Spine DXA Research Articles

Effects of an Exercise Intervention on Bone Mass in Pediatric Bone Tumor Patients

The aim was to evaluate the effects of additional exercises during inpatient stays on bone mass in pediatric bone tumor patients. 21 patients were non-randomly allocated either to the exercise group (n = 10) or the control group (n = 11). DXA of the lumbar spine, the non-affected femur and both calcanei was performed after completion of neoadjuvant chemotherapy (baseline), as well as 6 and 12 months after baseline. Bone mineral content (BMC), bone mineral density (BMD) and height-corrected lumbar spine Z-scores were determined. Group changes after 6 and 12 months were compared by covariance analyses. Additionally, daily physical activities (PA) were assessed by means of accelerometry. After adjusting for initial age, height and weight, mean reductions in lumbar spine and femoral BMC were lower in the exercise group (not significant). Effect sizes during the observational period for lumbar spine and femur BMC were generally small (partial η² = 0.03). The exercise group demonstrated substantially higher PA levels in terms of gait cycles per day, per hour and moderate PA (activities above 40 gait cycles per minute). Additional exercises for bone tumor patients are feasible during hospitalization. Though the intervention did not influence BMC, it appeared beneficial regarding PA promotion with respect to volume and intensity.

Vertebral microarchitecture and fragility fracture in men: A TBS study

IntroductionAlthough osteoporosis is considered a disease of women, 25% of the individuals with osteoporosis are men. BMD measurement by DXA is the gold standard used to diagnose osteoporosis and assess fracture risk. Nevertheless, BMD does not take into account alterations of microarchitecture. TBS is an index of bone microarchitecture extracted from the spine DXA. Previous studies have reported the ability of the spine TBS to predict osteoporotic fractures in women. This is the first case-controlled study in men to evaluate the potential diagnostic value of TBS as a complement to bone mineral density (BMD), by comparing men with and without fractures. MethodsTo be eligible for this study, subjects had to be non-Hispanic US white men aged 40 and older. Furthermore, subjects were excluded if they have or have had previously any treatment or illness that may influence bone metabolism. Fractured subjects were included if the presence of at least one fracture was confirmed. Cases were matched for age (±3years) and BMD (±0.04g/cm2) with three controls. BMD and TBS were first retrospectively evaluated at AP spine (L1–L4) with a Prodigy densitometer (GE-Lunar, Madison, USA) and TBS iNsight® (Med-Imaps, France) in Lausanne University Hospital blinded from clinical outcome. Inter-group comparisons were undertaken using Student's t-tests or Wilcoxon signed rank tests. Odds ratios were calculated per one standard deviation decrease as well as areas under the receiver operating curve (AUC). ResultsAfter applying inclusion/exclusion criteria, a group of 180 male subjects was obtained. This group consists of 45 fractured subjects (age=63.3±12.6years, BMI=27.1±4.2kg/m2) and 135 control subjects (age=62.9±11.9years, BMI=26.7±3.9kg/m2) matched for age (p=0.86) and BMD (p=0.20). A weak correlation was obtained between TBS and BMD and between TBS and BMI (r=0.27 and r=−0.28, respectively, p<0.01). Subjects with fracture have a significant lower TBS compared to control subjects (p=0.013), whereas no differences were obtained for BMI, height and weight (p>0.10). TBS OR per standard deviation is 1.55 [1.09–2.20] for all fracture type. When considering vertebral fracture only TBS OR reached 2.07 [1.14–3.74]. ConclusionThis study showed the potential use of TBS in men. TBS revealed a significant difference between fractured and age- and spine BMD-matched nonfractured subjects. These results are consistent with those previously reported on for men of other nationalities.

MRI‐based abnormalities in young adults at risk of adverse bone health due to childhood‐onset metabolic &amp; endocrine conditions

Traditional methods of bone densitometry may not provide a comprehensive assessment of bone health. We aimed to assess bone micro-architecture and bone marrow adiposity (BMA) by MRI in adults with osteogenesis imperfecta (OI) and endocrinopathy including GH deficiency and/or hypogonadism. High-resolution micro-MRI images were acquired at the tibia using 3T MRI to calculate parameters of bone micro-architecture in seven adults with OI and 10 adults with endocrinopathies. MR Spectroscopy was performed in participants to calculate vertebral BMA, which was expressed as percentage fat fraction (%FF). Lumbar spine DXA was performed to assess bone mineral density. The MRI data were compared with a group of 22 healthy adults who were divided into two age-matched control groups. Intra-operator repeatability was high, with an average CoV of 1% for micro-MRI and 2·5% for MRS. The ratio of apparent bone volume to total volume (appBV/TV) in the endocrinopathy and OI groups was lower than in age-matched control groups (P = 0·003 and P = 0·008 respectively). A weak association between DXA BMD and appBV/TV was also observed (r = 0·5, P = 0·045). %FF was higher in the endocrinopathy group than in the age-matched control group (P = 0·005), but no difference in %FF was observed between the OI group and their age-matched control group (P = 0·26). MRI provides valuable detailed information on the micro-architecture and adiposity of bones and is capable of showing clear differences in bone parameters in a range of clinical conditions associated with abnormal bone health.

Impact of the growth hormone replacement on bone status in growth hormone deficient adults

IntroductionGrowth hormone deficiency (GHD) is associated with reduced bone mineral density (BMD). GH replacement has positive effect on BMD but the magnitude of this effect and its mechanism are debated. ObjectivesThe objectives of this study was first, to assess the effect of GH replacement on BMD, and second, to evaluate the effect of GH treatment on bone turnover and microarchitecture and to assess the factors influencing the effect of the therapy on BMD. Patients and MethodsAdult GHD (AO-GHD) and childhood onset GHD (CO-GHD) patients treated with GH using IGF-I normalization GH replacement regimen were prospectively followed during 2years. Lumbar spine (L1–L4) and total femur BMD by Hologic discovery, in the subset of patients also bone turnover markers; osteocalcin and carboxy-terminal collagen crosslinks (CTx) were assessed at baseline and at months 3, 6, 12 and 24, respectively. The trabecular bone score (TBS) derived from lumbar spine DXA by the iNsight® software was assessed in a subset of study population at baseline and months 12 and 24. ResultsIn total, 147 GHD patients (age 35.1years, 84 males/63 females, 43 of childhood onset GHD/104 AO-GHD) were included. BMD of lumbar spine and femur increased significantly during the treatment (14% and 7% increase at 2years, respectively; p<0.0001).Bone markers increased during the first 12months of treatment with subsequent decrease of CTx. At month 24, significant increase in TBS was observed (4%, p=0.02).BMD increase was significantly higher in males (15% increase in males vs. 10% in females, p=0.037) and childhood onset GHD (CO-GHD) patients (13% increase in CO-GHD, p=0.004). ConclusionGH supplementation leads to an increase of BMD with corresponding changes in bone turnover markers and changes in microarchitecture as assessed by trabecular bone score. Positive effect of GH on bone status is more pronounced in males and CO-GHD adults.

Engage: A Phase 3, Randomized, Double-blind, Placebo-controlled, Multi-center Study To Investigate The Efficacy and Safety Of Eliglustat In Adults With Gaucher Disease Type 1: 9 Month Results

BackgroundGaucher disease type 1 is one of the most common lysosomal storage disorders. Deficiency of the lysosomal enzyme acid-β-glucosidase leads to accumulation of glucosylceramide (GL-1) in the spleen, liver, and bone marrow. Enzyme replacement therapy has been the mainstay of therapy for the last 20 years. Substrate reduction therapy is another treatment approach that inhibits GL-1 synthase and ultimately restores the balance between synthesis and degradation of the substrate. Eliglustat is a novel oral substrate reduction therapy that is currently in development for the treatment of Gaucher disease type 1. ENGAGE (NCT00891202) is a randomized, double-blind, placebo-controlled, Phase 3 trial sponsored by Genzyme, a Sanofi company investigating the efficacy and safety of eliglustat in untreated adults with Gaucher disease type 1. MethodForty patients (mean age: 31.8 years; 20 males) with splenomegaly and thrombocytopenia and/or anemia were stratified by spleen volume and randomized 1:1 to receive eliglustat (50 or 100 mg BID depending on plasma levels) or placebo for 9 months. The primary efficacy endpoint was percent change in spleen volume (multiples of normal). Other efficacy measures included hemoglobin, liver volume, and platelets. Bone endpoints included bone marrow burden (BMB) scores and bone mineral density changes (DXA). Quality of life assessments included the Gaucher Disease Severity Scoring System (DS3). Safety monitoring included adverse event reporting, and lab and electrocardiogram evaluations. ResultsIn patients receiving eliglustat vs. placebo, mean spleen volume decreased (-28% vs. +2%, P<0.0001), mean hemoglobin increased (0.69 vs. -0.54 g/dL, P<0.0006), liver volume decreased (-5.20% vs. +1.44%, P<0.0072), and platelets increased (+32% vs. -9.06%, P<0.0001). Significant improvements (eliglustat vs. placebo) were observed for total (-1.1 vs. 0.0, p=0.002), spine (-0.6 vs. 0.1, p=0.002), and femur (-0.5 vs. 0.0, p=0.026) BMB scores. Although patients with symptomatic bone disease were excluded, absolute change in total spine DXA Z-scores approached significance (least square mean treatment difference=0.2, p=0.06). Burden of disease, as measured by the Gaucher DS3, was significantly reduced following treatment with eliglustat vs. placebo (least square mean treatment difference=-0.3, p=0.0452). No patients discontinued due to an adverse event, all of which were classified as mild to moderate, and 39/40 patients transitioned into the ongoing open-label trial. Arthralgia and nasopharyngitis occurred in >10% of eliglustat vs. placebo patients. ConclusionENGAGE met its primary and secondary efficacy endpoints. Significant effects on bone marrow and a trend toward BMD improvement in spine were observed. Eliglustat treatment was effective and well-tolerated in untreated adults with Gaucher disease type 1. Disclosures:Shankar:Genzyme, a Sanofi company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Lukina:Genzyme, a Sanofi company: Consultancy, Honoraria, Speakers Bureau. Amato:Genzyme, a Sanofi company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Packman:Genzyme, a Sanofi company: Consultancy, Research Funding. Pastores:Genzyme, a Sanofi company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Balwani:Genzyme, a Sanofi company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Mistry:Genzyme, a Sanofi company: Consultancy, Honoraria, Research Funding. Ross:Genzyme, a Sanofi company: Employment. Marulkar:Genzyme, a Sanofi company: Employment. Peterschmitt:Genzyme, a Sanofi company: Employment.

Osteoporosis detection in postmenopausal women using axial transmission multi-frequency bone ultrasonometer: Clinical findings

The objective of this study was to evaluate if the Bone UltraSonic Scanner (BUSS) can detect osteoporosis in postmenopausal women. BUSS is an axial transmission multi-frequency ultrasonometer for acquisition of wave propagation profiles along the proximal anterior tibia. We derived 10 diagnostically significant BUSS parameters that were then compared with the DXA spine T-score, which was used in this study as the “gold standard” for the assessment of osteoporosis (T-score<−2.5). BUSS wave parameters were studied in 331 postmenopausal women examined by 9 trained operators at 3 clinical sites with use of 3 devices. The efficiency of each BUSS parameter in osteoporosis detection was assessed using a receiver operating characteristic curve analysis. Area under the curve (AUC) for each of 10 parameters ranged from 58.1% to 70.2%. Using these parameters a linear classifier was derived which provided at its output 83.0% AUC, 87.7% sensitivity and 63.2% specificity to DXA-identified osteoporosis. The results of this study confirm BUSS’s capability to detect osteoporosis in postmenopausal women.

OP0044 The effects of multiple doses of sclerostin antibody AMG 785 in healthy men and postmenopausal women with low bone mass

BackgroundAMG 785 is a sclerostin antibody (Scl-Ab) that blocks sclerostin from inhibiting osteoblast maturation and function and has been shown to stimulate bone formation.ObjectivesEvaluate the pharmacokinetics (PK), pharmacodynamics (PD), and...

SAT0371 The Impact of Trabecular and Cortical Alterations in Patients with Bone Marrow Edema and Arthralgia of the Lower Limbs

BackgroundBone marrow edema (BME) is a localised painful bone lesion which is diagnosed by MRI and a frequent cause for severe pain in the joints of the lower limbs and....

AB1472-HPR Association between the age of the knee osteoarthritis manifestation and bone mineral density

BackgroundThere are data demonstrated association between BMD and the risk of manifestation OA. Some researchers revealed association between high BMD score in hip and lumbar region and high risk of...

SP0122 Osteoporosis and bone disease

Osteoporosis can be divided in primary osteoporosis and secondary osteoporosis. In the field of primary osteoporosis, the new focus is the diagnostic and therapeutic follow-up of individuals 50 years and...

Trabecular bone score applied to normal children's lumbar spine DXA scans

Trabecular bone score applied to normal children's lumbar spine DXA scans

Evaluation of the efficacy, safety and pharmacokinetic profile of oral recombinant human parathyroid hormone [rhPTH(1–31)NH2] in postmenopausal women with osteoporosis

ContextTreatment of osteoporosis with subcutaneous (SC) injections of rhPTH(1–34) or rhPTH(1–84) is associated with significant improvements in BMD and reductions in osteoporotic fractures. However, subcutaneous injections can be associated with discomfort and thus deteriorating compliance. ObjectiveThe UGL-OR1001 trial aimed to establish the efficacy and safety parameters of a novel oral tablet formulation of rhPTH(1–31)NH2 and matching placebo tablets and open-label teriparatide positive control in postmenopausal women with osteoporosis. Design24weeks of randomized, double-blind treatment with once daily doses of 5mg oral treatment or corresponding placebo, or open-label subcutaneous teriparatide. Patients or other participantsWomen diagnosed with postmenopausal osteoporosis as detected by lumbar spine DXA, with an exclusion of those with prior treatment with bone active agents. Intervention(s)Orally formulated recombinant human PTH(1–31)NH2 and placebo, or open-label subcutaneous teriparatide as a positive control. Main outcome measure(s)The primary endpoint was to characterize the percent change from baseline in bone mineral density (BMD) at L1–L4 axial lumbar spine after 24weeks in the rhPTH(1–31)NH2 arm. Secondary and exploratory endpoints included safety and tolerability of the oral formulation, measurement of biochemical markers of bone turnover, and evaluation of the PK profile at first and last dose. The study was registered at ClinicalTrials.gov with the identifier: NCT01321723. ResultsThe oral tablet formulation of rhPTH(1–31)NH2 resulted in similar PK profiles at both timepoints with mean Cmax values similar to subcutaneous administration. In the rhPTH(1–31)NH2 arm, a 2.2% increase in lumbar spine BMD was observed compared to baseline (p<0.001), while no change was observed in the placebo arm. Open-label teriparatide resulted in a 5.1% increase in LS BMD (p<0.001). In the oral PTH study arm, the bone formation marker osteocalcin was increased by 32%, 21% and 23% at Weeks 4, 12 and 24, respectively. There was no significant increase in the level of the bone resorption marker CTx-1. ConclusionsIn summary, these data demonstrate that enteric-coated oral tablet formulation technology consistently generated robust levels of exposure of rhPTH(1–31)NH2 leading to induction of bone formation without inducing bone resorption resulting in significantly increased levels of LS BMD. Few adverse events were observed, recommending this orally delivered drug candidate for further development.

Bone health in children with long–term idiopathic subclinical hypothyroidism

BackgroundSubclinical hypothyroidism (SH) is a relatively common condition characterized by a mild persistent thyroid failure. The management of children with SH is still a controversial issue and the decision to treat with L-thyroxine represents a clinical dilemma. Thyroid hormone and TSH play an important role in skeletal growth and bone mineral homeostasis.AimTo evaluate whether untreated idiopathic SH may affect bone health in childhood and to compare two different diagnostic tools such as dual-energy X-ray densitometry (DXA) and quantitative ultrasound (QUS).Patients and MethodsTwenty-five children and adolescents (11 males) aged 9.8 ± 3.5 years (range 4.2-18.7) with untreated idiopathic SH were enrolled in the study. SH was diagnosed on the basis of normal FT4 levels with TSH concentrations between 4.2 and 10 mU/l. Children have been followed for 3.3 ± 0.3 years from the time of SH diagnosis. Twenty-five healthy children, age- and sex-matched, were enrolled as controls. Patients and controls underwent DXA to evaluate lumbar spine bone mineral density (BMD) and QUS at proximal phalanges of the non-dominant hand to assess bone quality, measured as amplitude-dependent speed of sound (Ad-SoS) and bone transmission time (BTT).ResultsMean BMD Z-score was −0.4 ± 1.36 in patients and −0.2 ± 1.2 in controls. Mean Ad-SoS Z-score was 0.01 ± 1.0 in patients and 0.1 ± 1.2 in controls and mean BTT Z-score was −0.03 ± 0.8 and 0.04 ± 1.1 respectively. All values were within the normal range, both in patients and in controls. There were no statistically significant differences between the two groups.ConclusionBone health, evaluated by lumbar spine DXA and phalangeal QUS, is not impaired in our children, despite long-term duration of idiopathic SH. Data about bone status provided by QUS are comparable to those provided by DXA. Therefore, QUS may represent a good, cheaper and safe screening test for bone evaluation in children with SH.

Trabecular bone score improves fracture risk prediction in non-osteoporotic women: the OFELY study

The use of areal bone mineral density (aBMD) for fracture prediction may be enhanced by considering bone microarchitectural deterioration. Trabecular bone score (TBS) helped in redefining a significant subset of non-osteoporotic women as a higher risk group. TBS is an index of bone microarchitecture. Our goal was to assess the ability of TBS to predict incident fracture. TBS was assessed in 560 postmenopausal women from the Os des Femmes de Lyon cohort, who had a lumbar spine (LS) DXA scan (QDR 4500A, Hologic) between years 2000 and 2001. During a mean follow-up of 7.8 ± 1.3years, 94 women sustained 112 fragility fractures. At the time of baseline DXA scan, women with incident fracture were significantly older (70 ± 9 vs. 65 ± 8years) and had a lower LS_aBMD and LS_TBS (both -0.4SD, p < 0.001) than women without fracture. The magnitude of fracture prediction was similar for LS_aBMD and LS_TBS (odds ratio [95% confidence interval] = 1.4 [1.2;1.7] and 1.6 [1.2;2.0]). After adjustment for age and prevalent fracture, LS_TBS remained predictive of an increased risk of fracture. Yet, its addition to age, prevalent fracture, and LS_aBMD did not reach the level of significance to improve the fracture prediction. When using the WHO classification, 39% of fractures occurred in osteoporotic women, 46% in osteopenic women, and 15% in women with T-score > -1. Thirty-seven percent of fractures occurred in the lowest quartile of LS_TBS, regardless of BMD. Moreover, 35% of fractures that occurred in osteopenic women were classified below this LS_TBS threshold. In conclusion, LS_aBMD and LS_TBS predicted fractures equally well. In our cohort, the addition of LS_TBS to age and LS_aBMD added only limited information on fracture risk prediction. However, using the lowest quartile of LS_TBS helped in redefining a significant subset of non-osteoporotic women as a higher risk group which is important for patient management.

Changes of circulating sclerostin levels after different kinds of physical exercise with high impact on musculoskeletal system in healthy young females

Changes of circulating sclerostin levels after different kinds of physical exercise with high impact on musculoskeletal system in healthy young females

Dairy calcium intake and lifestyle risk factors for bone loss in hiv-infected and uninfected mediterranean subjects

BackgroundDespite the reported high prevalence of osteoporosis in the human immunodeficiency virus (HIV)-population, there have been no previous studies examining dairy calcium intake and bone mineral density (BMD) in HIV-subjects.We assessed the prevalence of low BMD in HIV-infected and uninfected subjects and analyzed the effects of calcium intake, lifestyle and HIV-related risk factors on BMD.MethodsOne hundred and twelve HIV-infected subjects were consecutively enrolled. Seventy- six HIV-uninfected subjects matched for age and sex were enrolled as the control group. The HIV-subjects were interviewed about lifestyle habits and completed a weekly food-frequency questionnaire to estimate calcium intake. HIV-RNA, CD4+ T-cell count and data on antiretroviral therapy were also recorded. Both biochemical bone turnover markers and BMD, assessed by dual-energy radiographic absorptiometry (DXA) were recorded in the HIV-cases and controls. We also calculated the 10-year fracture risks using the WHO FRAX equation.ResultsOsteoporosis prevalence was significantly higher in the HIV-cases than controls (p < 0.05). BMI values were positively correlated with BMD (p < 0.05). Vitamin D levels were lower in the HIV-subjects (p < 0.02). No correlation was found with daily calcium intake.BMI values were significantly correlated with dairy intake quartiles (p < 0.003). In HIV-subjects, the mean of FRAX score was 1.2 % for hip and 4.7 % for major osteoporotic fractures. On multivariate analysis of the lumbar spine DXA T-score, age (p < 0.005) and HIV/hepatitis C virus co-infection (p < 0.0001) were negatively correlated with BMD, while yogurt intake was a protective predictor of BMD (p < 0.05). In the femur DXA T-score, age (p < 0.01), nadir CD4 + T-cell count < 200 cells/μL (p < 0.05) and drug addiction ( p < 0.0001) were negatively correlated with BMD.ConclusionsAmong the foods rich in calcium, yogurt was a protective predictor of BMD in HIV-subjects. HIV/HCV co-infection, nadir CD4 + T-cell count < 200 cells/μL and drug addiction were independent predictors of severe BMD. Promoting behavioral changes in food intake and lifestyle, aimed at the primary prevention of bone disease in the chronically-infected subjects seems to be essential for implementing medical intervention in these cases.

Comparative study of the results of heel ultrasound screening and DXA findings (lumbar spine and left hip) of postmenopausal women

Introduction: Osteoporosis is a silent and invisible disease of bone, great presence and is considered to suffer from osteoporosis at least 200 million women worldwide. The goal of this paper is to show average ageof postmenopausal respondents, values of anthropometric parameters (weight, height, BMI), anamnestic data on clinical symptoms, fractures of women in menopause, analysis of heel ultrasound screening results,analysis of lumbar spine DXA results, analysis of left hip DXA results.Methods: In retrospective study 61 respondents were involved, 33 to 79 years old, treated in u Center for Physical Medicine and Acupuncture “AD” in Sarajevo during the period from 01.01.2008 till 31.12.2009. Alldate are shown numerically and percentage account with calculation of mean value, expressed in the form of tables and charts.Results: Finding of heel ultrosound screening compared to T values of postmenopausal respondents indicates on osteoporosis in case of 17 (27,87%), in case of 44 (72,13%) respondents osteopenia, while normalvalues were not found. T value with lumbar spine DXA method in postmenopausal female respondents correspond to 43 (70,5%) respondents, in 15 respondents (24,6%) finding corresponded to osteopenia, while 3 respondents (4,9%) had physiological finding. Left hip DXA finding shows 36 (59%) respondents corresponded osteoporosis, 19 (31,2%) respondents corresponded osteopenia, while physiological finding was found in 6 respondents (9,8%). T value of lumbar spine DXA finding was - 2,71 ± 1,16; DXA finding of left hip -2,35 ±1,36; heel ultrasound screening -2,19 ± 0,54.Conclusion: Research results indicate that DXA finding in relation to the heel ultrasound screening confirms gold standard in diagnosing osteoporosis.

Short-term in vivo precision of BMD and parameters of trabecular architecture at the distal forearm and tibia

In vivo hr-pQCT precision was determined in 42 postmenopausal women using double baseline measurements from a multicenter trial of odanacatib. Errors, e.g., at the radius below 1.3% for BMD and below 6.3% for trabecular structure, were comparable to single-center results. Motion artifacts remain a challenge, particularly at the forearm. The short-term in vivo precision of BMD, trabecular bone structure, cortical thickness and porosity of the forearm and tibia was measured by hr-pQCT. Also the effect of image quality on precision was evaluated. In 42 postmenopausal women (age 64.4 ± 6.8years) out of 214 subjects enrolled in a multi center advanced imaging phase III study of odanacatib (DXA spine or hip T-scores between -1.5 and -3.5), double baseline hr-pQCT (XtremeCT) measurements with repositioning were performed. The standard ultradistal location and a second, more proximally located VOI were measured at the radius and tibia to better assess cortical thickness and porosity. Image analysis and quality grading (grades: perfect, slight artifacts, pronounced artifacts, unacceptable) were performed centrally. At the radius RMS%CV values varied from 0.7% to 1.3% for BMD and BV/TV and from 5.6% to 6.3% for Tb.Sp, Tb.Th, Tb.N, and cortical porosity. Numerically at the tibia, precision errors were approx. 0.5% lower for BMD and 1% to 2% lower for structural parameters although most differences were insignificant. In the radius but not in the tibia, precision errors for cortical thickness were smaller at the distal compared to the ultradistal location (1% versus 2%). BMD precision errors were lower than those for trabecular architecture and cortical porosity. Motion artifacts remain a challenge, particularly at the forearm. Quality grading remains subjective, and more objective evaluation methods are needed. Precision in the context of a multicenter clinical trial, with centralized training and scan analysis, was comparable to single-center results previously reported.

Patients with POEMS Syndrome Have High Bone Turnover and Increased Circulating Angiogenic Cytokines; Should Angiopoietin-2 and Bone-Specific Alkaline Phosphatase Be Used As Minor Criteria for the Diagnosis of the Disease?

Abstract 806▪FN2▪This icon denotes a clinically relevant abstractPOEMS syndrome is defined by the presence of peripheral neuropathy (P), monoclonal plasma cell disorder (M), organomegaly (O), endocrinopathy (E) and skin changes (S). The majority of patients have sclerotic bone lesions, although the underlying mechanisms are still unclear. Increased circulating vascular endothelial growth factor (VEGF) is another feature of the disease. However, there is almost no information on the role of other angiogenic molecules in POEMS biology. The aim of the study was to evaluate bone metabolism and angiogenic cytokines in POEMS and compare the results with multiple myeloma (MM) and osteosclerotic patients of other etiology.We retrospectively studied 61 POEMS patients (40M/21F, median age 52 years) who were diagnosed between 1996 and 2010 and were treated and followed in Mayo Clinic Rochester (MN, USA), Hôpital Saint-Louis, Paris (France) and in Alexandra Hospital, Athens (Greece). We evaluated the following indices of bone remodeling and angiogenesis in all patients at diagnosis and in 22 of them one month after front-line treatment: i) osteoclast regulators [sRANKL and osteoprotegerin (OPG)]; ii) osteoblast inhibitor dickkopf-1 (Dkk-1); iii) bone resorption marker CTX; iv) bone formation markers [bone-specific alkaline phosphatase (bALP) and osteocalcin]; and v) angiogenic cytokines [VEGF, angiogenin (ang), angiopoietin (angp)-1 and -2]. These molecules were also measured in 60 newly diagnosed, untreated MM patients (34M/26F, median age: 54 years) and 44 healthy controls. Bone markers were also evaluated in 24 patients with HbS/beta-thalassemia (10M/14F, median age: 43 years) who presented with osteosclerosis, defined as osteosclerotic bone lesions in plain radiography and high T-score of lumbar spine DXA (median: +3.6, range: +2 to +7.9).All POEMS patients presented with P and M, while 90% had E, 83% had S, 61% had O and 32% had papilloedema. One or more documented sclerotic bone lesions in plain X-rays were observed in 78% of patients (diffuse lesions in 44%), while 43% of patients had also an osteolytic component. Seven patients had Castleman disease.At diagnosis, compared to controls, POEMS patients had increased levels of bALP (mean ± SD: 48.3 ± 22.9 IU/L vs. 21.6 ± 8.2 IU/L; p<0.001), CTX (0.97 ± 0.94 ng/ml vs. 0.33 ± 0.24 ng/ml; p<0.001), Dkk-1 (p<0.001), sRANKL (p<0.001) and sRANKL/OPG ratio (p<0.001). Patients with diffuse osteosclerosis had increased levels of Dkk-1 compared to others (p = 0.05), suggesting a balance effect to increased formation activity. Patients with POEMS had increased levels of bALP and decreased levels of CTX compared to MM patients (p<0.001 and p = 0.03, respectively), while they had increased levels of CTX and sRANKL/OPG ratio compared to HbS/beta-thal patients (p = 0.001 for both comparisons). There were no other differences regarding bone markers among studied groups.Regarding angiogenic cytokines, at diagnosis, POEMS patients had elevated VEGF (1232 ± 565 pg/ml vs. 195 ± 211 pg/ml; p<0.001), ang (266 ± 82 ng/ml vs. 190 ± 45; p<0.001) and angp-2 (3.5 ± 2.2 ng/ml vs. 1.2 ± 0.6 ng/ml; p<0.001) and decreased angp-1 (p =0.05) and angp-1/angp-2 ratio (reflects increased angiogenic capacity; 9.1 ± 8.8 vs. 44.8 ± 76.1; p<0.001) compared to normal controls. We found no strong correlations between the levels of VEGF, ang and angps. When compared to MM patients, POEMS patients had increased circulating VEGF (p = 0.001) without any difference regarding the other angiogenic cytokines. Response to therapy was accompanied by a dramatic reduction of VEGF only (551 ± 541 pg/ml compared to baseline 1800 ± 1510 pg/ml; p = 0.003).Receiver-operating characteristic (ROC) curve analysis showed that high levels of angiopoietin-2 (≥ 2.3 ng/ml) and high bALP (≥ 38 IU/l) each have a 95% specificity for patients with POEMS syndrome.These results suggest that patients with POEMS syndrome have high bone turnover with increased bone formation as compared to healthy subjects, to MM patients, who have reduced bone formation, and to osteosclerotic HbS/beta-thal patients, who have diminished bone resorption. Importantly, our analysis supports the use of angp-2, bALP along with VEGF as minor criteria for the diagnosis of POEMS. Successful treatment reduced VEGF, which seems to be a suitable marker for the follow-up of POEMS patients. Furthermore the imbalance of angp-1/angp-2 pathway may indicate possible targets for the development of novel agents against POEMS. Disclosures:No relevant conflicts of interest to declare.

Alteraciones del metabolismo óseo en 100 pacientes con enfermedad inflamatoria intestinal

Objectives To evaluate the prevalence of osteopenia and osteoporosis in patients with inflammatory bowel disease (IBD) and to study the factors involved in their pathogenesis. Methods One hundred consecutive patients with IBD (57 women, mean age 41 years) were included in this study. Data were collected about their life habits, disease characteristics of medication use (mainly corticosteroids). Bone turnover markers were analyzed and the presence of osteoporosis or osteopenia was assessed with total hip and lumbar spine bone densitometry (DXA). Results Osteopenia percentages ranged from 37% (t-score measured by lumbar spine DXA) to 39% (hip DXA t-score). The prevalence of osteoporosis ranged from 2% (t-score measured by hip DXA) to 15% (lumbar spine DXA t-score). In the multivariate analysis, diagnosis of Crohn's disease (vs. ulcerative colitis; odds ratio 2.9, 95% CI 1-8.7) and the number of flares controlled by the cumulative dose of steroids (number of flares ≥3: odds ratio 8.7; 95%CI 1.6-45) were associated with a higher risk of osteopenia/osteoporosis. None of the analytical parameters significantly correlated with bone mineral density values. Conclusions The prevalence of osteopenia/osteoporosis is higher in patients with IBD (mainly those with Crohn's disease) than in the general population. Changes in bone metabolism seem to be more closely related to the inflammatory activity of IBD than to the steroid dose per se. Bone turnover markers did not correlate with the presence of osteopenia and osteoporosis.