Measures Of Bone Microarchitecture Research Articles

Prednisolone impairs trabecular bone score changes in adolescents with 21-hydroxylase deficiency.

Individuals with 21-hydroxylase deficiency (21OHD) require lifelong glucocorticoid (GC) therapy, which increases their risk of fragility fractures. However, fractures in GC-treated individuals can occur at normal bone mineral density (BMD) levels, suggesting an alteration in the bone microarchitecture. To evaluate trabecular bone microarchitecture and its changes in adolescents with 21OHD. We enrolled 38 adolescents with 21OHD for whom complete clinical data and baseline and follow-up lumbar spine bone mineral density (LSBMD) measurements were available. The mean duration was 1.5 ± 0.6 years. Trabecular bone score (TBS), an indirect measurement of bone microarchitecture, was analyzed using iNsight™ software version 3.0. Impaired BMD and TBS were defined at Z-scores ≤ -1.5. At baseline, participants (55% female; 68% salt-wasting type; mean age, 15.2 ± 3.8 years; bone age, 17.5 ± 2.8 years; mean GC dose, 18.5 ± 6.5 mg/m2/day) had the prevalence of impaired BMD and TBS of 5% and 18%, respectively. During follow-up, adolescents with 21OHD receiving prednisolone showed a lower annual percentage change in TBS than those who received hydrocortisone (p = 0.028). A stepwise regression analysis showed that body mass index percentile (p < 0.001) and testosterone concentration (p = 0.002) were independent positive predictors of the baseline TBS Z-score, whereas prednisolone use was the only negative predictor of the annual percentage change in TBS (p = 0.002). Adolescents with 21OHD have a high prevalence of impaired bone microarchitecture. Furthermore, prednisolone therapy is associated with impaired bone microarchitecture development, suggesting that hydrocortisone may better preserve bone microarchitecture and should be considered the first-line treatment for this population.

Bone health in young adults with type 1 diabetes and progressive eGFR decline

BackgroundType 1 Diabetes (T1D) is associated with increased risk of fractures, worsened by presence of microvascular complications. This study’s objective is to determine the impact of progressive decline in estimated glomerular filtration rate (eGFR) on bone biomarkers and bone microarchitecture in youth with T1D.MethodsSlopes of eGFR were calculated using measures obtained at four timepoints from adolescence to young adulthood. Participants were identified as eGFR decliners if eGFR decreased ≥ 3ml/min/1.73m2/year. Bone health was assessed in young adulthood by high resolution peripheral quantitative computed tomography (HRpQCT Xtreme CTII) and bone biomarkers; osteocalcin, procollagen 1 intact n-terminal pro-peptide (P1NP), c-terminal telopeptide (CTX), and bone specific alkaline phosphatase. The relationship between diabetes duration, glycated hemoglobin, body mass index (BMI) and vitamin D level on bone biomarkers and microarchitecture was evaluated. Linear regression analysis was used for the statistical analysis in this study.ResultsNinety-nine study participants were studied with longitudinal evaluation of eGFR over 7.4 ± 1.0 years with mean age of 14.7 ± 1.7 years at baseline. Cross sectional evaluation of bone was performed at 21.3 ± 2.1 years. 44% participants had eGFR decline and showed 5% higher cortical porosity diameter than non-decliners (p = 0.035). Greater diabetes duration was associated with higher trabecular separation (p = 0.004) and lower trabecular number (p = 0.01). Higher level of 25 hydroxy-vitamin D was associated with lower trabecular separation (p = 0.01). Elevated glycated hemoglobin (p = 0.0008) and BMI (p = 0.009), were associated with lower markers of bone formation.ConclusionMild increase in cortical porosity diameter was found in youth with T1D and eGFR decline, however, overall measures of bone microarchitecture on HR-pQCT were similar between both groups and there were no statistically significant changes in bone biomarkers. Hence, skeletal impairments were limited in youth with different eGFR trajectories near peak bone mass. Longitudinal HR-pQCT studies are needed to further understand the impact of eGFR decline on bone microarchitecture. Optimal glycemic control, normal BMI and vitamin D status were supported by this study as important markers for good bone health.

Biomechanical properties of a suture anchor system from human allogenic mineralized cortical bone matrix for rotator cuff repair

BackgroundSuture anchors (SAs) made of human allogenic mineralized cortical bone matrix are among the newest developments in orthopaedic and trauma surgery. Biomechanical properties of an allogenic mineralized suture anchor (AMSA) are not investigated until now. The primary objective was the biomechanical investigation of AMSA and comparing it to a metallic suture anchor (MSA) and a bioabsorbable suture anchor (BSA) placed at the greater tuberosity of the humeral head of cadaver humeri. Additionally, we assessed the biomechanical properties of the SAs with bone microarchitecture parameters.MethodsFirst, bone microarchitecture of 12 fresh frozen human cadaver humeri from six donors was analyzed by high-resolution peripheral quantitative computed tomography. In total, 18 AMSAs, 9 MSAs, and 9 BSAs were implanted at a 60° angle. All three SA systems were systematically implanted alternating in three positions within the greater tuberosity (position 1: anterior, position 2: central, position 3: posterior) with a distance of 15 mm to each other. Biomechanical load to failure was measured in a uniaxial direction at 135°.ResultsMean age of all specimens was 53.6 ± 9.1 years. For all bone microarchitecture measurements, linear regression slope estimates were negative which implies decreasing values with increasing age of specimens. Positioning of all three SA systems at the greater tuberosity was equally distributed (p = 0.827). Mean load to failure rates were higher for AMSA compared to MSA and BSA without reaching statistical significance between the groups (p = 0.427). Anchor displacement was comparable for all three SA systems, while there were significant differences regarding failure mode between all three SA systems (p < 0.001). Maximum load to failure was reached in all cases for AMSA, in 44.4% for MSA, and in 55.6% for BSA. Suture tear was observed in 55.6% for MSA and in 22.2% for BSA. Anchor breakage was solely seen for BSA (22.2%). No correlations were observed between bone microarchitecture parameters and load to failure rates of all three suture anchor systems.ConclusionsThe AMSA showed promising biomechanical properties for initial fixation strength for RCR. Since reduced BMD is an important issue for patients with chronic rotator cuff lesions, the AMSA is an interesting alternative to MSA and BSA. Also, the AMSA could improve healing of the enthesis.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12891-022-05371-0.

HR-pQCT Measures of Bone Microarchitecture in Type 1 and Type 2 Diabetes Mellitus: Systematic Review and Meta-analysis

HR-pQCT Measures of Bone Microarchitecture in Type 1 and Type 2 Diabetes Mellitus: Systematic Review and Meta-analysis

Long-term Effect of Denosumab on Bone Microarchitecture as Assessed by Tissue Thickness-Adjusted Trabecular Bone Score (TBS) in Postmenopausal Women with Osteoporosis: Results from the Freedom and Open-Label Extension (OLE)

TBS is an indirect measure of bone microarchitecture assessed on lumbar spine (LS) DXA scans and provides information beyond bone mineral density (BMD). TBS algorithm has been updated to account for regional soft tissue noise in DXA images. This retrospective analysis applied updated built-in tissue thickness-adjusted TBS algorithm to investigate the long-term effect of denosumab on bone microarchitecture in FREEDOM and OLE. This analysis included 279 postmenopausal women with LS or total hip BMD T-score <−2.5 and ≥−4.0 who completed the FREEDOM DXA sub study and continued in the OLE study: 150 women received denosumab 60 mg subcutaneously every 6 months for 3 years and same-dose open-label denosumab for 7 years (long-term denosumab group); 129 women received placebo for 3 years and open-label denosumab for 7 years (crossover denosumab group). BMD and TBS were assessed on LS DXA scans, blinded from treatment allocation, at FREEDOM: baseline, Month 1, and Years 1, 2, and 3; and at OLE: baseline, Years 1, 2, 3, 5, and 7. Baseline characteristics were similar between groups. Long-term denosumab led to significant and progressive increases in TBS over 10 years of treatment (Figure). A similar trend was observed in the crossover group during 7 years of denosumab therapy. In the long-term denosumab group, % of patients with normal microarchitecture (TBS >1.074) increased from 26.1% at baseline to 53.2% up to Year 10, and % of patients with degraded (TBS ≤1.027) or partially degraded (1.027< TBS≤1.074) microarchitecture decreased from 48.6% to 29.1% and from 25.4% to 17.7%, respectively (P < 0.0001; TBS thresholds equivalent to 1.230 and 1.310 for the classical TBS algorithm corrected for body mass index). A similar improvement in bone microarchitecture was observed in the crossover group from OLE baseline up to OLE Year 7 (P < 0.0001). Over the course of long-term denosumab treatment, TBS changes were largely unrelated to LS BMD changes: r2 was 0.05 from baseline to Year 10 in the long-term group and 0.28 from OLE baseline to OLE Year 7 in the crossover group. Up to 10 years of denosumab treatment significantly and progressively improved TBS assessment of bone microarchitecture independently of BMD in postmenopausal women with osteoporosis.

Usefulness of the Trabecular Bone Score in Assessing the Risk of Vertebral Fractures in Patients with Cirrhosis.

The trabecular bone score (TBS), a surrogate measure of bone microarchitecture, provides complementary information to bone mineral density (BMD) in the assessment of osteoporotic fracture risk. This cross-sectional study aimed to determine whether TBS can identify patients with liver cirrhosis that are at risk of vertebral fractures. We enrolled 275 patients who completed evaluations for lumbar BMD, TBS, and vertebral fractures between November 2018 and April 2021. BMD was measured using dual-energy X-ray absorptiometry (DXA), TBS was calculated by analyzing DXA images using TBS iNsight software, and vertebral fractures were evaluated using Genant’s semi-quantitative method with lateral X-ray images. Factors associated with vertebral fractures and their correlation with the TBS were identified using regression models. Of the enrolled patients, 128 (47%) were female, the mean age was 72 years, and 62 (23%) were diagnosed with vertebral fractures. The prevalence of vertebral fractures was higher in women than in men (33% vs. 14%; p < 0.001). The unadjusted odds ratio (OR) of the vertebral fractures for one standard deviation decrease in TBS and BMD was 2.14 (95% confidence interval [CI], 1.69–2.73) and 1.55 (95% CI, 1.26–1.90), respectively. After adjusting for age, sex, and BMD, the adjusted OR of the vertebral fractures in TBS was 2.26 (95% CI, 1.52–3.35). Multivariate linear regression analysis showed that TBS was independently correlated with age (β = −0.211), body mass index (β = −0.251), and BMD (β = 0.583). TBS can help identify patients with cirrhosis at risk of vertebral fractures.

Dairy Food Intake Is Not Associated with Measures of Bone Microarchitecture in Men and Women: The Framingham Osteoporosis Study.

Previous studies reported that dairy foods are associated with higher areal bone mineral density (BMD) in older adults. However, data on bone strength and bone microarchitecture are lacking. We determined the association of dairy food intake (milk, yogurt, cheese, milk + yogurt, and milk + yogurt + cheese, servings/week) with high resolution peripheral quantitative computed tomography (HR-pQCT) measures of bone (failure load, cortical BMD, cortical thickness, trabecular BMD, and trabecular number). This cross-sectional study included participants with diet from a food frequency questionnaire (in 2005–2008 and/or 1998–2001) and measurements of cortical and trabecular BMD and microarchitecture at the distal tibia and radius (from HR-pQCT in 2012–2015). Sex-specific multivariable linear regression estimated the association of dairy food intake (energy adjusted) with each bone measure adjusting for covariates. Mean age was 64 (SD 8) years and total milk + yogurt + cheese intake was 10.0 (SD 6.6) and 10.6 (6.4) servings/week in men and women, respectively. No significant associations were observed for any of the dairy foods and bone microarchitecture measures except for cheese intake, which was inversely associated with cortical BMD at the radius (p = 0.001) and tibia (p = 0.002) in women alone. In this cohort of primarily healthy older men and women, dairy intake was not associated with bone microarchitecture. The findings related to cheese intake and bone microarchitecture in women warrant further investigation.

Higher Serum 25-Hydroxy Vitamin D Is Associated With Better Measures of Bone Microarchitecture and Strength

ObjectivesTo determine whether serum 25-hydroxy vitamin D (25-OH D) levels are associated with bone microarchitecture and strength in a multi-racial cohort of young adults. We also determined if race and calcium intake modified these associations. MethodsThis cross-sectional study included 176 young adults who identified as Asian, Black, or White (50% women). High-resolution peripheral quantitative computed tomography (HR-pQCT, 2nd generation) scans of the distal radius and tibia were used to assess bone microarchitecture and strength by micro-finite element analysis. We measured 25-OH D levels (ng/mL, immunoassay), dietary intake (Block’s Food Frequency Questionnaire), and physical activity (questionnaire). We used linear regression to estimate the association between 25-OH D and standardized bone measures, adjusting for race, sex, age, weight, height, calcium intake, and physical activity. The interactions of 25-OH D with race and calcium intake (mg/d) were tested and models were stratified for significant interactions (P < 0.05). ResultsMean age and BMI were 23.7 ± 3.1 years and 24.1 ± 3.1 kg/m2, respectively. 43.9% of the subjects were vitamin D deficient (<20 ng/ml) with greater prevalence in Asian (38.9%) and Black (43.1%) compared to White (18.1%) subjects (P < 0.001 for group differences). At the distal radius, higher 25-OH D was related with higher cortical area (β ± SE = 0.018 ± 0.006, P = 0.005), cortical porosity (β ± SE = 0.023 ± 0.008, P = 0.006) and failure load (β ± SE = 0.023 ± 0.007, P = 0.001). At the distal tibia, higher 25-OH D was related with higher trabecular density (β ± SE = 0.020 ± 0.008, P = 0.015), trabecular thickness (β = 0.016 ± 0.008 P = 0.044) and lower trabecular separation (β ± SE = –0.017 ± 0.008 P = 0.046). There were no significant interactions for 25-OH D and calcium intake. Significant interactions were seen for 25-OH D and race, with stronger associations observed in White compared to Asian or Black subjects. ConclusionsThis study suggests that higher 25-OH D is associated with better bone microarchitecture and strength at the distal radius and tibia in young adults. As poor bone microarchitecture is associated with increased fracture risk, these findings may have implications for fracture risk later in life. Funding SourcesU.S. Army Medical Research Acquisition Activity.

P159 Patients with Inflammatory Bowel Disease Present with Lower Trabecular Bone Scores

Abstract Background Patients with inflammatory bowel diseases (IBD) have lower bone mineral density (BMD). However, BMD does not reflect bone micro-structure/geometry, nor indicates the intrinsic properties of bone tissue. The trabecular bone score (TBS) delivers an indirect measurement of bone microarchitecture and predicts fracture risk independent of bone density. The aim of this study was to assess if patients with IBD present with lower TBS vs a healthy control (HC) population and to identify variables associated with lower TBS. Methods This prospective cohort study included patients with active Crohn’s disease (CD) or ulcerative colitis (UC) and a matched HC group. Patients with ostomies, short gut or known endocrine co-morbidities associated with low BMD, patients with osteoporosis on pharmacologic therapy were excluded. L1-L4 TBS and BMD parameters were determined by dual-energy X-ray absorptiometry (DXA) using a GE Lunar iDXA scan and TBS iNsight™ and GE enCORE™. Other collected variables included demographics, disease phenotype, laboratories (25-OH vitamin D [25OHD] and parathyroid hormone levels [PTH]), disease activity (c-reactive protein [CRP], simple endoscopic score [SES-CD] in CD, and endoscopic Mayo score [EMS] in UC). IBD severity was stratified based on endoscopy: mild (EMS=1 in UC or SES-CD=3–6), moderate (EMS=2 or SES-CD=7–15) and severe (EMS=3 or SES-CD&amp;gt;15). The primary outcome was the L1-L4 TBS. Secondary outcomes were left total and neck femoral BMD and the L1-L4 region BMD. Results A total of 141 patients were included (115 IBD and 26 HC). Patients with IBD had significantly lower TBS, femoral and L1-L4 BMD and Z-Scores when compared to controls (Figure 1). Endoscopic disease activity was not associated with TBS (Figure 2) or total/neck femur and L1-L4 BMD and Z-scores (p&amp;gt;0.05 for all). When stratifying levels by 25OHD quartiles, patients with 25OHD ≥28 ng/mL (the highest 50th percentile of the study population) had significantly higher TBS Z-scores when compared to those with 25OHD ≤28 ng/mL (0.3 [-0.2 – 1.1] vs -0.1 [-1.1 – 0.5], p=0.002). No associations were seen between TBS Z-scores and use of steroids, gender, type of IBD (UC vs CD), smoking status or when comparing females 50 years or older vs the rest of the group (p&amp;gt;0.05 for all). Moreover, there were no differences in TBS between patients who did or did not engage in resistance exercises (p=0.22) and/or regular aerobic exercises (RAPA ≥6) (p=0.84). Conclusion Patients with IBD present with lower TBS Z-scores when compared to HC and there is no correlation with disease activity. The only variable associated with lower TBS was a 25OHD &amp;lt;28 ng/mL. Further studies looking at the implications of these findings are warranted. FIGURE 1 FIGURE 2

Intermediate monocytes correlate with CXCR3+ Th17 cells but not with bone characteristics in untreated early rheumatoid arthritis.

BackgroundRheumatoid arthritis (RA) is associated with development of generalized osteoporosis. Bone-degrading osteoclasts are derived from circulating precursor cells of monocytic lineage, and the intermediate monocyte population is important as osteoclast precursors in inflammatory conditions. T cells of various subsets are critical in the pathogenesis of both RA and associated osteoporosis, but so far, no studies have examined associations between circulating intermediate monocytes, T cell subsets and bone characteristics in patients with RA. The aim of this study was to investigate the frequency of intermediate monocytes in patients with untreated early rheumatoid arthritis (ueRA) compared to healthy controls (HC), and to explore the correlation between intermediate monocytes and a comprehensive panel of T helper cell subsets, bone density and bone microarchitecture in ueRA patients.Methods78 patients with ueRA fulfilling the ACR/EULAR 2010 criteria were included and compared to 29 age- and sex-matched HC. Peripheral blood samples were obtained before start of treatment and proportions of monocyte subsets and CD4+ helper and regulatory T cell subsets were analyzed by flow cytometry. Bone densitometry was performed on 46 of the ueRA patients at inclusion using DXA and HR-pQCT.ResultsFlow cytometric analyses showed that the majority of ueRA patients had frequencies of intermediate monocytes comparable to HC. The intermediate monocyte population correlated positively with CXCR3+ Th17 cells in ueRA patients but not in HC. However, neither the proportions of intermediate monocytes nor CXCR3+ Th17 cells were associated with bone density or bone microarchitecture measurements.ConclusionsOur findings suggest that in early RA, the intermediate monocytes do not correlate with bone characteristics, despite positive correlation with circulating CXCR3+ Th17 cells. Future longitudinal studies in patients with longer disease duration are required to fully explore the potential of intermediate monocytes to drive bone loss in RA.

Validation of Bone Density and Microarchitecture Measurements of the Load-Bearing Femur in the Human Knee Obtained Using In Vivo HR-pQCT Protocol

High resolution peripheral quantitative computed tomography (HR-pQCT) was designed to study bone mineral density (BMD) and microarchitecture in peripheral sites at the distal radius and tibia. With the introduction of the second generation HR-pQCT scanner (XtremeCT II, Scanco Medical) that has a larger, longer gantry it is now possible to study the human knee in vivo using HR-pQCT. Previous validation of HR-pQCT measurements at the distal radius and tibia against micro-CT is not representative of the knee because the increased cross-sectional area, greater amount of soft tissue surrounding the scan region, and different imaging protocol result in potentially increased beam hardening effects and photon scatter and different signal-to-noise ratio. The objective of this study is to determine the accuracy of density and microarchitecture measurements in the human knee measured by HR-pQCT using an in vivo protocol. Twelve fresh-frozen cadaver knees were imaged using in vivo HR-pQCT (60.7 µm) protocol. Subsequentially, distal femurs were extracted and imaged using a higher resolution (30.3 µm) ex vivo protocol, replicating micro-CT imaging. Scans were registered so that agreement of density and bone microarchitecture measurements could be determined using linear regression and Bland-Altman plots. All density and microarchitecture outcomes were highly correlated between the 2 protocols (R2 > 0.89) albeit with statistically significant differences between absolute measures based on paired t tests. All parameters showed accuracy between 4.5% and 8.7%, and errors were highly systematic, particularly for trabecular BMD and trabecular thickness (R2 > 0.93). We found that BMD and microarchitecture measurements in the distal femur obtained using an in vivo HR-pQCT knee protocol contained systematic errors, and accurately represented measurements obtained using a micro-CT equivalent imaging protocol. This work establishes the validity and limitations of using HR-pQCT to study the BMD and microarchitecture of human knees in future clinical studies.

The reference value of trabecular bone score (TBS) in the Iranian population.

Trabecular bone score (TBS), as a tool for measurement of bone microarchitecture, represents fracture risk independently of bone density. The aim of this study was to estimate the reference values of TBS in both genders among the Iranian population to evaluate osteoporotic fractures in the future. The study was performed on healthy Iranian subjects who live in urban areas of Bushehr city, the capital of Bushehr province in southwestern Iran. The participants in this study were selected through a multistage, age and sex stratified, cluster random sampling. The TBS of L1-L4 was assessed by spine DXA images using TBS iNsight software (Discovery WI, Hologic Inc, USA). Age-related models of TBS were constructed using piecewise linear regression analysis. In total, 691 participants aged ≥ 18 years (381 men and 310 women) were selected for the study. The mean and standard deviation (SD) of TBS value for men was 1.420 ± 0.094 and the age at the peak TBS was 30.0 years. Among women, the corresponding value for the mean of TBS was 1.428 ± 0.070 and the age at the peak TBS was 24.5 years. Two SDs below the mean of TBS were 1.326 in men and 1.357 in women. Therefore, the following normal range for TBS values has been proposed: Among men, TBS ≥ 1.326 is considered to be normal; TBS between 1.231 and 1.326 is considered to be partially degraded microarchitecture; and TBS ≤ 1.231defined degraded microarchitecture. Among women, TBS categories are defined as normal ≥ 1.357, partially degraded between 1.287 and 1.357 and degraded ≤ 1.287. This was the first study to propose evaluation of the normal range for TBS values in both genders in the Middle- East and Iran. According to our results: TBS ≤ 1.231 in men and TBS ≤ 1.287 in women is considered to be degraded microarchitecture among the Iranian population.

Effects of Estrogen Replacement on Bone Geometry and Microarchitecture in Adolescent and Young Adult Oligoamenorrheic Athletes: A Randomized Trial.

Oligoamenorrheic athletes (OAs) have lower bone mineral density (BMD) and greater impairment of bone microarchitecture, and therefore higher fracture rates compared to eumenorrheic athletes. Although improvements in areal BMD (aBMD; measured by dual-energy X-ray absorptiometry) in OAs have been demonstrated with transdermal estrogen treatment, effects of such treatment on bone microarchitecture are unknown. Here we explore effects of transdermal versus oral estrogen versus no estrogen on bone microarchitecture in OA. Seventy-five OAs (ages 14 to 25 years) were randomized to (i) a 100-μg 17β-estradiol transdermal patch (PATCH) administered continuously with 200 mg cyclic oral micronized progesterone; (ii) a combined 30 μg ethinyl estradiol and 0.15 mg desogestrel pill (PILL); or (iii) no estrogen/progesterone (NONE) and were followed for 12 months. Calcium (≥1200 mg) and vitamin D (800 IU) supplements were provided to all. Bone microarchitecture was assessed using high-resolution peripheral quantitative CT at the distal tibia and radius at baseline and 1 year. At baseline, randomization groups did not differ by age, body mass index, percent body fat, duration of amenorrhea, vitamin D levels, BMD, or bone microarchitecture measurements. After 1 year of treatment, at the distal tibia there were significantly greater increases in total and trabecular volumetric BMD (vBMD), cortical area and thickness, and trabecular number in the PATCH versus PILL groups. Trabecular area decreased significantly in the PATCH group versus the PILL and NONE groups. Less robust differences between groups were seen at the distal radius, where percent change in cortical area and thickness was significantly greater in the PATCH versus PILL and NONE groups, and changes in cortical vBMD were significantly greater in the PATCH versus PILL groups. In conclusion, in young OAs, bone structural parameters show greater improvement after 1 year of treatment with transdermal 17β-estradiol versus ethinyl estradiol-containing pills, particularly at the tibia. © 2019 American Society for Bone and Mineral Research.

Association of Dairy Food Intake with Measures of Bone Microarchitecture in Men and Women from the Framingham Study (OR18-08-19)

ObjectivesPrevious studies reported that dairy foods are associated with higher areal bone mineral density (BMD) in older adults. However, data on bone strength and bone microarchitecture are lacking. The objective of this study was to determine the association of milk, yogurt, cheese, cream, milk + yogurt and milk + yogurt + cheese intakes with high resolution peripheral quantitative computed tomography (HR-pQCT) measures of bone in older adults from the Framingham Offspring study. MethodsThis cross-sectional study included 532 men and 694 women (aged 32–81y, mean 64y) with measures of dairy food intake (servings/wk.) from a food frequency questionnaire. Cortical and trabecular BMD and microarchitecture at the distal tibia and radius were measured using HR-pQCT. We focused on five bone parameters: 1) Bone strength assessed via failure load from micro–finite element analysis, 2) Two cortical bone measures: cortical BMD and cortical thickness; and 3) Two trabecular bone measures: trabecular bone density and trabecular number. Sex-combined and sex-specific multivariable linear regression was used to estimate the association of dairy food intake (energy adjusted) with each bone measure adjusting for covariates (sex, age, height, weight, current smoking, energy intake, calcium supplement use, vitamin D supplement use, physical activity and multivitamin use). ResultsOver 90% of the participants consumed the recommended ≥ 3 servings of dairy per day. Mean milk intake ± SD was 5.5 servings/week in both men and women. In sex combined analyses, only cheese intake was associated with cortical BMD at the radius and tibia (Table). None of the other dairy foods were significantly associated with any of the bone measures. In sex-stratified analysis higher cheese intake was associated with lower cortical BMD at the radius and tibia in women alone (radius: β = –9.61 ± 2.73, P = 0.001, tibia: β = –9.41 ± 3.10, P = 0.001). In men, higher cream intake was associated with higher trabecular number (radius: β = 0.021 ± 0.011, P = 0.02, tibia: β = 0.024 ± 0.012, P = 0.05). Higher yogurt intake was also associated with higher trabecular volumetric BMD at the tibia in men alone (tibia: β = 4.86 ± 2.00, P = 0.02). ConclusionsIn this cohort of primarily healthy older men and women with high dairy food consumption, specific dairy foods seem to be more beneficial in men than women. Negative associations for cheese intake and cortical BMD in women should be further confirmed in longitudinal studies. Funding SourcesNIH AR # 053205; FHS N01-HC-25195 R01 AR/AG 41398 and unrestricted institutional research grant from Dairy Management Inc. Supporting Tables, Images and/or Graphs▪

The Correction of Systematic Error due to Plaster and Fiberglass Casts on HR-pQCT Bone Parameters Measured In Vivo at the Distal Radius

Due to difficulty assessing healing of distal radius fractures using conventional radiography, there is interest in using high resolution peripheral quantitative computed tomography (HR-pQCT) to track healing at the microarchitectural level. Unfortunately, the plaster-of-Paris and fiberglass casts used to immobilize fractures affect HR-pQCT measurements due to beam hardening, and increased noise. The challenge is compounded because casts have variable thickness, and an individual patient will often have their cast changed 2–3 times during the course of treatment. This study quantifies the effect of casts within a clinically relevant range of thicknesses on measured bone parameters at the distal radius, and establishes conversion equations to correct for systematic error in due to cast presence. Eighteen nonfractured participants were scanned by HR-pQCT in three conditions: no cast, plaster-of-Paris cast, and fiberglass cast. Measured parameters were compared between the baseline scan (no cast) and each cast scan to evaluate if systematic error exists due to cast presence. A linear regression model was used to determine an appropriate conversion for parameters that were found to have systematic error. Plaster-of-Paris casts had a greater range of thicknesses (3.2–9.5 mm) than the fiberglass casts (3.0–5.4 mm), and induced a greater magnitude of systematic error overall. Key parameters of interest were bone mineral density (total, cortical, and trabecular) and trabecular bone volume fraction, all of which were found to have systematic error due to presence of either cast type. Linear correlations between baseline and cast scans for these parameters were excellent (R2 > 0.98), and appropriate conversions could be determined within a margin of error less than a ±6% for the plaster-of-Paris cast, and ±4% for the fiberglass cast. We have demonstrated the effects of cast presence on bone microarchitecture measurements, and presented a method to correct for systematic error, in support of future use of HR-pQCT to study fracture healing.

Measurement of Bone Microarchitecture by Trabecular Bone Score in Patients with Gaucher Disease

To assess the vitamin D status in postmenopausal women with osteoporotic fractures, determine its concentration by fracture site at the clinical setting, and compare the proportion of vitamin D deficiency with that reported in literature.The prospective study included 317 postmenopausal women with osteoporotic fractures who were treated consecutively from 2016 to 2018. After obtaining informed consent for participation in the seamless treatment of osteoporosis against fractures study, which is our initiative to prevent secondary osteoporotic fractures, we registered the patients, examined bone mineral density (BMD) at the unfractured femoral neck and lumbar spine, serum 25-hydroxyvitamin D (25(OH)D) concentration, blood chemistry, and bone turnover markers.The mean age of the patients was 80.7 years. Moreover, 78% of patients of all fractures had 25(OH)D concentration < 20 ng/mL, whereas 12% of patients had 25(OH)D concentration ≥ 30 ng/mL 25(OH)D concentration in hip fractures was significantly lower than that in vertebral or distal radius fractures (P < 0.05). Multiple regression analysis revealed that 25(OH)D concentration is significantly associated with femoral neck BMD (β = 0.16; 95% confidence interval [CI], 0.78–12.17, P = 0.03) and serum albumin concentration (β = 0.21; 95% CI, 0.62–2.96, P < 0.001) in patients with 25(OH)D concentration < 30 ng/mL.The results of this study show that the proportion of postmenopausal women with osteoporotic fractures who had vitamin D deficiency was higher than the proportion in previous reports that examined general postmenopausal women (35.2%–52.0%).

Proper Positioning and Restraint of a Rat Hind Limb for Focused High Resolution Imaging of Bone Micro-architecture Using &lt;em&gt;In Vivo&lt;/em&gt; Micro-computed Tomography

The use of in vivo micro-computed tomography (µCT) is a powerful tool which involves the non-destructive imaging of internal structures at high resolutions in live animal models. This allows for repeated imaging of the same rodent over time. This feature not only reduces the total number of rodents required in an experimental design and thereby reduces the inter-subject variation that can arise, but also allows researchers to assess longitudinal or life-long responses to an intervention. To acquire high quality images that can be processed and analyzed to more accurately quantify outcomes of bone micro-architecture, users of in vivo µCT scanners must properly anesthetize the rat, and position and restrain the hind limb. To do this, it is imperative that the rat be anesthetized to a level of complete relaxation, and that pedal reflexes are lost. These guidelines may be modified for each individual rat, as the rate of isoflurane metabolism can vary depending on strain and body size. Proper technique for in vivo µCT image acquisition enables accurate and consistent measurement of bone micro-architecture within and across studies.

Proper Positioning and Restraint of a Rat Hind Limb for Focused High Resolution Imaging of Bone Micro-architecture Using In Vivo Micro-computed Tomography.

The use of in vivo micro-computed tomography (µCT) is a powerful tool which involves the non-destructive imaging of internal structures at high resolutions in live animal models. This allows for repeated imaging of the same rodent over time. This feature not only reduces the total number of rodents required in an experimental design and thereby reduces the inter-subject variation that can arise, but also allows researchers to assess longitudinal or life-long responses to an intervention. To acquire high quality images that can be processed and analyzed to more accurately quantify outcomes of bone micro-architecture, users of in vivo µCT scanners must properly anesthetize the rat, and position and restrain the hind limb. To do this, it is imperative that the rat be anesthetized to a level of complete relaxation, and that pedal reflexes are lost. These guidelines may be modified for each individual rat, as the rate of isoflurane metabolism can vary depending on strain and body size. Proper technique for in vivo µCT image acquisition enables accurate and consistent measurement of bone micro-architecture within and across studies.

Trabecular bone score for the diagnostics of osteoporosis in subjects with type 2 diabetes mellitus: a clinical case

Type 2 diabetes mellitus (T2DM) is associated with higher fracture risk but, better bone mineral density (BMD). Alteration of the skeletal material or microstructure may be an underlying mechanism for the discrepancy between BMD and fracture risk in diabetes. The trabecular bone score has been proposed as an indirect measurement of bone microarchitecture with the routine dual energy absorptiometry. We present a clinical case of diagnosis and treatment of osteoporosis associated with T2DM in patient with a low-trauma fracture and concomitant endocrine disorder.

P312 Trabecular bone score in patients with inflammatory bowel diseases

Background: Osteopenia and osteoporosis are known chronic complications of inflammatory bowel diseases (IBD). It is known that areal bone mineral density (aBMD) does not sufficiently reflect bone strength and quality. The trabecular bone score (TBS) provides an indirect measurement of bone microarchitecture, independent of aBMD. Methods: The aim was to assess TBS and BMD of lumbar spine (LS) in IBD patients. Furthermore we analyzed the impact of clinical factors on TBS. The cohort consisted of consecutive IBD patients from tertiary IBD centre. Clinical characteristics i.e. age, gender, anthropometry, clinical behaviour, medication were recorded. The BMD was determined by dual-energy X-ray absorptiometry (DXA, Hologic Discovery) at the lumbar spine. TBS was determined by TBS Insight® software (Medimaps, France). Results: The cohort consisted of 84 IBD patients (53 with Crohn's disease (CD) and 31 with ulcerative colitis (UC)). The mean age was 42.0±14.2 years with the mean disease duration of 11.0±7.0 years. There were 14% (12/84) postmenopausal women, 8 patients (9.5%) were on long term corticosteroids and 21 CD patients had prior major IBD surgery. The percentage of patients with substitution of vitamin D (800IU) and calcium (0.5–1g) was similar between CD and UC (24.5% vs. 29.0%), none of the patients was on anti-porothic treatment. The mean LS BMD of the cohort was 0.964±0.113 g/cm2 and TBS 1.36±0.14. We observed significantly lower mean TBS LS in patients with fistulising CD compared to luminal CD, 1.36±0.09 and 1.47±0.05 (p=0.0039) respectively. No similar finding was observed using BMD. We did not observe any significant impact of clinical characteristics nor medication in UC patients. Conclusions: We observed that spine TBS can identify quality of bone mineral density in patients with Crohn's disease better than BMD itself. CD patients with severe disease are at higher risk of low bone mineral density.