Lower Lumbar Spine Bone Mineral Research Articles

Bidirectional mediation of bone mineral density and brain atrophy on their associations with gait variability

This mediation analysis aimed to investigate the associations among areal bone mineral density, mobility-related brain atrophy, and specific gait patterns. A total of 595 participants from the Taizhou Imaging Study, who underwent both gait and bone mineral density measurements, were included in this cross-sectional analysis. We used a wearable gait tracking device to collect quantitative gait parameters and then summarized them into independent gait domains with factor analysis. Bone mineral density was measured in the lumbar spine, femoral neck, and total hip using dual-energy X-ray absorptiometry. Magnetic resonance images were obtained on a 3.0-Tesla scanner, and the volumes of brain regions related to mobility were computed using FreeSurfer. Lower bone mineral density was found to be associated with higher gait variability, especially at the site of the lumbar spine (β = 0.174, FDR = 0.001). Besides, higher gait variability was correlated with mobility-related brain atrophy, like the primary motor cortex (β = 0.147, FDR = 0.006), sensorimotor cortex (β = 0.153, FDR = 0.006), and entorhinal cortex (β = 0.106, FDR = 0.043). Bidirectional mediation analysis revealed that regional brain atrophy contributed to higher gait variability through the low lumbar spine bone mineral density (for the primary motor cortex, P = 0.018; for the sensorimotor cortex, P = 0.010) and the low lumbar spine bone mineral density contributed to higher gait variability through the primary motor and sensorimotor cortices (P = 0.026 and 0.010, respectively).

Bone mineral density in adults with arthrogryposis multiplex congenita: a retrospective cohort analysis

The primary objective of this study was to evaluate the prevalence of low femoral and lumbar spine bone mineral density (BMD) in adults with arthrogryposis multiplex congenita (AMC). We performed a retrospective cohort analysis of adults with AMC who were enrolled in the French Reference Center for AMC and in the Pediatric and Adult Registry for Arthrogryposis (PARART, NCT05673265). Patients who had undergone dual-energy X-ray absorptiometry (DXA) and/or vitamin D testing were included in the analysis. Fifty-one patients (mean age, 32.9 ± 12.6 years) were included; 46 had undergone DXA. Thirty-two (32/51, 62.7%) patients had Amyoplasia, and 19 (19/51, 37.3%) had other types of AMC (18 distal arthrogryposis, 1 Larsen). Six patients (6/42, 14.3%) had a lumbar BMD Z score less than − 2. The mean lumbar spine Z score (− 0.03 ± 1.6) was not significantly lower than the expected BMD Z score in the general population. Nine (9/40, 22.5%) and 10 (10/40, 25.0%) patients had femoral neck and total hip BMD Z scores less than − 2, respectively. The mean femoral neck (− 1.1 ± 1.1) and total hip (− 1.2 ± 1.2) BMD Z scores in patients with AMC were significantly lower than expected in the general population (p < 0.001). Femoral neck BMD correlated with height (rs = 0.39, p = 0.01), age (rs = − 0.315, p = 0.48); total hip BMD correlated with height (rs = 0.331, p = 0.04) and calcium levels (rs = 0.41, p = 0.04). Twenty-five patients (25/51, 49.0%) reported 39 fractures. Thirty-one (31/36, 86.1%) patients had 25-hydroxyvitamin D levels less than 75 nmol/l, and 6 (6/36, 16.7%) had 25-hydroxyvitamin D levels less than 75 nmol/l. Adults with AMC had lower hip BMD than expected for their age, and they more frequently showed vitamin D insufficiency. Screening for low BMD by DXA and adding vitamin D supplementation when vitamin D status is insufficient should be considered in adults with AMC, especially if there is a history of falls or fractures.

PLS3 Mutations in X-Linked Osteoporosis: Clinical and Genetic Features in Five New Families.

Childhood-onset osteoporosis is a rare but clinically significant condition. Studies have shown pathogenic variants in more than 20 different genes as causative for childhood-onset primary osteoporosis. The X-chromosomal PLS3, encoding Plastin-3, is one of the more recently identified genes. In this study, we describe five new families from four different European countries with PLS3-related skeletal fragility. The index cases were all hemizygous males presenting with long bone and vertebral body compression fractures. All patients had low lumbar spine bone mineral density (BMD). The age at the first clinical fracture ranged from 1.5 to 13&nbsp;years old. Three of the identified PLS3 variants were stop-gain variants and two were deletions involving either a part or all exons of the gene. In four families the variant was inherited from the mother. All heterozygous women reported here had normal BMD and no bone fractures. Four patients received bisphosphonate treatment with good results, showing a lumbar spine BMD increment and vertebral body reshaping after 10months to 2years of treatment. Our findings expand the genetic spectrum of PLS3-related osteoporosis. Our report also shows that early treatment with bisphosphonates may influence the disease course and reduce the progression of osteoporosis, highlighting the importance of early diagnosis for prompt intervention and appropriate genetic counseling.

Osteosarcopenia later in life: Prevalence and associated risk factors

The identification of risk factors for osteosarcopenia in older adults is important for planning preventative strategies in clinical practice. Therefore, our study aimed to investigate the prevalence and risk factors associated with osteosarcopenia in older adults using different diagnostic criteria. The sample included 171 community-dwelling older adults with a mean age of 79.4±5.9 years and mean body mass index of 25.67±4.70kg/m2. We analyzed sociodemographic, biomarkers, lifestyle, and health condition data from participants of the "Projeto Idosos - Goiânia" cohort study. The outcome osteosarcopenia was defined as the simultaneous occurrence of sarcopenia and osteopenia. Osteopenia was diagnosed by low lumbar spine bone mineral density (BMD) using dual-energy X-ray absorptiometry (DEXA). Sarcopenia was diagnosed using handgrip dynamometry and appendicular skeletal mass index assessed by DEXA following the criteria of the two European consensuses on sarcopenia (2010 and 2018). Two osteosarcopenia outcome variables were evaluated: OsteoSarc1 and OsteoSarc2 using the 2010 and 2018 European sarcopenia consensus criteria, respectively. Multivariate Poisson regression analysis was used to calculate the prevalence ratios (PRs). The prevalence of OsteoSarc1 and OsteoSarc2 were 12.8% and 7.2%, respectively, with no significant gender differences. OsteoSarc1 was associated with low potassium (PR: 3.39, 95% confidence interval [CI]: 1.10-10.43) and malnutrition (PR: 3.84, 95% CI: 1.78-8.30). OsteoSarc2 was associated with being ≥80 years (PR: 7.64, 95% CI: 1.57-37.07), >4 years of education (PR: 3.25, 95% CI: 1.03-10.22), alcohol consumption (PR: 2.41, 95% CI: 1.01-5.77), low potassium (PR: 2.22, 95% CI: 1.45-6.87), low serum vitamin D (PR: 4.47, 95% CI: 1.68-11.88), and malnutrition (PR: 5.00, 95% CI: 1.06-23.51). OsteoSarc1 had a higher prevalence. The risk factors associated with the two outcomes were malnutrition and potassium level, as well as other risk factors, such as alcohol consumption and low vitamin D level. These findings may contribute to the prevention or treatment of this health condition in older adults.

Causal Effect of Serum Magnesium on Osteoporosis and Cardiometabolic Diseases.

Serum magnesium is associated with osteoporosis and cardiometabolic diseases, but their causal associations remain elusive. We used the two-sample Mendelian randomization (MR) study to explore the causal roles of serum magnesium on osteoporosis and cardiometabolic diseases by using the aggregated genome-wide association studies (GWASs). Six single-nucleotide polymorphisms (SNPs, p < 5 × 10−8) associated with serum magnesium concentrations were all used as instrumental variables. A genetic predisposition to higher serum magnesium concentrations was inversely associated with lower lumbar spine bone mineral density (BMD, beta-estimate: −1.982, 95% CI: −3.328 to −0.635, SE: 0.687, p = 0.004), which was further confirmed by multiple sensitivity analyses. There was limited evidence of associations between serum magnesium and type 2 diabetes, coronary artery disease, heart failure, and atrial fibrillation. This work provided strong evidence that genetically increased serum magnesium concentrations were causally associated with low lumbar spine BMD and suggested that serum magnesium concentrations may be crucial to prevent osteoporosis.

A Validated Risk Prediction Model for Bone Fragility in Children with Acute Lymphoblastic Leukemia

▪IntroductionDue to bone fragility, children with acute lymphoblastic leukemia (ALL) have a 6-fold greater fracture risk during therapy compared to peers. Osteoporotic fractures are a concern, as they lead to adverse health outcomes including pain, loss of height due to vertebral deformity, and (transient) disability. In previous studies, lower lumbar spine bone mineral density (LS BMD) at ALL diagnosis was found to be prognostic for the occurrence of future fractures. However, routinely performing dual-energy X-ray absorptiometry (DXA) in each newly diagnosed child is not universally feasible. The aim of this study is to develop and validate an easy to use clinical risk prediction model for low lumbar spine bone mineral density (LS BMD Z-score ≤-2.0) at diagnosis, as an important indicator for fracture risk and further treatment-related BMD aggravation.MethodsChildren treated for ALL according to the Dutch Childhood Oncology Group (DCOG-ALL9; model development) protocol (n=249; median age: 7.6 years [range: 4.0-16.6 years]) and children from the Canadian STeroid‐Associated Osteoporosis in the Pediatric Population (STOPP; model validation) cohort (n=99; median age: 7.3 years [range: 4.0-16.6 years]) were included in this study.Multivariable logistic regression analyses were used to develop the prediction model for low LS BMD at diagnosis, defined as a Z-score ≤-2.0 (evaluated with DXA). Candidate predictors included sex, age, height and weight Z-scores at diagnosis of ALL. The receiver operating characteristic area under the curve (AUC) was assessed for model performance.To confirm the association between low LS BMD at diagnosis and bone fragility during and shortly following ALL therapy, we performed multivariable logistic regression analyses. The dependent variables were: one or more symptomatic fractures from ALL diagnosis to 12 months following treatment cessation and low LS BMD at cessation of treatment.In addition, because of homogeneity in the intended glucocorticoid doses, we combined data from the DCOG-ALL9 and STOPP cohorts and performed multivariable pooled cohort analyses (meta-analysis). Potential associations between the six-month cumulative glucocorticoid dose and fractures that occurred in the first year of therapy, were explored. Furthermore, we assessed potential associations between the cumulative glucocorticoid dose at cessation of therapy, and the endpoints ‘low LS BMD at therapy cessation’ and ‘fractures that occurred during treatment and within 12 months following treatment cessation’.ResultsThe prediction model for low LS BMD at diagnosis included weight Z-scores (β = -0.70) and age (β = -0.10) at diagnosis. This model had an AUC of 0.71 (0.63 to 0.78) in the DCOG-ALL9 cohort, and resulted in correct identification of 71% of patients with low LS BMD at ALL diagnosis. Validation on the STOPP cohort showed an AUC of 0.74 (95% CI = 0.63 to 0.84). To calculate the probability of low LS BMD at ALL diagnosis for an individual patient, an online calculator is available at http://lsbmd-risk-calculator.azurewebsites.net/We confirmed that low LS BMD at diagnosis is associated with LS BMD at treatment cessation (OR = 5.9; 95% CI = 3.2 to 10.9) and with symptomatic fractures (OR = 1.7; 95% CI = 1.3 to 2.4) that occurred from diagnosis until 12 months following treatment cessation.In pooled meta-analysis, lower LS BMD at diagnosis (OR = 1.6, 95% CI = 1.1 to 2.4) and six-month cumulative glucocorticoid dose (OR = 1.9, 95% CI = 1.1 to 3.3, for every gram increase) were associated with symptomatic fractures that occurred in the first year of therapy. Higher cumulative glucocorticoid dose at cessation of therapy (OR = 1.5, 95% CI = 1.2 to 2.0, for every gram increase), lower LS BMD Z-scores at diagnosis (OR = 7.9, 95% CI = 4.8 to 13.1) and higher age at diagnosis (OR = 1.6, 95% CI = 1.4 to 1.8), were associated with low LS BMD at cessation of therapy.ConclusionWe developed and successfully validated a risk prediction model for low LSBMD at diagnosis in children aged 4-18 years with ALL. This is important because low LS BMD at diagnosis was strongly associated with bone fragility and fractures during and shortly following treatment for ALL. Our easy to use prediction model, can facilitate awareness and early identification of bone fragility in individual pediatric ALL patients, without performing DXA examination. DisclosuresNo relevant conflicts of interest to declare.

Pubertal Suppression, Bone Mass, and Body Composition in Youth With Gender Dysphoria.

Puberty onset and development contribute substantially to adolescents' bone mass and body composition. Our objective with this study was to examine the effects of gonadotropin-releasing hormone agonists (GnRHa) on these puberty-induced changes among youth with gender dysphoria (GD). Medical records of the endocrine diversity clinic in an academic children's hospital were reviewed for youth with GD seen from January 2006 to April 2017 with at least 1 baseline dual-energy radiograph absorptiometry measurement. At baseline, transgender females had lower lumbar spine (LS) and left total hip (LTH) areal bone mineral density (aBMD) and LS bone mineral apparent density (BMAD) z scores. Only 44.7% of transgender youth were vitamin D sufficient. Baseline vitamin D status was associated with LS, LTH aBMD, and LS BMAD z scores. Post-GnRHa assessments revealed a significant drop in LS and LTH aBMD z scores (transgender males and transgender females) without fractures and LS BMAD (transgender males), an increase in gynoid (fat percentage), and android (fat percentage) (transgender males and transgender females), and no changes in BMI z score. GnRHa monotherapy negatively affected bone mineral density of youth with GD without evidence of fractures or changes in BMI z score. Transgender youth body fat redistribution (android versus gynoid) were in keeping with their affirmed gender. The majority of transgender youth had vitamin D insufficiency or deficiency with baseline status associated with bone mineral density. Vitamin D supplementation should be considered for all youth with GD.

The Accuracy of Incident Vertebral Fracture Detection in Children Using Targeted Case-Finding Approaches.

Vertebral fractures are clinically important sequelae of a wide array of pediatric diseases. In this study, we examined the accuracy of case-finding strategies for detecting incident vertebral fractures (IVF) over 2 years in glucocorticoid-treated children (n=343) with leukemia, rheumatic disorders, or nephrotic syndrome. Two clinical situations were addressed: the prevalent vertebral fracture (PVF) scenario (when baseline PVF status was known), which assessed the utility of PVF and low lumbar spine bone mineral density (LS BMD; Z-score <-1.4), and the non-PVF scenario (when PVF status was unknown), which evaluated low LS BMD and back pain. LS BMD was measured by dual-energy X-ray absorptiometry, vertebral fractures were quantified on spine radiographs using the modified Genant semiquantitative method, and back pain was assessed by patient report. Forty-four patients (12.8%) had IVF. In the PVF scenario, both low LS BMD and PVF were significant predictors of IVF. Using PVF to determine which patients should have radiographs, 11% would undergo radiography (95% confidence interval [CI] 8-15) with 46% of IVF (95% CI 30-61) detected. Sensitivity would be higher with a strategy of PVF or low LS BMD at baseline (73%; 95% CI 57-85) but would require radiographs in 37% of children (95% CI 32-42). In the non-PVF scenario, the strategy of low LS BMD and back pain produced the highest specificity of any non-PVF model at 87% (95% CI 83-91), the greatest overall accuracy at 82% (95% CI 78-86), and the lowest radiography rate at 17% (95% CI 14-22). Low LS BMD or back pain in the non-PVF scenario produced the highest sensitivity at 82% (95% CI 67-92), but required radiographs in 65% (95% CI 60-70). These results provide guidance for targeting spine radiography in children at risk for IVF. © 2021 American Society for Bone and Mineral Research (ASBMR).

A Validated Risk Prediction Model for Bone Fragility in Children With Acute Lymphoblastic Leukemia.

Although bone fragility may already be present at diagnosis of pediatric acute lymphoblastic leukemia (ALL), routine performance of dual-energy X-ray absorptiometry (DXA) in every child is not universally feasible. The aim of this study was to develop and validate a risk prediction model for low lumbar spine bone mineral density (LS BMD Z-score ≤ -2.0) at diagnosis, as an important indicator for fracture risk and further treatment-related BMD aggravation. Children with ALL (4-18 years), treated according to the Dutch Childhood Oncology Group protocol (DCOG-ALL9; model development; n=249) and children from the Canadian Steroid-Associated Osteoporosis in the Pediatric Population cohort (STOPP; validation; n=99) were included in this study. Multivariable logistic regression analyses were used to develop the prediction model and to confirm the association of low LS BMD at diagnosis with symptomatic fractures during and shortly after cessation of ALL treatment. The area under the receiver operating characteristic curve (AUC) was used to assess model performance. The prediction model for low LS BMD at diagnosis using weight (β=-0.70) and age (β=-0.10) at diagnosis revealed an AUC of 0.71 (95% CI, 0.63-0.78) in DCOG-ALL9 and 0.74 (95% CI, 0.63-0.84) in STOPP, and resulted in correct identification of 71% of the patients with low LS BMD. We confirmed that low LS BMD at diagnosis is associated with LS BMD at treatment cessation (OR 5.9; 95% CI, 3.2-10.9) and with symptomatic fractures (OR 1.7; 95% CI, 1.3-2.4) that occurred between diagnosis and 12 months following treatment cessation. In meta-analysis, LS BMD at diagnosis (OR 1.6; 95% CI, 1.1-2.4) and the 6-month cumulative glucocorticoid dose (OR 1.9; 95% CI, 1.1-3.2) were associated with fractures that occurred in the first year of treatment. In summary, a prediction model for identifying pediatric ALL patients with low LS BMD at diagnosis, as an important indicator for bone fragility, was successfully developed and validated. This can facilitate identification of future bone fragility in individual pediatric ALL patients. © 2021 American Society for Bone and Mineral Research (ASBMR).

Association between Geriatric Nutrition Risk Index and Skeletal Muscle Mass Index with Bone Mineral Density in Post-Menopausal Women Who Have Undergone Total Thyroidectomy.

Background: Osteoporosis is highly prevalent in postmenopausal women and may result in fractures and disabilities. Total thyroidectomy has also been associated with loss of bone mass. The aim of this cross-sectional study was to evaluate associations among nutritional status, skeletal muscle index and markers of bone turnover to bone mineral density in postmenopausal women who had undergone total thyroidectomy. Methods: Fifty postmenopausal women who had undergone total thyroidectomy were included. Body composition was measured using dual-energy X-ray absorptiometry (DXA). The Geriatric Nutritional Risk Index (GNRI) was calculated using baseline body weight and serum albumin level. Skeletal muscle mass index was calculated as the appendicular skeletal muscle mass (ASM) divided by the height squared and assessed using DXA. Results. Multivariate stepwise linear regression analysis showed that a low GNRI was significantly associated with low lumbar spine bone mineral density (BMD) and T-score, and that a low ASM/height2 was significantly associated with low femoral neck BMD and T-score. A low vitamin D level was significantly associated with low femoral neck BMD and T-score and low total hip BMD and T-score. A high bone alkaline phosphatase (ALP) level was significantly associated with low femoral neck T-score and low total hip BMD and T-score. A low insulin-like growth factor-1 (IGF-1) was significantly associated with low total hip BMD and T-score. Conclusion: In the postmenopausal women who had undergone total thyroidectomy in this study, BMD was positively associated with GNRI, skeletal muscle mass index, and levels of vitamin D and serum IGF-1, and inversely associated with bone ALP level. Nutritional status, skeletal muscle mass index and bone turnover biomarkers can be used to early identify patients with a high risk of osteoporosis in this high-risk group.

Effects of supervised high-intensity resistance and impact training or machine-based isometric training on regional bone geometry and strength in middle-aged and older men with low bone mass: The LIFTMOR-M semi-randomised controlled trial.

Few data exist on the effects of bone-targeted exercise on geometric and biomechanical indices of bone strength in men. The Lifting Intervention For Training Muscle and Osteoporosis Rehabilitation for Men (LIFTMOR-M) trial was designed to compare the efficacy and safety of two novel, supervised, twice-weekly, high-intensity exercise programs in middle-aged and older men with osteopenia and osteoporosis on musculoskeletal health and risk factors related to falls and fractures. The current report includes secondary outcomes of the LIFTMOR-M exercise intervention trial. Our goal was to determine the effects of two supervised, twice-weekly, high-intensity exercise programs on bone geometry and strength of the proximal femur, and distal and proximal sites of the tibia and radius in middle-aged and older men with osteopenia and osteoporosis. Generally-healthy men (≥45years), with low lumbar spine (LS) and/or proximal femur areal bone mineral density (aBMD), were recruited from the community. Eligible participants were randomised to either eight months of twice-weekly supervised high-intensity progressive resistance and impact training (HiRIT) or supervised machine-based isometric axial compression (IAC) exercise training. Intervention group outcomes were compared at baseline and eight months with a matched but non-randomised control group (CON) who self-selected to usual activities. DXA scans (Medix DR, Medilink, France) of the skeletally non-dominant proximal femur were analysed using 3D hip software (DMS Group, France) to derive femoral neck (FN) and total hip (TH) bone mineral content (BMC), volume, and volumetric bone mineral density (vBMD) for total, trabecular and cortical bone compartments. Total FN cortical thickness was determined as well as anterior, posterior, lateral and medial subregions. pQCT scans (XCT-3000, Stratec, Germany) of the 4 and 38% sites of the tibia, and 4 and 66% sites of the radius were conducted to determine a range of geometric and bone structural strength indices. Intervention effects were examined using univariate ANCOVA of percent change, and repeated measures ANCOVA of raw baseline and follow-up data, controlling for initial values, using intention-to-treat and per-protocol approaches. Ninety-three men (67.1±7.5yrs, 175.2±6.7cm, 82.1±11.6kg, 26.7±3.5kg/m2) with lower than average aBMD (LS T-score -0.06±1.04, FN T-score -1.58±0.58, TH T-score -1.00±0.58) were recruited, and designated CON (n=26) or randomised to HiRIT (n=34) or IAC (n=33). Compliance to the supervised exercise programs did not differ (HiRIT 77.8±16.6% versus IAC 78.5±14.8%, p=0.872). HiRIT improved medial FN cortical thickness compared with CON (5.6±1.7% versus -0.1±1.9%, p=0.028) and IAC (5.6±1.7% versus 0.7±1.7%, p=0.044). Distal tibia total BMC, vBMD, area and bone strength index, and trabecular BMC and bone strength index all declined for CON compared with maintenance for both HiRIT and IAC (all p<0.05). HiRIT maintained distal tibia trabecular area compared with a loss in CON (0.2±0.5% versus -1.6±0.5%, p=0.013). HiRIT and IAC maintained distal radius total BMC compared with loss in CON (-0.1±0.7% versus -3.7±0.8%, p=0.001; 1.3±0.7% versus -3.7±0.8%, p<0.001, respectively). HiRIT and IAC maintained distal radius total bone strength index compared with loss in CON (1.4±1.4% versus -6.0±1.6%, p=0.001; 0.2±1.3% versus -6.0±1.6%, p=0.004, respectively). HiRIT reduced proximal radius cortical area compared with CON (-3.1±1.0% versus 1.1±1.2%, p=0.011) and IAC (-3.1±1.0% versus -0.2±1.0%, p=0.042). No between-group differences were detected in any pQCT-derived bone outcome at the diaphyseal tibia 38% site. Findings indicate that supervised HiRIT provides a positive stimulus to cortical bone at the medial FN compared with supervised IAC exercise, and both HiRIT and IAC preserve bone strength at the distal tibia and distal radius. These effects may translate into a reduced risk of lower and upper extremity fracture in middle-aged and older men with low bone mass.

Tu1982 - Prevalence of Low Lumbar Spine Bone Mineral Density in Pediatric Patients with Celiac Disease: A Retrospective Cohort Study

Tu1982 - Prevalence of Low Lumbar Spine Bone Mineral Density in Pediatric Patients with Celiac Disease: A Retrospective Cohort Study

Determinants of bone mineral density in young Australian women; results from the Safe-D study.

The implementation of prevention strategies during young adulthood may be crucial for osteoporosis prevention in later life, yet literature examining the determinants of bone health in premenopausal women is limited. We aimed to assess determinants of bone health, including serum 25-hydroxyvitamin D (25OHD), in females aged 16-25years, living in Victoria, Australia, recruited through Facebook advertising. Serum 25OHD was measured by liquid chromatography-tandem mass spectrometry and bone health was measured using dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) in 326 participants. Mean (± standard deviation) serum 25OHD was 69±28nmol/L and the prevalence of vitamin D deficiency (serum 25OHD <50nmol/L) was 26%. Seven percent of participants (n=23) reported taking a vitamin D supplement. Two percent of participants had low lumbar spine bone mineral density (Z-score <-2.0), 5% at the hip and 7% at the femoral neck. Serum 25OHD levels were not associated with DXA bone parameters, nor with pQCT bone parameters. Most bone parameters were positively associated with height and lean mass. Vitamin D status was not associated with bone health in young women in the current study. Our findings suggest that targeting other modifiable factors, such as lean body mass, is likely to be beneficial to bone health in young women. Longitudinal studies examining the association between vitamin D status and bone health in young women are necessary to confirm our findings. In addition, whether raising 25OHD levels is advantageous for young women's bone health is yet to be determined.

Fragility Fracture Incidence in Chronic Obstructive Pulmonary Disease (COPD) Patients Associates With Nanoporosity, Mineral/Matrix Ratio, and Pyridinoline Content at Actively Bone-Forming Trabecular Surfaces

Chronic obstructive pulmonary disease (COPD) is associated with low areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry (DXA) and altered microstructure by bone histomorphometry and micro-computed tomography. Nevertheless, not all COPD patients sustain fragility fractures. In the present study, we used Raman microspectroscopic analysis to determine bone compositional properties at actively forming trabecular surfaces (based on double fluorescent labels) in iliac crest biopsies from 19 postmenopausal COPD patients (aged 62.1 ± 7.3 years). Additionally, we analyzed trabecular geometrical centers, representing tissue much older than the forming surfaces. Eight of the patients had sustained fragility fractures, and 13 had received treatment with inhaled glucocorticoids. None of the patients had taken oral glucocorticoids. The monitored parameters were mineral/matrix ratio (MM), nanoporosity, and relative glycosaminoglycan (GAG), lipid, and pyridinoline contents (PYD). There were no significant differences between the glucocorticoid-treated patients and those who did not receive any. On the other hand, COPD patients sustaining fragility fractures had significantly lower nanoporosity and higher MM and PYD values compared with COPD patients without fragility fractures. To the best of our knowledge, this is the first study to discriminate between fracture and non-fracture COPD patients based on differences in the material properties of bone matrix. Given that these bone material compositional differences are evident close to the cement line (a major bone interface), they may contribute to the inferior bone toughness and coupled with the lower lumbar spine bone mineral density values result in the fragility fractures prevalent in these patients. © 2016 American Society for Bone and Mineral Research.

High Vegetable Protein Diet is Associated with Low Lumbar Spine Bone Mineral Density in Amenorrheic Athletes

PURPOSE: We have reported that amenorrheic athletes (AA) have a higher intake of dietary fiber compared to eumenorrheic athletes (EA) and non-athletes (NA), which is negatively associated with lumbar BMD. High fiber diets are rich in vegetable proteins, and food rich in vegetable protein has high concentrations of phytic acid and isoflavones, and low concentrations of saturated fatty acids (SFA). Fiber and isoflavones are reported to have negative associations with serum estrogen. We hypothesized that a diet high in vegetable protein may contribute to low BMD in AA. METHODS: 4-day food records and serum samples were collected from 68 AA, 24 EA, and 26 NA 14–23 yo. Energy availability was calculated as (energy intake- energy expenditure)/ fat free mass. DXA was used to assess lumbar spine BMD. RESULTS: EA were younger than AA and NA (p=.04), and AA had lower BMI (p=.04). Exercise activity did not differ in AA and EA. There was no difference in energy availability among groups. Compared with EA and NA, AA had higher intake of fiber (AA=34.8±15.3; EA=22.5±11.7; NA=17.2±6.6g; p<.0001), phytic acid (AA=1276±621; EA=621±384; NA=700±370mg; p<.0001), and vegetable protein (AA=45.6±19.2; EA=31.9±12.9; NA=26.8±8.8g; p<.0001). Intake of isoflavones was higher in AA than NA (genistein: AA=7.4±10.1; EA=2.7±6.7; NA=1.4±4.2g; p=.003; daidzein: AA=5.9±8.0; EA=2.0±4.8; NA=1.0±2.9g; p=.0002). AA had a lower intake of % calories from SFA than NA (AA=8.6±2.6; EA=9.8±2.2; NA=10.6±2.6; p=.002). After controlling for menstrual status, calcium intake and serum vitamin D, spine Z-scores were associated inversely with vegetable protein (SE=−.34, p=.006), phytic acid (SE=−.32, p=.005), genistein (SE=−.29, p=.003), and daidzein (SE=−.28, p=.005) ; and positively with %SFA after also controlling for fiber (SE=.26,p=.02). CONCLUSIONS: We found a higher vegetable protein diet in AA than EA and C, associated inversely with spine Z-scores. Because phytic acid and dietary fiber decrease energy and mineral absorption, some AA may have adequate energy intake but be nutrient deficient. Furthermore, the ability of dietary fiber and isoflavones to decrease estrogen may affect BMD. Studies examining nutrients affecting bone metabolism and estrogen levels in female athletes are needed to develop optimal dietary recommendations.

Estimating the prevalence of low-lumbar spine bone mineral density in older men with or at risk for HIV infection using normal mixture models

Bone mineral density decreases naturally as we age because existing bone tissue is reabsorbed by the body faster than new bone tissue is synthesized. When this occurs, bones lose calcium and other minerals. What is normal bone mineral density for men 50 years and older? Suitable diagnostic cutoff values for men are less well defined than for women. In this paper, we propose using normal mixture models to estimate the prevalence of low-lumbar spine bone mineral density in men 50 years and older with or at risk for human immunodeficiency virus infection when normal values of bone mineral density are not generally known. The Box–Cox power transformation is used to determine which transformation best suits normal mixture distributions. Parametric bootstrap tests are used to determine the number of mixture components and to determine whether the mixture components are homoscedastic or heteroscedastic.

Polymorphisms in the P2X7 receptor gene are associated with low lumbar spine bone mineral density and accelerated bone loss in post-menopausal women

The P2X7 receptor gene (P2RX7) is highly polymorphic with five previously described loss-of-function (LOF) single-nucleotide polymorphisms (SNP; c.151+1G>T, c.946G>A, c.1096C>G, c.1513A>C and c.1729T>A) and one gain-of-function SNP (c.489C>T). The purpose of this study was to determine whether the functional P2RX7 SNPs are associated with lumbar spine (LS) bone mineral density (BMD), a key determinant of vertebral fracture risk, in post-menopausal women. We genotyped 506 post-menopausal women from the Aberdeen Prospective Osteoporosis Screening Study (APOSS) for the above SNPs. Lumbar spine BMD was measured at baseline and at 6–7 year follow-up. P2RX7 genotyping was performed by homogeneous mass extension. We found association of c.946A (p.Arg307Gln) with lower LS-BMD at baseline (P=0.004, β=−0.12) and follow-up (P=0.002, β=−0.13). Further analysis showed that a combined group of subjects who had LOF SNPs (n=48) had nearly ninefold greater annualised percent change in LS-BMD than subjects who were wild type at the six SNP positions (n=84; rate of loss=−0.94%/year and −0.11%/year, respectively, P=0.0005, unpaired t-test). This is the first report that describes association of the c.946A (p.Arg307Gln) LOF SNP with low LS-BMD, and that other LOF SNPs, which result in reduced or no function of the P2X7 receptor, may contribute to accelerated bone loss. Certain polymorphic variants of P2RX7 may identify women at greater risk of developing osteoporosis.

Risk factors for prediction of inadequate response to antiresorptives

Some patients sustain fractures while on antiresorptives. Whether this represents an inadequate response (IR) to treatment or a chance event has not been elucidated. We performed a study to identify which patients are more likely to fracture while on treatment. This is a multicentric, cross-sectional study of postmenopausal women on antiresorptives for osteoporosis in 12 Spanish hospitals, classified as adequate responders (ARs) if on treatment with antiresorptives for 5 years with no incident fractures or inadequate responders (IRs) if an incident fracture occurred between 1 and 5 years on treatment. Poor compliance, secondary osteoporosis, and previous anti-osteoporosis treatment other than the assessed were exclusion criteria. Clinical, demographic, analytical, dual-energy X-ray absorptiometry (DXA) variables, and proximal femur structure analysis (ImaTx™) and structural/fractal analyses of distal radius were performed. A total of 179 women (76 IRs; mean (SD): age 68.2 (9.0) years; 103 ARs, age 68.5 (7.9) years) were included. History of prior fracture (p = 0.005), two or more falls in the previous year (p = 0.032), low lumbar spine bone mineral density (BMD) (p = 0.02), 25 hydroxyvitamin D (p = 0.017), and hip ImaTx fracture load index (p = 0.004) were associated with IR. In the logistic regression models a fracture before treatment (odds ratio [OR], 3.60; 95% confidence interval [CI], 1.47-8.82; p = 0.005) and levels of 25 hydroxyvitamin D below 20 ng/mL (OR, 3.89; 95% CI, 1.55-9.77; p = 0.004) significantly increased risk for IR, while increased ImaTx fracture load (OR, 0.96; 95% CI, 0.93-0.99; p = 0.006; per every 100 units) was protective, although the latter became not significant when all three variables were fitted into the model. Therefore, we can infer that severity of the disease, with microarchitectural and structure deterioration, as shown by previous fracture and hip analysis, and low levels of 25 hydroxy vitamin D carry higher risk of inadequate response to antiresorptives. More potent regimes should be developed and adequate supplementation implemented to solve this problem.

Does early nutrition program later bone health in preterm infants?

Preterm infants are at risk of metabolic bone disease (MBD) because of an inadequate mineral intake. Although infants with MBD are frequently asymptomatic during the neonatal period, we previously reported that MBD predicted reduced linear growth in infancy and midchildhood. Nevertheless, some studies suggest that preterm infants undergo catch-up growth in bone mineralization during infancy. To examine the hypothesis that early nutrition programs affect later bone health and peak bone mass, we studied 20-y-old subjects who were born preterm and who were randomly assigned to a diet during the neonatal period; the diets used varied markedly in nutrient and mineral content, and phosphate supplements were not provided. Despite large variations in early nutrient and mineral intakes (and the occurrence of MBD) during the neonatal period, the randomly assigned diets did not influence peak bone mass or turnover. However, the proportion of (unsupplemented) human milk in the neonatal diet was significantly positively associated with later whole-body bone size and mineral content. Compared with population reference data, preterm subjects were significantly shorter and had lower lumbar spine bone mineral density; the deficits were greatest in those born small for gestational age (ie, a birth weight <1250 g). The lack of effect of the randomly assigned diets on peak bone mass suggests that the observed deficits in height and lumbar spine bone mass may not be related to suboptimal early nutrient or mineral intake. The higher whole-body bone mass associated with human milk intake, despite its very low nutrient content, may instead reflect nonnutritive factors in breast milk. These findings are relevant to discussions on the mineral requirements of preterm infants.

Oral Cyclosporin Plus Topical Corticosteroid Therapy Diminishes Bone Mass in Children with Eczema

Topical corticosteroids remain the most common treatment for eczema; however, it is uncertain whether long-term use of these agents has any adverse effect on bone mass. Cyclosporin is very useful in patients with severe atopic dermatitis who have failed conventional therapy. It has been shown to induce bone loss. We compared 43 children with severe eczema who were using topical corticosteroids with 73 healthy children. Of the 43 patients, six were also taking cyclosporin. Bone mineral density was measured in the lumbar spine and in the femoral neck using dual-energy X-ray absorptiometry. In multivariate analysis, subjects with eczema had lower lumbar spine bone mineral density (-0.03 g/cm(2); p = 0.015) and bone mineral apparent density (-0.01 g/cm(3); p = 0.008) but higher FN BMAD (+0.02 g/cm(3); p = 0.029) compared with controls. Patients with eczema on topical corticosteroids who had used cyclosporin had lower lumbar spine bone mineral apparent density (-0.01; p = 0.006) compared with those only on topical corticosteroids in both adjusted and unadjusted analysis. In conclusion, children with severe eczema have decreased lumbar spine bone mass, which is primarily mediated by cyclosporin use rather than by topical corticosteroid use. This effect is likely to lead to a modest increase in the risk of wrist and forearm fractures in children using this agent.