Bone Mineral Density Data Research Articles

Evaluation of Serum Vitamin D Level and Bone Mineral Density in Patients of Non Alcoholic Fatty Liver Disease

Low serum vitamin D may predispose to intra hepatic lipid accumulation leading to Non Alcoholic Fatty Liver Disease (NAFLD). Emerging data indicates that NAFLD is associated with low Bone mineral density (BMD). An observational cross sectional study was conducted with 80 adults out of which 40 patients with the diagnosis of NAFLD fulfilling the selection criteria were selected as cases and rest 40 adults were controls. BMD, ultrasonographic grading of NAFLD and serum vitamin D levels were done in all cases and controls and their correlation with each other were analyzed. Basic parameters like age and sex were comparable. The mean BMD in the case population is 0.82 ± 0.07 whereas in control population it was 0.96 ± 0.34 (p<0.005). The mean T score in the case population is -1.84 ± 0.65 whereas in control population it was -0.55 ± 0.72 (p <0.005). The mean vitamin D level in the case population is 21.57 ± 8.74 ng/ml and in the control population was 30.43 ± 4.65 ng/ml (p <.0005). BMD and serum vitamin D levels were less in patients of NAFLD as compared to control population and were found to be statistically significant. The recorded data of BMD and vitamin D were inversely related to the grading of fatty liver such as higher grading of fatty liver was associated with lower BMD and vitamin D levels in the case population. Our findings confirm prior research that NAFLD patients have low Vitamin D Levels and low BMD.

Bisphosphonate therapy for osteogenesis imperfecta.

Osteogenesis imperfecta is caused by a genetic defect resulting in an abnormal type I collagen bone matrix which typically results in multiple fractures with little or no trauma. Bisphosphonates are used in an attempt to increase bone mineral density and reduce these fractures in people with osteogenesis imperfecta. This is an update of a previously published Cochrane Review. To assess the effectiveness and safety of bisphosphonates in increasing bone mineral density, reducing fractures and improving clinical function in people with osteogenesis imperfecta. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Inborn Errors of Metabolism Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of journals and conference proceedings. We additionally searched PubMed and major conference proceedings.Date of the most recent search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Register: 28 April 2016. Randomised and quasi-randomised controlled trials comparing bisphosphonates to placebo, no treatment, or comparator interventions in all types of osteogenesis imperfecta. Two authors independently extracted data and assessed the risk of bias of the included trials. Fourteen trials (819 participants) were included. Overall, the trials were mainly at a low risk of bias, although selective reporting was an issue in several of the trials. Data for oral bisphosphonates versus placebo could not be aggregated; a statistically significant difference favouring oral bisphosphonates in fracture risk reduction and number of fractures was noted in two trials. No differences were reported in the remaining three trials which commented on fracture incidence. Five trials reported data for spine bone mineral density; all found statistically significant increased lumbar spine density z scores for at least one time point studied. For intravenous bisphosphonates versus placebo, aggregated data from two trials showed no statistically significant difference for the number of participants with at least one fracture, risk ratio 0.56 (95% confidence interval 0.30 to 1.06). In the remaining trial no statistically significant difference was noted in fracture incidence. For spine bone mineral density, no statistically significant difference was noted in the aggregated data from two trials, mean difference 9.96 (95% confidence interval -2.51 to 22.43). In the remaining trial a statistically significant difference in mean per cent change in spine bone mineral density z score favoured intravenous bisphosphonates at six and 12 months. Data describing growth, bone pain, and functional outcomes after oral or intravenous bisphosphonate therapy, or both, as compared to placebo were incomplete among all studies, but do not show consistent improvements in these outcomes. Two studies compared different doses of bisphosphonates. No differences were found between doses when bone mineral density, fractures, and height or length z score were assessed. One trial compared oral versus intravenous bisphosphonates and found no differences in primary outcomes. Two studies compared the intravenous bisphosphonates zoledronic acid and pamidronate. There were no significant differences in primary outcome. However, the studies were at odds as to the relative benefit of zoledronic acid over pamidronate for lumbosacral bone mineral density at 12 months. Bisphophonates are commonly prescribed to individuals with osteogenesis imperfecta. Current evidence, albeit limited, demonstrates oral or intravenous bisphosphonates increase bone mineral density in children and adults with this condition. These were not shown to be different in their ability to increase bone mineral density. It is unclear whether oral or intravenous bisphosphonate treatment consistently decreases fractures, though multiple studies report this independently and no studies report an increased fracture rate with treatment. The studies included here do not show bisphosphonates conclusively improve clinical status (reduce pain; improve growth and functional mobility) in people with osteogenesis imperfecta. Given their current widespread and expected continued use, the optimal method, duration of therapy and long-term safety of bisphosphonate therapy require further investigation. In addition, attention should be given to long-term fracture reduction and improvement in quality of life indicators.

Safety, efficacy, and pharmacokinetics of a single-tablet regimen containing elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in treatment-naive, HIV-infected adolescents: a single-arm, open-label trial

The prodrug tenofovir alafenamide is associated with improved renal and bone safety compared with tenofovir disoproxil fumarate. We aimed to assess safety, pharmacokinetics, and efficacy of this single-tablet, fixed-dose combination of elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in HIV-infected, treatment-naive adolescents. We did a 48 week, single-arm, open-label trial in treatment-naive adolescents with HIV from ten hospital clinics in South Africa, Thailand, Uganda, and the USA. Eligible participants were aged 12-18 years, with plasma HIV-1 RNA of at least 1000 copies per mL, a CD4 count of at least 100 cells per μL, and estimated glomerular filtration rate of at least 90 mL/min per 1·73 m2 by the Schwartz formula, bodyweight of at least 35 kg, and an HIV-1 genotype with sensitivity to elvitegravir, emtricitabine, and tenofovir. Participants received a single-tablet regimen once per day with food (administered by their parent or carer) containing 150 mg elvitegravir, 150 mg cobicistat, 200 mg emtricitabine, and 10 mg tenofovir alafenamide. Study visits to the clinic occurred at weeks 1, 2, 4, 8, 12, 16, 24, 32, 40, and 48. The coprimary endpoints were the pharmacokinetic parameters of area under the curve (AUC) concentration at the end of the dosing interval (AUCtau) for elvitegravir and the AUC from time zero to the last quantifiable concentration (AUClast) for tenofovir alafenamide, incidence of treatment-emergent serious adverse events, and all adverse events that emerged after treatment started (including data for bone mineral density). All participants who received one dose of study drug were included in the primary and safety analyses. This trial is registered with ClinicalTrials.gov, number NCT01854775. Between May 22, 2013, and July 22, 2014, we enrolled 50 participants, and all 50 received the assigned treatment; 24 participated in the intensive pharmacokinetic assessment. 48 patients completed the 48 weeks of treatment; two discontinued (one withdrew consent at week 8, one was lost to follow-up at week 12). The regimen was well tolerated and no discontinuations related to adverse events occurred. The mean AUCtau for elvitegravir was 23 840 ng × h per mL (coefficient of variation [CV] 25·5%), and the mean AUClast for tenofovir alafenamide was 189 ng × h per mL (CV 55·8%). Four participants (8%) had a serious adverse event, one of which (intermediate uveitis) was deemed related to the study regimen but resolved without treatment interruption. The most common study drug-related adverse events were nausea (in ten participants), abdominal pain (in six), and vomiting (in five). Exposures to the elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide regimen were similar to those previously noted in adults. The elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide regimen was well tolerated and achieved component plasma pharmacokinetic exposures similar to those in adults. Although non-comparative with a small sample size, these data support the use of this regimen in HIV-infected adolescents and its timely assessment in younger children. Gilead Sciences.

Effect of simulated microgravity and space radiation on bone and dental implant

Objective To observe the effect of microgravity and ionizing radiation on bone and dental implant. Methods 28 SD rats were randomly divided into 4 groups: control group, microgravity group, radiation group and microgravity + radiation group. Each rat had a dental implant putting in the right tibia. The knees of rats in the radiation groups were exposed to ionizing radiation. Microgravity groups were mechanically unloaded. Blood osteocalcin (OCN), alkaline phosphatase (ALP), calcium (Ca) and phosphatase (P) were detected. The tibia and thigh bone specimens were observed by histological methods and scanned by micro CT. 3D reconstruction was made and data of bone mineral density (BMD), bone volume/total volume (BV/TV), trabecular thickness and trabecular number were analysed stastically. Results OCN, ALP and Ca were significantly changed in microgravity group and microgravity + radiation group (P<0.05). The bone density was decreased in the microgravity groups. BMD, BV/TV, trabecular thickness and trabecular number were all lower than those in the non-microgravity groups (P<0.05, P<0.01), and radiation made BMD decreased more significantly (P<0.05). Tissue congestion and peri-implant bone resorption were observed in the radiation groups. Conclusions Microgravity and ionizing radiation can change bone in both quantity and quality. The interaction of the two factors will make the change greater. The secondary radiation from metal implant is an important factor affecting the dental implant stability in bone. Key words: Simulated microgravity; Radiation; Implant; Bone

A systematic review and economic evaluation of bisphosphonates for the prevention of fragility fractures.

Fragility fractures are fractures that result from mechanical forces that would not ordinarily result in fracture. To evaluate the clinical effectiveness and safety of bisphosphonates [alendronic acid (Fosamax® and Fosamax® Once Weekly, Merck Sharp & Dohme Ltd), risedronic acid (Actonel® and Actonel Once a Week®, Warner Chilcott UK Ltd), ibandronic acid (Bonviva®, Roche Products Ltd) and zoledronic acid (Aclasta®, Novartis Pharmaceuticals UK Ltd)] for the prevention of fragility fracture and to assess their cost-effectiveness at varying levels of fracture risk. For the clinical effectiveness review, six electronic databases and two trial registries were searched: MEDLINE, EMBASE, The Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Web of Science and BIOSIS Previews, Clinicaltrials.gov and World Health Organization International Clinical Trials Registry Platform. Searches were limited by date from 2008 until September 2014. A systematic review and network meta-analysis (NMA) of effectiveness studies were conducted. A review of published economic analyses was undertaken and a de novo health economic model was constructed. Discrete event simulation was used to estimate lifetime costs and quality-adjusted life-years (QALYs) for each bisphosphonate treatment strategy and a strategy of no treatment for a simulated cohort of patients with heterogeneous characteristics. The model was populated with effectiveness evidence from the systematic review and NMA. All other parameters were estimated from published sources. A NHS and Personal Social Services perspective was taken, and costs and benefits were discounted at 3.5% per annum. Fracture risk was estimated from patient characteristics using the QFracture® (QFracture-2012 open source revision 38, Clinrisk Ltd, Leeds, UK) and FRAX® (web version 3.9, University of Sheffield, Sheffield, UK) tools. The relationship between fracture risk and incremental net benefit (INB) was estimated using non-parametric regression. Probabilistic sensitivity analysis (PSA) and scenario analyses were used to assess uncertainty. Forty-six randomised controlled trials (RCTs) were included in the clinical effectiveness systematic review, with 27 RCTs providing data for the fracture NMA and 35 RCTs providing data for the femoral neck bone mineral density (BMD) NMA. All treatments had beneficial effects on fractures versus placebo, with hazard ratios varying from 0.41 to 0.92 depending on treatment and fracture type. The effects on vertebral fractures and percentage change in BMD were statistically significant for all treatments. There was no evidence of a difference in effect on fractures between bisphosphonates. A statistically significant difference in the incidence of influenza-like symptoms was identified from the RCTs for zoledronic acid compared with placebo. Reviews of observational studies suggest that upper gastrointestinal symptoms are frequently reported in the first month of oral bisphosphonate treatment, but pooled analyses of placebo-controlled trials found no statistically significant difference. A strategy of no treatment was estimated to have the maximum INB for patients with a 10-year QFracture risk under 1.5%, whereas oral bisphosphonates provided maximum INB at higher levels of risk. However, the PSA suggested that there is considerable uncertainty regarding whether or not no treatment is the optimal strategy until the QFracture score is around 5.5%. In the model using FRAX, the mean INBs were positive for all oral bisphosphonate treatments across all risk categories. Intravenous bisphosphonates were estimated to have lower INBs than oral bisphosphonates across all levels of fracture risk when estimated using either QFracture or FRAX. We assumed that all treatment strategies are viable alternatives across the whole population. Bisphosphonates are effective in preventing fragility fractures. However, the benefit-to-risk ratio in the lowest-risk patients may be debatable given the low absolute QALY gains and the potential for adverse events. We plan to extend the analysis to include non-bisphosphonate therapies. This study is registered as PROSPERO CRD42013006883. The National Institute for Health Research Health Technology Assessment programme.

Effect of conjugated estrogens/bazedoxifene on postmenopausal bone loss: pooled analysis of two randomized trials.

Conjugated estrogens/bazedoxifene reduces vasomotor symptoms and prevents postmenopausal bone loss without stimulating the breast and endometrium. We analyzed changes in bone mineral density (BMD) and bone markers using pooled data from two phase-3 trials. Selective Estrogens, Menopause, and Response to Therapy (SMART)-1 and SMART-5 were randomized, double-blind, placebo- and active-controlled studies conducted in postmenopausal nonhysterectomized women. BMD and turnover marker data were pooled for women given conjugated estrogens (0.45 or 0.625 mg) plus bazedoxifene 20 mg or placebo over 12 months. Sensitivity analyses were conducted using baseline Fracture Risk Assessment Tool score, age, years since menopause, body mass index, race, and geographic region. There were 1,172 women, mean age 54.9 years, mean 6.21 years since menopause, mean lumbar spine, and total hip T scores -1.05 and -0.58; 58.8% had a Fracture Risk Assessment Tool score less than 5% indicating low fracture risk. At 12 months, adjusted differences (vs placebo) in BMD change in the groups taking conjugated estrogens 0.45 or 0.625 mg plus bazedoxifene 20 mg were 2.3% and 2.4% for lumbar spine, 1.4% and 1.5% for total hip, and 1.1% and 1.5% for femoral neck (all P < 0.001 vs placebo). These increases were unrelated to baseline Fracture Risk Assessment Tool score, age, years since menopause, body mass index, or geographic region. Both doses reduced bone turnover markers (P < 0.001). Conjugated estrogens/bazedoxifene significantly improved BMD and turnover in a large population of younger postmenopausal women at low fracture risk and is a promising therapy for preventing postmenopausal bone loss.

Evaluation of bone quality, measured by trabecular bone score in patients with primary hyperparathyroidism

Introduction. Evaluation of bone quality represents a clinical challenge. Analysis of bone mineral density (BMD) provides useful, but incomplete, information, and new tools are needed. Trabecular Bone Score (TBS) is emerging as a new surrogate marker of bone texture and microarchitecture and, may, therefore, be useful to potentially evaluate the risk of osteoporosis.Materials and methods. Retrospective study of 18 patients with primary hyperparathyroidism. Clinical, analytical and BMD data were collected form clinical records. TBS was calculated by reevaluating the already existing BMD images. Patients were classified into two different groups according to their treatment: 1) 10 patients who underwent surgery, in whom TBS was evaluated before (B-S) and after surgery (A-S), and 2) 8 patients who received standard medical treatment, in whom TBS was evaluated with a time-lapse of one year.Results. Basal age, body mass index (BMI), serum calcium, PTH and vitamin 25-OH-D levels, and T-Scores were not significantly different between the two groups. We observed a significant improvement of TBS one year after surgery in the first group (TBS B-S 1.24±0.13 vs TBS A-S 1.29±0.11,p=0.03). A subtle deterioration on TBS was observed one year after standard treatment in the second group (1.25±0.7 vs 1.22±0.7, p=0.29). Overall, surgical patients experienced a TBS increase 4.2%, whilst a decrease of 1.6% was observed in the second group (p=0.026)Conclusion. Bone microarchitecture, measured by TBS, improves after surgery in patients with primary hyperparathyroidism. This parameter seems promising in the evaluation of bone status in primary hyperparathyroidism. Larger and longer follow-up studies deem necessary to better evaluate the potential utilities of using TBS in the assessment of bone quality.

Tilting the lasso by knowledge-based post-processing.

BackgroundIt is useful to incorporate biological knowledge on the role of genetic determinants in predicting an outcome. It is, however, not always feasible to fully elicit this information when the number of determinants is large. We present an approach to overcome this difficulty. First, using half of the available data, a shortlist of potentially interesting determinants are generated. Second, binary indications of biological importance are elicited for this much smaller number of determinants. Third, an analysis is carried out on this shortlist using the second half of the data.ResultsWe show through simulations that, compared with adaptive lasso, this approach leads to models containing more biologically relevant variables, while the prediction mean squared error (PMSE) is comparable or even reduced. We also apply our approach to bone mineral density data, and again final models contain more biologically relevant variables and have reduced PMSEs.ConclusionOur method leads to comparable or improved predictive performance, and models with greater face validity and interpretability with feasible incorporation of biological knowledge into predictive models.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-016-1210-7) contains supplementary material, which is available to authorized users.

CE/BZA effects on bone and quality of life in European postmenopausal women: a pooled analysis

Objectives: To evaluate the efficacy of conjugated estrogens/bazedoxifene (CE/BZA) on bone mineral density (BMD), bone turnover markers (BTM), and menopause-specific quality of life (MENQOL) in European women.Methods: Data through 12 months were pooled from two double-blind, randomized, controlled trials in non-hysterectomized postmenopausal women who received CE/BZA or placebo. Women from European study sites with evaluable BMD (n = 60), BTM (n = 56), and MENQOL questionnaire (n = 236) data were included and compared with 1523 women from US study sites (n = 730 with evaluable data for bone outcomes).Results: At month 12, CE 0.45 mg/BZA 20 mg and CE 0.625 mg/BZA 20 mg, respectively, significantly improved BMD (adjusted difference vs. placebo) in lumbar spine (2.5%, 2.9%; both p ≤ 0.011) and total hip (1.7%, 2.2%, both p ≤ 0.002), significantly improved serum BTMs (osteocalcin: –31.1%, –33.1%; C-telopeptide: –48.5%, –36.8%) vs. placebo (osteocalcin: 6.7%, C-telopeptide: 4.2%; all p < 0.001), and significantly improved MENQOL vasomotor function scores (–2.1, –2.2) vs. placebo (–0.7; both p < 0.001). No significant treatment × subpopulation interactions were observed for any of the outcomes.Conclusions: Twelve-month CE/BZA treatment prevented bone loss and improved vasomotor function in European postmenopausal women. Findings were similar to those in the subpopulation of women enrolled at US study sites.

Applying ethnic-specific bone mineral density T-scores to Chinese women in the USA.

Caucasian reference data are used for osteoporosis classification in US postmenopausal women regardless of race, including Asians who tend to have lower bone mineral density (BMD) than women of white race. This study examines BMD classification by ethnic T-scores for Chinese women. Using BMD data in a Northern California healthcare population, Chinese women aged 50-79years were compared to age-matched white women (1:5 ratio), with femoral neck (FN), total hip (TH), and lumbar spine (LS) T-scores calculated using Caucasian versus Chinese American reference data. Comparing 4039 Chinese and 20,195 white women (44.8% age 50-59years, 37.5% age 60-69years, 17.7% age 70-79years), Chinese women had lower BMD T-scores at the FN, TH, and LS (median T-score 0.29-0.72 units lower across age groups, p < 0.001) using Caucasian reference data. Using Chinese American BMD reference data resulted in an average +0.47, +0.36, and +0.48 units higher FN, TH, and LS T-scores, respectively, reducing the prevalence of osteoporosis (T-score ≤ -2.5) in Chinese women at the FN (16.7 to 6.6%), TH (9.8 to 3.2%), and LS (23.2 to 8.9%); osteoporosis prevalence at any one of three sites fell from 29.6 to 12.6% (22.4 to 8.1% for age 50-64years and 43.2 to 21.0% for age 65-79years). Use of Chinese American BMD reference data yields higher (ethnic) T-scores by 0.4-0.5 units, with a large proportion of Chinese women reclassified from osteoporosis to osteopenia. The reduction in osteoporosis labeling with ethnic T-scores may be relevant for younger Chinese women at low fracture risk.

Bone Mineral Density in Patients With Cirrhosis of Liver Awaiting Liver Transplantation

Background and Aim: There is association between cirrhosis and low bone mineral density (BMD) and limited data regarding prevalence of low BMD in patients awaiting liver transplantation in India. Aim of this study is to determine the prevalence of low BMD and factors associated with it in Indian patients with cirrhosis awaiting liver transplantation. Methods: Patients with Child–Turcotte–Pugh (CTP) class B or C cirrhosis awaiting liver transplantation who fulfilled the inclusion criteria were included in study. BMD measurement at lumbar spine and femoral neck were obtained by Dual Energy X-ray Absorptiometry (DXA). Prevalence of low BMD (defined as T score below −1) among the study population was determined by using Hologic DXA database (Caucasian reference standards) and newly generated ICMR database. Results: Study group comprised of 100 Indian cirrhotic patients awaiting transplantation (79 males). Mean age was 51.2 + 9.7 years with most common etiology of cirrhosis was alcohol (36%). Cirrhosis was CTP class B in 42% and class C in 58%. By using Hologic DXA database and ICMR database prevalence of low BMD was 82% (osteopenia 42% and osteoporosis 40%) and 62% (osteopenia in 43%; osteoporosis in 19%), respectively. Low BMD prevalence was high at the lumbar spine (82%) compared to femoral neck (54%) (P < 0.05). Conclusion: Present study revealed high prevalence of low BMD in Indian patients with cirrhosis awaiting liver transplantation using both database. To decrease complications, correction of osteopenia and osteoporosis in cirrhotic patients should be considered, for which further studies are required. The authors have none to declare.

Clinical effectiveness of bisphosphonates for the prevention of fragility fractures: A systematic review and network meta-analysis

ObjectivesTo assess the relative efficacy of bisphosphonates (alendronate, risedronate, ibandronate and zoledronic acid) for the treatment of osteoporosis using network meta-analysis (NMA). MethodsA systematic review of the literature was conducted using PRISMA guidelines. A network meta-analysis was used to determine the relative efficacy of treatments on four fracture outcomes (vertebral, non-vertebral, hip and wrist) and percentage change in femoral neck bone mineral density (BMD). Treatment effects were modelled using an exchangeable treatment effects model. Heterogeneity in treatment effects was explored by considering potential treatment effect modifiers using meta-regression. Where appropriate, inconsistency between direct and indirect evidence was assessed using node-splitting. Results46 randomised controlled trials (RCTs) were identified. Twenty seven RCTs provided fracture data and 35 RCTs provided BMD data for analysis. Zoledronic acid was associated with the greatest treatment effect on vertebral fractures (HR 0.41, 95% CrI: 0.28, 0.56) and percentage change in BMD (3.21, 95%: CrI 2.52, 3.86) compared to placebo. The greatest treatment effect on non-vertebral and wrist fractures was given by risedronate (HR 0.72, 95%: CrI 0.53, 0.89 and HR 0.77, 95%: CrI 0.44, 1.24, respectively). For hip fractures the greatest treatment effect was given by alendronate (HR 0.78, 95% CrI: 0.44, 1.30). ConclusionsAll treatments examined were associated with beneficial effects on fractures and femoral neck BMD relative to placebo. For vertebral fractures and percentage change in femoral neck BMD the treatment effects were statistically significant for all treatments. Pairwise comparisons between treatments indicated that no active treatment was statistically significantly more effective than any other active treatment for fracture outcomes. There was some heterogeneity in treatment effects between studies suggesting differential treatment effects according to study characteristics; however, there was no evidence of differential treatment effects with respect to gender and age.

Long-term glucocorticoid effect on bone mineral density in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

Patients with 21-hydroxylase deficiency (21OHD) assume a lifelong glucocorticoid (GC) therapy. Excessive GC treatment increases the risk of osteoporosis and bone fractures, even though the role of substitutive therapy is not fully established: we analyzed the effect of GC dose on bone metabolism and bone mineral density (BMD) over time in patients with 21OHD. We studied bone metabolism markers and BMD in 38 adult patients with 21OHD (19-47 years, 24 females and 14 males) and 38 matched healthy control. In 15 patients, BMD data were available at both baseline and after a long-term follow-up. BMD was lower in patients than in controls at lumbar spine (0.961±0.1g/cm(2) vs 1.02±0.113g/cm(2), P=0.014) and femur neck (0.736±0.128g/cm(2) vs 0.828±0.103g/cm(2), P=0.02); otherwise, after height correction, only femoral neck BMD was lower in patients (0.458±0.081g/cm(2) vs 0.498±0.063g/cm(2), P=0.028). In those 21OHD subjects with at least 10 years follow-up, we observed an increase in lumbar BMD (P=0.0429) and a decrease in femur neck BMD values (P=0.004). Cumulative GC dose was not related to bone metabolism or BMD. No patient experienced clinical fragility fractures. BMD values are decreased in patients with 21OHD, which are in part explained by decreased height, but not by the dose of glucocorticoids. Nevertheless, bone status should be carefully monitored in patients with 21OHD.

Body composition analysis by dual-energy X-ray absorptiometry in young preschool children.

Dual-energy X-ray absorptiometry (DXA) is considered a specific method for measuring body composition to assess obesity and osteoporosis, although few studies have been conducted in preschool children. The aim of this study was to provide sex - and age-specific references for bone mineral density (BMD), bone mineral content (BMC), fat mass (FM) and fat-free mass (FFM) normative data for children aged 2 to <6 years. One hundred and eighty seven healthy white children from Buenos Aires City suburbs, Argentina, were studied by the Lunar DPX-L DXA, pediatric software: BMC less head (g), BMD (g/cm2), FM (%) and FFM (g). BMD and BMC increased significantly with age (P<0.0001), but only BMD was significantly different between boys and girls of similar age, being greater for boys (P=0.013). FM was not significantly different among the various age groups of boys and girls. However, the FFM/height was higher in boys and the BMC/FFM was higher in girls. The Z-scores and centile curves were derived separately for each sex and age. Q-Q detrended plots and LMS curves produced robust, unbiased fits that generated references for the 3rd, 50th and 97th percentiles for BMD, BMC, FM and FFM data, respectively. These DXA scans add to the scarcity of accurate measurements of body composition of white young children. The data analyses provided greater accuracy, particularly at the upper and lower ends of the distribution, which is important in clinical settings for identification of children with impaired body composition.

Genome-wide association study using family-based cohorts identifies the WLS and CCDC170/ESR1 loci as associated with bone mineral density.

BackgroundOsteoporosis is a common and debilitating bone disease that is characterised by a low bone mineral density (BMD), a highly heritable trait. Genome-wide association studies (GWAS) have proven to be very successful in identifying common genetic variants associated with BMD adjusted for age, gender and weight, however a large portion of the genetic variance for this trait remains unexplained. There is evidence to suggest significant genetic correlation between body size traits and BMD. It has also recently been suggested that unintended bias can be introduced as a result of adjusting a phenotype for a correlated trait. We performed a GWAS meta-analysis in two populations (total n = 6,696) using BMD data adjusted for only age and gender, in an attempt to identify genetic variants associated with BMD including those that may have potential pleiotropic effects on BMD and body size traits.ResultsWe observed a single variant, rs2566752, associated with spine BMD at the genome-wide significance level in the meta-analysis (P = 3.36 × 10−09). Logistic regression analysis also revealed an association between rs2566752 and fracture rate in one of our study cohorts (P = 0.017, n = 5,654). This is an intronic variant located in the wntless Wnt ligand secretion mediator (WLS) gene (1p31.3), a known BMD locus which encodes an integral component of the Wnt ligand secretion pathway. Bioinformatics analyses of variants in moderate LD with rs2566752 produced strong evidence for a regulatory role for the variants rs72670452, rs17130567 and rs1430738. Expression quantitative trait locus (eQTL) analysis suggested that the variants rs12568456 and rs17130567 are associated with expression of the WLS gene in whole blood, cerebellum and temporal cortex brain tissue (P = 0.034–1.19 × 10−23). Gene-wide association testing using the VErsatile Gene-based Association Study 2 (VEGAS2) software revealed associations between the coiled-coil domain containing 170 (CCDC170) gene, located adjacent to the oestrogen receptor 1 (ESR1) gene, and BMD at the spine, femoral neck and total hip sites (P = 1.0 × 10−06, 2.0 × 10−06 and 2.0 × 10−06 respectively).ConclusionsGenetic variation at the WLS and CCDC170/ESR1 loci were found to be significantly associated with BMD adjusted for only age and gender at the genome-wide level in this meta-analysis.

Associations between genetic variants and the effect of letrozole and exemestane on bone mass and bone turnover

Adjuvant therapy for hormone receptor (HR) positive postmenopausal breast cancer patients includes aromatase inhibitors (AI). While both the non-steroidal AI letrozole and the steroidal AI exemestane decrease serum estrogen concentrations, there is evidence that exemestane may be less detrimental to bone. We hypothesized that single nucleotide polymorphisms (SNP) predict effects of AIs on bone turnover. Early stage HR-positive breast cancer patients were enrolled in a randomized trial of exemestane versus letrozole. Effects of AI on bone mineral density (BMD) and bone turnover markers (BTM), and associations between SNPs in 24 candidate genes and changes in BMD or BTM were determined. Of the 503 enrolled patients, paired BMD data were available for 123 and 101 patients treated with letrozole and exemestane, respectively, and paired BTM data were available for 175 and 173 patients, respectively. The mean change in lumbar spine BMD was significantly greater for letrozole-treated (-3.2%) compared to exemestane-treated patients (-1.0%) (p=0.0016). Urine N-telopeptide was significantly increased in patients treated with exemestane (p=0.001) but not letrozole. Two SNPs (rs4870061 and rs9322335) in ESR1 and one SNP (rs10140457) in ESR2 were associated with decreased BMD in letrozole-treated patients. In the exemestane-treated patients, SNPs in ESR1 (Rs2813543) and CYP19A1 (Rs6493497) were associated with decreased bone density. Exemestane had a less negative impact on bone density compared to letrozole, and the effects of AI therapy on bone may be impacted by genetic variants in the ER pathway.

Localized femoral BMD T-scores according to the fracture site of hip and the evaluation of the sensitivity of the high risk group designated by FRAX® in hip fracture patients

ObjectivesIn hip fracture patients, studies about relevance between localized proximal femoral bone mineral density (BMD) and the fracture sites of hip are very rare. We compared T-scores of each femoral neck and trochanteric portion in a femoral neck fracture patients group (NFP) and in an intertrochanteric fracture patients group (IFP). Our hypothesis is that the T-score of neck portion is lower than the T-score of trochanteric portion in NFP and vice versa. We evaluated how the FRAX® probability is meaningful in hip fracture patients. Methods180 hip fracture patients were included and evaluated by BMD. We compared the average of T-scores between neck and trochanteric portion in each group. Differences between the regional T-score of neck and trochanteric portion were calculated in each patient and compared between two groups. We calculated the FRAX® probability in each patient and compared between two groups. ResultsFor the two groups, the average of the T-scores in neck portion was lower than the T-scores in trochanteric portion. In NFP, the average of difference between the regional BMD of neck portion and trochanteric portion was greater than that of IFP. FRAX® probability of hip fracture in NFP was higher than that in IFP. 77.3% of NFP and 80.8% of IFP were classified as high risk group for hip fracture. ConclusionThe localized femoral BMD data supports that localized femoral T-scores are relevant to the fracture sites of the hip. The high risk group designated by FRAX® is a sensitive tool to evaluate hip fractures in osteoporotic patients.

Does Increased Coefficient of Friction of Highly Porous Metal Increase Initial Stability at the Acetabular Interface?

BackgroundHighly porous metal acetabular components illustrate a decreased rate of aseptic loosening in short-term follow-up compared with previous registry data. This study compared the effect of component surface roughness at the bone–implant interface and the quality of the bone on initial pressfit stability. The null hypothesis is that a standard porous coated acetabular cup would show no difference in initial stability as compared with a highly porous acetabular cup when subjected to a bending moment. Second, would bone mineral density (BMD) be a significant variable under these test conditions. MethodsIn a cadaveric model, acetabular cup micromotion was measured during a 1-time cantilever bending moment applied to 2 generations of pressfit acetabular components. BMD data were also obtained from the femoral necks available for associated specimen. ResultsThe mean bending moment at 150 μm was not found to be significantly different for Gription (24.6 ± 14.0 N m) cups vs Porocoat (25 ± 10.2 N m; P > .84). The peak bending moment tolerated by Gription cups (33.9 ± 20.3 N m) was not found to be significantly different from Porocoat (33.5 ± 12.2 N m; P > .92). No correlation between BMD and bending moment at 150 μm of displacement could be identified. ConclusionThe coefficient of friction provided by highly porous metal acetabular shells used in this study did not provide better resistance to migration under bending load when compared with a standard porous coated component.

74. Bone density in heart transplanted patients in Kingdom of Saudi Arabia

Background Osteopenia and osteoporosis are prevalent in heart transplant candidates. Early, rapid bone loss is a well documented complication of steroid administration after heart transplantation. Purpose of our study was to determine incidence of osteopenia and osteoporosis in heart transplant candidates and heart transplanted patients and association with demographics characteristics, vitamin D deficiency, renal and thyroid function and long-term use of corticosteroids and immunosuppressive drugs. Methods This is a non-randomized, retrospective, observational study. Medical files of all consecutive heart transplanted patients since the beginning of 2009 until August 2013 were reviewed. Results Pre-transplant bone mineral density data (BMD) were available in 63 heart transplant recipients; 54 and 32, respectively, also had 1- and 2-years post-transplant BMD data. Pre-transplant lumbar spine (LS) osteopenia or osteoporosis was 35% and 8% compared with 30% and 3% in femoral neck (FN). We found significant decrease in pre-transplant BMD compared with BMD data 1 year after heart transplantation in LS (1.034 ± 0.17 vs.0.994 ± 0.13; p p p = 0.98) and FN ( p = 0.11), respectively. BMD in LS and FN were significantly lower in female (0.92 ± 0.157 vs. 1.06 ± 0.163, p = 0.009 and 0.869 ± 0.11 vs. 0.985 ± 0.147, p = 0.017) despite younger age (26 ± 10 vs. 39 ± 13 year, p Conclusion Anti-resorptive agents, calcium and vitamin D can reduce post transplant bone loss but to eliminate major contributing factor for development of osteoporosis, our patients should undergo steroid weaning 6–9 months after transplantation.

High Prevalence of Low Bone Mineral Density and Substantial Bone Loss over 4 Years Among HIV-Infected Persons in the Era of Modern Antiretroviral Therapy.

HIV-infected persons are living longer on combination antiretroviral therapy (cART) but experiencing more comorbidities including low bone mineral density (BMD). Using data from the Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (SUN Study), we determined the prevalence of low BMD (T-score below one standard deviation of the reference mean) and compared it with matched controls from the National Health and Nutrition Examination Survey (NHANES). We also assessed 4-year longitudinal BMD changes among participants virologically suppressed on cART. Of 653 participants included in this analysis (77% male, 29% black, median age 41 years, median CD4(+) cell count 464 cells/mm(3), 89% with HIV RNA <400 copies/ml), 51% and 10% had baseline osteopenia and osteoporosis, respectively. Low BMD at the femoral neck was significantly more prevalent than for the NHANES controls (47% versus 29%, p<0.001). Lower body mass index, nonwhite race, longer tenofovir exposure, older age, being unemployed or retired, and lower apolipoprotein E were independently associated with baseline osteoporosis. Among 170 participants virologically suppressed on cART and with longitudinal BMD data, 31% experienced substantial bone loss (≥5% BMD decline from baseline) over 4 years. Female sex, current smoking, and longer stavudine use were more common among participants who had substantial bone loss, although these variables failed to reach statistical significance. Low BMD was highly prevalent among HIV-infected persons. One-third of participants experienced substantial bone loss despite cART, suggesting the need for monitoring and potential clinical interventions.