Total vBMD Research Articles

Bone turnover, areal BMD, and bone microarchitecture by second-generation high-resolution peripheral quantitative computed tomography in transfusion-dependent thalassemia.

Thalassemic osteopathy includes low bone mass and impaired bone microarchitecture. We aimed to evaluate the prevalence and determinants of bone quantity (osteoporosis) and quality (microarchitecture) in a cohort of adult patients with transfusion-dependent thalassemia (TDT). Patients with TDT (n = 63) and age- and BMI-matched controls (n = 63) were recruited in the study. Areal bone mineral density (BMD) was measured using DXA Hologic scanner. P1NP and β-CTX were estimated by electrochemiluminescence assay. Bone geometry and volumetric BMD (vBMD) were estimated by second-generation high-resolution peripheral quantitative computed tomography. Bone turnover marker β-CTX was significantly lower in the TDT group, but there was no difference in P1NP levels. Low bone mass (Z ≤ -2) was present in greater proportion of patients both at lumbar spine (LS) (54 vs 0%; p = .001) and femoral neck (FN) (33 vs 8%; p = .001). Hypogonadism was associated with low BMD at FN (OR 10.0; 95% CI, 1.2-86; p = .01) and low hemoglobin with low BMD at LS (OR 1.58; 95% CI, 0.96-2.60; p = .07). The mean trabecular bone score was also significantly lower in patients compared with controls (1.261 ± 0.072 vs 1.389 ± 0.058). Total, cortical and trabecular vBMD were significantly lower in cases than controls. The trabecular number and cortical thickness were significantly lower and trabecular separation higher in cases than controls. Adults with TDT have significantly lower areal, cortical and trabecular vBMD. The bone microarchitecture is also significantly impaired in terms of lower number and wider spacing of trabeculae as well as lower cortical thickness and area at both radius and tibia.

Low-Magnitude Mechanical Signals to Preserve Skeletal Health in Female Adolescents With Anorexia Nervosa

Malnourished adolescents and young adults with anorexia nervosa (AN) are at high risk for skeletal deficits. To examine whether low-magnitude mechanical signals (LMMS) could preserve bone mineral density (BMD) throughout 6 months in adolescents and young adults with AN. This double-blind, sham-controlled randomized clinical trial, conducted in a hospital-based specialty clinic, assessed female adolescents and young women without medical comorbidity or medication use that would compromise bone health. A total of 837 female adolescents were screened from January 1, 2012, to December 31, 2019, of whom 317 met the study criteria. Data analysis was performed from 2020 to 2024. Platform delivering low-magnitude mechanical signals (LMMS) (0.3 g at 32-37 Hz) or sham (ie, placebo) signals for 10 minutes daily for 6 months. The primary outcome was trabecular volumetric BMD (vBMD) as measured by peripheral quantitative computed tomography of the tibia at baseline and 6 months. Secondary outcomes included cortical vBMD, cross-sectional area (CSA), areal BMD and body composition measured by dual-energy x-ray absorptiometry, and serum bone turnover markers. Forty female adolescents and young women (median [IQR] age, 16.3 [15.1-17.6] years; median [IQR] percentage median BMI for age, 87.2% [81.0%-91.6%]) completed the trial. Total bone vBMD changes were nonsignificant in both groups (95% CI for difference in median change between groups, -57.11 to 2.49): in the LMMS group, vBMD decreased from a median (IQR) of 313.4 (292.9-344.6) to 309.4 (290.4-334.0) mg/cm3, and in the placebo group, it increased from a median (IQR) of 308.5 (276.7-348.0) to 319.2 (309.9-338.4) mg/cm3. Total CSA at the 4% tibia site increased from a median (IQR) of 795.8 (695.0-844.8) mm2 to 827.5 (803.0-839.4) mm2 in the LMMS group, whereas in the placebo group, it decreased from 847.3 (770.5-915.3) mm2 to 843.3 (828.9-857.7) mm2 (95% CI for difference in median change between groups, 2.94-162.53). Median (IQR) trabecular CSA at the 4% tibia site increased from 616.3 (534.8-672.3) mm2 to 649.2 (638.0-661.4) mm2 in the LMMS group but decreased in the placebo group from 686.4 (589.0-740.0) mm2 to 647.9 (637.3-661.9) mm2 (95% CI for difference in median change between groups, 2.80-139.68 mm2). Changes in cortical vBMD, cortical section modulus, and muscle CSA were not significant between groups. The 6-month changes in trabecular and total bone CSA at the tibia 4% site (weight-bearing trabecular bone) were significantly different between groups (these measures increased in the LMMS group but decreased in the placebo group; total bone CSA: 95% CI, 2.94-162.53; P = .01; trabecular CSA: 95% CI, 2.80-139.68; P = .02). Greater increases in body mass index were seen in the placebo group (median [IQR] gain, 0.5 [-0.3 to +2.1]) than in the LMMS group (median [IQR] gain, +0.4 [-0.3 to +2.1]), perhaps due to differences in fat mass accrual. No adverse events occurred related to the LMMS intervention. In this randomized clinical trial of female adolescents and young women with AN, a 6-month LMMS intervention did not yield improvement in tibial trabecular vBMD. However, LMMS led to increases in total and trabecular CSA at the tibia. These results suggest an early positive response of increased bone turnover and trabecular bone quantity due to the LMMS intervention. Future studies should use a longer duration of intervention, consider strategies to optimize adherence, and potentially focus on a more profoundly malnourished patient population. ClinicalTrials.gov Identifier: NCT01100567.

Patella Fractures are Associated with Bone Fragility - A Retrospective Study.

Patella fractures are not typically considered osteoporotic fractures. We compared bone mineral density (BMD) and microstructure in elderly women from a multiethnic population-based study in New York City with any history of a patella fracture (n = 27) to those without historical fracture (n = 384) and those with an adult fragility forearm fracture (n = 28) using dual energy x-ray absorptiometry (DXA) and high resolution peripheral quantitative computed tomography (HR-pQCT). Compared to those without fracture, women with patella fracture had 6.5% lower areal BMD (aBMD) by DXA only at the total hip (P=.007), while women with forearm fracture had lower aBMD at multiple sites and lower trabecular bone score (TBS), adjusted for age, body mass index (BMI), race and ethnicity (all P<.05). By HR-pQCT, adjusted radial total and trabecular (Tb) volumetric BMD (vBMD) and Tb number were 10-24% lower while Tb spacing was 12-23% higher (all P<.05) in the fracture groups versus women without fracture. Women with a forearm, but not a patella, fracture also had lower adjusted radial cortical (Ct) area and vBMD and 21.8% (P<.0001) lower stiffness vs. women without fracture. At the tibia, the fracture groups had 9.3-15.7% lower total and Tb vBMD (all P<.05) compared to the non-fracture group. Women with a forearm fracture also had 10.9, and 14.7% lower tibial Ct area and thickness versus those without fracture. Compared to women without fracture, tibial stiffness was 9.9 and 12% lower in the patella and forearm fracture groups, respectively (all P<.05). By HR-pQCT, the patella vs. forearm fracture group had 36% higher radial Tb heterogeneity (P<.05). In summary, women with patella fracture had Tb deterioration by HR-pQCT associated with lower tibial mechanical competence that was similar to those with fragility forearm fracture, a more universally accepted "osteoporotic" fracture. These data suggest patella fractures are associated with skeletal fragility and warrant skeletal evaluation.

7892 Longitudinal Changes in Bone Microarchitecture and Strength in Girls with Type 1 Diabetes

Abstract Disclosure: R. Dhaliwal: None. R.K. Saunders: None. M. Misra: None. M.L. Bouxsein: None. D.M. Mitchell: None. Introduction: Type 1 diabetes (T1D) confers an increased fracture risk, only partly explained by low areal bone mineral density (aBMD). We have previously shown in a cross-sectional study that bone microarchitecture is altered early in the course of T1D. The goal of this study is to evaluate how T1D influences longitudinal changes in volumetric BMD (vBMD) and microarchitecture. Methods: This is a 2-year prospective study of girls ages 10-16 years (62 with T1D and 59 controls). We used dual-energy x-ray absorptiometry (DXA) to measure aBMD, and high-resolution peripheral quantitative computed tomography (HR-pQCT) at the distal radius (7% site) and tibia (8% site) to measure vBMD and microarchitecture. We used linear mixed models to assess the effects of T1D on change in bone parameters over time, adjusting for bone age as an index of skeletal maturity, height, lean mass index (LMI), and fat mass index (FMI). Results: At baseline, mean duration of disease in T1D was 4.8 ± 3.2 years, and mean HbA1c was 8.6 ± 1.4%. The groups did not differ by age, bone age, and height, while T1D participants had higher LMI (p&amp;lt;0.001) and borderline higher FMI (p=0.107). Linear growth, weight gain, and changes in body composition over time did not differ between groups. Growth-mediated aBMD gains were observed in both groups at the subtotal body, total hip, femoral neck, and spine. While adjusted aBMD as well as trabecular bone score were lower in T1D, we did not observe between-group differences in changes in these endpoints over time. In both groups, at the distal radius, we observed significant increases over time in total and cortical vBMD, cortical thickness, trabecular (Tb) thickness, and estimated failure load, while cortical porosity decreased. While several microarchitectural parameters were altered in T1D participants, we did not observe significant between-group differences in changes in these measures over time. Of note, trabecular development was subtly altered, with T1D participants demonstrating a borderline significant decrease in Tb vBMD (-14.3 ± 9.0 mg HA/cm3, p=0.112) and Tb number (-0.14 ± 0.07 mm-[1], p=0.057), while control participants had no change in Tb vBMD or number, but a significant increase in Tb thickness (5.8 ± 2.5 µm, p=0.018). At the distal tibia, we observed similar overall detrimental effects of T1D at baseline. However, we did not observe between-group differences in microarchitectural change over time. Glycemic control as measured by HbA1c was not associated with changes in skeletal parameters among T1D participants. Conclusions: T1D leads to substantially altered areal and volumetric BMD as well as microarchitectural parameters in girls. While our data suggest that much of this deficit appears to occur early in the course of disease as prospective change is similar in T1D and controls, subtle changes in trabecular bone development at the radius may indicate ongoing impairment of bone accrual. Presentation: 6/3/2024

5043 Skeletal Microstructure in Men with Celiac Disease

Abstract Disclosure: A. Rubenstein: None. A. Kondapalli: None. S. Agarwal: None. M. Bucovsky: None. I. Colon: None. N. Kil: None. S. Lewis: None. B. Lebwohl: None. P. Green: None. M. Walker: Advisory Board Member; Self; Alexion Pharmaceuticals, Inc.. The pathophysiology of osteoporosis related to celiac disease (CD) remains incompletely understood. High resolution peripheral quantitative computed tomography (HRpQCT) has revealed microarchitectural deficits in women with CD, but no data exist in men. We prospectively studied bone health using DXA and HRpQCT in 17 men with duodenal biopsy-confirmed CD (mean age 43±16 years; 82% white, 6% Asian, 12% other) and 5 male controls (mean age 40±12 years; 80% white, 20% Asian). Compared to controls, men with CD had lower self-rated health scores (p&amp;lt;0.05), but age, BMI, alcohol use, physical activity, acid blocker use, and vitamin D intake did not differ. Among patients with CD, 23.5% had other autoimmune diseases (type 1 diabetes, hypothyroidism, vitiligo, systemic sclerosis). At CD diagnosis, mean age was 34.3 ± 14.8. CD patients had a mean CD and gluten-free diet duration of 8 years. 29% of patients (n=5/17) were enrolled within 13 months of CD diagnosis. Mean tissue transglutaminase IgA, serum calcium, PTH, Vitamin D, and alkaline phosphatase were normal, but vitamin D levels were &amp;lt; 30 ng/mL in 36% (n=5/14) and PTH was elevated in 11% (n=1/9). T- (-0.5±1.5 vs. 0.8±0.8, p=0.03) and Z-scores (-0.1±1.4 vs. 1.1±0.9, p=0.05) by DXA were normal at all sites but tended to be lower at the 1/3-radius only in CD compared to controls. By HRpQCT, there were no differences. Compared to a larger control group including HRpQCT data from an additional 14 normative database controls (n=19), CD had lower radial cortical (-4.7%, p=0.02) and tibial trabecular (-13.3%, p=0.04) vBMD and a trend toward lower cortical volumetric BMD (vBMD; -3.5%, p=0.06) at the tibia. Within the CD group, longer CD duration was associated with worse tibial cortical vBMD at (r=-0.55, p=0.02). Higher PTH (n=9) correlated with lower lumbar spine areal BMD (r=-0.75, p=0.02), tibial trabecular thickness (Tb.Th; r=-0.77, p=0.02) as well as radial cortical vBMD (r=-0.81, p&amp;lt;0.01), trabecular Tb.Th (r=-0.78, p=0.01), and cortical thickness (r=-0.75, p=0.02). Those with greater dietary vitamin D intake had higher total vBMD (r=0.50, p=0.04) and trabecular thickness at the tibia (r=0.51, p=0.04). Similarly, higher 25-hydroxy vitamin D levels were associated with higher total hip aBMD (r=0.58, p=0.03). In summary, CD in men is associated with lower areal BMD at the 1/3-radius by DXA and lower vBMD at the radius and tibia by HRpQCT. Low vitamin D levels and secondary hyperparathyroidism may contribute. Further work is needed to understand the extent and pathophysiology of skeletal disease in men with CD. Presentation: 6/3/2024

Short-term risk of fracture is increased by deficits in cortical and trabecular bone microarchitecture independent of DXA BMD and FRAX: Bone Microarchitecture International Consortium (BoMIC) prospective cohorts.

Identifying individuals at risk for short-term fracture is essential to offer prompt beneficial treatment, especially since many fractures occur in those without osteoporosis by DXA-aBMD. We evaluated whether deficits in bone microarchitecture and density predict short-term fracture risk independent of the clinical predictors, DXA-BMD and FRAX. We combined data from eight cohorts to conduct a prospective study of bone microarchitecture at the distal radius and tibia (by HR-pQCT) and 2-year incidence of fracture (non-traumatic and traumatic) in 7327 individuals (4824 women, 2503 men, mean 69 ± 9years). We estimated sex-specific hazard ratios (HR) for associations between bone measures and 2-year fracture incidence, adjusted for age, cohort, height, and weight, and then additionally adjusted for FN aBMD or FRAX for major osteoporotic fracture. Only 7% of study participants had FN T-score ≤ -2.5, whereas 53% had T-scores between -1.0 and -2.5 and 37% had T-scores ≥-1.0. Two-year cumulative fracture incidence was 4% (296/7327). Each SD decrease in radius cortical bone measures increased fracture risk by 38%-76% for women and men. After additional adjustment for FN-aBMD, risks remained increased by 28%-61%. Radius trabecular measures were also associated with 2-year fracture risk independently of FN-aBMD in women (HRs range: 1.21 per SD for trabecular separation to 1.55 for total vBMD). Decreased failure load (FL) was associated with increased fracture risk in both women and men (FN-aBMD ranges of adjusted HR = 1.47-2.42). Tibia measurement results were similar to radius results. Findings were also similar when models were adjusted for FRAX. In older adults, FL and HR-pQCT measures of cortical and trabecular bone microarchitecture and density with strong associations to short-term fractures improved fracture prediction beyond aBMD and FRAX. Thus, HR-pQCT may be a useful adjunct to traditional assessment of short-term fracture risk in older adults, including those with T-scores above the osteoporosis range.

Causal relationships between height and weight with distal tibia microarchitecture and geometry in adult female twin pairs.

Higher stature and lower weight are associated with increased risk of fracture. However, the pathophysiology for the associations of height and weight with bone microarchitecture and geometry is unclear. We examined whether these associations were consistent with causation and/or with shared familial factors. In this cross-sectional study of 566 female twins aged 26-76yr, a regression analysis for twin data, Inference about Causation by Examination of FAmilial CONfounding (ICE FALCON), was used for testing causation. The bone microarchitecture and geometry of the distal tibia was assessed using HR-pQCT and the StrAx1.0 software. Higher stature was associated with larger total bone cross-sectional area (CSA), lower total bone volumetric bone mineral density (vBMD), larger cortical CSA, thinner cortices, higher porosity of the total cortex, compact cortex, outer and inner transitional zone (TZ), lower cortical vBMD, and larger medullary CSA (regression coefficients (β) ranging from -.37 to .60, all p<.05). Using ICE FALCON, the cross-pair cross-trait associations attenuated toward zero after adjusting for the within-individual association (absolute values of β ranging from .05 to .31, all p<.001). Higher weight was associated with higher total bone vBMD, larger cortical CSA and thicker cortices, lower porosity of the total cortex and inner TZ, and higher cortical vBMD (β ranging from -.23 to .34, all p<.001), and thinner trabeculae, higher trabecular number, lower trabecular separation, and higher trabecular vBMD (β ranging from -.31 to .39, all p<.05). Only cortical CSA attenuated toward zero after adjusting for the within-individual association between weight and bone microarchitecture (β = .042, p=.046). Higher stature was associated with a weaker cortical, not trabecular bone traits, whereas higher weight was associated with stronger cortical and trabecular bone traits. The results were consistent with height having a causal effect on weaker cortical bone structure, whereas weight had a casual effect on the larger cortical CSA.

Trabecular and cortical bone microarchitecture using high-resolution peripheral quantitative computed tomographic imaging in diabetic peripheral neuropathy

ContextType 2 Diabetes Mellitus (T2D) is associated with an increased risk of fragility fracture despite normal areal bone mineral density (BMD). The contribution of diabetic peripheral neuropathy (PN) to volumetric BMD (vBMD) and bone microarchitecture in T2D is not explored. ObjectiveTo assess vBMD and microarchitectural properties of bone using high-resolution peripheral quantitative computed tomography (HR-pQCT) in patients of T2D with or without PN. DesignThis is a cross-sectional study of patients of T2D divided into two groups [patients with T2D without PN (Group A) and T2D with PN (Group B)]. All patients underwent clinical examination, biochemical evaluation, dual-energy X-ray absorptiometry (DXA), and HR-pQCT of the radius and tibia. ResultsA total of 296 patients were included in the study [Group A (n = 98), Group B (n = 198)]. HR-pQCT demonstrated a significant difference in total vBMD[mg/cm3] at tibia (291.6 ± 61.8 vs. 268.2 ± 63.0; p-0.003); cortical vBMD[mg/cm3] at tibia [912.5 (863.3, 962.4) vs. 853.8 (795.3, 913.2) p-0.000], among groups A and B respectively. Among the microarchitecture parameters, there was a significant difference in cortical porosity at the tibia (2.5% ±1.7% vs. 3%±1.7%; p-0.004), trabecular number[mm-1] at the tibia [1.080 (0.896, 1.237) vs. 1.140 (0.983, 1.286), p-0.045] and trabecular thickness[mm] at the radius [0.228 (0.217, 0.247) Vs. 0.238 (0.224, 0.253); p-0.006], among groups A and B respectively. ConclusionDespite comparable areal BMD, T2D patients with PN have diminished vBMD and deteriorated skeletal microarchitecture, compared to those without PN.

Disease Activity and Bone Microarchitectural Phenotype in Patients With Axial Spondyloarthritis

Background: Axial spondyloarthritis (AxSpA) is a chronic rheumatic disease characterized by spine inflammation, abnormal bone growth, and paradoxically osteoporosis and vertebral fractures. The pathogenesis of skeletal deficits in this disease is poorly understood. Purpose: We sought to evaluate volumetric bone mineral density (vBMD) and bone microarchitecture in patients with AxSpA and to identify disease-related factors associated with skeletal abnormalities. Methods: We enrolled patients between 2018 and 2021 as part of a 2-year prospective study at a single institution investigating skeletal health and the skeletal effects of interleukin-17 (IL-17) treatment. Patients with AxSpA who met Assessment in SpondyloArthritis International Society (ASAS) classification criteria by X-ray or had evidence of active inflammation on magnetic resonance imaging suggestive of sacroiliitis were referred to the study by their rheumatologists. We excluded those with a history of fragility fracture, multiple myeloma, Cushing’s disease, primary hyperparathyroidism, osteomalacia, untreated vitamin D deficiency, secondary osteoporosis, or other systemic rheumatic diseases, as well as use of oral steroids for 2 or more weeks in the 6 months prior or current use of hormone replacement therapy, current oral bisphosphonate, past or current intravenous bisphosphonate, teriparatide, or denosumab therapies. A total of 1606 patients were screened for eligibility. Of these, 30 participants were enrolled (mean age 43 years, 50% male). Patients with AxSpA had dual-energy X-ray absorptiometry (DXA) measurements of areal BMD (aBMD) and high-resolution peripheral quantitative computed tomography (HR-pQCT) measurements of vBMD microarchitecture and failure load by finite element analysis. Standardized disease assessment tools used included the Bath Ankylosing Spondylitis Disease Activity (BASDAI), Metrology Index (BASMI), and Functional Index (BASFI). Results: In the 30 included patients, mean DXA and HR-pQCT Z-scores were within 1 standard deviation (SD) of normal for all indices, except for total vBMD in males (–1.2 SD below mean). Mean symptom duration was 11.7 years and mean scores for BASDAI, BASFI, and BASMI were 4.6, 3.6, and 2.7, respectively (range 1–10, 10 = severe limitation). Longer disease duration was associated with more severe skeletal deficits at the hip and tibia—specifically, lower hip aBMD, lower meta- and inner-trabecular vBMD, lower trabecular number, and higher trabecular separation and heterogeneity. Conclusion: This study of 30 patients with AxSpA found that abnormalities in bone density and microarchitecture at weightbearing sites were associated with longer disease duration. Because of its small sample size, larger studies are needed to better characterize the pathogenic disease factors that govern skeletal damage in AxSpA.

Evaluation of bone density and microarchitecture in adult patients with X-linked hypophosphatemic rickets: A pilot longitudinal study

X-linked Hypophosphatemia (XLH) is the most common type of inherited rickets. Although the clinical features are well characterized, bone structure, mineralization, and biomechanical properties are poorly known. Our aim was to analyze bone properties in the appendicular and axial skeleton of adults with XLH. In this observational case-control study, each affected patient (N = 14; 9 females; age 50 ± 15 years) was matched by sex, age and body mass index to a minimum of two healthy controls (N = 34). Dual-energy X-ray Absorptiometry (DXA) analyses revealed that areal bone mineral density (aBMD) was higher in XLH patients at the lumbar spine (Z score mean difference = +2.47 SD, P value = 1.4 × 10−3). Trabecular Bone Score was also higher at the lumbar spine (P value = 1.0 × 10−4). High Resolution peripheral Quantitative Computed Tomography (HRpQCT) demonstrated that bone cross-sectional area was larger at the distal radius (P value = 6 × 10−3). Total and trabecular volumetric BMD were lower at both sites. Trabecular bone volume fraction was also lower with fewer trabecular numbers at both sites. However, bone strength evaluated by micro-finite element analyzes revealed unaffected bone stiffness and maximum failure load. Evaluation of bone mineralization with aBMD by DXA at the distal radius correlated with vBMD by HRpQCT measurements at both sites. PTH levels were inversely correlated with trabecular vBMD and BV/TV at the tibia. We then followed a subset of nine patients (median follow-up of 4 years) and reassessed HRpQCT. At the tibia, we observed a greater decrease than expected from an age and sex standardized normal population in total and cortical vBMD as well as a trabecularization of the cortical compartment. In conclusion, in adult patients with XLH, bone mineral density is high at the axial skeleton but low at the appendicular skeleton. With time, microarchitectural alterations worsen. We propose that noninvasive evaluation methods of bone mineralization such as DXA including the radius should be part of the management of XLH patients. Larger studies are needed to evaluate the clinical significance of BMD changes in XLH patients under conventional or targeted therapies.

Fractures in women with type 2 diabetes are associated with marked deficits in cortical parameters and trabecular plates.

The basis for increased fracture risk in type 2 diabetes (T2DM) is not well understood. In this multi-ethnic, population-based study (n = 565), we investigated bone microstructure, trabecular plate/rod morphology, and mineralization in women with T2DM (n = 175) with and without fracture using a second-generation HRpQCT and individual trabecula segmentation and mineralization (ITS; ITM). Covariate-adjusted aBMD was 3.0%-6.5% higher at all sites (all p<.005) in T2DM vs controls. By HRpQCT, T2DM had higher covariate-adjusted trabecular vBMD (5.3%-6.4%) and number (3.8%-5.1%) and greater cortical area at the radius and tibia. Covariate-adjusted cortical porosity was 10.0% higher at the tibia only in T2DM vs controls, but failure load did not differ. Among women with T2DM, those with adult atraumatic fracture (n = 59) had 5.2%-8.5% lower adjusted aBMD at all sites by DXA compared with those without fracture (n = 103). By HRpQCT, those with fracture had lower adjusted total vBMD and smaller cortical area (10.2%-16.1%), lower cortical thickness (10.5-15.8%) and lower cortical vBMD associated with 18.1 and 17.2% lower failure load at the radius and tibia, respectively (all p<.05); plate volume and thickness were 5.7% and 4.7% lower, respectively, (p<.05) while rod volume fraction was 12.8% higher in the fracture group at the tibia only. Sodium glucose cotransporter 2 inhibitor users (SGLT2i; n = 19), tended to have lower radial rod tissue mineral density by ITS (p=.06). GLP1 agonist users (n = 19) had trabecular deficits at both sites and higher cortical porosity and larger pores at the distal tibia. In summary, T2DM is associated with increased cortical porosity while those with T2DM and fracture have more marked cortical deficits and fewer trabecular plates associated with lower failure load.

Bone microarchitectural alterations associated with spinal cord injury: Relation to sex hormones, metabolic factors, and loading

ContextPeople living with spinal cord injury (SCI) are at high risk for bone fractures. Neural, hormonal and metabolic contributors to bone microarchitectural alterations are incompletely understood. ObjectiveTo determine the relationship of physical, metabolic and endocrine characteristics with bone microarchitecture, characterized using high-resolution peripheral quantitative computed tomography (HRpQCT) in SCI. DesignCross-sectional analyses of bone properties in people with SCI. ParticipantsTwenty adults with SCI and paraplegia (12) or motor incomplete quadriplegia (8). Outcome measuresDistal tibia and radius HRpQCT parameters, including density, microstructure and strength by microfinite element anaysis (μFEA); sex hormones; metabolic and inflammatory markers. ResultsThe mean age of the participants with SCI was 41.5 ± 10.3 years, BMI 25.7 ± 6.2 kg/m2, time since injury 10.4 ± 9.0 years. Participants with SCI had significantly lower median total (Z score − 3.3), trabecular (−2.93), and cortical vBMD (−1.87), and Failure Load by μFEA (−2.48) at the tibia than controls. However, radius vBMD, aBMD and microarchitecture were similar in participants with SCI and un-injured controls. Unexpectedly, C-Reactive Protein (CRP) was positively associated with tibial trabecular vBMD (β = 0.77, p = 0.02), thickness (β = 0.52, p = 0.04) and number (β = 0.92, p = 0.02). At the radius, estradiol level was positively associated with total vBMD (β = 0.59, p = 0.01), trabecular thickness (β = 0.43, p = 0.04), cortical thickness (β = 0.63, p = 0.01) and cortical porosity (β = 0.74 p = 0.04). ConclusionsRadius vBMD and microarchitecture is preserved but tibial total, cortical and trabecular vBMD, and estimated bone strength are markedly lower and bone microarchitectural parameters substantially degraded in people with SCI. The alterations in bone microarchitecture in people with SCI are likely multifactorial, however marked degradation of bone microarchitecture in tibia but not radius suggests that unloading is an important contributor of site-specific alterations of bone microarchitecture after SCI. Fracture prevention in SCI should focus on strategies to safely increase bone loading.ClinicalTrials.gov registration #: (NCT03576001).

Evaluation of Bone Health Using High Resolution Peripheral Quantitative Computed Tomography in Survivors of Paediatric Acute Lymphoblastic Leukemia

Bone mass accrual, bone architecture, and strength may be impaired in children with a history of acute lymphoblastic leukemia (ALL) resulting in low bone mineral density (BMD) and fractures. The Children's Oncology Group recommends evaluating ALL survivors' bone health with dual-energy X-ray absorptiometry (DXA) testing. However, DXA testing may not accurately measure bone health in survivors due to low bone area for height, short stature, growth delays or decreased lean muscle mass. Further, it does not differentiate between trabecular and cortical bone, nor does it provide insights into bone microarchitecture and strength. High-resolution peripheral quantitative computed tomography (HR-pQCT) is a three-dimensional non-invasive imaging modality that provides a comprehensive assessment bone microarchitecture, volumetric BMD (vBMD) of both cortical and trabecular bone, and bone strength. In adult patients, HR-pQCT parameters have been shown to predict incident fractures. In this pilot study we utilized HR-pQCT to evaluate bone microarchitecture, vBMD, bone geometry and bone strength of peri-pubertal and pubertal survivors of ALL compared to healthy controls. Methods: We prospectively recruited ALL survivors (&amp;gt;1 year off therapy) with a DXA BMD Z-score between -2.0 to 0 within the proceeding six months, who were in early-late puberty (pre-pubertal patients excluded), and aged 11 to 18 years, along with healthy controls in the same age range at a single academic pediatric center in Canada. While a BMD Z-score of -2.0 to 0 has historically been considered normal, many children with Z-scores in this range have skeletal fragility and an increased fracture risk. Patients were excluded if they had comorbidity that impacts bone microarchitecture (ex. chronic kidney disease), were on a medication that impacts bone health (ex. corticosteroids) or had a genetic syndrome that increased their sensitivity to radiation (ex. Ataxia Telangiectasia). HR-pQCT of the distal radius and tibia was performed using the a standardized protocol. Bone mass was compared using total, trabecular and cortical vBMD, bone architecture was compared using cortical porosity and bone strength was compared using failure load. HR-pQCT derived variables were compared between ALL and control groups following stratification by sex. HR-pQCT values were summarized using medians and interquartile ranges and medians were compared using the Wilcoxon signed-rank test. Demographic and clinical characteristics were compared using the chi-square test. All tests were two tailed and p&amp;lt;0.05 was considered significant. Results: A total of 59 subjects were recruited (34 ALL survivors, 25 healthy controls). The sex of participants was male for 56.0% (n=14) of controls and 61.7% (n=21) of ALL survivors and female for 44.0% (n=11) of controls and 38.3% (n=13) of survivors. All survivors had received corticosteroids and methotrexate, and five (15%) had received cranial radiation. ALL survivors were not more likely than controls to report a history of a fracture (32.4%, n=11 vs. 16%, n=4). Additional data regarding the participants demographics is presented in Table 1. Male survivors had a lower radial trabecular vBMD, tibial total vBMD, and tibial trabecular vBMD, and a higher tibial failure load compared to healthy male controls. Female survivors had a lower radial total vBMD, radial trabecular vBMD, tibial total vBMD, and tibial trabecular vBMD. Female ALL survivors also had higher radial and tibial failure loads compared to healthy female controls. No differences in cortical porosity or cortical vBMD were identified between survivors and healthy controls. Complete HR-pQCT data is presented in Table 2. Conclusions: We demonstrated differences in the HR-pQCT parameters of peripubertal and pubertal ALL survivors compared to healthy controls. Survivors had reductions in key HR-pQCT parameters and an increased tibial failure load compared to healthy controls. In future studies HR-pQCT should be performed at a uniform time point post ALL therapy and used to predict future adverse bone health outcome such as fractures. Using this HR-pQCT guided approach ALL survivors at greatest risk of an adverse bone health outcome can be offered early interventions to prevent these outcomes.

Bone mineral density differences between femurs of scoliotic patients undergoing quantitative computed tomography analysis

PurposeScoliosis is a cause of loading imbalance between the lower limbs, which can result in BMD differences between the two femurs. We investigated the discrepancy in BMD values assessed by quantitative computed tomography (QCT) between femurs in patients with and without scoliosis, also assessing if this difference can be related to spine convexity.MethodsAbdominal CT examinations were retrospectively reviewed. An ‘‘asynchronous’’ calibration of CT images was performed to obtain BMD values from QCT. Scoliosis was evaluated on the antero-posterior CT localizer to calculate the Cobb angle. Differences between aBMD and vBMD of femurs were assessed in both scoliotic and non-scoliotic subjects.ResultsFinal study cohort consisted of 263 subjects, 225 of them without scoliosis (85.6%) and 38 with scoliosis (14.4%). No significant differences were found in the general population without scoliosis, except for vBMD at the neck. Comparison of femurs in scoliotic patients showed statistically significant differences at neck aBMD −0.028 g/cm2, p = 0.004), total femur aBMD (−-0.032 g/cm2, p = 0.008) and total femur vBMD (−-8.9 mg/cm3, p = 0.011), with lower BMD values on the convexity side. In 10 cases (26%) a change in the final T-score diagnosis was observed.ConclusionQCT analysis demonstrated a difference in both areal and volumetric BMD between the two femurs of scoliotic patients, in relation to the side of the scoliotic curve. If these data will be confirmed by larger studies, bilateral femoral DXA acquisition may be proposed for these patients.

Effects of Moderate- to High-Impact Exercise Training on Bone Structure Across the Lifespan: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Moderate- to high-impact exercise improves bone mineral density (BMD) across the lifespan, but its effects on bone structure, which predicts fracture independent of areal BMD, are unclear. This systematic review and meta-analysis investigated effects of impact exercise on volumetric BMD (vBMD) and bone structure. Four databases (PubMed, Embase, SPORTDiscus, Web of Science) were searched up to March 2022 for randomized controlled trials (RCTs) investigating the effects of impact exercise, with ground reaction forces equal to or greater than running, compared with sham or habitual activity, on bone vBMD and structure. Bone variables were measured by quantitative computed tomography or magnetic resonance imaging at the tibia, radius, lumbar spine, and femur. Percentage changes in bone variables were compared among groups using mean differences (MD) and 95% confidence intervals (CI) calculated via random effects meta-analyses. Subgroup analyses were performed in children/adolescents (<18 years), adults (18-50 years), postmenopausal women, and older men. Twenty-eight RCTs (n = 2985) were included. Across all studies, impact exercise improved trabecular vBMD at the distal tibia (MD = 0.54% [95% CI 0.17, 0.90%]), total vBMD at the proximal femur (3.11% [1.07, 5.14%]), and cortical thickness at the mid/proximal radius (1.78% [0.21, 3.36%]). There was no effect on vBMD and bone structure at the distal radius, femoral shaft, or lumbar spine across all studies or in any subgroup. In adults, impact exercise decreased mid/proximal tibia cortical vBMD (-0.20% [-0.24, -0.15%]). In postmenopausal women, impact exercise improved distal tibia trabecular vBMD (0.79% [0.32, 1.25%]). There was no effect on bone parameters in children/adolescents in overall analyses, and there were insufficient studies in older men to perform meta-analyses. Impact exercise may have beneficial effects on bone structure and vBMD at various skeletal sites, but additional high-quality RCTs in different age and sex subgroups are needed to identify optimal exercise protocols for improving bone health across the lifespan. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

The Vitamin D Metabolite Ratio Is Associated With Volumetric Bone Density in Older Men.

Serum 25-hydroxyvitamin D (25(OH)D) is the current marker of vitamin D adequacy, but its relationship with bone health has been inconsistent. The ratio of 24,25-dihydroxyvitamin D3 to 25(OH)D3 (vitamin D metabolite ratio or VMR) is a marker of vitamin D that has been associated with longitudinal changes in bone mineral density (BMD) and fracture risk. High-resolution peripheral quantitative computed tomography (HR-pQCT) provides information on bone health beyond standard dual-energy x-ray absorptiometry, in that it measures volumetric BMD (vBMD) as well bone strength. The relationship of the VMR with vBMD and bone strength remains unknown. We evaluated the associations of the VMR and 25(OH)D3 with vBMD and bone strength in the distal radius and tibia, assessed by HR-pQCT in 545 older men participating in the Osteoporotic Fractures in Men (MrOS) Study. Primary outcomes were vBMD and estimated failure load (EFL, a marker of bone strength) at the distal radius and tibia. The mean age was 84 ± 4 years, 88.3% were White, and 32% had an estimated glomerular filtration rate <60 mL/min/1.73 m2. In adjusted models, each twofold higher VMR was associated with a 9% (3%, 16%) higher total vBMD and a 13% (5%, 21%) higher EFL at the distal radius. Results were similar at the distal tibia. 25(OH)D3 concentrations were not associated with any of the studied outcomes. Among older men, a higher VMR was associated with greater vBMD and bone strength while 25(OH)D3 was not. The VMR may serve as a valuable marker of skeletal health in older men.

FRI038 Differences In Bone Accrual Over One Year In Young Girls With Obesity Compared To Normal Weight Controls

Abstract Disclosure: S. Kaur: None. V. Singhal: None. L.A. Haidar: None. M. Bredella: None. M. Misra: None. Introduction: Despite higher bone mineral density (BMD), women with obesity are at an increased risk of fracture compared to normal-weight women. Optimal adolescent bone accrual is critical for normal peak bone mass acquisition and future bone health. Whereas several studies have examined the impact of low body weight on bone accrual in youth, data are lacking regarding the impact of obesity on bone accrual. We aimed to assess changes in areal and volumetric BMD, bone geometry and microarchitecture, and estimates of bone strength over one year in young females with moderate to severe obesity compared to their normal-weight counterparts. Methods: We recruited females between 13-25 years of age with moderate to severe obesity (OB) (n=21) and compared their bone accrual over one year with normal-weight controls (NWC) (n=50). Dual-energy X-ray absorptiometry to assess areal BMD (aBMD), high-resolution peripheral quantitative computed tomography (distal radius and tibia) to assess volumetric BMD (vBMD), bone geometry, and microarchitecture, and micro finite element analysis for estimates of bone strength was used. Analyses were controlled for age and race. Results: The mean age was 18.7 ± 2.7 years. OB and NWC were similar for age, race, height, and physical activity at baseline. OB had higher weight and BMI (p&amp;lt;0.0001 for both) and younger menarchal age (p=0.022) than NWC. Over one year, there was no difference between the groups for change in height, weight, and BMI. However, OB did not demonstrate the increase in total hip BMD observed in NWC (p=0.03) over a year. OB also had lesser increases in percent cortical area, cortical thickness, cortical and total vBMD at the radius over a year than the NWC group (p≤0.037 for all). The groups did not differ for tibial bone accrual. Conclusions: Our study demonstrates that longitudinal bone accrual over one year is impaired at the total hip and radius in adolescents and young adult females with obesity compared to normal-weight controls, while no differences are observed in tibial bone accrual. This raises concerns regarding future bone health in women with obesity, particularly at certain skeletal sites. Presentation: Friday, June 16, 2023

OR13-04 Risk Of Wrist Fracture In Gastric Bypass Compared To Gastric Banding As Estimated By The Load-To-Strength Ratio

Abstract Disclosure: G.H. Jung: None. B. Zahedi: None. K. Lindeman: None. C.C. Rushin: None. M.C. Cheney: None. M.L. Bouxsein: None. E.W. Yu: Grant Recipient; Self; Amgen Inc. Background: Bariatric surgeries such as Roux-en-Y gastric bypass (RYGB) and adjustable gastric banding (AGB) lead to long-term deficits in bone density but are also accompanied by decreased weight, which may lower the impact force with falls. Given that risk of fracture is dependent on both bone strength and the external force applied to bone, the clinical implications of these opposing effects are unclear. The aim of this study is to compare the long-term skeletal impact of RYGB and AGB using a biomechanical evaluation of load-to-strength ratio as a surrogate for fracture risk. Methods: We examined a cohort of adults who received RYGB and AGB surgery ≥ 10 years ago (RYGB: n=25; AGB: n=25). We computed the load-to-strength ratio at the distal radius as a ratio of impact force to bone strength, with higher load-to-strength ratios representing a higher susceptibility to fracture. Impact force (F) was calculated for a forward fall via a single-spring biomechanical model. High-resolution peripheral quantitative CT was used to estimate bone strength via microfinite element analysis. Participants also had dual-energy X-ray absorptiometry measurements of areal bone mineral density (aBMD) at the spine, hip, and distal radius, along with laboratory evaluations (parathyroid hormone, PTH; C-telopeptide, CTX; type 1 procollagen, P1NP; 25OH-vitamin D). Differences in bone outcomes between RYGB and AGB groups were compared using generalized linear modeling in R version 4.2.2 and adjusted for age, sex/menopausal status, and race/ethnicity. Results: The RYGB and AGB groups were each comprised of 22 women and 3 men. Compared to AGB, the RYGB group was younger (56 vs 62 years), had more premenopausal women (41% vs 9%), more individuals who identified as Black (36% vs 8%) and longer duration since surgery (13 vs 11 years) (p&amp;lt;0.05 for all). Current BMI (34.5 kg/m^2) was similar between groups, although postsurgical weight loss was higher in RYGB (45 vs. 27 kg, p&amp;lt;0.001). In multivariate analysis, in comparison to AGB, the RYGB group had 98% higher CTX and 34% higher P1NP levels (P&amp;lt;0.01 for both), as well as 20% lower total vBMD at the distal radius, 12% lower total hip, 10% lower femoral neck and 8% lower spinal aBMD (P&amp;lt;0.05 for all). Although impact forces were similar in the 2 groups, RYGB had a 12% lower estimated bone strength (3768 ± 182 vs. 4236 ± 193 N, p=0.01). Load-to-strength ratio was numerically higher in RYGB as compared with AGB (0.78 ± 0.05 vs 0.69± 0.06, p=0.1), suggestive of higher fracture risk, although this did not reach statistical significance. Conclusions: Despite achieving similar postoperative weight as AGB, RYGB patients had lower estimated bone strength at the distal radius, higher bone turnover markers, lower BMD and a trend for higher load-to-strength ratio ≥10 years after surgery. Taken together, these results indicate the long-term deleterious skeletal effects are more concerning with RYGB than AGB. Presentation: Friday, June 16, 2023

A two-cohort study on the association between the gut microbiota and bone density, microarchitecture, and strength.

The gut microbiome affects the inflammatory environment through effects on T-cells, which influence the production of immune mediators and inflammatory cytokines that stimulate osteoclastogenesis and bone loss in mice. However, there are few large human studies of the gut microbiome and skeletal health. We investigated the association between the human gut microbiome and high resolution peripheral quantitative computed tomography (HR-pQCT) scans of the radius and tibia in two large cohorts; Framingham Heart Study (FHS [n=1227, age range: 32 - 89]), and the Osteoporosis in Men Study (MrOS [n=836, age range: 78 - 98]). Stool samples from study participants underwent amplification and sequencing of the V4 hypervariable region of the 16S rRNA gene. The resulting 16S rRNA sequencing data were processed separately for each cohort, with the DADA2 pipeline incorporated in the16S bioBakery workflow. Resulting amplicon sequence variants were assigned taxonomies using the SILVA reference database. Controlling for multiple covariates, we tested for associations between microbial taxa abundances and HR-pQCT measures using general linear models as implemented in microbiome multivariable association with linear model (MaAslin2). Abundance of 37 microbial genera in FHS, and 4 genera in MrOS, were associated with various skeletal measures (false discovery rate [FDR] ≤ 0.1) including the association of DTU089 with bone measures, which was independently replicated in the two cohorts. A meta-analysis of the taxa-bone associations further revealed (FDR ≤ 0.25) that greater abundances of the genera; Akkermansia and DTU089, were associated with lower radius total vBMD, and tibia cortical vBMD respectively. Conversely, higher abundances of the genera; Lachnospiraceae NK4A136 group, and Faecalibacterium were associated with greater tibia cortical vBMD. We also investigated functional capabilities of microbial taxa by testing for associations between predicted (based on 16S rRNA amplicon sequence data) metabolic pathways abundance and bone phenotypes in each cohort. While there were no concordant functional associations observed in both cohorts, a meta-analysis revealed 8 pathways including the super-pathway of histidine, purine, and pyrimidine biosynthesis, associated with bone measures of the tibia cortical compartment. In conclusion, our findings suggest that there is a link between the gut microbiome and skeletal metabolism.

Site specific differences in vBMD and geometry in postmenopausal women with primary hyperparathyroidism.

Primary Hyperparathyroidism (PHPT) is associated with catabolic effects at both trabecular and cortical bone. Mechanical loading is one of the most important natural anabolic stimuli for bone at all ages. The present study was designed to assess the impact of PHPT on vBMD and bone geometry using peripheral quantitative computed tomography (pQCT) at the radius and tibia, sites with similar structural characteristics, but subject to different loading conditions. We evaluated the impact of PHPT on bone, by comparing the z-scores of volumetric Bone Mineral Density (vBMD) and indices of bone geometry simultaneously at the tibia and the radius by pQCT, skeletal sites with similar structure, but subject to different loading conditions. Forty-one postmenopausal women with PHPT and 79 controls, comprised the study group. At both trabecular and cortical sites, vBMD and bone geometry indices were significantly lower in patients compared with controls. In patients with PHPT, apart from a lower z-score for total vBMD (p = 0.01) at the radius, there was no other difference between the radius and the tibia at the trabecular sites. On the contrary, at cortical sites, the z-scores of cortical bone mineral content (p = 0.02), cortical vBMD (p = 0.01) and cortical cross-sectional area (p = 0.05) were significantly lower at the radius compared with the tibia, indicating that cortical bone at the weight bearing tibia might be less affected by the catabolic actions of continuous parathyroid hormone (PTH) exposure. PTH levels were positively associated with the difference in z-scores of cort BMD (r = 0.439, p < 0.01) indicating that in more severe cases, as expressed by higher PTH levels, the deleterious effects at the non-weight bearing radius might be accentuated. We found that in postmenopausal women with PHPT, both trabecular and cortical bone are adversely affected. However, at the weight bearing tibia as compared with the radius, the deleterious effects, especially on cortical bone, seem to be attenuated. NCT05426512, 21/06/2022, "retrospectively registered".