Usefulness of Dual X-ray Absorptiometry-Derived Bone Geometry and Structural Indexes in Mastocytosis.

Reduced bone mass with or without fragility fractures is a common feature of mastocytosis, particularly in adult males. However, bone mineral density does not account for all the fragility fractures, being a part of them attributable to impairment in bone quality. Aim of this study is to assess the usefulness of DXA-derived geometry and structural indexes in the assessment of bone status in mastocytosis. Ninety-six consecutive patients (46 women and 50 men) affected by cutaneous (CM) or systemic (SM) mastocytosis were studied. Mean age (± SD) was 53.3 ± 14.23. Spine lateral X-rays for Genant's scale, DXA for lumbar (L) and femoral (F) bone mineral density (BMD), bone strain index (BSI), lumbar trabecular bone score (TBS), and hip structural analysis (HSA) were performed. Among the laboratory variables, data of serum tryptase were reported. Tryptase was higher in SM (p = 0.035), inversely correlated with LBMD (r = - 0.232; p = 0.022) and TBS (r = - 0.280; p = 0.005), and directly with L-BSI (r = 0.276; p = 0.006). L-BSI remained statistically significant (p = 0.006; adjusted R2 = 0.101) together with mastocytosis (SM or CM: p = 0.034) in the multivariate regression model with tryptase as dependent variable, being LBMD and TBS not statistically significant (p = 0.887, and p = 0.245, respectively). Tryptase increased about 22 units for each unit increase of L-BSI and about 18 units for SM against CM. L-BSI was lower (p = 0.012), while FN-BSI and FT-BSI were higher in women (p < 0.001) than in men. HSA indexes were significantly higher in men, particularly with SM. SM is a risk factor for reduced bone mass, texture and strength. Since mean L-BSI and Z-modulus of all the femoral sites are statistically higher in men than in female, it could be argued that men have a better femoral bone resistance to bending forces than women, but a worse lumbar bone resistance to compressive loads. DXA indexes of bone quality are useful in mastocytosis' bone assessment and its clinical management.

Reproducibility of DXA-based bone strain index and the influence of body mass: an in vivo study.

OBJECTIVES: Bone strain index (BSI) is a dual-energy X-ray absorptiometry (DXA)-derived index of bone strength obtained from lumbar densitometric scan. We estimated the reproducibility of BSI in healthy women with different body mass index. METHODS: We enrolled postmenopausal women (mean age ± SD: 66 ± 10 years) divided into three groups (A, B and C) according to body mass index (BMI: < 25; 25-29.9; ≥ 30 kg/m2) and two groups (D and E) according to waist circumference (WC: ≤ 88; > 88 cm), each of 30 subjects. They underwent two DXA examinations with in-between repositioning, according to the International Society for Clinical Densitometry guidelines for precision estimation. Bone mineral density (BMD) and BSI were expressed as g/cm2 and absolute value, respectively. The coefficient of variation (CoV) was calculated as the ratio between root-mean-square standard deviation and mean; least significant change percentage (LSC%) as 2.77 × CoV; reproducibility as the complement to 100% LSC. RESULTS: BSI increased proportionally to BMI and WC and significantly in group C compared to B and A (p = 0.032 and 0.006, respectively). BSI was significantly higher in E compared to D (p = 0.017), whereas no differences were observed in BMD. Although BSI reproducibility was slightly lower in group C (89%), the differences were not significant between all groups. BMD reproducibility did not significantly differ between all groups. CONCLUSIONS: BSI reproducibility was significantly lower than that of BMD and decreased proportionally to BMI and WC increase. This reduction of BSI reproducibility was more pronounced in patients with BMI ≥ 30 and WC > 88, as expected, being BSI a parameter sensible to weight.

Usefulness of bone microarchitectural and geometric DXA-derived parameters in haemophilic patients.

INTRODUCTION: Haemophilia is a recessive X-linked inherited bleeding disorder, whose typical symptom is spontaneous intra-articular haemorrhage leading to joint damage, which can be quantified by the Haemophilia Joint Health Score (HJHS). Arthropathy and other characteristics of haemophilic patients may reduce bone mineral density (BMD), increasing the risk for fragility fractures, which also may occur due to bone quality impairment. AIM: To evaluate bone quantity by BMD and bone quality by Trabecular Bone Score (TBS), bone strain (BS) and hip structural analysis (HSA) in a haemophilic population, and to relate these parameters to general and specific risk factors for osteoporosis and to HJHS. METHODS: Seventy haemophilic patients ≥18 years were enrolled. Densitometric derived lumbar spine and femoral BMD with TBS, BS and HSA were performed. Data regarding risk factors for osteoporosis, presence of arthroprosthesis or arthrodesis were collected, and HJHS was calculated. A Z-score ≤-2.0 defined a low bone mass. RESULTS: Overall, a reduced bone mass was present in 52 patients at the femur and in 38 at the lumbar spine. Lumbar spine BMD, TBS and BS did not correlate with HJHS. HSA bone geometric parameters correlated negatively with HJHS. BMD and HSA correlated with some risk factors for osteoporosis, namely HIV and its therapy, hepatitis C and smoking. CONCLUSIONS: Haemophilic patients showed a reduced BMD at lumbar spine and/or femur. Femoral bone density and geometry correlated with HJHS. The microarchitecture of the trabecular vertebral bone seemed to be not influenced by the haemophilic joint damage.

Dose absorption in lumbar and femoral dual energy X-ray absorptiometry examinations using three different scan modalities: an anthropomorphic phantom study.

The aim of this study was to measure the effective dose on an anthropomorphic phantom undergoing lumbar and femoral dual energy X-ray absorption (DXA) examinations, using 3 different scan modalities (fast-array [FA], array [A], high-definition [HD]), and assess the differences in the lifetime attributable risk (LAR) of cancer due to radiation. An anthropomorphic phantom was used. Thermoluminescent dosimeters were placed over 12 anatomic phantom regions and outside the room (to measure background radiation). Fifty scans on the femur and spine were performed for each mode. The dose relative to a single DXA scan for each dosimeter was measured (mean over the 50 scans) and the background radiation was then subtracted. The equivalent dose per organ was obtained. The total body effective dose was calculated by adding the equivalent doses. We estimated the lifetime dose absorption and LAR for cancer for a male and a female patient undergoing 36 DXA studies (18 lumbar, 18 femoral) every 21 months for 32 years. The effective dose for lumbar scans was FA = 17.79 µSv, A = 32.88 µSv, HD = 31.08 µSv; for femoral scans, FA = 5.29 µSv, A = 9.55 µSv, HD = 7.54 µSv. LAR estimation showed a minimal increase in cancer risk (range 4.55 × 10⁻4% [FA, femoral, male] to 4.02 × 10⁻³% [A, lumbar, female]). The lifetime dose absorption and LAR for cancer for a male and a female patient undergoing 36 DXA studies (18 lumbar, 18 femoral) every 21 months for 32 years were 0.756 mSv, 3.82 × 10(-3)% and 0.756 mSv, 5.11 × 10⁻³%, respectively. DXA examinations cause radiation levels that are comparable to the background radiation. Regardless of the scan modality or the anatomic site, a patient undergoing DXA scans for a lifetime has a negligible increased risk of developing cancer.

Dual X-ray absorptiometry-derived bone status indexes and videocapsule intestinal aspects in celiac disease.

BACKGROUND AND AIM: Celiac disease is a risk factor for osteopenia and osteoporosis. Our aim was to evaluate the possible correlation between villous atrophy extension and dual-energy X-ray absorptiometry (DXA)-derived parameters of bone status. METHODS: We have retrospectively analyzed data of 47 celiac patients (36 women, 52 ± 14 years of age) who underwent video capsule endoscopy and DXA scans within 1 year of interval from 2006 to 2019. Quantitative, qualitative and geometric DXA parameters were collected only from the most recent DXA measurements. RESULTS: . Patients were divided into three categories; the first included those with no lesions at video capsule endoscopy (23 patients), the second those with typical lesions (mucosal atrophy, mosaicism and scalloping) in less than one-third of the small bowel (SB) (16 patients) and the third those with typical lesions in more than one-third of the SB (7 patients). In the third group, bone mineral density seemed to be lower in both the lumbar spine and the hip ( P = 0.026 and P = 0.011, respectively). The deterioration of bone structure in patients with severe and extended SB atrophy was statistically significant ( P = 0.032). Furthermore, bone density, structure and geometry did not correlate with the duration of the gluten-free diet. Notably, autoimmune comorbidities did not affect DXA results. CONCLUSION: Neither endoscopic nor histological atrophy itself can explain the deterioration of bone mineralization and structure, whereas atrophy extension appeared to be responsible for bone impairment.

Absence of mucosal inflammation in uncomplicated diverticular disease.

BACKGROUND: Uncomplicated diverticular disease is a common condition in patients older than 50 years. Symptoms are aspecific and overlapping with those of irritable bowel syndrome. Nowadays, patients are often treated with antinflammatory drugs (5-aminosalicilic acid). AIM: Our purpose was to evaluate the presence of inflammation in the colonic mucosa of patients with symptomatic uncomplicated diverticular disease compared with subjects without diverticula. METHODS: Endoscopic biopsies of colon from 10 patients with symptomatic uncomplicated diverticular disease and 10 from subjects without diverticula (controls) were taken. Specimens were homogenised and IL2, IL4, IL5, IL8, IL10, IL12p70, IL13, IFN gamma, TNF alfa (searchlight multiplex technique), TGF beta, transglutaminase type 2 and caspase 9 were measured. Histochemistry for transglutaminase type 2 and TUNEL were performed on the histological sections, in addition to morphologic evaluation, as markers of tissue remodelling and apoptosis. For statistical analysis Student's t test and Spearman correlation test were used. RESULTS: No histological differences were detected between the patients with an uncomplicated diverticular disease and controls. Mean values of mucosal cytokines and of the other tested parameters did not show statistically significant differences between patients with uncomplicated diverticular disease and controls. CONCLUSIONS: Even if based on a small number of patients, the study demonstrates the absence of inflammation in the mucosa of subjects affected by uncomplicated diverticular disease.

Bone strain index as a predictor of further vertebral fracture in osteoporotic women: An artificial intelligence-based analysis.

BACKGROUND: Osteoporosis is an asymptomatic disease of high prevalence and incidence, leading to bone fractures burdened by high mortality and disability, mainly when several subsequent fractures occur. A fragility fracture predictive model, Artificial Intelligence-based, to identify dual X-ray absorptiometry (DXA) variables able to characterise those patients who are prone to further fractures called Bone Strain Index, was evaluated in this study. METHODS: In a prospective, longitudinal, multicentric study 172 female outpatients with at least one vertebral fracture at the first observation were enrolled. They performed a spine X-ray to calculate spine deformity index (SDI) and a lumbar and femoral DXA scan to assess bone mineral density (BMD) and bone strain index (BSI) at baseline and after a follow-up period of 3 years in average. At the end of the follow-up, 93 women developed a further vertebral fracture. The further vertebral fracture was considered as one unit increase of SDI. We assessed the predictive capacity of supervised Artificial Neural Networks (ANNs) to distinguish women who developed a further fracture from those without it, and to detect those variables providing the maximal amount of relevant information to discriminate the two groups. ANNs choose appropriate input data automatically (TWIST-system, Training With Input Selection and Testing). Moreover, we built a semantic connectivity map usingthe Auto Contractive Map to provide further insights about the convoluted connections between the osteoporotic variables under consideration and the two scenarios (further fracture vs no further fracture). RESULTS: TWIST system selected 5 out of 13 available variables: age, menopause age, BMI, FTot BMC, FTot BSI. With training testing procedure, ANNs reached predictive accuracy of 79.36%, with a sensitivity of 75% and a specificity of 83.72%. The semantic connectivity map highlighted the role of BSI in predicting the risk of a further fracture. CONCLUSIONS: Artificial Intelligence is a useful method to analyse a complex system like that regarding osteoporosis, able to identify patients prone to a further fragility fracture. BSI appears to be a useful DXA index in identifying those patients who are at risk of further vertebral fractures.

Bone Strain Index predicts fragility fracture in osteoporotic women: an artificial intelligence-based study.

BACKGROUND: We applied an artificial intelligence-based model to predict fragility fractures in postmenopausal women, using different dual-energy x-ray absorptiometry (DXA) parameters. METHODS: One hundred seventy-four postmenopausal women without vertebral fractures (VFs) at baseline (mean age 66.3 ± 9.8) were retrospectively evaluated. Data has been collected from September 2010 to August 2018. All subjects performed a spine x-ray to assess VFs, together with lumbar and femoral DXA for bone mineral density (BMD) and the bone strain index (BSI) evaluation. Follow-up exams were performed after 3.34 ± 1.91 years. Considering the occurrence of new VFs at follow-up, two groups were created: fractured versus not-fractured. We applied an artificial neural network (ANN) analysis with a predictive tool (TWIST system) to select relevant input data from a list of 13 variables including BMD and BSI. A semantic connectivity map was built to analyse the connections among variables within the groups. For group comparisons, an independent-samples t-test was used; variables were expressed as mean ± standard deviation. RESULTS: For each patient, we evaluated a total of n = 6 exams. At follow-up, n = 69 (39.6%) women developed a VF. ANNs reached a predictive accuracy of 79.56% within the training testing procedure, with a sensitivity of 80.93% and a specificity of 78.18%. The semantic connectivity map showed that a low BSI at the total femur is connected to the absence of VFs. CONCLUSION: We found a high performance of ANN analysis in predicting the occurrence of VFs. Femoral BSI appears as a useful DXA index to identify patients at lower risk for lumbar VFs.

Bone strain index in the prediction of vertebral fragility refracture.

Dual-energy x-ray absorptiometry (DXA) can provide quantitative (bone mineral density, BMD) and qualitative (trabecular bone score, TBS) indexes of bone status, able to predict fragility fractures in most osteoporotic patients. A new qualitative index of bone strength, based on finite element analysis and named bone strain index (BSI), has been recently developed from lumbar DXA scan. We present the preliminary results about the BSI ability to predict a refracture in patients with fragility fractures. A total of 143 consecutive fractured patients with primary osteoporosis (121 females) performed a spine x-ray examination for the calculation of spine deformity index (SDI) and a DXA densitometry for BMD, TBS, and BSI at basal time and in the follow-up. A refracture was considered as a one-unit increase in SDI. For each unit increase of the investigated indexes, the hazard ratio of refracture, 95% confidence interval, p value, and proportionality test p value were for BSI 1.201, 0.982-1.468, 0.074, and 0.218; for lumbar BMD 0.231, 0.028-1.877, 0.170, and 0.305; and for TBS 0.034, 0.001-2.579, 0.126, and 0.518, respectively. BSI was the index predictive of refracture nearest to statistical significance. If confirmed, it may be used for a better risk assessment of osteoporotic patients.

Artificial neural network analysis of bone quality DXA parameters response to teriparatide in fractured osteoporotic patients.

Teriparatide is a bone-forming therapy for osteoporosis that increases bone quantity and texture, with uncertain action on bone geometry. No data are available regarding its influence on bone strain. To investigate teriparatide action on parameters of bone quantity and quality and on Bone Strain Index (BSI), also derived from DXA lumbar scan, based on the mathematical model finite element method. Forty osteoporotic patients with fractures were studied before and after two years of daily subcutaneous 20 mcg of teriparatide with dual X-ray photon absorptiometry to assess bone mineral density (BMD), hip structural analysis (HSA), trabecular bone score (TBS), BSI. Spine deformity index (SDI) was calculated from spine X-ray. Shapiro-Wilks, Wilcoxon and Student's t test were used for classical statistical analysis. Auto Contractive Map was used for Artificial Neural Network Analysis (ANNs). In the entire population, the ameliorations after therapy regarded BSI (-13.9%), TBS (5.08%), BMD (8.36%). HSA parameters of femoral shaft showed a worsening. Dividing patients into responders (BMD increase >10%) and non-responders, the first presented TBS and BSI ameliorations (11.87% and -25.46%, respectively). Non-responders presented an amelioration of BSI only, but less than in the other subgroup (-6.57%). ANNs maps reflect the mentioned bone quality improvements. Teriparatide appears to ameliorate not only BMD and TBS, but also BSI, suggesting an increase of bone strength that may explain the known reduction in fracture risk, not simply justified by BMD increase. BSI appears to be a sensitive index of TPD effect. ANNs appears to be a valid tool to investigate complex clinical systems.

Isolation and culture of fibroblasts from endoscopic duodenal biopsies of celiac patients.

BACKGROUND: Fibroblasts are actually considered pivotal in inflammation and tissue remodelling process and for these reasons they are involved in the pathogenesis of autoimmune disorders such as celiac disease. Investigations to define the role of fibroblasts in celiac diseases are obstructed by the absence of specific models. Our objective is to isolate and culture primary fibroblasts from endoscopic duodenal biopsies of celiac and non-celiac subjects, to analyze their growth patterns and the morphometric characteristics. METHODS: 60 duodenal bioptic specimens from 20 celiac patients and 114 from 38 non-celiac subjects were mechanically chopped and enzymatically digested in order to obtain primary cell cultures. Growth patterns, karyotype (Q-banding analysis), expression of typing proteins (fibroblast surface protein and cytokeratin 20) and morphometric parameters (diameters and their ratio, perimeter, area and perimeter/area ratio at computerised image analysis) were investigated on cultured cells. RESULTS: Primary cells were successfully cultured in 78% of the collected duodenal biopsies. Cultured cells, expressing the fibroblast surface protein, were negative for cytokeratine 20 and maintained a normal kariotype. Cells grew slowly without differences between the celiac and the non celiac group. Morphometric analysis of celiac fibroblasts revealed significantly increased dimensions, with a preserved diameters ratio, and a reduced perimeter/area ratio. CONCLUSION: For the first time this study demonstrates the feasibility of culturing primary fibroblast cell from endoscopic duodenal biopsies in celiac and non-celiac subjects, opening a new window of opportunity in studies intended to establish the role of fibroblasts as a possible partaker in the pathogenesis of the celiac mucosal damage.

Increasing soft tissue thickness does not affect trabecular bone score reproducibility: a phantom study.

PURPOSE: Trabecular Bone Score (TBS) provides an indirect score of trabecular microarchitecture from lumbar spine (LS) dual energy X-ray absorptiometry. Increasing soft tissue thickness artifactually reduces TBS values; we evaluated the effect of a fictitious increase of soft tissue thickness on TBS and bone mineral density (BMD) reproducibility on a phantom model. METHODS: A Hologic spine phantom was scanned with a QDR-Discovery W Hologic densitometer. Fresh pork rind layers of 5 mm were used to simulate the in-vivo soft tissues. For each scan mode (fast array [FA], array, high definition [HD]), 25 scans were consecutively performed without phantom repositioning, at 0 (no layers), 1 cm, 3 cm, and 6 cm of thickness. BMD and TBS reproducibility was calculated as the complement to 100% of least significant change. RESULTS: Both BMD and TBS reproducibility slightly decreased with increasing soft tissue; this difference was statistically significant only for BMD using HD modality (reproducibility decreased from 99.4% at baseline to 98.4% at 6-cm of thickness). TBS reproducibility was slightly lower compared to that of BMD, and ranged between 98.8% (array, 0 cm) and 97.4% (FA, 6 cm). Without taking into account manufacturer BMI optimization, we found a progressive decrease of TBS mean values with increasing soft tissue thickness. The highest TBS difference between baseline scan and 6 cm was -0.179 (-14.27%) using HD. CONCLUSIONS: Despite being slightly lower than that of BMD, TBS reproducibility was not affected up to 6 cm of increasing soft tissue thickness, and was even less influenced by fat than BMD reproducibility.

Assessment of Bone Quality in Osteoporosis Treatment with Bone Anabolic Agents: Really Something New?

Osteoporosis is a chronic pathologic condition, particularly of the elderly, in which a reduction of bone mineral density (BMD) weakens bone, leading to the so-called fragility fractures, most often of spine and femur. The gold standard exam for the quantitative measurement of BMD is the dual X-ray photon absorptiometry (DXA), a radiological method. However, a relevant number of fragility fractures occurs in the range of normal BMD values, meaning that also qualitative aspects of bone play a role, namely bone architecture and bone geometry. Bone structure is investigated by microCT and histomorphometry, which necessitate an invasive approach with a biopsy, usually taken at the iliac crest, not the typical site of fragility fractures. New tools, trabecular bone score (TBS) and hip structural analysis (HSA), obtained during DXA, can supply informations about bone structure of spine and femur, respectively, in a not invasive way. Therapy of osteoporosis is based on two types of drugs leading to an increase of BMD: antiresorptive and anabolic treatments. The antiresorptive drugs inhibit the osteoclasts, whereas teriparatide and, in part, strontium ranelate ameliorate bone structure. The present review deals with the relation between the anabolic drugs for osteoporosis and the cited new tools which investigate bone architecture and geometry, in order to clarify if they represent a real advantage in monitoring efficacy of osteoporosis' treatment. Data from the studies show that increases of TBS and HSA values after anabolic therapy are small and very close to their least significant change at the end of the usual period of treatment. Therefore, it is questionable if TBS and HSA are really helpful in monitoring bone quality and in defining reduction of individual fragility fracture risk during osteoporosis treatment with bone anabolic agents.

Pediatric dual-energy X-ray absorptiometry in clinical practice: What the clinicians need to know.

The importance of childhood and adolescence for bone development and mineral accrual is increasingly accepted, leading to a need of suitable methods for monitoring bone health even in pediatric setting. Among the several different imaging methods available for clinical measurement of bone mineral density (BMD) in children, dual-energy X-ray absorptiometry (DXA) is the most widely available and commonly used due to its reproducibility, negligible radiation dose and reliable pediatric reference data. Nevertheless, DXA in children has some technical specific features that should be known by those physicians who interpret and report this examination. We provide recommendations for optimal DXA scan reporting in pediatric setting, including indications, skeletal sites to be examined, parameters to be measured, timing of follow-up BMD measurements. Adequate report and analysis of DXA examinations are essential to prevent over- and underdiagnosis of bone mineral impairment in pediatric patients. In conclusion, a complete and exhaustive DXA report in children and adolescents is mandatory for an accurate diagnosis and a precise monitoring of pediatric bone status.

The role of carboxy-terminal cross-linking telopeptide of type I collagen, dual x-ray absorptiometry bone strain and Romberg test in a new osteoporotic fracture risk evaluation: A proposal from an observational study.

The consolidated way of diagnosing and treating osteoporosis in order to prevent fragility fractures has recently been questioned by some papers, which complained of overdiagnosis and consequent overtreatment of this pathology with underestimating other causes of the fragility fractures, like falls. A new clinical approach is proposed for identifying the subgroup of patients prone to fragility fractures. This retrospective observational study was conducted from January to June 2015 at the Nuclear Medicine-Bone Metabolic Unit of the of the Fondazione IRCCS Ca' Granda, Milan, Italy. An Italian population of 125 consecutive postmenopausal women was investigated for bone quantity and bone quality. Patients with neurological diseases regarding balance and vestibular dysfunction, sarcopenia, past or current history of diseases and use of drugs known to affect bone metabolism were excluded. Dual X-ray absorptiometry was used to assess bone quantity (bone mineral density) and bone quality (trabecular bone score and bone strain). Biochemical markers of bone turnover (type I collagen carboxy-terminal telopeptide, alkaline phosphatase, vitamin D) have been measured. Morphometric fractures have been searched by spine radiography. Balance was evaluated by the Romberg test. The data were evaluated with the neural network analysis using the Auto Contractive Map algorithm. The resulting semantic map shows the Minimal Spanning Tree and the Maximally Regular Graph of the interrelations between bone status parameters, balance conditions and fractures of the studied population. A low fracture risk seems to be related to a low carboxy-terminal cross-linking telopeptide of type I collagen level, whereas a positive Romberg test, together with compromised bone trabecular microarchitecture DXA parameters, appears to be strictly connected with fragility fractures. A simple assessment of the risk of fragility fracture is proposed in order to identify those frail patients at risk for osteoporotic fractures, who may have the best benefit from a pharmacological and physiotherapeutic approach.

PNPLA3 148M Carriers with Inflammatory Bowel Diseases Have Higher Susceptibility to Hepatic Steatosis and Higher Liver Enzymes.

BACKGROUND: Inflammatory bowel diseases (IBD) are characterized by chronic relapsing inflammation of the gastrointestinal tract and encompass Crohn's disease and ulcerative colitis. IBD are often associated with extraintestinal manifestations affecting multiple organs including the liver. Increased levels of serum aminotransferases, possibly related to nonalcoholic fatty liver disease, constitute one of the most frequently described IBD-related liver diseases. The PNPLA3 I148M substitution is a major common genetic determinant of hepatic fat content and progression to chronic liver disease. The aim of this study was to investigate whether carriers of PNPLA3 148M allele with IBD have higher risk of liver steatosis and increase in transaminases levels. METHODS: The PNPLA3 I148M (rs738409) genotype was performed by Taqman assays in 158 individuals from Southern Italy (namely, Catanzaro cohort) and in 207 individuals from Northern Italy (namely, Milan cohort) with a definite diagnosis of IBD. Demographic and clinical data and also alanine transaminase levels were collected for both cohorts. The Catanzaro cohort underwent liver evaluation by sonography and liver stiffness and controlled attenuation parameter measurements by transient elastography. RESULTS: Here, we show for the first time that carriers of the PNPLA3 148M allele with IBD have a greater risk of hepatic steatosis (odds ratio, 2.9, and confidence interval, 1.1-7.8), higher controlled attenuation parameter values (P = 0.029), and increased circulating alanine transaminase (P = 0.035) in the Catanzaro cohort. We further confirm the higher alanine transaminase levels in the Milan cohort (P < 0.001). CONCLUSIONS: Our results show that PNPLA3 148M carriers with IBD have higher susceptibility to hepatic steatosis and liver damage.

Effect of kidney transplantation on bone mass and body composition in males.

BACKGROUND: Bone loss is a frequent and well-known complication in the first months after renal transplantation, but there are no data considering body composition variables (bone, fat, and lean mass) together in transplant recipients. This prospective study investigated total body bone density, fat mass, and lean mass before and 1, 2, 3, 4, and 6 months after renal transplantation in male patients who underwent hemodialysis. METHODS: Twenty consecutive renal transplant male patients aged 23-64 years (mean, 40 years; median, 41 years) received one of two immunosuppressive therapies (cyclosporine+methylprednisolone, or cyclosporine+methylprednisolone+azathioprine). The bone, fat, and lean mass of the total body and its related subregions were assessed by means of dual X-ray photon absorptiometry. Mixed factorial analysis of variance for repeated measurements was used for the statistical analysis. RESULTS: During the 6 months after transplantation, there was a reduction in trabecular bone mass in the spine, ribs, and pelvis total body subregions; the reduction was statistically significant in the last two subregions. There was no statistically significant difference in the lean mass of the total body or its subregions over time, but there was a statistically significant increase in the fat mass of the total body and all of its subregions; the increase in total and trunk fat mass seemed to be greater in the patients not receiving azathioprine. CONCLUSIONS: Up to 6 months after renal transplantation in male patients who underwent hemodialysis, there is a marked increase in fat mass, a significant loss of trabecular bone mass, and no change in cortical bone and lean mass.

LC-MS/MS and FT-IR analyses of stones from a patient with Crohn's disease: a case report.

This report describes the unusual case of a patient affected by Crohn's disease suffering from intestinal obstruction with recurrent occlusive symptoms not due to the intestinal disease, but to the presence of two calcified foreign bodies in the pelvis. The stones were surgically removed and analysed by reverse-phase liquid chromatography coupled to UV diode array detection and mass spectrometry (LC-UV-DAD-MS/MS), Chromatoprobe-MS/MS and by Fourier-transform-infrared spectroscopy (FT-IR) techniques. The combined mass spectrometric approaches allowed unequivocally to identify 5-aminosalicylic acid (5-ASA) in stone 1, and to demonstrate that its formation was due to an unmodified 5-ASA tablet, a formulation that must undergo complete dissolution in the small bowel. The second stone was constituted by a solid layer (no solvent-extractable material) identified by FT-IR as a polystyrene fragment. This indicates that accidental ingestion of a plastic material, followed by its calcification, was responsible for its formation.

Managing osteoporosis in ulcerative colitis: something new?

The authors revise the latest evidence in the literature regarding managing of osteoporosis in ulcerative colitis (UC), paying particular attention to the latest tendency of the research concerning the management of bone damage in the patient affected by UC. It is wise to assess vitamin D status in ulcerative colitis patients to recognize who is predisposed to low levels of vitamin D, whose deficiency has to be treated with oral or parenteral vitamin D supplementation. An adequate dietary calcium intake or supplementation and physical activity, if possible, should be guaranteed. Osteoporotic risk factors, such as smoking and excessive alcohol intake, must be avoided. Steroid has to be prescribed at the lowest possible dosage and for the shortest possible time. Moreover, conditions favoring falling have to been minimized, like carpets, low illumination, sedatives assumption, vitamin D deficiency. It is advisable to assess the fracture risk in all UC patient by the fracture assessment risk tool (FRAX(®) tool), that calculates the ten years risk of fracture for the population aged from 40 to 90 years in many countries of the world. A high risk value could indicate the necessity of treatment, whereas a low risk value suggests a follow-up only. An intermediate risk supports the decision to prescribe bone mineral density (BMD) assessment and a subsequent patient revaluation for treatment. Dual energy X-ray absorptiometry bone densitometry can be used not only for BMD measurement, but also to collect data about bone quality by the means of trabecular bone score and hip structural analysis assessment. These two indices could represent a method of interesting perspectives in evaluating bone status in patients affected by diseases like UC, which may present an impairment of bone quality as well as of bone quantity. In literature there is no strong evidence for instituting pharmacological therapy of bone impairment in UC patients for clinical indications other than those that are also applied to the patients with osteoporosis. Therefore, a reasonable advice is to consider pharmacological treatment for osteoporosis in those UC patients who already present fragility fractures, which bring a high risk of subsequent fractures. Therapy has also to be considered in patients with a high risk of fracture even if it did not yet happen, and particularly when they had long periods of corticosteroid therapy or cumulative high dosages. In patients without fragility fractures or steroid treatment, a medical decision about treatment could be guided by the FRAX tool to determine the intervention threshold. Among drugs for osteoporosis treatment, the bisphosphonates are the most studied ones, with the best and longest evidence of efficacy and safety. Despite this, several questions are still open, such as the duration of treatment, the necessity to discontinue it, the indication of therapy in young patients, particularly in those without previous fractures. Further, it has to be mentioned that a long-term bisphosphonates use in primary osteoporosis has been associated with an increased incidence of dramatic side-effects, even if uncommon, like osteonecrosis of the jaw and atypical sub-trochanteric and diaphyseal femoral fractures. UC is a long-lasting disease and the majority of patients is relatively young. In this scenario primary prevention of fragility fracture is the best cost-effective strategy. Vitamin D supplementation, adequate calcium intake, suitable physical activity (when possible), removing of risk factors for osteoporosis like smoking, and avoiding falling are the best medical acts.

Increased serum OPG in atrophic nonunion shaft fractures.

BACKGROUND: Bone repair alteration is hypothesized for nonunion fracture pathogenesis. Since it is involved in osteoclast regulation, the RANK/RANKL/OPG system (receptor activator of nuclear factor kB/its ligand/osteoprotegerin) may play a role. MATERIALS AND METHODS: Serum OPG, free RANKL, bone alkaline phosphatase (BAP), osteocalcin (OC), and urinary deoxypyridinoline (DPD) were determined in 16 male patients (20-39 years) with long bone atrophic nonunion fractures. Serum markers were also measured in 18 age-matched male controls who healed from the same type of fractures within six months, and in 14 age-matched male controls who were healing from the same fractures one month after injury. One-way ANOVA and Bonferroni's test were used for statistical analysis. RESULTS: Only OPG was significantly higher (0.56 sd 0.11 ng/ml) in the patients compared to healed (0.26 sd 0.04 ng/ml; P < 0.001) and healing (0.29 sd 0.09 ng/ml; P < 0.001) controls. The patients' DPD levels were normal. No correlations were found between bone markers and the characteristics of the subjects in all groups. CONCLUSIONS: A normal steady state of bone metabolism seems to be present in patients with atrophic nonunion fractures, despite the high serum OPG. The reason for the inability of the patients' OPG to inhibit osteoclastic activity is unknown. Osteoblast activity also appears normal, so another cellular source of OPG can be hypothesized.