Ultradistal Tibia Research Articles

Microvascular disease not type 2 diabetes is associated with increased cortical porosity: A study of cortical bone microstructure and intracortical vessel characteristics

IntroductionFracture risk is elevated in type 2 diabetes (T2D) despite normal or even high bone mineral density (BMD). Microvascular disease (MVD) is a diabetic complication, but also associated with other diseases, for example chronic kidney disease. We hypothesize that increased fracture risk in T2D could be due to increased cortical porosity (Ct.Po) driven by expansion of the vascular network in MVD. The purpose of this study was to investigate associations of T2D and MVD with cortical microstructure and intracortical vessel parameters. MethodsThe study group consisted of 75 participants (38 with T2D and 37 without T2D). High-resolution peripheral quantitative CT (HR-pQCT) and dynamic contrast-enhanced MRI (DCE-MRI) of the ultra-distal tibia were performed to assess cortical bone and intracortical vessels (outcomes). MVD was defined as ≥1 manifestation including neuropathy, nephropathy, or retinopathy based on clinical exams in all participants. Adjusted means of outcomes were compared between groups with/without T2D or between participants with/without MVD in both groups using linear regression models adjusting for age, sex, BMI, and T2D as applicable. ResultsMVD was found in 21 (55 %) participants with T2D and in 9 (24 %) participants without T2D. In T2D, cortical pore diameter (Ct.Po.Dm) and diameter distribution (Ct.Po.Dm.SD) were significantly higher by 14.6 μm (3.6 %, 95 % confidence interval [CI]: 2.70, 26.5 μm, p = 0.017) and by 8.73 μm (4.8 %, CI: 0.79, 16.7 μm, p = 0.032), respectively. In MVD, but not in T2D, cortical porosity was significantly higher by 2.25 % (relative increase = 12.9 %, CI: 0.53, 3.97 %, p = 0.011) and cortical BMD (Ct.BMD) was significantly lower by −43.6 mg/cm3 (2.6 %, CI: −77.4, −9.81 mg/cm3, p = 0.012). In T2D, vessel volume and vessel diameter were significantly higher by 0.02 mm3 (13.3 %, CI: 0.004, 0.04 mm3, p = 0.017) and 15.4 μm (2.9 %, CI: 0.42, 30.4 μm, p = 0.044), respectively. In MVD, vessel density was significantly higher by 0.11 mm−3 (17.8 %, CI: 0.01, 0.21 mm−3, p = 0.033) and vessel volume and diameter were significantly lower by −0.02 mm3 (13.7 %, CI: −0.04, −0.004 mm3, p = 0.015) and − 14.6 μm (2.8 %, CI: −29.1, −0.11 μm, p = 0.048), respectively. ConclusionsThe presence of MVD, rather than T2D, was associated with increased cortical porosity. Increased porosity in MVD was coupled with a larger number of smaller vessels, which could indicate upregulation of neovascularization triggered by ischemia. It is unclear why higher variability and average diameters of pores in T2D were accompanied by larger vessels.

Development of a novel method to measure bone marrow fat fraction in older women using high-resolution peripheral quantitative computed tomography

SummaryBone marrow adipose tissue (BMAT) has been implicated in a number of conditions associated with bone deterioration and osteoporosis. Several studies have found an inverse relationship between BMAT and bone mineral density (BMD), and higher levels of BMAT in those with prevalent fracture. Magnetic resonance imaging (MRI) is the gold standard for measuring BMAT, but its use is limited by high costs and low availability. We hypothesized that BMAT could also be accurately quantified using high-resolution peripheral quantitative computed tomography (HR-pQCT).MethodsIn the present study, a novel method to quantify the tibia bone marrow fat fraction, defined by MRI, using HR-pQCT was developed. In total, 38 postmenopausal women (mean [standard deviation] age 75.9 [3.1] years) were included and measured at the same site at the distal (n = 38) and ultradistal (n = 18) tibia using both MRI and HR-pQCT. To adjust for partial volume effects, the HR-pQCT images underwent 0 to 10 layers of voxel peeling to remove voxels adjacent to the bone. Linear regression equations were then tested for different degrees of voxel peeling, using the MRI-derived fat fractions as the dependent variable and the HR-pQCT-derived radiodensity as the independent variables.ResultsThe most optimal HR-pQCT derived model, which applied a minimum of 4 layers of peeled voxel and with more than 1% remaining marrow volume, was able to explain 76% of the variation in the ultradistal tibia bone marrow fat fraction, measured with MRI (p < 0.001).ConclusionThe novel HR-pQCT method, developed to estimate BMAT, was able to explain a substantial part of the variation in the bone marrow fat fraction and can be used in future studies investigating the role of BMAT in osteoporosis and fracture prediction.

Association Between DXA And HR-pQCT Measurements Of BMD In Active, Recruit-aged Men And Women

Dual-energy X-ray absorptiometry (DXA) areal bone mineral density (aBMD) measurements are routinely employed to assess fracture risk despite the limitations of a two-dimensional, estimated projection of bone volume. Conversely, high-resolution peripheral quantitative computed tomography (HR-pQCT) provides three-dimensional volumetric BMD (vBMD) measurements of total, trabecular, and cortical bone, offering better characterization of fracture risk. It remains unclear whether regional aBMD accurately reflects vBMD of specific bone compartments in the distal tibia, a common injury site for military personnel. PURPOSE: To determine if lower limb aBMD correlates with distal total (Tt), trabecular (Tb) and cortical (Ct) vBMD in healthy, recruit-aged men and women. METHODS: Seventy-six recreationally active men (n = 43;26.4 ± 0.8 yrs.), and women (n = 33;26.2 ± 4.7 yrs.), free of any musculoskeletal conditions that could influence BMD, completed two HR-pQCT (XtremeCT; Scanco Medical) and one total body DXA (Lunar iDXA; GE Healthcare) scans. Total body DXA and non-dominant tibial HR-pQCT scans at the metaphysis (4% site) and diaphysis (30% site) were obtained. Lower leg aBMD was assessed in DXA scans with custom region of interest (ROI) analysis between the ultradistal tibia and the tibial plateau. Associations between variables were analyzed with Pearson’s correlation coefficient (r2); alpha was set at p < 0.05. RESULTS: aBMD positively correlated with Tt vBMD at the 4% site for men (r2 = 0.42; p < 0.001) and women (r2 = 0.17; p = 0.016) but only in men at the 30% site (r2 = 0.16; p = 0.008). aBMD positively correlated with Tb vBMD at the 4% site for men (r2 = 0.35; p < 0.001) and women (r2 = 0.20; p = 0.010), but not at the 30% site for either sex. aBMD was not correlated with Ct vBMD at the 4% site for either sex but was positively correlated with Ct vBMD at the 30% site in men (r2 = 0.12; p = 0.032). CONCLUSIONS: There is poor to moderate association between lower limb aBMD and tibial vBMD at both sites, with greater association in men than in women. aBMD is unlikely to provide a suitable assessment of distal tibial bone health. aBMD and tibial vBMD should, therefore, not be used interchangeably to examine the bone response to interventions or for the prediction of fracture risk. Supported by UK Ministry of Defence (WGCC 5.5.6-Task 0107).

A prospective case\u2013control pilot study to evaluate bone microarchitecture in children and teenagers on long-term parenteral nutrition using HR-pQCT

Long-term parenteral nutrition (PN) may induce bone complications. Tridimensional bone imaging techniques such as high-resolution peripheral quantitative computed tomography (HR-pQCT) allow the assessment of both compartmental volumetric densities and microarchitecture. Our aim was to evaluate these parameters in children and teenagers receiving long-term PN. This cross-sectional, case–control study included children older than 9 years undergoing PN for at least 2 years. They were age-, gender- and puberty-matched with healthy controls (1:2). Evaluation included biological assessment of bone metabolism (serum calcium, phosphate, and albumin; urinary calcium and creatinine; 25-OH vitamin D, osteocalcin and PTH), dual X-ray absorptiometry (DXA) and HR-pQCT at the ultradistal tibia and radius. Results are presented as median [range]. Eleven patients (3 girls) with a median age of 16 [9–19] years were included. Bone parameters assessed by HR-pQCT at the ultradistal radius and tibia were similar in patients and controls. Parathyroid hormone (PTH) levels were higher (14 [7–115] vs 16 [12–27]) and osteocalcin levels were lower (44 [15–65] vs 65 [38–142]) in patients than in controls, although within the normal range. Conclusions: there were no differences for compartmental bone densities and microarchitecture in patients undergoing chronic PN. Further longitudinal studies are required to confirm these quite reassuring preliminary results.

Longitudinal Evolution of Bone Microarchitecture and Bone Strength in Type 2 Diabetic Postmenopausal Women With and Without History of Fragility Fractures-A 5-Year Follow-Up Study Using High Resolution Peripheral Quantitative Computed Tomography.

IntroductionDiabetic bone disease is characterized by an increased fracture risk which may be partly attributed to deficits in cortical bone quality such as higher cortical porosity. However, the temporal evolution of bone microarchitecture, strength, and particularly of cortical porosity in diabetic bone disease is still unknown. Here, we aimed to prospectively characterize the 5-year changes in bone microarchitecture, strength, and cortical porosity in type 2 diabetic (T2D) postmenopausal women with (DMFx) and without history of fragility fractures (DM) and to compare those to nondiabetic fracture free controls (Co) using high resolution peripheral quantitative computed tomography (HR-pQCT).MethodsThirty-two women underwent baseline HR-pQCT scanning of the ultradistal tibia and radius and a FU-scan 5 years later. Bone microarchitectural parameters, including cortical porosity, and bone strength estimates via µFEA were calculated for each timepoint and annualized. Linear regression models (adjusted for race and change in BMI) were used to compare the annualized percent changes in microarchitectural parameters between groups.ResultsAt baseline at the tibia, DMFx subjects exhibited the highest porosity of the three groups (66.3% greater Ct.Po, 71.9% higher Ct.Po.Volume than DM subjects, p < 0.022). Longitudinally, porosity increased significantly over time in all three groups and at similar annual rates, while DMFx exhibited the greatest annual decreases in bone strength indices (compared to DM 4.7× and 6.7× greater decreases in failure load [F] and stiffness [K], p < 0.025; compared to Co 14.1× and 22.2× greater decreases in F and K, p < 0.020).ConclusionOur data suggest that despite different baseline levels in cortical porosity, T2D women with and without fractures experienced long-term porosity increases at a rate similar to non-diabetics. However, the annual loss in bone strength was greatest in T2D women with a history of a fragility fractures. This suggests a potentially non-linear course of cortical porosity development in T2D bone disease: major porosity may develop early in the course of disease, followed by a smaller steady annual increase in porosity which in turn can still have a detrimental effect on bone strength—depending on the amount of early cortical pre-damage.

Bone Microarchitecture and Strength in Long-Standing Type 1 Diabetes.

ABSTRACTType 1 diabetes (T1DM) is associated with an increased fracture risk, specifically at nonvertebral sites. The influence of glycemic control and microvascular disease on skeletal health in long‐standing T1DM remains largely unknown. We aimed to assess areal (aBMD) and volumetric bone mineral density (vBMD), bone microarchitecture, bone turnover, and estimated bone strength in patients with long‐standing T1DM, defined as disease duration ≥25 years. We recruited 59 patients with T1DM (disease duration 37.7 ± 9.0 years; age 59.9 ± 9.9 years.; body mass index [BMI] 25.5 ± 3.7 kg/m2; 5‐year median glycated hemoglobin [HbA1c] 7.1% [IQR 6.82–7.40]) and 77 nondiabetic controls. Dual‐energy X‐ray absorptiometry (DXA), high‐resolution peripheral quantitative computed tomography (HRpQCT) at the ultradistal radius and tibia, and biochemical markers of bone turnover were assessed. Group comparisons were performed after adjustment for age, gender, and BMI. Patients with T1DM had lower aBMD at the hip (p < 0.001), distal radius (p = 0.01), lumbar spine (p = 0.04), and femoral neck (p = 0.05) as compared to controls. Cross‐linked C‐telopeptide (CTX), a marker of bone resorption, was significantly lower in T1DM (p = 0.005). At the distal radius there were no significant differences in vBMD and bone microarchitecture between both groups. In contrast, patients with T1DM had lower cortical thickness (estimate [95% confidence interval]: −0.14 [−0.24, −0.05], p < 0.01) and lower cortical vBMD (−28.66 [−54.38, −2.93], p = 0.03) at the ultradistal tibia. Bone strength and bone stiffness at the tibia, determined by homogenized finite element modeling, were significantly reduced in T1DM compared to controls. Both the altered cortical microarchitecture and decreased bone strength and stiffness were dependent on the presence of diabetic peripheral neuropathy. In addition to a reduced aBMD and decreased bone resorption, long‐standing, well‐controlled T1DM is associated with a cortical bone deficit at the ultradistal tibia with reduced bone strength and stiffness. Diabetic neuropathy was found to be a determinant of cortical bone structure and bone strength at the tibia, potentially contributing to the increased nonvertebral fracture risk. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Changes in Volumetric Bone Mineral Density Over 12 Months After a Tibial Bone Stress Injury Diagnosis: Implications for Return to Sports and Military Duty

Background: Bone stress injuries (BSIs) occur in up to 20% of runners and military personnel. Typically, after a period of unloading and gradual return to weightbearing activities, athletes return to unrestricted sports participation or military duty approximately 4 to 14 weeks after a BSI diagnosis, depending on the injury location and severity. However, the time course of the recovery of the bone’s mechanical competence is not well-characterized, and reinjury rates are high. Purpose: To assess the bone microarchitecture and volumetric bone mineral density (vBMD) over 12 months after a tibial BSI diagnosis. Study Design: Case-control study; Level of evidence, 3. Methods: We enrolled 30 female athletes from the local community (aged 18-35 years) with a tibial BSI (grade ≥2 of 4 on magnetic resonance imaging) for this prospective observational study. Participants completed a baseline visit within 3 weeks of the diagnosis. At baseline and 6, 12, 24, and 52 weeks after the BSI diagnosis, we collected high-resolution peripheral quantitative computed tomography scans of the ultradistal tibia (4% of tibial length) of the injured and uninjured legs as well as pain and physical activity assessment findings. Results: From baseline to 12 weeks after the diagnosis, total, trabecular, and cortical vBMD declined by 0.58% to 0.94% (P < .05 for all) in the injured leg. Total and trabecular vBMD also declined by 0.61% and 0.67%, respectively, in the uninjured leg (P < .05 for both). At 24 weeks, mean values for all bone parameters were nearly equivalent to baseline values, and by 52 weeks, several mean values had surpassed baseline values. Of the 30 participants, 10 incurred a subsequent BSI during the course of the study, and 1 of these 10 incurred 2 subsequent BSIs. Participants who suffered an additional BSI were younger and had a later age of menarche, a greater incidence of previous fractures, and lower serum parathyroid hormone levels (P < .05 for all). Conclusion: Bone density declined in both the injured and the uninjured legs and, on average, did not return to baseline for 3 to 6 months after a tibial BSI diagnosis. The observed time to the recovery of baseline vBMD, coupled with the high rate of recurrent BSIs, suggests that improved return-to-sports and military duty guidelines may be in order.

Prior Tobacco Use Is Associated With Tibial Microarchitecture In U.S. Army Recruits: A Preliminary Analysis

Tobacco use is common and is associated with less favorable bone properties in older adults at risk for osteoporosis. Baseline bone properties are related to stress fracture risk in military populations. Whether a history of tobacco use is associated with less favorable bone microarchitectural properties in military recruits is unknown. PURPOSE: To examine the influence of prior tobacco use on bone microarchitecture using data from a large prospective field study (789 men and women from a larger planned cohort of 4000 U.S. Army recruits). METHODS: We collected high-resolution peripheral quantitative computed tomography images of the ultradistal tibia at the 4% site during the first week of basic combat training (BCT) from 556 male and 233 female recruits. Also, self-reported history of tobacco use was assessed via questionnaire. Generalized linear models stratified by sex were used to evaluate the relationship between a history of tobacco use and baseline bone microarchitecture. Models were further stratified by tobacco type. All models were adjusted for prior physical activity, recruit and parents’ level of education, race/ethnicity, age, and body mass index (BMI). RESULTS: 21.29% of recruits reported prior tobacco use. Tobacco users were more likely to be male (25.5%, p<0.0001) and white (26.8%, p=0.0007). There were no differences in tobacco use by socioeconomic status, prior physical activity, or BMI. At the ultradistal tibia, tobacco use in female recruits was associated with lower indices of cortical thickness and cortical area, with decrements ranging from -2.53% to -10.46% depending on the method of tobacco consumption (all p<0.05). In male recruits, use of tobacco pipe was associated with a 17.39% lower cortical thickness (p=0.026). There were no significant differences reported in trabecular bone parameters associated with prior tobacco use in male or female recruits. CONCLUSIONS: These data show that recruits, particularly female recruits, with a history of tobacco use may enter BCT with some less favorable microarchitectural properties, potentially placing them at greater risk for stress fracture, although this remains to be determined.

Participation In Sports During Adolescence Positively Impacts Bone Health In Recruits Entering Basic Combat Training

It is well documented that participation in sports during childhood is beneficial to skeletal health. Almost 40% of bone mineral content is attained during years of peak height velocity (females 10-14y; males 12-16y). Improving bone development during these years may be beneficial in mitigating musculoskeletal injuries (MSKIs) in Soldiers. PURPOSE: To evaluate the relationship between participation in sports during adolescence and baseline bone microarchitectural parameters in recruits entering Basic Combat Training (BCT). METHODS: Survey data on sport participation from 840 Army recruits entering BCT were analyzed (611M, 25.0±3.7 kg/m2, 20.6±3.6y; 229F, 23.6±2.7 kg/m2, 20.4±3.5y). Low impact (LI) and high impact (HI) sports were categorized according to effective load stimulus scores. Middle school (MS) was defined as grades 6-8 (11-14y) and high school (HS) as grades 9-12 (14-18y). Baseline bone characteristics were measured at the ultradistal tibia using a high resolution CT scanner. Linear models were used to evaluate the association between bone microarchitecture and timing and impact category of sport played. Models were adjusted for ethnicity, BMI, age, and parents’ education. Effect estimates (EE) and p values for bone parameters compared to recruits who did not play sports (98M, 46F) are presented. RESULTS: Table 1 shows that participation in both low and high impact sports during adolescence had a significant effect on baseline bone measures in male and female recruits compared to those who did not participate in sports. While male sports participation in HS had a greater effect than MS sports participation, the opposite was observed in females. We found no significant effects in trabecular thickness, spacing or number. CONCLUSION: Promoting sports participation in children and adolescents, particularly during peak growth years, is important in providing long term skeletal health benefits and may help to reduce MSKIs in Soldiers.

Skeletal loading score is associated with bone microarchitecture in young adults.

We determined the association between a new skeletal loading (SkL) score reflecting physical activity from age 11 to adulthood, the bone specific physical activity questionnaire (BPAQ) and bone microarchitecture in young Black and White men and women. We conducted a cross-sectional study of young ([mean ± SD] 23.7 ± 3.3 years) Black (n = 51 women, n = 31 men) and White (n = 50 women, n = 49 men) adults. Microarchitecture and estimated bone strength (by micro-finite element analysis) were assessed at the ultradistal tibia using high-resolution peripheral quantitative computed tomography (HR-pQCT). Physical activity questionnaires were administered and a SkL score was derived based on ground reaction force, rate of loading, frequency, duration, and life period of participation per activity from age 11 onwards. BPAQ score was also calculated. We used multiple linear regression to determine associations between both SkL score and BPAQ score and bone outcomes, adjusting for age, height, weight, sex, and race. We found that SkL score, which accounts for current and historical physical activity, was significantly associated with most cortical bone parameters at the tibia including area, area fraction, porosity, thickness, and tissue mineral density (R2 = 0.27-0.55, all p < 0.01). Further, trabecular thickness, separation, number, and bone mineral density (R2 = 0.22-0.32, all p < 0.01), as well as stiffness and failure load (R2 = 0.63-0.65, all p < 0.01), were associated with the SkL score. The BPAQ was also significantly associated with most bone parameters, but to a lesser degree than SkL score. These findings suggest that among young adults, greater amounts of osteogenic physical activity, as assessed by the SkL score and BPAQ are associated with improved bone microarchitecture and strength. With the potential to predict bone parameters in young adults, these scores may ultimately serve to identify those most vulnerable to fracture.

Changes in Bone Microarchitecture and Estimated Bone Strength Over 12 Months After Tibial Stress Fracture Diagnosis: Implications for Return to Sport

Stress fractures (SF), common injuries among athletes, have been reported in up to 20% of track and field athletes. Typically, after a period of unloading and gradual return to weight-bearing activities, athletes return to unrestricted participation in their given sport 12-14 weeks after SF diagnosis. However, the time course of the recovery of mechanical competence of the bone is not well characterized, and reinjury rates are high. PURPOSE: To determine changes in bone microarchitecture and estimated bone strength over 12 months following tibial SF diagnosis. METHODS: We enrolled 30 women, ages 18-35, with a tibial SF (grade 2 or higher) for this prospective observational study. Participants completed a baseline visit within 3 weeks of SF diagnosis. At baseline, 6, 12, 24, and 52 weeks following SF diagnosis, we collected high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the ultradistal tibia (4% of tibia length), background and lifestyle questionnaires, and a physical activity assessment. RESULTS: Over the initial 12 weeks, total volumetric bone mineral density (vBMD) declined by 1.2% (p=0.001), trabecular vBMD by 1.2% (p=0.006), cortical thickness by -1.0% (p=0.007), and bone volume/total volume by 1.2% (p=0.008). At 24 weeks, mean values for all bone parameters were nearing baseline values, and by 52 weeks, mean values had surpassed baseline values. A similar trend was seen in estimated bone strength, though changes did not reach statistical significance. Of the 30 participants, 7 incurred a subsequent SF during the course of the 12 month-follow up and 2 incurred ≥2 subsequent SFs. CONCLUSION: Persisting decrements in bone microarchitecture and estimated bone strength suggest bone mechanical integrity does not return to baseline for 3-6 months after tibial SF diagnosis. This, coupled with the high rate of recurrent SFs, suggests more conservative return to sport guidelines may be in order. The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the U.S. Army or of the U.S. Department of Defense. This abstract has been approved for public release with unlimited distribution.

Regional Changes in Density and Microarchitecture in the Ultradistal Tibia of Female Recruits After U.S. Army Basic Combat Training

Musculoskeletal injuries, such as stress fracture, are responsible for over 10-million lost-duty days among U.S. Army Soldiers. During Basic Combat Training (BCT), an 8- to 10-week program that transforms civilians into Soldiers, women are four times more likely than men to sustain a stress fracture. In this work, we performed high-resolution peripheral quantitative computed tomography scans on the ultradistal tibia of 90 female recruits [age = 21.5 ± 3.3 (mean ± standard deviation) years] before the start of BCT and after 8 weeks into BCT. Then, we divided the scanned bone volume into four sectors—lateral, posterior, medial, and anterior—and computed the bone density and microarchitectural parameters in each of the four sectors pre- and post-BCT. We used linear mixed models to estimate the mean difference for bone density and microarchitectural parameters, while controlling for age, race, and pre-BCT body mass index. Our results revealed that the total volumetric bone mineral density, trabecular volumetric bone mineral density, and trabecular thickness increased (p < 0.05) in each of the four sectors. In addition, cortical thickness and trabecular bone volume/total volume increased in both medial and posterior sectors (p < 0.05). Overall, six and five out of nine parameters improved in the medial and posterior sectors, respectively, after BCT. In conclusion, the heightened physical activity during BCT led to the most beneficial bone adaptation in the medial and posterior sectors of the ultradistal tibia, which is indicative of higher loading in these sectors during activities performed in the course of BCT.

Pediatric bone evaluation with HR-pQCT: A comparison between standard and height-adjusted positioning protocols in a cohort of teenagers with chronic kidney disease

BackgroundHigh-resolution peripheral quantitative computed tomography (HR-pQCT) evaluates different components of bone fragility. The positioning and length of the region of interest (ROI) in growing populations remain to be defined. MethodsUsing HR-pQCT at the ultradistal tibia, we compared a single-center cohort of 28 teenagers with chronic kidney disease (CKD) at a median age of 13.6 (range, 10.2–19.9) years to local age-, gender-, and puberty-matched healthy peers. Because of the potential impact of short stature, bone parameters were assessed on two different leg-length-adjusted ROIs in comparison to the standard analysis, namely the one applied in adults. The results are presented as median (range). ResultsAfter matching, SDS height was −0.9 (−3.3;1.6) and 0.3 (−1.4;2.0) in patients and controls, respectively (P<0.001). In younger children (e.g., prepubertal, n=11), bone texture parameters and bone strength were not different using standard analysis. However, using a height-adjusted ROI enabled better characterization of cortical bone structure. In older patients (e.g., pubertal, n=17), there were no differences for height between patients and controls: with the standard evaluation, cortical bone area and cortical thickness were significantly lower in CKD patients: 85 (50–124) vs. 108 (67–154) mm2 and 0.89 (0.46–1.31) vs 1.09 (0.60–1.62) mm, respectively (both P<0.05). ConclusionsAdapting the ROI to leg length enables better assessment of bone structure, especially when height discrepancies exist between controls and patients. Larger cohorts are required to prospectively validate this analytic HR-pQCT technique.

The interplay between bone and vessels in pediatric CKD: lessons from a single-center study.

Mineral and bone disorders associated to chronic kidney disease (CKD-MBD) are a daily challenge for pediatric nephrologists, with a significant risk of long-term bone and vascular comorbidities. This single-center study is a prospective transversal evaluation of pediatric CKD patients of our center, part of the European 4C study. In addition to clinical and biochemical data, vascular and bone evaluation was performed: 24-h blood pressure assessment, carotid intima-media thickness (cIMT), pulse wave velocity (PWV), and high-resolution peripheral quantitative computed tomography (HR-pQCT) at the ultra-distal tibia. Results are presented as median (range). At a median age of 12.9years (10.2-17.9), SDS height of - 1.0 (- 3.3-1.2) and estimated glomerular filtration rate (eGFR) of 33mL/min/1.73m2 (11-72), 32 patients (8 girls) were evaluated. Median calcium, phosphate, parathyroid hormone (PTH), and 25 OHD3 levels were 2.44mmol/L (2.24-2.78), 1.43mmol/L (1.0-2.7), 80pg/mL (9-359), and 70nmol/L (32-116), respectively. Bivariate Spearman and backward multivariable analyses showed that calcium and bone trabecular thickness (Tb.Th), were positively associated with diastolic and mean arterial blood pressure (both for the 24h, day and night assessment), whereas PTH and vitamin D did not predict blood pressure. We show that the greater the serum levels of calcium, the greater the (diastolic and mean) blood pressure; moreover, the greater the Tb. Th, the greater the (diastolic and mean) blood pressure. The role of calcium supplements to explain such findings in early pediatric CKD can be discussed.

Regional variation of bone density, microarchitectural parameters, and elastic moduli in the ultradistal tibia of young black and white men and women.

Whole-bone analyses can obscure regional heterogeneities in bone characteristics. Quantifying these heterogeneities might improve our understanding of the etiology of injuries, such as lower-extremity stress fractures. Here, we performed regional analyses of high-resolution peripheral quantitative computed tomography images of the ultradistal tibia in young, healthy subjects (age range, 18 to 30 years). We quantified bone characteristics across four regional sectors of the tibia for the following datasets: white women (n = 50), black women (n = 51), white men (n = 50), black men (n = 34), and all subjects (n = 185). After controlling for potentially confounding variables, we observed statistically significant variations in most of the characteristics across sectors (p < 0.05). Most of the bone characteristics followed a similar trend for all datasets but with different magnitudes. Regardless of race or sex, the anterior sector had the lowest trabecular and total volumetric bone mineral density and highest trabecular separation (p < 0.001), while cortical thickness was lowest in the medial sector (p < 0.05). Accordingly, the anterior sector also had the lowest elastic modulus in the anterior-posterior and superior-inferior directions (p < 0.001). In all sectors, the mean anisotropy was ~3, suggesting cross-sector similarity in the ratios of loading in these directions. In addition, the bone characteristics from regional and whole-bone analyses differed in all datasets (p < 0.05). Our findings on the heterogeneous nature of bone microarchitecture in the ultradistal tibia may reflect an adaptation of the bone to habitual loading conditions.

Children and adolescents with cystic fibrosis display moderate bone microarchitecture abnormalities: data from high-resolution peripheral quantitative computed tomography.

Cystic fibrosis-related bone disease (CFBD) may alter bone health, ultimately predisposing patients to bone fractures. Our aim was to assess bone microstructure using high-resolution peripheral quantitative tomography (HR-pQCT) in a cohort of children and teenagers with CF in comparison to age-, puberty-, and gender-matched healthy volunteers (HVs). In this single-center, prospective, cross-sectional study, we evaluated the HR-pQCT bone parameters of CF patients and compared them to those of the healthy volunteers. At a median age of 15.4 [range, 10.5-17.9]years, 37 CF patients (21 boys) with 91% [range, 46-138%] median forced expiratory volume in 1s were included. At the ultradistal tibia, CF patients had a smaller bone cross-sectional area (579 [range, 399-1087]mm2) than HVs (655 [range, 445-981]mm2) (p=0.027), related to a decreased trabecular area, without any significant differences for height. No other differences were found (trabecular number, separation, thickness, or distribution) at the radial or tibial levels. Bone structure was different in patients receiving ursodeoxycholic acid and those bearing two F508del mutations. In our cohort of children and teenagers with good nutritional and lung function status, bone microstructure evaluated with HR-pQCT was not severely affected. Minimal microstructure abnormalities observed at the tibial level may be related to the cystic fibrosis transmembrane conductance regulator defect alone; the long-term consequences of such impairment will require further evaluation.

Bone Strength Estimated by Micro-Finite Element Analysis (µFEA) Is Heritable and Shares Genetic Predisposition With Areal BMD: The Framingham Study.

Genetic factors contribute to the risk of bone fractures, partly because of effects on bone strength. High-resolution peripheral quantitative computed tomography (HR-pQCT) estimates bone strength using micro-finite element analysis (µFEA). The goal of this study was to investigate if the bone failure load estimated by HR-pQCT-based µFEA is heritable and to what extent it shares genetic regulation with areal bone mineral density (aBMD). Bone microarchitecture was measured by HR-pQCT at the ultradistal tibia and ultradistal radius in adults from the Framingham Heart Study (n = 1087, mean age 72 years; 57% women). Radial and tibial failure load in compression were estimated by µFEA. Femoral neck (FN) and ultradistal forearm (UD) aBMD were measured by dual-energy X-ray absorptiometry (DXA). Heritability (h2 ) of failure load and aBMD and genetic correlations between them was estimated adjusting for covariates (age and sex). Failure load values at the non-weight-bearing ultradistal radius and at the weight-bearing ultradistal tibia were highly correlated (r = 0.906; p < 0.001). Estimates of h2 adjusted for covariates were 0.522 for the radius and 0.497 for the tibia. Additional adjustment for height did not impact on the h2 results, but adjustment for aBMD at the UD and FN somewhat decreased h2 point estimates: 0.222 and 0.380 for radius and tibia, respectively. In bivariate analysis, there was a high phenotypic and genetic correlation between covariate-adjusted failure load at the radius and UD aBMD (ρP = 0.826, ρG = 0.954, respectively), whereas environmental correlations were lower (ρE = 0.696), all highly significant (p < 0.001). Similar correlations were observed between tibial failure load and femoral neck aBMD (ρP = 0.577, ρG = 0.703, both p < 0.001; ρE = 0.432, p < 0.05). These data from adult members of families from a population-based cohort suggest that bone strength of distal extremities estimated by micro-finite element analysis is heritable and shares some genetic composition with areal BMD, regardless of the skeletal site. © 2017 American Society for Bone and Mineral Research.

Determinants of microstructural, dimensional and bone mineral changes postpartum in Swedish women.

During lactation, areal (a) and volumetric (v) bone mineral density (BMD) are known to temporarily decrease. Factors that affect skeletal changes postpartum are not fully elucidated. The aim was to study determinants of the previously observed changes in aBMD at lumbar spine, and cortical vBMD, microstructure and dimensions at ultra-distal tibia postpartum. Women (25-40 years) were studied longitudinally at 2 weeks (baseline) and 4 months (n 81), 12 months (n 79) and 18 months (n 58) postpartum. At each visit, blood samples were collected, body weight and height were measured and information about lactation habits, oestrogen contraceptives and physical activity was obtained. Ca intake was measured using 4-d food diaries at 4 months postpartum. Serum 25-hydroxyvitamin D (25OHD) was analysed by liquid chromatography-tandem MS. Skeletal changes were assessed with dual-energy X-ray absorptiometry and high-resolution peripheral quantitative computed tomography. Mean baseline BMI was 24·8 (sd 3·1) kg/m2. Median (quartiles 1-3) duration of total lactation was 8·1 (6·8-10·4) months. Longer duration of full lactation was associated with larger decreases of lumbar spine aBMD and tibia vBMD and microstructure. Higher baseline body weight was associated with smaller decreases in tibia vBMD and microstructure. Higher Ca intake was associated with smaller decreases in tibia cortical vBMD and thickness. Higher baseline 25OHD was only associated with larger decreases in lumbar spine aBMD. In conclusion, lactation and body weight were the main determinants of skeletal changes during the first 18 months postpartum. Ca intake and serum concentrations of 25OHD appear to have different associations with cortical and trabecular bone.

Current Physical Activity Is Independently Associated With Cortical Bone Size and Bone Strength in Elderly Swedish Women.

Physical activity is believed to have the greatest effect on the skeleton if exerted early in life, but whether or not possible benefits of physical activity on bone microstructure or geometry remain at old age has not been investigated in women. The aim of this study was to investigate if physical activity during skeletal growth and young adulthood or at old age was associated with cortical geometry and trabecular microarchitecture in weight-bearing and non-weight-bearing bone, and areal bone mineral density (aBMD) in elderly women. In this population-based cross-sectional study 1013 women, 78.2 ± 1.6 (mean ± SD) years old, were included. Using high-resolution 3D pQCT (XtremeCT), cortical cross-sectional area (Ct.CSA), cortical thickness (Ct.Th), cortical periosteal perimeter (Ct.Pm), volumetric cortical bone density (D.Ct), trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular separation (Tb.Sp) were measured at the distal (14% level) and ultra-distal tibia and radius, respectively. aBMD was assessed using DXA (Hologic Discovery A) of the spine and hip. A standardized questionnaire was used to collect information about previous exercise and the Physical Activity Scale for the Elderly (PASE) was used for current physical activity. A linear regression model (including levels of exercise during skeletal growth and young adulthood [10 to 30 years of age], PASE score, and covariates) revealed that level of current physical activity was independently associated with Ct.CSA (β = 0.18, p < 0.001) and Ct.Th (β = 0.15, p < 0.001) at the distal tibia, Tb.Th (β = 0.11, p < 0.001) and BV/TV (β = 0.10, p = 0.001) at the ultra-distal tibia, and total hip aBMD (β = 0.10, p < 0.001). Current physical activity was independently associated with cortical bone size, in terms of thicker cortex but not larger periosteal circumference, and higher bone strength at the distal tibia on elderly women, indicating that physical activity at old age may decrease cortical bone loss in weight-bearing bone in elderly women. © 2016 American Society for Bone and Mineral Research.

FES-rowing attenuates bone loss following spinal cord injury as assessed by HR-pQCT.

Neurologically motor complete spinal cord injury (SCI) presents a unique model of bone loss whereby specific regional sites are exposed to a complete loss of voluntary muscle-induced skeletal loading against gravity. This results in a high rate of bone loss, especially in the lower limbs where trabecular bone mass decreases by ~50-60% and cortical bone mass decreases by 25-34% before the rate of bone loss slows. These SCI-induced losses that are likely superimposed on continual age-related bone losses, increase the risk of low-impact fragility fracture. The fracture incidence 20 years post SCI is reported to be 4.6% per year. An intervention that effectively prevents, attenuates, or reverses bone loss is therefore highly desirable. We present a case study of an individual with chronic complete SCI, where bone loss has been attenuated following long-term functional electrical stimulation (FES)-rowing training. In this case study, we characterize the ultradistal tibia and ultradistal radius of the FES-rower with chronic complete SCI using high-resolution-peripheral quantitative computed tomography. These data are compared with a group of FES-untrained individuals with chronic complete SCI and to a normative non-SCI cohort. The evidence suggests, albeit from a single individual, that long-term FES-rowing training can attenuate bone loss secondary to chronic complete SCI. Indeed, key FES-rower's bone metrics for the ultradistal tibia more closely resemble normative age-matched values, which may have clinical significance since the majority of fragility fractures in chronic SCI occur in the lower extremities.