Absence of relationships between depression and anxiety and bone mineral density in patients hospitalized for severe anorexia nervosa.

INTRODUCTION: Low BMD is frequent in anorexia nervosa (AN), depression, and during SSRI treatment but relation between these elements in AN is not established. The aims of this study were to assess the relationships between depression and anxiety, SSRI prescription, and (1) low BMD during inpatient treatment and (2) BMD change 1 year after hospital discharge. METHODS: From 2009 to 2011, 212 women with severe AN have been included in the EVHAN study (EValuation of Hospitalisation for AN). Depression, anxiety and obsessive-compulsive symptoms and comorbidity were evaluated using psychometric scales and CIDI-SF. BMD was measured by dual-energy X-ray absorptiometry. RESULTS: According to the CIDI-SF, 56% of participants (n = 70) had a lifetime major depressive disorder, 27.2% (n = 34) had a lifetime obsessive-compulsive disorder, 32.8% (n = 41) had a lifetime generalized anxiety disorder and 25.6% (n = 32) had a lifetime social phobia disorder. Half of the sample (50.7%; n = 72) had a low BMD (Z score ≤ - 2). In multivariate analysis, lifetime lowest BMI was the only determinant significantly associated with low BMD (OR = 0.56, p = 0.0008) during hospitalization. A long duration of AN (OR = 1.40 (0.003-3.92), p = 0.03), the AN-R subtype (OR = 4.95 (1.11-26.82), p = 0.04), an increase of BMI between the admission and 1 year (OR = 1.69 (1.21-2.60), p = 0.005) and a gain of BMD 1 year after the discharge explained BMD change. CONCLUSION: We did not find any association between depression and anxiety or SSRI treatment and a low BMD or variation of BMD. LEVEL OF EVIDENCE: Level III, cohort study.

Cystatin C improves the diagnosis and stratification of chronic kidney disease, and the estimation of glomerular filtration rate in diabetes.

AIMS: Estimation of glomerular filtration rate (GFR) is recommended to diagnose and stratify chronic kidney disease (CKD). Can cystatin-C (cysC) assay improve the results in diabetic patients? METHODS: In 124 diabetic patients with a wide range of GFR, as determined by 51Cr-EDTA clearance (i-GFR), we estimated 'e-GFR' by: the recommended Cockcroft-Gault (CG) formula and Modification of Diet in Renal Disease (MDRD) study equation; the new Mayo Clinic quadratic (MCQ) equation; the recently proposed composite estimation including both serum creatinine and cysC; and a simplified approach dividing the MDRD by cysC if less than 1.10mg/L. RESULTS: The highest diagnostic accuracy (receiver operating characteristic [ROC] curves) and the highest proportions of well-stratified patients were obtained by cysC and the MDRD which, however, underestimated i-GFR for patients without CKD (-17%, P<0.001). The CG overestimated GFR in KDOQI stages 1 and 2, ignored stage 5 and was the least accurate. The MCQ equation overrepresented stage 2, overestimating GFR at this stage (+23%, P<0.005). The composite estimation (54.7+/-27.0mL per minute 1.73m(2)) correlated best with i-GFR (56.1+/-35.3; r=0.90, P<0.001), and did not significantly differ from it across the entire population and within each Kidney Disease Outcome Quality Initiative (KDOQI) stage but was also biased (Bland-Altman procedure). Simply dividing the MDRD by cysC ifless than1.10mg/L produced a comparable performance and eliminated the bias. CONCLUSION: The recommended creatinine-based estimations of GFR need to be improved. CysC assay helps in the diagnosis and stratification of CKD and leads to better estimates of GFR in diabetic patients without any substantial increase in complexity.

A simplified Cockcroft-Gault formula to improve the prediction of the glomerular filtration rate in diabetic patients.

AIM: The National Kidney Foundation recommends stratification of renal failure into moderate (Glomerular Filtration Rate: GFR = 30-60 mL/min/1.73 m2), severe (15-30) or terminal (<15) using the Cockcroft-Gault (CG) or the Modification of Diet in Renal Disease (MDRD) equations. We studied the biases in these methods in an attempt to improve the standard CG (MCG) and devise a strategy for stratification. METHODS: GFR was measured by 51Cr-EDTA clearance in 200 diabetic patients: 100 (Group 1: study of concordance) before 2003 and 100 thereafter (Group 2: validation of MCG). The CG was modified by replacing body weight by its mean value: 76. RESULTS: In group 1, the recommended equations only correctly stratified 50 patients. The CG, not the MDRD, underestimated GFR if BMI was normal, and overestimated it in obese patients. In group 2, the MCG was well correlated with GFR and not biased by weight. Over the whole population, the MCG and MDRD were more accurate for the diagnosis of moderate and severe renal failure. The MDRD showed the lowest differences with GFR, except if GFR > 60, where the MCG performed better. All formulae overestimated low GFR, the MDRD also underestimated high GFR. The best stratification (147/200) was obtained using the MCG if creatininemia < 120 micromol/l and the MDRD if creatininemia > or =120 micromol/l. CONCLUSION: The CG is biased by weight, the MCG corrects this. The more accurate MDRD cannot be used in all patients as it underestimates high GFR. The best stratification was obtained using the MCG at low and the MDRD at high creatininemia.

Bone mass and dynamic parathyroid function according to bone histology in nondialyzed uremic patients after long-term protein and phosphorus restriction.

One year of a very low protein diet (VLPD) can reverse secondary hyperparathyroidism in uremic patients. We studied bone histology, bone mineral density (BMD), and dynamic parathyroid function (calcium/PTH curves) in 16 nondialyzed patients with advanced renal failure who had been receiving a VLPD for a mean of 5 yr (mean protein intake, 0.34 +/- 0.12 mg/kg x day; mean phosphorus intake, 8.2 +/- 2.1 mg/kg x day) and daily supplementation with essential amino acids and their ketoanalogs (1000 IU vitamin D2 and 1-2 g calcium carbonate). Three patients exhibited a high bone formation rate (BFR), 7 patients had normal bone remodeling, and 6 patients had a low BFR, including 2 with osteomalacia and 4 with adynamic bone disease without aluminum overload. A longer diet duration and lower caloric intake were associated with low BFR. More than half of the patients exhibited moderate or severe osteoporosis at the appendicular skeleton. The t score of femur BMD explained 65% of the BFR variance. Patients with a low BFR had a dynamic parathyroid function similar to that of patients with a normal BFR, except they had a lower capacity to buffer a calcium load, whereas patients with a high BFR had a higher basal PTH/maximum PTH and a steeper calcium/PTH curve slope; the calcium set-point was identical in the three groups.

Optimization of a new scintillation gas detector used to localize electrons emitted by 99mTc.

UNLABELLED: We have developed a scintillation gas detector to localize electrons emitted by 99mTc. This type of detector allows direct quantification of images and so provides a clear advantage over autoradiographic film. We have optimized the device to give an image spatial resolution that closely approximates that of typical autoradiographic film. To improve this resolution, it was necessary to select only low-energy electrons (2 and 15 keV) and to devise novel detection and localization techniques for the ionizing particles. METHODS: A parallel-plate proportional avalanche chamber is subject to a uniform electrical field and amplifies the number of released electrons through collisions of ionizing particles in the gas mixture. Light emitted by the gas scintillator during the avalanche process is collected by a highly intensified charge coupled device camera. The centroid of each resulting light distribution is calculated, resulting in a quantitative mapping of the sample's activity. Insertion of the sample within the gas volume improves the efficiency and so provides a method that is both very sensitive and linear. RESULTS: We have shown that in a parallel-plate structure, the application of a high electrical field to the surface of the sample and the selection of appropriate light spots, according to their morphology, can overcome localization errors due to the particles' trajectories. We have obtained a resolution of the order of 30 microm, using electrons from 99mTc. CONCLUSION: This detection technique allows considerable improvement in image resolution. This "electron camera" is a serious rival to existing autoradiographic techniques, because it provides certain other advantages, including direct quantification, linearity, high dynamic range and low noise levels. Thus, new perspectives are made available in quantitative double tracer autoradiography, because electrons can be selected for imaging as a function of their energy.

No change of hyperleptinemia despite a decrease in insulin concentration in patients with chronic renal failure on a supplemented very low protein diet.

Chronic renal failure (CRF) is often accompanied by hyperleptinemia caused by deficient renal metabolism of leptin and possibly increased leptin production, which in turn may result from the hyperinsulinemia and increased proinflammatory cytokine levels in patients with CRF. The hyperinsulinemia and insulin resistance observed in patients with CRF improve on supplemented very low protein diets (SVLPDs). The goal of our study is to determine whether the correction of hyperinsulinemia and insulin resistance in patients with CRF by SVLPDs is accompanied by improvement in hyperleptinemia. Thirteen patients were studied before and 1 year after following SVLPDs providing 0.3 g/kg/d of protein, supplemented with amino acids and ketoanalogues. After 1 year, patients showed markedly less hyperinsulinemia (7.4 +/- 1.6 versus 13.8 +/- 2 microU/mL at the start of diet; P: = 0.05) and insulin resistance, whereas serum leptin levels remained unchanged (16.1 +/- 4.7 versus 19.1 +/- 7.4 ng/mL at start of the study; P: = not significant). The initial correlation between serum leptin level and percentage of body fat persisted during follow-up. No correlation was found between insulin and leptin levels or between the variation of these two parameters during the study. Our study shows that the correction of hyperinsulinemia and insulin resistance in patients with CRF by SVLPDs is not accompanied by improvement in hyperleptinemia, which consequently does not appear to result from changes in carbohydrate metabolism.

Outcome of nutritional status and body composition of uremic patients on a very low protein diet.

Concern has been raised about the nutritional adequacy of a very low protein diet (VLPD). Monthly clinical evaluation by a physician and dietitian and quarterly dietary records, anthropometric measurements, blood testing, and dual energy X-ray absorptiometry (DEXA) were used to assess the course of nutritional status for 1 year in 10 clinically stable patients (six men, four women; age, 57.1 +/- 9.3 years) with advanced chronic renal failure (mean glomerular filtration rate, 13.2 +/- 4.8 mL/min/1.73 m(2)). These patients received a VLPD providing 0.3 g/kg/d of protein and were supplemented with amino acids and ketoanalogues. Conventional nutritional markers remained unchanged after 1 year of the VLPD. However, during the same period, whole-body DEXA showed a significant decrease in lean tissue from 46.2 +/- 10.2 to 45.0 +/- 9. 8 kg (P < 0.02); limb-trunk lean tissue ratio was reduced from 0.86 +/- 0.12 to 0.82 +/- 0.12 (P < 0.02), total-body fat increased from 20.0 +/- 6.9 to 21.4 +/- 7.0 kg (P < 0.05), and the percentage of total-body fat increased from 29.2% +/- 8.7% to 31.7% +/- 8.8% (P < 0.03). These different modifications occurred abruptly during the first 3 months, then stabilized or slightly improved thereafter. These mild changes do not appear to be deleterious given the favorable long-term outcome of these patients, even after they began treatment by dialysis or after renal transplantation.

Cellulose phosphates as biomaterials. In vivo biocompatibility studies.

Femoral implantation of regenerated cellulose hydrogels revealed their biocompatibility, but a complete osseointegration could not be observed. Phosphorylation was therefore envisaged as the means to enhance cellulose bioactivity. In vitro studies showed that regenerated cellulose hydrogels promote bone cells attachment and proliferation but do not mineralize in acellular simulated physiological conditions. On the contrary, phosphorylated cellulose has shown an opposite behavior, by inducing the formation of a calcium phosphate layer in simulated physiological conditions, but behaving as a poor substrate for bone cells attachment and proliferation. In order to investigate the in vivo behavior of these materials, and assess the influence of mineralization induction ability vs. bone cells compatibility, unmodified and phosphorylated cellulose hydrogels were implanted in rabbits for a maximum period of 6 months and bone regeneration was investigated. Despite the difficulties arising from the retraction of cellulose hydrogels upon dehydration during the preparation of retrieved implants, histological observations showed no inflammatory response after implantation, with bone intra-spongious regeneration of cells and the integration of the unmodified as well as the phosphorylated cellulose implants. After a maximum implantation period of 6 months, histological observations, histomorphometry and the measurement of the amount of 45Ca incorporated in the surrounding tissue indicated a slightly better osseointegration of phosphorylated cellulose, although no significant differences between the two materials were found.

Cyclo-(DfKRG) peptide grafting onto Ti-6Al-4V: physical characterization and interest towards human osteoprogenitor cells adhesion.

In the present paper, specific interest has been devoted to the design of new hybrid materials associating Ti-6Al-4V alloy and osteoprogenitor cells through the grafting of two RGD containing peptides displaying a different conformation (linear RGD and cyclo-DfKRG) onto titanium surface. Biomimetic modification was performed by means of a three-step reaction procedure: silanization with APTES, cross-linking with SMP and finally immobilization of peptides thanks to thiol bonding. The whole process was performed in anhydrous conditions to ensure homogeneous biomolecules layout as well as to guarantee a sufficient amount of biomolecules grafted onto surfaces. The efficiency of this new route for biomimetic modification of titanium surface was demonstrated by measuring the adhesion between 1 and 24 h of osteoprogenitor cells isolated from HBMSC. Benefits of the as-proposed method were related to the high concentration of peptides grafted onto the surface (around 20 pmol/mm(2)) as well as to the capacity of cyclo-DfKRG peptide to interact with integrin receptors. Moreover, High Resolution beta-imager (using [(35)S]-Cys) has exhibited the stability of peptides grafted onto the surface when treated in harsh conditions.

Evolution of the local calcium content around irradiated beta-tricalcium phosphate ceramic implants: in vivo study in the rabbit.

To evaluate whether dissolved calcium from tricalcium phosphate implants contributes to osseous wound healing in bone defects, the authors used nuclear radioactivated materials. Six months after irradiation, the calcium was still radioactive. Samples of the material were prepared and placed in rabbit condyles for 1, 3 and 9 months. Over time the condyles were retrieved and treated for histology or radiocounting. Measurements of the radioactivity of the slices and histomorphometry of the implants and surrounding tissues were performed. The authors observed that the radioactivity decreased regularly. Connective tissue had penetrated the pores and totally invaded the implants, first at the periphery of the implants, then inside the pores. Comparison of the results of radioactivity and histomorphometry suggest that part of the calcium from the implants was re-used specifically in the new osseous tissue.

Energy expenditure following oral glucose load in ten uremic patients before and after three months on a ketoacid-supplemented very-low-protein diet.

We have previously shown that a ketoacid-supplemented very-low-protein diet (KSVLPD), which has been proposed to slow down the rate of progression of chronic renal failure (CRF), improves tissue insulin sensitivity and decreases hyperinsulinemia in predialytic uremic patients. However, this diet may interfere with nutritional status. The aim of this study was to study basal energy expenditure (EE) and EE after an oral glucose load in patients with CRF before and during a KSVLPD (0.3 cal x kg wt(-1) x d(-1) supplemented with aminoacid and ketoanalogs) using oral glucose loading in combination with indirect calorimetry. We also monitored body weight and analyzed body composition by dual-energy x-ray (DEXA) during KSVLPD. In the third month of KSVLPD, no significant change in total body weight was observed, but DEXA showed a decrease in lean tissue mass (LTM; 46.2 +/- 3.6 kg before v 44 +/- 3.4 kg in the third month; P <.01) and an increase in body fat mass (20.1 +/- 2.4 kg before v 21.3 +/- 2.4 kg on KSVLPD; P <.05). Postabsorptive plasma glucose level was significantly lower, and glucose oxidation and energy expenditure per LTM were significantly increased (EE, 20 +/- 0.8 cal x kg LTM(-1) x min(-1) before diet v 21.9 +/- 1.1 cal x kg LTM(-1) x min(-1) after 3 months on KSVLPD; P <.01). Plasma glucose and serum insulin levels were significantly lower after glucose loading, and glucose oxidation increased. EE values were significantly higher after the oral glucose load, and cumulative EE after oral load increased from 20.7 +/- 0.7 cal x kg LTM(-1) x min(-1) before the diet to 22.9 +/- 1.1 cal x kg LTM(-1) x min(-1) in the third month of KSVLPD; P <.001). Glucose oxidation was higher and cumulative glucose storage was decreased after diet (29.6 +/- 4.2 g v 20.9 +/- 3.4 g on KSVLPD; P <.01). We conclude that KSVLPD increases EE in the postabsorptive state and after an oral glucose load with an adaptation of lean tissue mass in the third month of the diet. Therefore, during KSVLPD, strict monitoring of dietetic management is necessary to maintain energy requirements at high levels appropriate to the new EE.

Comparison of two Hologic DXA systems (QDR 1000 and QDR 4500/A).

Bone mineral content is reliably measured by dual energy X-ray absorptiometry (DXA), if manufacturers' recommendations and quality control (QC) procedures are followed. Several phantoms (Hologic anthropomorphic spine phantom, the Groupe de Recherche et d'Informations sur les Osteoporoses (GRIO) test objects and the European semi-anthropomorphic phantoms) were used to evaluate reproducibility, linearity, accuracy and spatial resolution of two DXA devices in vitro. These parameters were also evaluated in vivo from measurements performed on 120 volunteer patients. It was found that when one device (a single beam monodetector QDR 1000) is replaced by another (a fan beam multidetector QDR 4500/A), the novel combination of procedures described here, ensures that the accuracy of DXA study results is maintained when both devices are used in succession for the same patient. To study the possible responses in clinical situations, the influence of bone environment (soft and adipose tissues) was also evaluated. In both systems, similar performances (in vitro coefficients of variation of 0.5%) were established. At extreme bone density values, slight differences in linearity were found, as well as differences in accuracy and spatial resolution. Lumbar spine and femoral neck measurements were performed with both systems in 120 volunteers, both measurements being made on the same day. The corresponding bone mineral density (BMD) values were highly correlated (r2 = 0.985 for lumbar spine and 0.948 for the femoral neck), and the mean BMD differences were 0.68% and 0.37% for each anatomical site, respectively. Although small, these differences add to the precision error of the method, which is near 1%. A calibration curve has to be obtained in order that both devices can be equally used in regular clinical study. We concluded that when a DXA system is replaced by a new one, appropriate QC procedures must be strictly observed.

[Bone remodeling assessment after total hip replacement]. / Evaluation biologique et densitométrique du remodelage osseux induit par l'arthroplastie totale de hanche.

It is known that total hip arthroplasties (THA) lead to adaptative remodeling changes resulting in periprosthetic bone loss. DEXA is recognized as the most precise and accurate method for quantifying bone mineral density (BMD) in humans. The present study compares over two years after THA, DEXA data to those of urinary deoxypyridinoline (uDPYR), a pyridinium crosslink of bone collagen fibrils proven to be a reliable bone resorption marker. 41 patients (21 postmenopausal female, 20 male) underwent cemented THA. Urinary excretion of DPYR was determined using ACS : 180 SE (Bayer Diagnostics) and normalized for creatinine excretion while periprosthetic BMD (g/cm2) was measured (QDR 4500, Hologic), at post-operative day, 3 months, 1 year and 2 years after surgery. The 7 periprosthetic subregions (R1-R7) of the Gr en method are the regions of interest for evaluating bone remodeling process. uDPYR showed a significant decrease between postoperation and 1 year: 10.6 0.80 vs 4.8 0.6 nmol/mmol, p < 0.0001 (Wilcoxon Test for paired samples and statistical significance accepted at p < 0.05) and non significant variation between 1 and 2 years. Between post-operation and 3 months global and regional BMDs decrease significantly (p < 0.04) followed by an increase in distal BMD (R3, R4, R5). During the second year BMD increases also for other regions. At 2 years BMD in distal regions is recovered except in the proximal R7 when comparing post-operation and 2 years, pattern consistent with literature. Thus, a discrepancy is observed between uDPYR and DMO results that does not allow us to use a bone resorption urinary marker to monitore local bone periprosthetic remodeling.

Estimation of renal function in patients with diabetes.

Diabetes is the leading cause of chronic kidney disease (CKD), which makes estimation of renal function crucial. Serum creatinine is not an ideal marker of glomerular filtration rate (GFR), which also depends on digestive absorption, and the production of creatinine in muscle and its tubular secretion. Formulas have been devised to estimate GFR from serum creatinine but, given the wide range of GFR, proteinuria, body mass index and specific influence of glycaemia on GFR, the uncertainty of these estimations is a particular concern for patients with diabetes. The most popular recommended formulas are the simple Cockcroft-Gault equation, which is inaccurate and biased, as it calculates clearance of creatinine in proportion to body weight, and the MDRD equation, which is more accurate, but systematically underestimates normal and high GFR, being established by a statistical analysis of results from renal-insufficient patients. This underestimation explains why the MDRD equation is repeatedly found to give a poor estimation of GFR in patients with recently diagnosed diabetes and is a poor tool for reflecting GFR decline when started from normal, as well as the source of unexpected results when applied to epidemiological studies with a 60mL/min/1.73m(2) threshold as the definition of CKD. The more recent creatinine-based formula, the Mayo Clinic Quadratic (MCQ) equation, and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) improve such underestimation, as both were derived from populations that included subjects with normal renal function. Determination of cystatin C is also promising, but needs standardisation.

Bone loss in diabetic patients with chronic kidney disease.

OBJECTIVE: We investigated whether loss of bone is detectable during follow-up of diabetic patients with chronic kidney disease (CKD). RESEARCH DESIGN AND METHODS: In 40 initially non-dialysed diabetic patients with CKD (isotopic glomerular filtration rate < 60 ml/min/1.73 m(2) or albumin excretion rate > 30 mg/24 h), body composition (DEXA scan) and glomerular filtration rate (GFR determined from (51)Cr-EDTA clearance) were measured at a 2-year interval, and compared by paired t-tests. RESULTS: The 40 patients, mainly with Type 2 diabetes (n = 28), were men (n = 28), aged 65 +/- 11 years, with diabetes duration 18 +/- 11 years. GFR was initially 38.0 (range 8-89) ml/min/1.73 m(2). CKD progressed during follow-up: eight started haemodialysis and GFR declined in the 32 others (P < 0.05 vs. initial). T-scores for total body (initial -0.61 +/- 1.11, final -1.11 +/- 1.40; P < 0.001) and femoral neck (initial -1.88 +/- 0.15, final -2.07 +/- 0.15; P < 0.05) declined. Ten patients were osteopaenic at baseline (no osteoporosis), whereas most were osteopaenic (n = 21, P < 0.05) and five were osteoporotic at final assessment. The 16 patients who became osteopaenic or osteoporotic during follow-up did not differ from the others for the type of diabetes, age, GFR, albumin excretion rate, HbA(1c), GFR reduction and the requirement for dialysis during follow-up. They were all men (P < 0.01 by chi-squared test), with reduced initial total body T-score (-1.20 +/- 0.82, others -0.32 +/- 1.13; P < 0.05) and a lower body mass index (24.6 +/- 4.3; others 27.7 +/- 4.3; P < 0.05). CONCLUSION: Bone loss, especially in the femoral neck, is progressive in diabetic patients with CKD.

Measurement of bone mineral density in mother-daughter pairs for evaluating the family influence on bone mass acquisition: a GRIO survey.

The relative influence of genetic and environmental determinants on bone mass is still unclear. Using an original multicentric mode of recruitment, based on absorptiometry current practice, the hypothesis of a familial predisposition to low bone mineral content was assessed. The study was based on dual-energy X-ray absorptiometry (DXA) measurements of lumbar and femoral neck bone mineral density (BMD), using daughters of women with a low BMD (case mothers). These BMD values were compared with those of control daughters of women with a normal BMD. Case mothers (n = 72) aged 54.3 +/- 4.8 years were recruited on the basis of a questionnaire and a vertebral Z-score < -2 SD. Their healthy daughters of more than 20 years (n = 77) aged 28.2 +/- 4.9 years had their vertebral and femoral BMD Z-score determined. The control groups were composed of mothers aged 54.1 +/- 4.7 years, paired by age +/- 2 years to the case mothers, and of their daughters of more than 20 years old, aged 27.7 +/- 5.8 years. For daughters, a significant difference was found between the mean vertebral Z-scores (-0.82 +/- 1.08 for cases and 0.01 +/- 1.14 for controls, p < 0.0001). The difference was in the same direction but was not statistically significant for mean femoral Z-scores (-0.58 +/- 1.15 for cases and -0.22 +/- 1.33 for controls, p < 0.073). These findings confirm the hypothesis of a familial predisposition to low BMD.