Lower LS-BMD Research Articles

Bone mineral density in childhood acute lymphoblastic leukaemia survivors and factors affecting it

BackgroundLiterature on bone health in childhood acute lymphoblastic leukemia survivors (cALLS) is conflicting with most studies suggesting an adverse effect on bone mineral density (BMD). MethodsThis cross-sectional study enrolled cALLS>7 years of age. BMD was measured using dual-energy x-ray absorptiometry (DEXA) scan [Lumbo-sacral (LS-BMD) and whole-body (WB-BMD)]. Low BMD was defined as an LS-BMD ≤2 z-score. Demographic, anthropometry-related, therapy/disease-related and endocrine factors affecting LS-BMD were noted in two groups: low verses normal BMD. ResultsFifty-nine cALLS were analyzed with a median age of 66 months (range: 6–212) at diagnosis and a median duration postcompletion of therapy for 14 months (range 1–113). Two-thirds were male, and 25/59 (42%) had Tanner staging>1. Low LS-BMD was seen in 15/59 (25%), and a low WB-BMD in 3/59 (5%). The mean therapeutic doses of steroids and methotrexate were comparable in two groups. In univariate analysis, age at diagnosis >10 years was associated with low BMD (p = 0.02), while high adiposity was seen commonly with normal BMD (p = 0.01). On multivariate analysis, high adiposity was the single-most factor associated with normal BMD, with an odds ratio of 5.2. The correlation between LS-BMD and WB-BMD was statistically significant (r = 0.55).The median values of hormonal and mineral assays affecting calcium and vitamin D homeostasis and BMD in the two groups were comparable. ConclusionWe report a high prevalence of low LS-BMD (25%) in our cohort. Out of the studied demographics, therapy-related, disease-related, and endocrine factors; high adiposity as defined by a high body fat percentage, was protective against low BMD. We also found a significant correlation between LS-BMD and WB-BMD.

Are associations between physical activity and bone mineral density in adults sex- and age-dependent? An analysis of the UK Biobank study.

Although physical activity (PA) is recognized as a key bone mass determinant across life, athlete studies suggest that it may be less effective in women and older individuals. This has not been explored within the general population. We aimed to address this knowledge gap using data from the UK Biobank Study, a large population-based study of middle-aged and older adults. Free-living PA data collected at 100Hz for 7 d using wrist-worn accelerometers were classified as sedentary behavior (0-29 milligravities [mg]), light (30-124mg), or moderate-to-vigorous PA (125 + mg). LS and FN-BMD were assessed using DXA. The associations between PA and BMD were assessed using linear regression models, with formal assessments of sex and age interactions undertaken and adjustments made for accelerometer wear time, height, body mass index, education, ethnicity, disability, and (in women only) menopausal status. In total, 15 133 UK Biobank participants (52% women) had complete PA, bone, and covariate data. In this sample, greater overall and moderate-to-vigorous PA was associated with higher LS BMD. In women, these associations were typically weaker in older individuals, for example, regression coefficients in women aged 70 yr or older were ~50% lower than at 45-54 yr (age-by-PA interactions P< .01 in all models). Similar associations were observed in basic but not full models for FN BMD. Greater sedentary time was associated with lower LS BMD in men only, and greater light PA and sedentary time were associated with higher and lower FN BMD, respectively, in both sexes. These results suggest that associations between PA and bone health at clinically-relevant sites are weaker in older than younger women. That positive associations are evident between overall and moderate-vigorous PA and FN BMD even in women ≥70 yr suggests that PA for bone health should still be promoted in older women.

THU231 Thyroid Function And Childhood Bone Mineral Density: Abnormal Thyrotropin Concentration May Be Another Predictor Of Pediatric Low Bone Mass

Abstract Disclosure: M. Ahn: None. Backgrounds: Thyroid hormone (TH) whose synthesis and secretion are mainly regulated by thyrotropin (TSH) play a critical role in the metabolism, growth, and development of human body. While TH is responsible for normal growth and differentiation of various organs, bone is known to be one of the major endocrine organs affected by the regulation of TH. Low bone mass or osteoporosis of child and adolescents can occur in numerous chronic conditions, however the influence of abnormal TH and TSH on low bone mineral density (BMD) of children and adolescents remains controversial. Investigating the effect of excessive or deficient TH and TSH on childhood BMD may unveil a better understanding of uncertain role of thyroid function in bone density of pediatric population. Objective: To elucidate the connection between thyroid function and childhood low bone mass. Methods: Serum T3, FT4 and TSH of 619 children aged between 10 to 18 years and previously diagnosed with hemato-oncologic, rheumatoid, gastrointestinal, endocrine conditions whose treatment was completed were assessed simultaneously with mineral density of lumbar spine and femur measured by dual energy x-ray absorptiometry. Serum T3, FT4, and TSH were subcategorized as either high/normal/low or normal/abnormal group with respect to age-matched reference range, then LSBMD data were compared. Comparison, correlation and regression analyses were performed to examine the association between the abnormality of thyroid function and low BMD. Results: Mean LSBMD z-scores of 619 children and adolescents were 0.49±1.28 and those who were less than -1.0 accounted for 37.7 % while serum T3, FT4, and TSH levels were 1.25±0.29 ng/mL, 1.28±0.19 ng/dL, and 2.76±1.87 µU/mL, respectively. Both lumbar and femoral BMD z-scores were not significantly different in between subjects with either abnormal or normal serum T3 and FT4, however were lower in children with abnormal serum TSH. LSBMD (g/cm2) was negatively correlated with serum T3 whereas its z-scores showed no correlation with any of serum T3, FT4 and TSH. In linear regression, BMI z-scores were positively associated whereas serum T3, FT4, TSH were not directly associated with LSMBD z-scores. When the abnormality of T3, FT4, and TSH was considered as determinants for decreasing LSBMD z-scores, TSH abnormality was a significant risk factor having highest odds ratio as LSBMD z-scores decreased. Conclusion: Although serum T3, FT4, and TSH did not show a direct correlation with childhood LSBMD z-scores, abnormal TSH concentration could predict low LSBMD z-scores, therefore indicate low bone mass of children with various underlying conditions. Presentation: Thursday, June 15, 2023

Bone Mineral Density in Mountain, Road Cyclists and Untrained Controls: Exercise, Diet and Hormones

ABSTRACT Purpose: The aim of the study was to compare bone mineral density (BMD) in the lumbar spine (LSBMD) and the femoral neck (FBMD) in male road cyclists (RC n = 39), mountain cyclists (MC n = 30) and controls (C n = 27) and to determine the factors associated with BMD in the same group of participants. Methods: BMD, fat mass (FM) and fat-free mass (FFM) were measured using DXA. Calcium intake (Cal), exercise energy expenditure (EEE) and energy availability (EA) were assessed using self-reported questionnaires. Samples for circulating hormones were also obtained. VO2max was estimated by a cycloergometric test. Results: After adjustment for body mass, in cyclists LSBMD (RC 0.98 ± 0.12; MC 0.98 ± 0.10 g/cm2) was significantly lower than in C (1.11 ± 0.10; p < .001), while FBMD resulted in no significant difference in cyclists compared to C (p = 0.213). EA (kcal/FFM/day) was different in cyclists and in C (p < .05). In C, EEE and EA were positively associated with LSBMD (R = 0.561, R = 0.656, respectively, p < .01), whereas only EA was associated with FBMD (R = 0.554, p < .05); a positive association between EA and FBMD was found in MC (R = 0.464, p < .05). A negative relationship between VO2max and LSBMD in RC (R = -0.418, p < .05) and a positive one between EEE and LSBMD in MC were found (R = 0.605, p < .001). CaI, free testosterone and cortisol were unrelated to BMD. Conclusion: Both the RC and MC had lower LSBMD than C, whereas no difference was found between the two groups of cyclists. The factors associated with BMD are manifold, vary in relation to the measurement site and are likely different in RC, MC and C.

A single-center study of bone mineral density in adult patients with severe hemophilia A in correlation with markers of bone metabolism

Osteopenia and osteoporosis are well-known hemophilia A comorbidities. The pathogenesis of bone turnover alteration resulting in reduced bone mass includes impaired osteoblastic differentiation and disinhibition of RANKL-induced osteoclastogenesis as a result of a low FVIII level. To evaluate the bone mineral density (BMD) in adult patients with severe hemophilia A and assess a possible correlation with the bone remodeling biomarkers OPG/RANKL, CTX-1, osteocalcin, and Vit D. 28 male subjects with severe hemophilia A and 33 age-matched controls were recruited. The biomarkers were tested with the ELISA assay and BMD with DEXA of the lumbar spine (LS) and total hip (TH). The patients had lower LS-BMD (-0.955±0.145 vs. 1.118±0.079, p=0.05) and TH-BMD (-0.840±0.147 vs. 0.951±0.075, p=0.05) than those of the controls. The TH T-scores were -1.41±0.91 vs. 0.4±0.49 (p=0.05) and the LS T-scores -1.16±1.046 vs. 0.14±0.72 (p=0.05). 66.6% of patients under 50 years had osteopenia and 8.3% had osteoporosis. Fifty percent of those over 50 years old had osteopenia and 20% had osteoporosis. We found significantly higher OPG levels (123.69±107.05 vs. 41.98±18.95, p=0.05) than that in controls and lower sRANKL levels (23.49±29.39 vs. 131.32±201.27, p=0.05) and sRANKL/OPG ratio (0.27±0.35 vs. 5.28±10.01, p=0.05) than those in controls. A positive correlation was found between sRANKL and the BMD T-score of lumbar spine (p=0.001) in the patient group. sRANKL level and ratio can be used as predictors of low BMD.

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.

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).

A Comparison of Bone-Targeted Exercise Strategies to Reduce Fracture Risk in Middle-Aged and Older Men with Osteopenia and Osteoporosis: LIFTMOR-M Semi-Randomized Controlled Trial.

The Lifting Intervention For Training Muscle and Osteoporosis Rehabilitation for Men (LIFTMOR-M) trial examined efficacy and safety of two novel exercise programs in older men with low BMD. Men with low hip and/or LS BMD were randomized to high-intensity progressive resistance and impact training (HiRIT) or machine-based isometric axial compression (IAC) and compared to a nonrandomized matched control (CON). Outcomes included: hip and LS BMD; calcaneal ultrasound parameters; anthropometry; body composition; function (timed up-and-go [TUG], five-times sit-to-stand [FTSTS]); back extensor strength (BES); leg extensor strength (LES); compliance and adverse events. Ninety-three men (67.1 ± 7.5 years; 82.1 ± 11.6 kg; 175.2 ± 6.7 cm; FN T-score -1.6 ± 0.6) were randomized to HiRIT (n = 34) or IAC (n = 33), or allocated to CON (n = 26). HiRIT improved trochanteric BMD (2.8 ± 0.8%; -0.1 ± 0.9%, p = .024), LS BMD (4.1 ± 0.7%; 0.9 ± 0.8%, p = .003), BUA (2.2 ± 0.7%; -0.8 ± 0.9%, p = .009), stiffness index (1.6 ± 0.9%; -2.0 ± 1.1%, p = .011), lean mass (1.5 ± 0.8%; -2.4 ± 0.9%, p = .002), TUG, FTSTS, BES, and LES (p < .05) compared with CON. IAC improved lean mass (0.8 ± 0.8%; -2.4 ± 0.9%, p = .013) and FTSTS (-4.5 ± 1.6%; 7.5 ± 2.0%, p < .001) compared with CON. HiRIT improved LS BMD (4.1 ± 0.7%; 2.0 ± 0.7%, p = .039), stiffness index (1.6 ± 0.9%; -1.3 ± 0.9%, p = .025), and FTSTS (-10.7 ± 1.6%; -4.5 ± 1.7%, p = .010) compared with IAC. Exercise compliance was high (HiRIT 77.8 ± 16.6%; IAC 78.5 ± 14.8%, p = .872). There were five minor adverse events (HiRIT, 2; IAC, 3). HiRIT was well-tolerated and improved bone, function and fracture risk more than CON or IAC. © 2020 American Society for Bone and Mineral Research.

Examining the causal role of leptin in bone mineral density: A Mendelian randomization study.

Leptin, a small polypeptide hormone secreted by the adipocytes, controls body weight and gonadal function by binding to a special receptor located in the hypothalamus. Observational studies have demonstrated a controversial association between leptin and bone mineral density (BMD), and functional studies of the relationship between leptin and BMD still largely vary by different studies. Using SNPs strongly associated with leptin levels in 52,140 individuals, we conducted a two-sample Mendelian randomization study to identify whether genetically lowered leptin levels were associated with BMD by using an inverse-variance weighted method, a weighted median method, MR-Egger and Robust Adjusted Profile Score. We found that circulating leptin levels may causally decrease lumbar spine BMD (effect size = -0.45, 95% CI: -0.82, -0.083; p value = 0.016). The association estimates of circulating leptin levels on femoral neck, forearm and total body BMD were not significant. Our study suggests that genetically predicted higher circulating leptin was associated with lower LS-BMD.

Individualized evaluation of lumbar bone mineral density in children with cerebral palsy.

DXA evaluation is considered useful in children with CP to assess bone health. For this purpose, LS-BMD is often used. The aim of the study was to estimate the effect of height, BMI, and reduced mobility level of children with CP on LS-BMD and to develop a method to adjust individual results of LS-BMD for these factors. We conducted a monocentric retrospective analysis of data collected in children and adolescents with CP, who participated in a rehabilitation program and had no history of recurrent fractures. The DXA scan was part of the routine examination for participants older than 4years of age. The relationship between height and BMI for age Z-scores and age-adjusted LS-BMD Z-scores was analyzed. LS-DXA scans of 500 children and adolescents with CP (Gross Motor Function Classification System levels I-V) were included in the statistical analysis (217 female). The mean age was 9.4years (± 3.7years). Children with moderate to severe CP had significantly (p < 0.001) lower LS-BMD Z-scores than children with mild CP. We provided nomograms to adjust individual LS-BMD results to their height, BMI, and mobility level. LS-BMD results in children with CP were influenced significantly by their height, BMI, and mobility level. An adjustment of the LS-BMD results to height, BMI, and mobility level might improve the clinical significance of an individual result.

Sex Hormone-Binding Globulin Is Associated With Markers Of Vertebral Fracture And Vertebral Fracture Risk

Background The relation between sex hormone-binding globulin (SHBG) and vertebral fracture (VFx) is unclear. We examined whether SHBG is associated with bone mineral density at lumbar spine (LS-BMD), trabecular bone score (TBS) and prevalent VFx. Methods Data of 6,224 men and women participants in the third visit of the first cohort (I-3) and the first visit of the second cohort (II-1) of the Rotterdam Study (RS), a prospective population based cohort, were available. Serum SHBG and prevalent VFx were assessed at RS I-3 and II-2, whereas LS-BMD and TBS were assessed 4 years later (RS I-4 and RS II-2). VFx were scored using the Quantitative Morphometry method (QM) and Algorithm Based Qualitative method (ABQ). Multivariate linear and logistic regression models were performed, adjusted for confounding factors such as medication use, lifestyle factors, body mass index, serum glucose, insulin, calcium and phosphate levels. Results We identified 854 prevalent VFxQM and 176 prevalent VFxABQ. After correcting for confounders, higher levels of SHBG were associated with lower LS-BMD (3rd tertile vs. 1st tertile: β: -0.04; 95%CIs= -0.06; -0.02) and higher TBS (3rd tertile vs. 1st tertile: β: 0.02; 95%CIs=0.01; 0.03). Higher levels of SHBG were positively associated with both VFxQM (3rd tertile vs. 1st tertile: OR: 1.25; 95%CIs=1.02; 1.55) and VFxABQ (3rd tertile vs. 1st tertile: OR: 2.11; 95%CIs=1.29; 3.5) independent of BMD and TBS. Adjustment for total testosterone and estradiol levels did not affect any of these associations. Also, no sex differences were observed. Conclusion This study suggests that SHBG concentration may be a sensitive and early biomarker of VFx. As measurement of serum SHBG is reliable, easy and inexpensive, its assessment may have clinical utility in identifying individuals at high risk of developing VFx later in life that could benefit from effective preventive interventions.

Bone health in elite Kenyan runners

ABSTRACTImpact loading in athletes participating in various sports has been positively associated with increased bone mineral density (BMD), but this has not been investigated in elite Kenyan runners. Body composition and site-specific BMD measures quantified with dual x-ray absorptiometry were measured in 15 elite male Kenyan runners and 23 apparently healthy South African males of different ethnicities. Training load and biomechanical variables associated with impact loading, such as joint stiffness, were determined in the elite Kenyan runners. Greater proximal femur (PF) BMD (g · cm−2) was higher (P = 0.001, ES = 1.24) in the elite Kenyan runners compared with the controls. Six of the 15 (40%) Kenyan runners exhibited lumbar spine (LS) Z-Scores below −2.0 SD, whereas this was not found in the apparently healthy controls. PFBMD was associated with training load (r = 0.560, P = 0.003) and ankle (r = 0.710, P = 0.004) and knee (r = 0.546, P = 0.043) joint stiffness. Elite Kenyan runners exhibit greater PFBMD than healthy controls, which is associated with higher training load and higher joint stiffness. Our results reaffirm the benefits of impact loading on BMD at a weight-bearing site, while a high prevalence of low LSBMD in the elite Kenyan runners is hypothesised to be the result of a mismatch between energy intake and high training load. Future research investigating energy availability in Kenyan runners and the possible association with musculoskeletal injury should be investigated.

Vertebral fracture prevalence among Greek healthy middle-aged postmenopausal women: association with demographics, anthropometric parameters, and bone mineral density

Background contextThe prevalence of skeletal fractures shows a marked geographic variability; however, data regarding the Greek population remain limited. PurposeTo evaluate the frequency of asymptomatic vertebral fractures (VFs), and potential risk factors, in a large sample of Greek postmenopausal women. Study designA cross-sectional study at the University Menopause Clinic. Patient sampleFour hundred fifty-four postmenopausal women aged 35 to 80 years, with an average menopausal age of 9.2±7.1 years. Outcome measuresThey included medical history, anthropometric and biochemical parameters, bone mineral density (BMD) at lumbar spine (LS) and femoral neck (FN), and LS lateral radiographs. MethodsLumbar spine lateral radiographs were evaluated according to quantitative procedures, aiming to identify VFs. Anthropometric and biochemical parameters and values of BMD were compared according to the presence of VFs. ResultsA total of 37 (8.15%) women had at least one VF. Lumbar spine and FN-osteoporosis was identified in up to 23.1% and 40.9% subjects with prevalent VFs, respectively. The prevalence of VFs was largely associated with age, with women aged 60 years or more presenting an up to fourfold risk compared with younger women. Moreover, the presence of VFs was associated with higher menopausal age, advanced age at menarche, a history of early menopause, and prolonged lactation. Lower LS-BMD and, especially, FN-BMD were negatively associated with VF prevalence (prevalent VF vs. no VF: LS-BMD, 0.89±0.16 g/cm2 vs. 0.98±0.16 g/cm2, p=.010; FN-BMD, 0.72±0.10 g/cm2 vs. 0.81±0.12 g/cm2, p=.008). ConclusionsAsymptomatic VFs are common among Greek healthy middle-aged postmenopausal women. More than 50% subjects with prevalent VFs present with normal BMD or osteopenia. Age and bone density classification at the FN presented the strongest association with the prevalence of VFs.

Can ultrasound be used to estimate bone mineral density in children with growth problems?

To assess predictability of bone mineral density (BMD) of the lumbar spine (LS) determined by dual-energy x-ray absorptiometry (DXA) using by ultrasound speed of sound of the right and left radii (SOS-R and SOS-L) in patients with growth problems. Ultrasound and DXA were compared in patients with advanced, normal and delayed bone ages assessed by Greulich and Pyle (GP) and Tanner and Whitehouse (TW3) methods. There was a strong correlation (r), of raw scores, between SOS-R and SOS-L, r = 0.81, p = 0.000 and their respective Z-scores, r = 0.78, p = 0.000. Z-score correlations were poor between SOS-R or SOS-L and LS-BMD. Sensitivity, specificity, positive and negative predictive values of SOS-R and Z-scores for predicting normal (>-1 to <1) and low (<-1) LS-BMD were poor. For high (>1) LS-BMD, Z-scores were 22%, 93%, 29% and 90%, respectively, for SOS-R and for SOS-L, 25%, 89%, 20% and 91%. For very low (<-2) LS-BMD, SOS-R and SOS-L were the same, respectively, 29%, 91%, 40% and 86%. Ultrasound of the radius is a poor predictor of radiologically assessed BMD at the LS, especially with delayed bone age.

Bone quality, as measured by trabecular bone score in patients with adrenal incidentalomas with and without subclinical hypercortisolism

Patients with adrenal incidentalomas (AIs) and subclinical hypercortisolism (SH) have increased risk of fracture independent of bone mineral density (BMD) and possibly due to reduced bone quality. The trabecular bone score (TBS) has been proposed as a index of bone microarchitecture. The aim of the study was to investigate TBS in AI. In 102 AI patients, SH was diagnosed in the presence of at least two of the following: (1) urinary free cortisol >70 µg/24 h (193.1 nmol/L); (2) cortisol after 1-mg dexamethasone suppression test (1-mg DST) >3.0 µg/dL (82.8 nmol/L); or (3) adrenocorticotropic hormone (ACTH) <10 pg/mL (<2.2 pmol/L). In patients and in 70 matched controls, BMD was measured at lumbar spine (LS) and femur (neck [FN] and total [FT]) by dual X-ray absorptiometry and TBS was assessed in the region of LS-BMD; BMD and TBS data were reported as Z-scores. In patients, vertebral deformities were assessed by radiograph. Patients with SH (n = 34) had lower LS-BMD (-0.31 ± 1.17), FT-BMD (-0.29 ± 0.91), and TBS (-3.18 ± 1.21) than patients without SH (n = 68, 0.31 ± 1.42, p = 0.03; 0.19 ± 0.97, p = 0.01; -1.70 ± 1.54, p < 0.0001, respectively) and controls (0.42 ± 1.52, p = 0.02; 0.14 ± 0.76, p = 0.02; -1.19 ± 0.99, p < 0.0001, respectively). TBS was inversely correlated with 1-mg DST (β = -0.26, t = -2.79, p = 0.006) regardless of age, LS-BMD, body mass index (BMI), and gender. The presence of fracture was associated with low TBS alone (odds ratio [OR], 4.8; 95% confidence interval [CI], 1.85-12.42, p = 0.001) and with the cluster low TBS plus low LS-BMD (OR, 4.37; 95% CI, 1.71-11.4, p = 0.002), after adjustment for age, BMI, and gender. Low TBS plus low LS-BMD showed a good specificity (79%) for predicting fractures, whereas normal TBS (ie, > -1.5) plus normal LS-BMD high specificity (88.1%) for excluding fractures. Finally, TBS predicted the occurrence of a new fracture in 40 patients followed for 24 months (OR, 11.2; 95%CI, 1.71-71.41, p = 0.012) regardless of LS-BMD, BMI, and age. In SH, bone quality, as measured by TBS, is altered. TBS is useful in detecting AI patients at risk of fractures.

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.

Predictors of bony morbidity in children with acute lymphoblastic leukemia

To evaluate the relationship between lumbar spine (LS) bone mineral density (BMD) and patient-, disease-, and therapy-related variables, and to define the risk-factors for fractures in children receiving therapy on Dana-Farber Cancer Institute acute lymphoblastic leukemia (ALL) protocols. Children (≤18 years) diagnosed with ALL during the period 1995-2006, who are in first clinical remission, were included (n = 124). Dual-energy X-ray absorptiometry provided LS-BMD at diagnosis (n = 46) and during continuation therapy. LS-BMD was expressed as Z scores based on local population norms. Regression analyses evaluated the risk of osteopenia (Z-score -1.01 to -1.99, osteoporosis (Z-score -2.00 or less) and fractures. At diagnosis, 14 0f 46 (30%) patients had osteopenia and 5 (11%) had osteoporosis; whereas, during continuation therapy, 47 of 124 (39.5%) patients had osteopenia, and 10 (8%) had osteoporosis. LS-BMD at diagnosis had a positive linear relationship with LS-BMD during continuation therapy (Pearson correlation coefficient 0.619, P < 0.0001). Multivariable analyses identified age ≥10 years and LS-BMD at diagnosis as independent predictors of LS-BMD during continuation therapy. Twenty-three (18.5%) patients developed fractures. Dexamethasone therapy (OR 3.4, 95% CI 1.31, 7.52, P = 0.01) and lower LS-BMD during the continuation therapy (OR 1.8, 95% CI 1.2, 2.8, P = 0.01) were independent predictors of fracture. Older age and lower LS-BMD at diagnosis are predictors of lower LS-BMD during continuation therapy. Dexamethasone and lower LS-BMD during continuation therapy are associated with fractures. Using these variables it is feasible to develop a predictor model to define the risk of bony morbidity in children receiving ALL therapy.

Effect of Cigarette Smoking on Bone Mineral Density in Healthy Taiwanese Middle-Aged Men

The effect of cigarette smoking in relation to bone mineral density (BMD) remains inconclusive, especially in middle-aged men. This cross-sectional study was conducted to examine the effect of smoking on BMD in 837 healthy Taiwanese males (532 never-smokers, 258 current smokers, 47 former smokers; aged 46–64 yr), recruited at their routine health examination. Subjects with suspected conditions affecting bone metabolism or receiving any medications affecting bone metabolism were excluded. BMD of the lumbar spine (LSBMD) and femoral neck (FNBMD) was measured with dual-energy X-ray absorptiometry. After adjustment for confounding variables (age, weight, physical activity, alcohol consumption, and caffeine intake), we found that the mean value of LSBMD was significantly (2.9%) lower in current smoker compared with never-smokers ( p = 0.024), but no significant difference was observed in FNBMD. No statistically significant association was observed between former smokers and never-smokers in any of the BMD sites, indicating that quitting smoking did have a positive effect on bone density. Compared with never-smokers, current heavy smokers who consumed at least 20 cigarettes/d (n = 94) had 3.8% lower LSBMD ( p = 0.04), but no significant difference was observed in FNBMD. In the correlation analysis, the duration of smoking was negatively associated with LSBMD ( r = −0.166, p = 0.004), but no association was shown in FNBMD. Our results suggested that both smoking status and duration of smoking were deleterious factors on the bone density of the lumbar spine, and the effect was cumulative with duration and quantity.

The Association of Bone Mineral Density with Estrogen Receptor Gene Polymorphisms

The purpose of this investigation was to evaluate single nucleotide polymorphism (SNP) variants of the estrogen receptor genes ESR1 and ESR2 and bone mineral density (BMD) of the lumbar spine (LS-BMD) or total hip (hip BMD) in women of 4 races/ethnicities who were premenopausal or in early perimenopause. The sample consisted of 1,301 participants from the Study of Women’s Health Across the Nation (SWAN) with measures of BMD and genotyping; of these, 295 were African American, 693 were Caucasian, 151 were Chinese, and 162 were Japanese. We evaluated the potential association of LS-BMD or hip BMD with 4 SNPs from the ESR1 gene ( ESR1 rs9340799, ESR1 rs2234693, ESR1 rs728524, and ESR1 rs3798577), and 3 SNPs from the ESR2 gene ( ESR2 rs1255998, ESR2 rs1256030, and ESR2 rs1256065). Unadjusted mean LS-BMD values ranged from 1.141 ± 0.14 g/cm 2 in African American women to 1.031 ± 0.11 g/cm 2 in Japanese women; unadjusted mean hip BMD values ranged from 1.053 ± 0.14 g/cm 2 in African American women to 0.862 ± 0.10 g/cm 2 in Chinese women. African American and Japanese women with the ESR1 rs2234693 ( PvuII) CC genotype had higher LS-BMDs than did their peers with the TT genotype ( P = 0.009 and P = 0.04, respectively). Japanese women with the ESR1 rs3798577 CC or TC genotypes had lower LS-BMD than did Japanese women with the TT genotype ( P = 0.02 and P = 0.01, respectively). Caucasian women with the TC genotype for ESR2 rs1256030 had lower LS-BMDs than did those with the CC genotype ( P = 0.02). Chinese women who were heterozygous for ESR2 rs1256030 or ESR2 rs1256065 had significantly higher LS-BMDs and hip BMDs than did the referent groups for each of these SNPs ( CC and AA, respectively). Associations between BMD and ESR1 and ESR2 genotypes varied by race/ethnicity and by bone site. Our results differ from those previously reported for 2 ESR1 genotypes ( ESR1 rs2234693 [ PvuII] and ESR1 rs9340799 [ XbaI]). Moreover, 2 ESR1 and 3 ESR2 SNPs we studied have not previously been examined with respect to BMD. Among these, ESR2 rs1256030 and ESR2 rs1256065 appear to have an effect at both the lumbar spine and hip in Chinese women and may warrant further study.