in the alendronate group (+5.3% +/- 0.9%/year). The increase was significantly greater with alendronate (P< 0.01). The lumbar spine BMD increase was largest in the patients on alendronate and HRT (+6.5% +/- 1.4%/year) and was smallest (and nonsignificant) in the patients on etidronate without HRT (+ 1.2% +/- 0.8%). Femoral neck BMD showed no significant changes in any group. In the intention-to-treat analysis, fractures occurred in 12 etidronate patients (22.6%) and six (13.0%) alendronate patients (nonsignificant). Adverse events requiring bisphosphonate discontinuation before the scheduled date of the follow-up BMD measurement occurred in one patient (1.9%) in the etidronate group (generalized osteomalacia) and in ten patients (21.7%) in the alendronate group (upper or lower gastrointestinal tract symptoms in six and four patients, respectively; P < 0.01). CONCLUSION: Both etidronate and alendronate significantly increased lumbar BMD, but the effect was significantly more marked with alendronate. Conversely, adverse effects, most notably gastrointestinal symptoms, were more common with alendronate, so that premature treatment discontinuation because of adverse events were more common in the alendronate group. Both differences should be taken into account when selecting the best drug for a patient with postmenopausal osteoporosis.

Simultaneous determination of pulmonary and intestinal permeability in patients with alcoholic liver cirrhosis.

The aim of this prospective study was to assess pulmonary and intestinal permeability (PP and IP, respectively) in patients with alcoholic liver cirrhosis (ALC). Thirty-five non-smoking patients with biopsy-proven ALC were included (mean grade B in Child's classification). None had a previous history of pulmonary disease and all had a normal chest radiograph and computed tomography scan. Lung function tests and bronchoalveolar lavage (BAL) were also performed. The PP was studied by measuring the lung to blood clearance of inhaled 99mTc-DTPA aerosol. Clearance half-time (T 1/2, in minutes) and residual activity (RA in %) were obtained from exponential fitting of the right pulmonary clearance curve. IP was concurrently evaluated by measuring the urinary recovery of ingested 51Cr-EDTA, according to Bjarnason's technique and expressed as a percentage of the total oral dose. Results were compared with those obtained in non-smoking healthy control subjects. PP was significantly (P<0.05) increased in patients with ALC (T 1/2 65.9 +/- 32.2 min, RA 87.1% +/- 6.7%) versus control subjects (T 1/2 85.2 +/- 20.8 min, RA 92.8% +/- 2.6%). IP was not significantly different between patients and controls (2.39% +/- 2.20% vs 1.74% +/- 0.81%). A significant correlation (P<0.05) was found between PP and total cell number in BAL and total lymphocyte number in BAL. In conclusion, in patients with ALC, PP is increased without any association with IP, the severity of cirrhosis according to Child's classification or the results of pulmonary function tests. These findings may reflect primary involvement of the alveolar epithelium. In patients with ALC, PP is correlated with total cell number and total lymphocyte number. Increased PP may be due to activated cytotoxic lymphocytes and/or abnormal macrophage activity.

Chromogranin A assay and (131)I-MIBG scintigraphy for diagnosis and follow-up of pheochromocytoma.

UNLABELLED: We assessed the performance of a new serum chromogranin A (CgA) assay in combination with the results of (131)I-metaiodobenzylguanidine (MIBG) scintigraphy for diagnosis and follow-up in 89 patients with clinical findings suggestive of pheochromocytoma. METHODS: The study population consisted of 41 patients with proven pheochromocytoma and 48 patients with refuted pheochromocytoma. Eighty-seven scintigraphy examinations were performed, 52 in patients with proven pheochromocytoma (39 before surgery and 13 after surgery) and 35 in patients with refuted pheochromocytoma. RESULTS: The sensitivity of the CgA level was 90.2%, and the specificity was 99.0% and 92.3% in the control and refuted pheochromocytoma groups, respectively. A significant relationship was seen between serum levels of CgA and tumor mass (r = 0.70; P < 10(-5)). The postoperative CgA level was an early and accurate predictor of curative surgery or relapse. The concordance between CgA levels and scintigraphic data was 90.8%. CONCLUSION: Serum CgA level is an effective marker of pheochromocytoma. Increased levels strongly correlate with tumor mass; therefore, small tumors may go undetected. The concordance between CgA level and the results of (131)I-MIBG scintigraphy is high. A CgA level in the reference range is highly predictive of normal scintigraphy findings.

Management of male osteoporosis.

UNLABELLED: The objective of this study was to evaluate the efficacy of treatments for male osteoporosis selected based on the cause of the disease. METHODS: Sixty-three men with osteoporosis (T-score at the lumbar spine and/or femoral neck lower than -2.5) with a mean age of 53+/-11 years were studied. Forty-three (68.3%) had a history of fracturing without trauma (vertebral fractures, 37 patients, 57%). Treatments were as follows: idiopathic osteoporosis: calcium and vitamin D supplements (N = 10) or cyclical etidronate for 2 weeks followed by calcium and vitamin D supplements for 76 days (N = 29); moderate idiopathic phosphate diabetes: calcitriol and phosphate (N = 15); idiopathic hypercalciuria: hydrochlorothiazide (N = 6); and hypogonadism: testosterone (N = 3). RESULTS: Percentage change in bone mineral density (mean +/- standard error of the mean) after 18 months: calcium and vitamin D (lumbar spine: 0.6+/-2; femoral neck: 2.2+/-2.2); etidronate (lumbar spine: 3.6+/-1.4*; femoral neck: 0.5+/-1); calcitriol (lumbar spine: 7.0+/-3.5*; femoral neck: 0.0+/-1.4); thiazide diuretic (lumbar spine: 1+/-3.2; femoral neck: -2.3+/-3.7); and testosterone (lumbar spine: 6.8+/-6.4; femoral neck: 2.5+/-2.7), where *P < 0.05 versus baseline. Gastrointestinal side effects occurred in three patients (4.8%), including two on calcitriol-phosphate therapy and one on etidronate therapy. Of the six (9.5%) patients who experienced incident fractures, four were on etidronate, one on calcitriol-phosphate, and one on calcium-vitamin D. No patients discontinued their treatment because of side effects. CONCLUSION: Etidronate and the combination of calcitriol-phosphate produce a significant increase in lumbar spine bone mass in men with idiopathic osteoporosis or moderate idiopathic phosphate diabetes.

Quantitative ultrasound of bone and markers of bone turnover in Cushing's syndrome.

Quantitative ultrasound (QUS) of bone is a valuable tool in the assessment of postmenopausal osteoporosis. QUS and new markers of bone turnover have been poorly assessed in Cushing's syndrome, however. Twenty-five patients with Cushing's syndrome (20 women, 3 men; mean age +/- SEM: 38+/-2 years) were studied and compared with 35 age- and sex-matched control patients (mean age +/- SEM: 38+/-2 years). The following variables were measured in both groups: QUS parameters at the heel (BUA; SOS; Stiffness Index, SI); bone mineral density (BMD) at both the lumbar spine (LS) and femoral neck (FN) by dual-energy X-ray absorptiometry; and serum markers of bone turnover (osteocalcin, procollagen type I N- and C-terminal propeptides (PINP and PICP), bone alkaline phosphatase (BAP), procollagen type I C-terminal telopeptide (ICTP) and urinary type I collagen C-telopepetide breakdown products (CTX)). Both BUA and SI were decreased in patients with Cushing's syndrome (p<0.01) but not SOS (p=0.08). BMD was also strongly decreased in Cushing's syndrome, at both the LS and FN (p<0.005). The two markers of bone turnover statistically significantly different between the two groups were osteocalcin (mean + SEM: 3.5 + 0.7 ng/ml (Cushing's syndrome) vs 6.4+/-0.5 ng/ml (controls, p<0.01)) and CTX (mean +/- SEM: 148.7+/-17.1 microg/mmol Cr (Cushing's syndrome) vs 220.8+/-22.9 microg/mmol Cr (controls), p<0.05). The areas under the receiver operating characteristic curve (AUC) were 0.72 (BUA), 0.73 (SI), 0.90 (BMD(LS)), 0.81 (BMD(FN)), 0.83 (osteocalcin) and 0.64 (CTX) respectively. AUC was significantly higher for BMD(LS) than for both BUA and SI (p<0.05). Conversely AUC was not statistically significantly different for BMDFN as compared with either BUA or SI. AUC was also higher for osteocalcin than for other markers of bone turnover. In conclusion, QUS of bone seems to be a relevant tool for assessing bone involvement in Cushing's syndrome. QUS does have a lower sensitivity compared with DXA, however, and the relevance of QUS cannot be ascertained until some longitudinal data are forthcoming. Except for CTX, the other new markers of bone turnover assessed in this study (PINP, PICP, BAP and ICTP) do not seem of interest in Cushing's syndrome.

[Dosimetry with radiosensitive gels in radiotherapy. Methods]. / Dosimétrie par gels radiosensibles en radiothérapie. Intérêt et méthodes.

The goal of conformal radiotherapy is to concentrate the dose in a well-defined volume by avoiding the neighbouring healthy structures. This technique requires powerful treatment planning software and a rigorous control of estimated dosimetry. The usual dosimetric tools are not adapted to visualize and validate complex 3D treatment. Dosimetry by radiosensitive gel permits visualization and measurement of the three-dimensional dose distribution. The objective of this work is to report on current work in this field and, based on our results and our experience, to draw prospects for an optimal use of this technique. Further developments will relate to the realization of new radiosensitive gels satisfying, as well as possible, cost requirements, easy realization and use, magnetic resonance imagery (MRI) sensitivity, tissue equivalence, and stability. Other developments focus on scanning methods, especially in MRI to measure T1 and T2.

In vivo comparison between computed tomography and magnetic resonance image analysis of the distal radius in the assessment of osteoporosis.

In a prospective case-control cross-sectional study, we investigated the usefulness of both computed tomography (CT) and magnetic resonance (MR) image analysis of the distal radius for distinguishing a small sample of fractured osteoporotic women from control women regardless of bone mineral density. The study population included 12 subjects who were divided into two groups according to their bone status. The first group consisted of six women with at least one vertebral fracture occurring in the absence of high-energy trauma, and the second group consisted of six women without disease affecting bone mass or bone metabolism. Cross-sectional and coronal slices were obtained from both CT and MR systems. For CT images, the slice thickness was 1000 jim and the plane resolution was approx 200 jim x 200 jim. MR images were obtained from a 1.5-T imager with a two-dimensional spin-echo Ti-weighted sequence leading to a slice thickness of 2000 jim and a plane resolution of 195 jim x 195 jim. Bone texture analysis was performed using fractal and structural methods leading to the measurement of 23 features. Most of the structural variables derived from histomorphometric parameters and were measured after segmentation from a binary or a skeletonized image. Bone densitometry was measured by dual-energy X-ray absorptiometry both at the lumbar spine and the nondominant femoral neck. On cross-sectional slices, 12 variables, mainly obtained from structural analysis, were significantly different between the two groups for CT images (p < 0.05) against two variables only for MR images (p < 0.05). The number of variables statistically different between the two groups was significantly higher for CT images compared with MR images (p = 0.003). In the same way, odds ratios for fracture per 1 control group standard deviation decrease were significant for 10 variables on CT images, whereas, in contrast, none of the variables measured on MRI images led to significant odds ratios. The results obtained for the two methods on coronal slices were poorer without a difference between either CT or MR images in terms of discrimination between fracture and nonfracture subjects. In conclusion, this study suggests that bone texture analysis obtained from CT compared with MRI offers a best discrimination between controls and osteoporotic patients, probably the result to the spatial resolution. which is better for CT than for MR images.

Does high-resolution computed tomography image analysis of the distal radius provide information independent of bone mass?

This study aimed to investigate the usefulness of computed tomography (CT) image analysis of the distal radius for comparing two groups of postmenopausal women matched for age and bone mineral density at both the lumbar spine and femoral neck. The first one consisted of 16 women with at least one vertebral fracture and the second consisted also of 16 women without disease affecting bone mass or bone metabolism. Eight slices were selected in each patient: four consecutive coronal slices and four consecutive axial slices. Bone texture analysis was performed using structural methods leading to the measurement of 24 features. Most of the structural variables derived from histomorphometric parameters and were measured after segmentation from a binary or a skeletonized image. Nine variables were significantly different between the two groups on axial slices: valley number, valley surface area, apparent bone volume/tissue volume (BV/TV), apparent trabecular separation, apparent trabecular number, trabecular bone pattern factor, trabecular skeletal length, node count, and node-to-node strut count. Also four variables were significantly different between osteoporotic women and controls on coronal slices: apparent BV/TV, trabecular partition, node-to-node strut count, and terminus-to-terminus strut count. In conclusion this study suggests that bone texture analysis could yield additional data on bone mass for explaining bone strength and therefore could be used for improving the prediction of fracture risk.

Factors influencing bone loss in rheumatoid arthritis: a longitudinal study.

OBJECTIVES: To assess the occurrence of bone loss in rheumatoid arthritis (RA) and to determine the factors influencing bone loss (particularly the usefulness of bone turnover markers) over an 18-month period. METHODS: A total of 51 patients were studied, 6 men and 45 females (of whom 35 were menopausal). Their mean age was 56 +/- 10 years and the mean RA duration was 12 +/- 10 years. Twenty-eight (55%) were receiving corticosteroids (10 mg/day for a mean duration of 6 +/- 5 years). Several clinical and biological parameters reflecting disease activity or severity were recorded both at the 0 and 18-month investigations. Bone turnover was assessed at baseline by measuring the serum levels of 4 biological markers. Three of them reflected bone formation, i.e., procollagen type I C-terminal propepeptide (PICP), procollagen type I N-terminal propeptide (PINP) and osteocalcin (OC). The fourth, procollagen type I-C terminal telopeptide (ICTP), reflected bone resorption. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry both at the lumbar spine (LS) and femoral neck (FN) at baseline and 18 months later. RESULTS: Bone loss occurred both at the LS: 2.1%, [95% CI: 0.8%-3.4%, P < 0.005] and femoral neck: 3.1%, [95% CI: 1.1%-5.1%, P < 0.005]. Bone loss was markedly increased for postmenopausal women at the FN: 5.3% [95% CI: 2.9%-7.6%, P < 0.005]. Bone loss was not statistically significantly different between users and non-users of steroids. Bone loss at the LS was significantly correlated with both osteocalcin (r = 0.51, P < 0.01) and ICTP levels (r = 0.32, P < 0.05). FN bone loss was correlated with the osteocalcin level only (r = 0.34, P < 0.05). Fast losers (bone loss at the LS above the median) had higher OC (P < 0.01) and ESR (P < 0.05) levels at baseline as compared with slow losers (bone loss at the LS below the median). CONCLUSION: Bone loss occurs in RA particularly at the FN and seems to be influenced by increased bone turnover and high levels of inflammation.

Adsorption and release of insulin-like growth factor-I on porous tricalcium phosphate implant.

In order to develop bone substitutes, the design of biomaterials like calcium phosphate ceramic loaded with bone growth factor are of great interest. However, it is necessary to control the amount of growth factor adsorbed onto ceramics and the kinetics of its release. Radiolabeling of insulin-like growth factor-I (IGF-I) with 125-iodine ([(125)I]-IGF-I) and its adsorption onto porous tricalcium phosphate (TCP) cylinders enabled us to establish the time-adsorption and time-release curves using various concentrations of IGF-I. The adsorption curve increased rapidly and then flattened out at 72 h; 90% of the maximum was already reached at 24 h; and 20% of the adsorbed IGF-I was released in water within 4 days. In human serum the release was faster at 82% within 4 days. In vivo evaluation on an animal model was then performed. Rabbits' bilateral femoral cylindrical bone defects were filled with the TCP cylinders, which were either carrying IGF-I or implanted alone as a control in each rabbit. Bone turnover and ceramic resorption were stimulated by IGF-I loaded TCP according to standard radiography, dual-energy X-ray absorptiometry, histology, and histomorphometry.

Bone ultrasonometry and turnover markers in primary hyperparathyroidism.

Quantitative ultrasound (QUS) of bone and new markers of bone remodeling have been poorly investigated in mild primary hyperparathyroidism (PHPT). In this study 26 patients (20 females and 6 males) were evaluated. BUA and SOS were measured by QUS at the heel. Markers of bone remodeling assessed were bone alkaline phosphatase (BAP), osteocalcin (OC), procollagen type I N- and C-terminal propeptides (PINP et PICP), and procollagen type I C-terminal telopeptide in blood and urine (ICTP and CTX). Bone mineral density (BMD) was measured at the lumbar spine (LS), femoral neck (FN), and Ward's triangle (WT). The control group comprised 35 sex- and age-matched subjects. The statistically significant variables between the two groups were (P < 0.05) BUA, BMD(LS), BMD(FN), BMD(WT), BAP, and OC. Corresponding z-scores were -0.55 +/- 0.75, -0.66 +/- 0.77, -0.66 +/- 0.71, -0.67 +/- 0.52, 1.87 +/- 3.87, and 1.93 +/- 3.53, respectively. Although PICP and PINP levels were higher in PHPT patients as compared with controls, the difference was not significant. Several markers of bone turnover were moderately correlated with both QUS (r = -0.39 to -0.55) and BMD (r = -0.48 to 0.63). In conclusion QUS seems to be a relevant tool in the assessment of bone status for patients with mild PHPT.