Bone Mineral Content Measurements Research Articles

Normative fat-free mass index values for a diverse sample of collegiate female athletes

ABSTRACTThe purpose of this study was to establish normative fat-free mass index (FFMI) ranges in collegiate female athletes. A sample of 266 female athletes (Mean±SD; Age: 19.7 ± 1.5 yrs, Height: 166.0 ± 6.4 cm, Weight: 63.2 ± 8.8 kg) were included in analyses. Dual-energy X-ray absorptiometry measured bone mineral content (BMC; kg) and lean mass (LM; kg). Fat-free mass index was calculated as follows: FFMI = (BMC + LM)/Height2. Participants were classified by sport: cross-country (XC), field hockey, football, gymnastics, lacrosse, resistance-trained, swimming track. Mean, range and percentile ranks of FFMI were calculated for the full sample for each cohort. For all females, mean FFMI was 16.9 ± 1.7 kg/m2, FFMI values ranged from 13.3 to 25.5 kg/m2. The XC athletes had the lowest FFMI (15.3 ± 0.96 kg/m2; p < 0.001). Mean FFMI measures were similar between all other female athletes. Percentile ranks varied across sport; median FFMI was highest for football (18.0 kg/m2), lowest for XC (15.1 kg/m2) and ranged between 16.4 and 17.3 kg/m2 for all other athletes. Establishing sport-specific FFMI values for female athletes may be beneficial for athletes and coaches by leading to more appropriate body composition goals based on FFM.

Interactive effects of calcium and top-dressed 25-hydroxy vitamin D3 on egg production, egg shell quality, and bones attributes in aged Lohmann LSL-lite layers

Calcium and vitamin D are critical in attenuating metabolic Ca insufficiency often observed in older hens. We investigated interactive effects of dietary Ca and top-dressed 25-hydroxy vitamin D3 (25OHD3) on egg production, eggshell quality (thickness, EST, and breaking strength, ESBS), serum Ca, kidney, liver, and bones attributes in 74-wk old Lohmann LSL-lite layers. A total of 4 levels of Ca (3.0, 3.5, 4.0, and 4.5%) and 3 levels of 25OHD3 (0, 69, and 138μg/kg) were tested. All diets had basal level of 3,300 IU of vitamin D3/kg, were allocated to 84 individually housed hens (n = 7), and fed to 81 wk of age. Dual-energy X-ray absorptiometry was used to measure bone mineral content (BMC) and density (BMD) in left ulna, femur, and tibia at week 74 (13 spare birds, baseline) and week 81. Birds fed diets containing 3.0, 3.5, 4.0, and 4.5% Ca consumed 3.4, 4.1, 4.2, and 4.8 Ca g/b/d. Interaction (P < 0.05) between Ca and 25OHD3 was such that 25OHD3 linearly increased egg weight and percentage of eggs graded as jumbo (≥70g) at 3.0, 3.5, and 4.5% Ca levels. There was no interaction (P > 0.05) between Ca and 25OHD3 on the rest of the parameters. Calcium increased EST and ESBS quadratically (P < 0.05), EST increased with Ca intake up to 4.1g of Ca/b/d whereas Ca intakes (3.4 and 4.8g of Ca/b/d) had poor ESBS relative to intermediate Ca intakes. Kidney ash concentration increased linearly (P = 009) with Ca intake. However, BMC and BMD in ulna, tibia, and femur declined (P < 0.05) at week 81 relative to baseline. In conclusion, top dressed 25OHD3 linearly increased egg weight at various Ca intakes with no negative effect on eggshell quality or bone attributes. Feeding 4.1 to 4.2g of Ca/b/d improved eggshell quality, however, higher intake deteriorated eggshell quality and increased renal ash accumulation with no benefit on skeletal integrity.

Passive Range-of-Motion Exercise and Bone Mineralization in Preterm Infants: A Randomized Controlled Trial.

To assess the effect of range-of-motion exercise program on bone mineralization and somatic growth of very low birth weight (VLBW) infants. A total of 36 VLBW infants were randomized into 18 VLBW infants receiving range-of-motion exercise and 18 VLBW control infants receiving tactile stimulation for 4 weeks. Laboratory investigations were performed at baseline and postexercise and included serum calcium, serum phosphorus (s.PO4), magnesium, alkaline phosphatase (ALP), urinary calcium/phosphate ratio, and serum carboxy-terminal cross-linked telopeptide of type 1 collagen (CTX). Dual-energy X-ray absorptiometry was performed at the end of the exercise protocol to measure bone mineral content, bone mineral density (BMD), bone area, lean mass, and fat mass. The weight and the rate of weight gain were significantly higher (p < 0.001) in the exercise group compared with controls postexercise. Also, higher s.PO4, lower ALP, and lower urinary calcium/phosphate ratio were observed postexercise in the exercise group (p = 0.001, p = 0.005, and p = 0.04, respectively), whereas serum CTX showed no difference between the two groups (p = 0.254). Postexercise BMD significantly improved in the exercise group (p < 0.001) compared with controls. Although the sample size was small, we may be able to suggest favorable effects of range-of-motion exercise versus tactile stimulation on bone metabolism, BMD, and short-term growth in VLBW infants.

Effects of Zumba® and Aquagym on Bone Mass in Inactive Middle-Aged Women.

Background and objectives: Regular exercise may stimulate bone formation and reduce the loss of bone mass in premenopausal women. This study aims to evaluate the effect of high-impact physical activity (Zumba®) and low-impact physical activity (Aquagym) on bone mass in inactive middle-aged women. Materials and methods: Fifty-five healthy inactive women (30–50 years old) were recruited in Spain in 2016 and were randomly allocated into one of three groups: High impact group (HIG: n = 15), low impact group (LIG: n = 12) and control group (CG: n = 28). HIG and LIG were recruited from Madrid and the CG from Toledo. HIG and LIG completed a 12-week intervention program with three 40′ sessions per week of Zumba® or Aquagym; respectively. Dual energy X-ray absorptiometry (DXA) measured bone mineral content (BMC) and areal bone mineral density (aBMD) at total body less head (TBLH), lumbar spine and right hip. Results: Post-intervention adjusted data showed no significant differences in BMC between any of the groups nor in aBMD between HIG and LIG. Interestingly; significant differences for the HIG vs. CG were found in the change in total hip aBMD (1.76% vs. −0.44%), femoral neck aBMD (1.80% vs. −2.71%), and intertrochanter aBMD (2.03% vs. −0.50%). Moreover, significant differences for the LIG vs. CG were also found in the change in femoral neck aBMD (−0.54% vs. −2.71%). Conclusions: The regular practice of Zumba® and Aquagym might reduce the progressive deterioration of bone mass in inactive middle-aged women

A discussion of statistical methods to characterise early growth and its impact on bone mineral content later in childhood

Background: Many statistical methods are available to model longitudinal growth data and relate derived summary measures to later outcomes.Aim: To apply and compare commonly used methods to a realistic scenario including pre- and postnatal data, missing data, and confounders.Subjects and methods: Data were collected from 753 offspring in the Southampton Women’s Survey with measurements of bone mineral content (BMC) at age 6 years. Ultrasound measures included crown-rump length (11 weeks’ gestation) and femur length (19 and 34 weeks’ gestation); postnatally, infant length (birth, 6 and 12 months) and height (2 and 3 years) were measured. A residual growth model, two-stage multilevel linear spline model, joint multilevel linear spline model, SITAR and a growth mixture model were used to relate growth to 6-year BMC.Results: Results from the residual growth, two-stage and joint multilevel linear spline models were most comparable: an increase in length at all ages was positively associated with BMC, the strongest association being with later growth. Both SITAR and the growth mixture model demonstrated that length was positively associated with BMC.Conclusions: Similarities and differences in results from a variety of analytic strategies need to be understood in the context of each statistical methodology.

A dietary pattern rich in calcium, potassium, and protein is associated with tibia bone mineral content and strength in young adults entering initial military training

Stress fracture risk is elevated during initial military training (IMT), particularly in lower-extremity bones such as the tibia. Although the etiology of stress fractures is multifactorial, lower bone strength increases risk. The objective of this study was to assess, through the use of peripheral quantitative computed tomography, whether adherence to a dietary pattern rich in calcium, potassium, and protein before IMT is positively associated with bone indexes in young adults entering IMT. A cross-sectional analysis was performed with the use of baseline data from 3 randomized controlled trials in Army, Air Force, and Marine recruits (n=401; 179 men, 222 women). Dietary intake was estimated from a food-frequency questionnaire. A dietary pattern characterized by calcium, potassium, and protein was derived via reduced rank regression and a pattern z score was computed for each volunteer, where higher scores indicated greater adherence to the pattern. At the 4% (metaphysis) and 14% (diaphysis) sites of the tibia, bone mineral content (BMC), volumetric bone mineral density, robustness, and strength indexes were evaluated. Associations between dietary pattern z score as the predictor variable and bone indexes as the response variables were evaluated by multiple linear regression. Pattern z score was positively associated with BMC (P=0.004) and strength (P=0.01) at the metaphysis and with BMC (P=0.0002), strength (P=0.0006), and robustness (P=0.02) at the diaphysis when controlling for age, sex, race, energy, smoking, education, and exercise. Further adjustment for BMI attenuated the associations, except with diaphyseal BMC (P=0.005) and strength (P=0.01). When height and weight were used in place of body mass index, the association with BMC remained (P=0.046). A dietary pattern rich in calcium, potassium, and protein is positively associated with measures of tibia BMC and strength in recruits entering IMT. Whether adherence to this dietary pattern before IMT affects injury susceptibility during training remains to be determined. These trials were registered at clinicaltrials.gov as NCT01617109 and NCT02636348.

Soft tissues and bone health in sedentary women: A cross-sectional study

Lean mass is a strong determinant of bone mass, however, there is controversial surrounding the role of fat mass. The aim of this study was to examine the association between lean mass and fat mass with bone mass in middle-aged sedentary women, including relevant covariates. A cross-sectional study was performed on a total of 55 healthy and sedentary women. Dual energy x-ray absorptiometry was used to measure bone mineral content and areal bone mineral density at the whole body, lumbar spine and hip. The relationships between lean and fat mass with bone outcomes were analysed using three regression models: model 0 using unadjusted data, model 1 was adjusted by age and stature and model 2 added lean mass or fat mass (depending on the predictor). Lean mass was positively associated with most bone mineral content and areal bone mineral density outcomes in models 0 and 1, and the majority of these associations remained significant in model 2 (after adjusted by fat mass). Fat mass was positively associated with some of the bone mineral content and areal bone mineral density outcomes in models 0 and 1, and interestingly all associations disappeared in model 2 (after adjusted by lean mass). The main finding of this study was that lean mass was positively related to bone outcomes, independent of age, stature and fat mass in middle-aged sedentary women. In addition, the association between fat mass and bone outcomes seems to be explained by lean mass.

Investigating a relationship between body composition and spinal curvature in farmed adult New Zealand king salmon (Oncorhynchus tshawytscha): A novel application of dual-energy X-ray absorptiometry

Characterising the pathology of skeletal anomalies in farmed finfish is key to elucidating the underlying causes. Spinal curvature is frequently observed in farmed New Zealand king salmon (Oncorhynchus tshawytscha), but its cause is currently unknown and knowledge about its pathology is limited. Dual-energy X-ray absorptiometry (DXA) was used to investigate the relationship between spinal curvature and body composition in farmed adult New Zealand king salmon. Differences in fat mass (FM), lean mass (LM) and bone mineral content (BMC) between harvest-sized fish affected and unaffected by spinal curvature were evaluated. As there is presently no evidence of an association between spinal curvature and vertebral mineral loss, between-group differences in BMC were not anticipated. Conversely, as spinal anomalies can alter the swimming and feeding of affected fish, and existing research suggests a role for soft tissues in spinal curvature development, differences in FM and LM were expected. Whole-body and regional (cranial, trunco-cranial, trunco-caudal and caudal spine) measurements of percent FM, LM and BMC were obtained from lateral DXA scans of size-matched adult female king salmon (1890–6903 g) affected (n = 31) and unaffected (n = 31) by spinal curvature. Repeatability was comparable to previous DXA studies. Measurements of FM and LM by DXA and chemical carcass analysis (CCA) were highly similar. As frequently reported in previous animal-based studies, DXA-derived BMC values were significantly lower than those obtained from CCA. Contrary to the overarching hypothesis, there were no significant between-group differences in whole-body or regional FM, LM or BMC, suggesting that there was no relationship between body composition and spinal curvature. Though the relationship between soft tissue changes and spinal curvature remains to be determined, DXA appears to be a viable tool for non-invasive assessment of king salmon body composition. However, studying end-stage disease has recognised limitations, so future investigations should utilise longitudinal designs.

2261. Phosphaturia in HIV-Exposed Uninfected Neonates Associated With Maternal Use of Tenofovir Disoproxil Fumarate in Late Pregnancy

BackgroundOur recent study showed significantly lower bone mineral content (BMC) in HIV-exposed uninfected (HEU) neonates born to HIV-infected (HIV+) mothers who took tenofovir disoproxil fumarate (TDF) in late pregnancy compared with no TDF use. In this cohort we sought to understand possible mechanisms for lower BMC by comparing markers of bone metabolism and renal function with TDF exposure in HEU neonates.MethodsAmong a subset of HEU children in the multicenter (United States and Puerto Rico) observational Surveillance Monitoring for ART Toxicities (SMARTT) Cohort study, we enrolled neonates (≥36 weeks gestational age) of HIV+ mothers who took TDF for ≥8 weeks in the third trimester (TDF+) or no TDF in pregnancy (TDF-). In addition to BMC measures, we collected a blood and urine sample on each child ≤30 days of birth to measure serum creatinine, phosphate, 25-OH vitamin D, parathyroid hormone and urine creatinine, phosphate and N-terminal telopeptide. Standard equations were used to estimate proximal tubular phosphate reabsorption and glomerular filtration rate (eGFR). Comparisons were made by TDF exposure using Wilcoxon and Fisher’s exact tests. We fit linear models to compare TDF+ and TDF− for each assay by age in days at sample collection (slope), stratified by age group at sample collection time (0–3 days, 4–30 days).ResultsOf 160 HEU neonates (Black 71%, Hispanic 31%), 82 were TDF+ and 78 TDF−. Sociodemographic and anthropometric characteristics did not differ by TDF exposure in each age group. Within 0–3 days of life, TDF+ had a greater decline in serum creatinine (P = 0.04) and a greater increase in eGFR compared with TDF− (P = 0.06), but no difference in slope by TDF exposure within 4–30 days of life, nor in serum phosphate in either age group. Proximal tubular phosphate reabsorption was similar for both groups within the first 3 days of life, with a significantly greater decline in phosphate reabsorption between 4 and 30 days of life in the TDF+ compared with the TDF− group (P = 0.006, Figure 1). Bone markers did not differ by TDF exposure for either age group.ConclusionUrinary phosphate loss was increased among HEU neonates of mothers who took TDF in late pregnancy. This suggests proximal tubular dysfunction and may explain, at least in part, the decrease in BMC previously described. Disclosures R. Van Dyke, Giliad Sciences: Grant Investigator, Research grant.

Assessing the accuracy of measurements obtained by dual-energy X-ray absorptiometry on pig carcasses and primal cuts

Accuracy, trueness, and precision of dual-energy X-ray absorptiometry (DXA) assessment of pig carcasses and primal cuts dissected tissues were evaluated using available region of interests (ROI) and Total Body and Small Animal software modes. Fat mass, lean mass, and bone mineral content (BMC) DXA values were compared to dissected tissue weights (fat, muscle, and bones). Used ROI influenced (P < 0.05) DXA measurements of BMC, fat mass, and lean mass. Configuration modes influenced (P < 0.05) DXA fat mass in shoulders and bellies, whereas BMC estimates differed (P < 0.05) among configuration modes. Equations predicting dissected composition on the basis of DXA measurements showed high coefficients of determination, particularly for fat and lean masses. DXA is able to accurately evaluate the composition of pig carcasses and primal cuts. From a methodological viewpoint, and considering the variations observed in this study, the method for image acquisition and analysis should be chosen on the basis of the item to be evaluated.

Bone health consequence of adjuvant Anastrozole in monotherapy or associated with biochanin-A in ovariectomized rat model

AimsWe investigate the consequence of adjuvant anastrozole (ANA) in monotherapy or associated with biochanin A (BCA) in ovariectomized (OVX) rat model and the degree of developing bone loss in both conditions. Materials and methodsSixty female rats were assigned to six groups. Five groups were bilaterally OVX, and one was sham operated. The five groups were; ANA group (0.5 mg/kg b.wt orally), BCA (5 mg/kg b.wt intraperitoneally (I/P), co-treated group (BCA + ANA), two control groups receiving even distilled water orally or DMSO I/P for twenty weeks. Bone turnover biomarkers BALP, OC, PTH, TRAP and TNFα were determined in serum. Bone mineral content, histological and morphometric measurements on rat femurs were performed. BMD by X-ray technique on tibias of rats and CT analysis of lumbar vertebrae of all treated and sham groups were applied. Key findingsThere was marked elevation in bone turnover biomarkers with high serum Ca and P content in the ANA-treated rats. Moreover marked elevation of TNFα, PTH, TC and TG, ANA caused severe changes in the BMD detected by X-ray in tibial bones and CT analysis of lumbar vertebrae of OVX rats. While I/P injection of BCA ameliorated the adverse bone health decrements caused by ANA. SignificanceThe study highlights the importance of the BCA supplementation in accordance with the ANA therapy in case of ovariectomized rat model of osteoporosis which is clinically presented in Postmenopausal women with breast cancer during which considerable risk of developing osteoporosis is predicted during treatment.

REGIONAL BODY COMPOSITION AND MUSCLE STRENGTH ARE RELATED TO BONE MINERAL CONTENT IN ELDERLY

ABSTRACT Introduction: The increase, or maintenance, of lean body mass and muscle strength are major determinants of functional independence in the elderly, since they are associated with bone remodeling, and therefore with a reduced risk of falls and fractures. However, the regional relationship between lean body mass/strength and bone mineral content (BMC) has not sufficient theoretical support. Objective: To analyze whether regional body composition and muscle strength are factors potentially related to BMC. Methods: Ten older men (63.3±6.4 years, 169.4±6.8 cm and 79.3±10.5 kg) underwent body composition assessments using dual energy X-ray absorptiometry (DXA) to obtain regional and whole-body lean mass and BMC measures. The subjects also underwent the one-repetition maximum (1RM) test involving flat bench press, 45° leg press, arm curl and knee extension. Regional/whole-body composition and 1RM values were correlated to BMC using Pearson's coefficient (r). The level of significance for the correlations was p ≤0.05, the confidence interval was 95% (Z1-a/2=1.96), and the sample power was 80% (1-b). Results: The flat bench press 1RM was related to BMC in the left (r=0.764) and right (r=0.748) arms, while the 45° leg press 1RM was associated with BMC in the left (r=0.677) and right (r=0.714) legs and trunk (r=0.810), with sample power of 77.7%, 66.8%, 12.7%, 40.4% and 97.0%, respectively. Whole-body BMC was related to abdominal skinfold (r=0.819), lean mass of left arm (r=0.834), left (r=0.845) and right (r=0.868) legs, and whole-body lean mass (r=0.787), with sample power of 98.4%, 99.6%, 99.9%, 100.0% and 90.1%, respectively. Conclusion: The results supported regional lean body mass as a parameter related to BMC, with potential similar to that consistently reported for whole-body lean mass. Results also suggested that muscle strength plays an important role in improving or maintaining regional and whole-body BMC. Level of Evidence II; Development of diagnostic criteria in consecutive patients (with “gold” benchmark standard applied).

Assessment of vertebral wedge strength using cancellous textural properties derived from digital tomosynthesis and density properties from dual energy X-ray absorptiometry and high resolution computed tomography

The purpose of this study was to examine the potential of digital tomosynthesis (DTS) derived cancellous bone textural measures to predict vertebral strength under conditions simulating a wedge fracture. 40 vertebral bodies (T6, T8, T11, and L3 levels) from 5 male and 5 female cadaveric donors were utilized. The specimens were scanned using dual energy X-ray absorptiometry (DXA) and high resolution computed tomography (HRCT) to obtain measures of bone mineral density (BMD) and content (BMC), and DTS to obtain measures of bone texture. Using a custom loading apparatus designed to deliver a nonuniform displacement resulting in a wedge deformity similar to those observed clinically, the specimens were loaded to fracture and their fracture strength was recorded. Mixed model regressions were used to determine the associations between wedge strength and DTS derived textural variables, alone and in the presence of BMD or BMC information. DTS derived fractal, lacunarity and mean intercept length variables correlated with wedge strength, and individually explained up to 53% variability. DTS derived textural variables, notably fractal dimension and lacunarity, contributed to multiple regression models of wedge strength independently from BMC and BMD. The model from a scan orientation transverse to the spine axis and in the anterior-posterior view resulted in highest explanatory capability (R2adj = 0.91), with a scan orientation parallel to the spine axis and in the lateral view offering an alternative (R2adj = 0.88). In conclusion, DTS can be used to examine cancellous texture relevant to vertebral wedge strength, and potentially complement BMD in assessment of vertebral fracture risk.

The Association of Thyroid Function With Bone Density During Childhood.

Although the skeleton is a well-known thyroid hormone target organ, very little data are available on the association of thyroid function with bone outcomes during childhood. To study the association of thyroid function with bone mass during childhood. Population-based prospective cohort including 4204 children with TSH and free T4 (FT4) measured at the age of 6 years. Bone density was assessed by a total body dual-energy X-ray absorptiometry scan at the median age of 6 years (95% range, 5.6 to 7.9) and at the age of 10 years (95% range, 9.0 to 10.9) in 4204 and 3404 participants, respectively. There was an inverse association of TSH with bone mineral density (BMD) at the age of 6 (β -0.028 ± 0.011, P = 0.009) and with follow-up measurements at the age of 10 (β -0.027 ± 0.011, P = 0.014), but not with bone mineral content (BMC) at the age of 6 (β -0.028 ± 0.015, P = 0.06) or for follow-up measurements of BMC at the age of 10 (β -0.011 ± 0.015, P = 0.47). There was an inverse association of FT4 with BMD (β -0.016 ± 0.006, P = 0.014) and BMC (β -0.023 ± 0.009, P = 0.009) cross-sectionally, and also at the age of 10 years (BMD: β -0.018 ± 0.007, P = 0.007; BMC: β -0.021 ± 0.009, P = 0.020). A higher FT4 concentration is associated with lower bone mass at the age of 6 and at the age of 10 years. These data provide insights into the effects of thyroid function on bone physiology during childhood.

From bed to bench: How in silico medicine can help ageing research

Driven by the raising ethical concerns surrounding animal experimentation, there is a growing interest for non-animal methods, in vitro or in silico technologies that can be used to reduce, refine, and replace animal experimentation. In addition, animal experimentation is being critically revised in regard to its ability to predict clinical outcomes. In this manuscript we describe an initial exploration where a set of in vivo imaging based subject-specific technologies originally developed to predict the risk of femoral strength and hip fracture in osteoporotic patients, were adapted to assess the efficacy of bone drugs pre-clinically on mice. The CT2S technology we developed generates subject-specific models based on Computed Tomography that can separate fractured and non-fractured patients with an accuracy of 82%. When used in mouse experiments the use of in vivo imaging and modelling was found to improve the reproducibility of Bone Mineral Content measurements to a point where up to 63% less mice would be required to achieve the same statistical power of a conventional cross-sectional study. We also speculate about a possible approach where animal-specific and patient-specific models could be used to better translate the observation made on animal models into predictions of response in humans.

How Is Adolescent Bone Mass and Density Influenced by Early Life Body Size and Growth? The Tromsø Study: Fit Futures-A Longitudinal Cohort Study From Norway.

ABSTRACTThe effect of birth weight and childhood body mass index (BMI) on adolescents’ bone parameters is not established. The aim of this longitudinal, population‐based study was to investigate the association of birth weight, childhood BMI, and growth, with adolescent bone mass and bone density in a sample of 633 adolescents (48% girls) from The Tromsø Study: Fit Futures. This population‐based cohort study was conducted in 2010–2011 and 2012–2013 in Tromsø, Norway. Bone mineral content (BMC) and areal BMD (aBMD) were measured at total hip (TH) and total body (TB) by dual‐energy X‐ray absorptiometry (DXA) and converted to internal Z‐scores. Birth weight and childhood anthropometric measurements were retrospectively obtained from the Medical Birth Registry of Norway and childhood health records. Associations between birth weight, BMI, and growth were evaluated by fitting linear mixed models with repeated measures of BMC and aBMD at ages 15 to 17 and 18 to 20 years as the outcome. In crude analysis, a significant positive association (p < 0.05) with TB BMC was observed per 1 SD score increase in birth weight, observed in both sexes. Higher rate of length growth, conditioned on earlier size, from birth to age 2.5 years, and higher rate of weight gain from ages 6.0 to 16.5 years, conditioned on earlier size and concurrent height growth, revealed stronger associations with bone accrual at ages 15 to 20 years compared with other ages. Compared with being normal weight, overweight/obesity at age 16.5 years was associated with higher aBMD Z‐scores: β coefficient (95% confidence interval [CI]) of 0.78 (0.53, 1.03) and 1.08 (0.85, 1.31) in girls, 0.63 (0.42, 0.85) and 0.74 (0.54, 0.95) in boys at TH and TB, respectively. Similar associations were found for BMC. Being underweight was consistently negatively associated with bone parameters in adolescence. In conclusion, birth weight influences adolescent bone mass but less than later growth and BMI in childhood and adolescence. © 2018 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research

Dietary Calcium and Phosphate levels affect bone development and mesenchymal stem cell lineage allocation in neonatal pigs

Deficits in bone deposition during early‐life have been associated with increased risk of osteoporosis later in life. Bone marrow mesenchymal stem cells (MSC) are a subset of multipotent stem cells residing within the bone which provide the life‐long supply of bone forming cells. Molecular mechanisms affecting the activity and differentiation potential of MSC are still poorly understood. Our previous work has revealed that the activity and differentiation potential of MSC are subject to alteration based on neonatal nutrition. Dietary calcium (Ca) and phosphate (PO4) levels play a critical role in regulation of bone development. With increasing interest in MSC therapies and an increasing incidence of bone diseases, we aimed to elucidate the impact of marginal dietary Ca and PO4 deficiency and excess on the activity and differentiation potential of MSC during neonatal development. During a 16‐day study, 27 neonatal pigs (n= 27, 24±6h old) were fed milk replacers that were isonitrogenous and isocaloric, but either 25% deficient (D), adequate (A), or 25% in excess (E) of Ca and PO4 requirements. Piglets were fed 8 times/d at a rate to match the growth rate of sow‐reared piglets. Body weight and feed intake were recorded daily. Blood was collected on d8 and d16 for analysis. Humeri were collected for the isolation of MSC and radial/ulna bones were collected for physical measurement and determination of bone mineral content. Serum PO4 concentrations were significantly higher in the A group compared to the D group on day 8, however at day 16 the D group had the highest serum PO4 concentrations with the E group having the lowest PO4 concentrations (P&lt;0.05). Serum FGF23 was greater in the D group than the E group at 16d (77.21±1.90 pg/mL vs. 70.38±1.90 pg/mL, P&lt;0.05), with values for the A group being intermediate to these groups. The D group had lower bone mineral content and bone volume as compared to the E group. Among the MSC, those isolated from D pigs had significantly lower rates of in vivo proliferation of than those isolated from A pigs, as determined by BrdU labelling (0.063±0.007 vs. 0.089±0.007), but significantly higher in vitro proliferation than those isolated from E pigs at both 12 and 24 h post‐plating (12 h: 0.40 ±0.04 vs 0.23±0.04; 24h: 0.28±0.04 vs 0.10±004). Ca and PO4 deficiency appears, based on the gene expression of key adipogenic factors as well as cellular accumulation of neutral lipids, to have predisposed MSC towards adipogenic differentiation. MSC from D pigs had increased expression of PPARγ2, FABP4, and LPL (P&lt;0.05) and greater accumulation of neutral lipids as indicated by Oil Red O staining. Coupled with this apparent predisposition for adipocytic differentiation, a decrease in osteogenic capabilities were seen among MSC isolated from D pigs. This was determined based on reduced expression of the osteogenic regulators osteocalcin and fibronectin at d6 post differentiation. These findings demonstrated that even minor dietary deficiencies of Ca and PO4 during the neonatal period can have a profound impact on bone development. These dietary deficiencies may also program future bone health by altering the differentiation capabilities of MSC.Support or Funding InformationThis project is support by USDA grantThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Relationships Between Dual‐Energy X‐Ray Absorptiometry Bone Mineral Content and Bone Mineral Density and Standing and Sitting Bioimpedance Spectroscopy Variables in Healthy Men and Women

Bioimpedance spectroscopy (BIS) is an advanced bioimpedance method utilizing data collected over hundreds of frequencies to generate complex Cole models. Standard gel‐backed wet electrodes used on supine patients/subjects has been the accepted method for collecting BIS data which can be used to accurately calculate fluid volumes such as intra‐cellular fluid (ICF), extracellular fluid (ECF), and total body water (TBW) as well as can be used to calculate other tissues and masses. However, the use of metal electrodes used in a standing or sitting position is not well known and offers a more rapid means of performing BIS assessments. If this new method of BIS can predict variables related to bone health, it may have the potential to help track bone loss over time in clinical populations. The purpose of the study was to compare BIS measurements taken when subjects were standing and sitting using fixed metal electrodes and evaluate the relationships of raw and fluid volume data to dual‐energy X‐ray absorptiometry (DXA) data [total bone mineral content (BMC), total bone mineral density (BMD), right forearm BMD (RA_BMD), right femur BMD (RF_BMD), anterior‐posterior spine BMD (APS_BMD)] in healthy men and women. Fifty‐five healthy men and women (m = 22, f = 33, 24 +/− 8 years, 169.5 +/− 10.5 cm, 72.3 +/− 14.9 kg) participated in the study. Whole body right side BIS measurements were taken in both a sitting and standing position with both methods utilizing metal electrodes (SOZO, ImpediMed, Inc.). Whole body DXA scans were performed using a Lunar Prodigy Primo (GE Healthcare). Raw BIS data included R0, Rinf, resistance at 50 kHz (R50), reactance at 50 kHz (Xc50), and phase angle at 50 kHz (Phase50). Calculated fluid volumes from BIS included intra‐cellular fluid (ICF), extra‐cellular fluid (ECF), and total body water (TBW). DXA variables included BMC, BMD, RA_BMD, RF_BMD, and APS_BMD. All raw variables and fluid volumes from BIS were significantly related to all DXA bone variables (p &lt; 0.047) apart from Xc50 for all DXA variables (p &gt; 0.08) other than standing and total BMC (r = −0.269, p = 0.047). Total BMC and ECF resulted in the best relationship for both sitting (r = 0.889) and standing (r = 0.914). However, ICF and TBW were also highly correlated with total BMC (r &gt; 0.860) for both sitting and standing BIS measurements. The next best relationship was between ICF and total BMD (r = 0.815). All standing BIS variables had higher relationships to DXA BMC compared to sitting BIS variables with an average improvement of r = 0.018 (0.002 to 0.056) with the exception of Phase50 (sitting r = 0.629, standing r = 0.617). In conclusion, measurements from BIS in a sitting or standing position with metal electrodes were shown to be highly related to all DXA BMC and BMD measurements with the exception of Xc50. Total body and segmental BMC and BMD may be predicted from multiple BIS variables, yet more research is needed to identify which BIS variables are ideal for each specific bone variable and measurement site. Future research is also needed to identify which BIS variables are optimal for tracking changes in bone over time in both healthy and diseased populations.Support or Funding InformationSupport provided by ImpediMed, Inc. to Eastern Kentucky University. JRM is an employee and stockholder of ImpediMed, Inc.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Evaluation of bone mineralization in former preterm born children: Phalangeal quantitative ultrasound cannot replace dual-energy X-ray absorptiometry

BackgroundPreterm infants are at risk of impaired bone health in later life. Dual-energy X-ray absorptiometry-scan (DXA) is the gold standard to determine bone mineralization. Phalangeal quantitative ultrasound (pQUS) is an alternative technique that is inexpensive, easy to use and radiation-free. The aim of this study was to investigate whether both techniques reveal equivalent results. Materials and methodsSixty former preterm infants (31 boys; 29 girls) received a DXA and pQUS at age 9 to 10 years. DXA measured bone mineral content (BMC) and bone mineral density (BMD) for total body and lumbar spine (L1-4), while pQUS measured the amplitude dependent speed of sound (AD-SoS) and bone transit time (BTT) at metacarpals II-IV providing continuous values and Z-scores based on age and sex. Four statistical methods evaluated the association between both techniques: Pearson's correlation coefficients, partial correlation coefficients adjusted for gestational age, height and BMI, Bland-Altman analysis and cross tabulation. ResultsBoth techniques showed a statistically significant weak correlation for continuous values as well as Z-scores (0.291–0.462, p < 0.05). Boys had significant and relatively high correlations (0.468–0.585, p < 0.05). In comparison, the correlations for girls were not significant. Correlation coefficients further decreased while calculating the partial correlations. The Bland-Altman plots showed poor agreement. Sensitivity ranged from 33% to 92% and specificity from 16% to 68%. Positive and negative predictive values ranged from 4% to 38% and 82% to 97%, respectively. ConclusionsWe found statistically significant weak correlations and poor agreement between DXA and pQUS measurements. DXA is not equivalent to pQUS and therefore not replaceable by this technique in former preterm born children at the age of 9 to 10 years.

Effect of early nutritional intake on long-term growth and bone mineralization of former very low birth weight infants.

Preterm infants are at risk for impaired bone mineralization and growth in length later in life due to inadequate nutritional intake in the early postnatal period. To investigate whether increased nutritional supplementation of calcium, phosphate and protein in Very Low Birth Weight (VLBW) infants during the first 14days after birth was associated with improvement in length and bone development until 9-10years of age. Observational follow-up study of VLBW infants (birth weight<1500g or gestational age<32weeks) born in two consecutive years (eligible infants: 2004 n: 63 and 2005: n: 66). Cohort 2005 received higher intake of calcium, phosphate and protein with parenteral nutrition compared to Cohort 2004. Anthropometric data were collected during standard follow-up visits until five years, and additionally at 9-10years of age including measurements of bone mineral content, bone mineral density of the whole body and lumbar spine determined by dual-energy X-ray absorptiometry. Long-term growth trajectories of both cohorts were evaluated separately for participants born appropriate (AGA) and small for gestational age (SGA), stratified by gender. Multivariate linear regression was used to examine the effect of nutritional intake and clinical covariates on length and bone mineralization. Both cohorts achieved a catch-up in length to SDS within the normal range by 6months (length SDS: estimated mean (95% confidence interval (CI): 6months: Cohort 2004: -0.7 (-1.1, -0.3) Cohort 2005: -0.5 (-0.8, -0.2)). Bone mineral content and density were within the normal range and not different between the cohorts. SGA children achieved a catch-up in length at 5years with bone mineralization comparable to AGA children. Only for girls birth weight was significantly associated with length SDS (per gram: β 0.001; 95% CI (0.000, 0.003); p=0.03) There was no evidence of an association between early nutritional intake and bone mineralization. Children born as appropriate or small for gestational age preterm infants are able to catch up in length after the postnatal period, and achieve a normal length and bone mineralization at age nine-ten years. An improvement of calcium and phosphate intake during the first 14days after birth was not associated with improvement in length and bone development.