Lower vBMD Research Articles

Individuals with Heterogenous Trabecular Bone Texture by Clinical MRI have Lower Bone Strength and Stiffness by QCT Based Finite Element Analysis.

Opportunistic screening is essential to improve the identification of individuals with osteoporosis. Our group has utilized image texture features to assess bone quality using clinical MRIs. We have previously demonstrated that greater heterogeneity of MRI texture related to history of fragility fractures, lower bone density, and worse microarchitecture. The present study investigated relationships between MRI-based texture features and biomechanical properties of bone using CT-based finite element analyses (FEA). We hypothesized that individuals with greater texture heterogeneity would have lower stiffness and failure load. Thirty individuals included in this prospective study had CT and MRI of L1 and L2 vertebrae. Using T1-weighted MR images, a gray-level co-occurrence matrix was generated to characterize the distribution and spatial organization of voxelar signal intensities to derive the following texture features: contrast (variability), entropy (disorder), angular second moment (ASM; uniformity), and inverse difference moment (IDM; homogeneity). Features were calculated in five directions relative to the image plane. Whole-bone stiffness and failure load were calculated from phantom-calibrated lumbar QCT. Mean age of subjects was 59 ± 11years (57% female). Individuals with lower vertebral stiffness had greater texture heterogeneity; specifically, higher contrast (r = -0.54, P<.01), higher entropy (r = -0.52, P<.01), lower IDM (r = 0.54, P<.01) and lower ASM (r = 0.51, P<.01). Lower vertebral failure load and lower vBMD were similarly associated with greater texture heterogeneity. Relationships were unchanged when using the average of texture in all directions or the vertical direction in isolation. In summary, individuals with more heterogeneous MRI-based trabecular texture had lower stiffness and failure load by FEA, and lower vBMD by central quantitative CT. These results-the first relating MRI-based texture features and biomechanical properties of bone-provide further support that MRI-based texture measurements can be used to opportunistically detect skeletal fragility.

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

The influence of lumbar vertebra and cage related factors on cage-endplate contact after lumbar interbody fusion: An in-vitro experimental study

Lumbar interbody fusion (LIF) using interbody cages is an established treatment for lumbar degenerative disc disease, but fusion results are known to be affected by risk factors such as bone mineral density (BMD), endplate geometry and cage position. At present, direct measurement of endplate-cage contact variables that affect LIF have not been fully identified. The aim of this study was to use cadaveric experiments to investigate the dependency between BMD, endplate geometry, cage parameters like type, orientation, position, and contact variables like stress and area. One vertebral body specimen from each of the five lumbar positions was harvested from five male donors. The lower half of each vertebra was potted and placed in a material testing machine (Instron 8874). A spinal cage was clamped to the machine then lowered to bring it into contact against the superior endplate. A lockable ball-joint was used to rotate the cage such that its inferior surface was congruent with the local endplate surface. A pressure sensor (Tekscan) was placed between the cage and endplate to record contact area and the peak and average contact pressures. Axial compression of 400 N was performed for five positions using a straight cage, and in one anterior position using a curved cage. The linear mixed model was utilised to perform data analyses for experimental results with statistical significance set at p < 0.05. The results indicated two trends toward significance for contact area, one for volumetric BMD (vBMD) of the vertebra (p = 0.081), and another for predicted contact area (p = 0.057). Peak contact pressure correlated significantly with vBMD (p = 0.041), and there was a trend between average contact pressure and lateral position of cage (p = 0.051). In addition, predicted contact area correlated significantly with cage orientation (p < 0.001). These results indicated that high vBMD of vertebra and a medially positioned cage led to higher contact pressures. Logically, low vBMD of vertebra and transverse cage orientation increased the contact area between the cage and endplate. In conclusion, the study identified significant influence of vBMD of vertebra, cage position and orientation on cage-endplate contact which may help to inform cage selection and design for LIF.

Imaging bone turnover assessment through volumetric density-adjusted standardized uptake value using quantitative bone SPECT/CT in osteoporosis

BackgroundSerum bone turnover markers offer limited insight into metabolic activity at the individual vertebra level in osteoporosis. This study introduces a novel image-derived bone turnover marker for individual vertebrae to address this limitation, utilizing volumetric density-adjusted quantitative bone single-photon emission computed tomography/computed tomography (SPECT/CT) with [99mTc]Tc-DPD. This retrospective study included 177 lumbar vertebrae from 55 postmenopausal South Korean women. The mean standardized uptake value (SUVmean, g/cm3) and volumetric bone mineral density (vBMD, mg/cm3) were determined within a 2-cm³ volume of interest in the trabecular portion of each vertebra using quantitative SPECT and CT. The density-adjusted mean standardized uptake value (dSUVmean) was calculated by dividing the SUVmean by the vBMD and multiplying by 1,000.ResultsSUVmean correlated positively with vBMD (r = 0.60, p < 0.001). Conversely, dSUVmean correlated negatively with vBMD (ρ = −0.66, p < 0.001), highlighting the inverse relationship between bone mass and turnover after density adjustment of SUVmean. Patients with major osteoporotic fractures had lower vBMD (62.5 ± 29.4 vs. 92.3 ± 27.4 mg/cm³, p = 0.001) but higher dSUVmean (100.8 ± 60.7 vs. 62.6 ± 17.5, p = 0.001) compared to those without fractures, reinforcing the association between fracture prevalence, low bone mass, and high bone turnover.ConclusionVolumetric density-adjusted quantitative bone SPECT/CT offers a novel image-derived bone turnover marker for assessing bone turnover in osteoporosis. This method provides a precise assessment of fragility at the individual vertebra level, which may enhance personalized osteoporosis management.

Sex differences and age-related changes in vertebral body volume and volumetric bone mineral density at the thoracolumbar spine using opportunistic QCT.

To quantitatively investigate the age- and sex-related longitudinal changes in trabecular volumetric bone mineral density (vBMD) and vertebral body volume at the thoracolumbar spine in adults. We retrospectively included 168 adults (mean age 58.7 ± 9.8 years, 51 women) who received ≥7 MDCT scans over a period of ≥6.5 years (mean follow-up 9.0 ± 2.1 years) for clinical reasons. Level-wise vBMD and vertebral body volume were extracted from 22720 thoracolumbar vertebrae using a convolutional neural network (CNN)-based framework with asynchronous calibration and correction of the contrast media phase. Human readers conducted semiquantitative assessment of fracture status and bony degenerations. In the 40-60 years age group, women had a significantly higher trabecular vBMD than men at all thoracolumbar levels (p<0.05 to p<0.001). Conversely, men, on average, had larger vertebrae with lower vBMD. This sex difference in vBMD did not persist in the 60-80 years age group. While the lumbar (T12-L5) vBMD slopes in women only showed a non-significant trend of accelerated decline with age, vertebrae T1-11 displayed a distinct pattern, with women demonstrating a significantly accelerated decline compared to men (p<0.01 to p<0.0001). Between baseline and last follow-up examinations, the vertebral body volume slightly increased in women (T1-12: 1.1 ± 1.0 cm3; L1-5: 1.0 ± 1.4 cm3) and men (T1-12: 1.2 ± 1.3 cm3; L1-5: 1.5 ± 1.6 cm3). After excluding vertebrae with bony degenerations, the residual increase was only small in women (T1-12: 0.6 ± 0.6 cm3; L1-5: 0.7 ± 0.7 cm3) and men (T1-12: 0.7 ± 0.6 cm3; L1-5: 1.2 ± 0.8 cm3). In non-degenerated vertebrae, the mean change in volume was <5% of the respective vertebral body volumes. Sex differences in thoracolumbar vBMD were apparent before menopause, and disappeared after menopause, likely attributable to an accelerated and more profound vBMD decline in women at the thoracic spine. In patients without advanced spine degeneration, the overall volumetric changes in the vertebral body appeared subtle.

Early bone loss in patients with obstructive sleep apnea: a cross-sectional study

BackgroundObstructive sleep apnea (OSA) and osteoporosis are both prevalent diseases with shared pathophysiological mechanisms and risk factors. However, the association between the two diseases is seldom studied. This study aimed to identify the link between OSA and bone metabolism.MethodsMale participants aged 30–59-years who visited the sleep clinic were continuously recruited. Polysomnography was used to evaluate sleep and respiratory conditions. Blood samples were collected to detect metabolic, inflammatory and bone turnover indicators. High-resolution peripheral quantitative computer tomography was used to measure the non-dominant lateral radius and tibia.ResultsNinety subjects were recruited. The cortical area (Ct.Ar) of tibia of the severe OSA group was significantly higher than that of the mild and moderate OSA groups (P = 0.06 and P = 0.048). There were significant differences between the four groups in terms of total volumetric bone mineral density (vBMD) (F = 2.990, P = 0.035), meta trabecular vBMD (F = 3.696, P = 0.015), trabecular thickness (Tb.Th) (F = 7.060, P = 0.000) and cortical thickness (Ct.Th) (F = 4.959, P = 0.003). The mean values of the OSA groups were lower than control group. Hypopnea index and percentage of total sleep time with SpO2 < 90% were both positively correlated with alkaline phosphatase (R = 0.213, P = 0.044; R = 0.212, P = 0.045). Sleep efficiency was correlated with multiple indicators of the radius.ConclusionsIn non-elderly male populations, OSA patients tended to have lower vBMD, Tb.Th and Ct.Th than non-OSA patients. The negative effect of OSA may mainly affect the osteogenesis process, and is presumed to be related to sleep-related hypoxemia and sleep efficiency.

Incidental vertebral fracture prediction using neuronal network-based automatic spine segmentation and volumetric bone mineral density extraction from routine clinical CT scans.

To investigate vertebral osteoporotic fracture (VF) prediction by automatically extracted trabecular volumetric bone mineral density (vBMD) from routine CT, and to compare the model with fracture prevalence-based prediction models. This single-center retrospective study included patients who underwent two thoraco-abdominal CT scans during clinical routine with an average inter-scan interval of 21.7 ± 13.1 months (range 5-52 months). Automatic spine segmentation and vBMD extraction was performed by a convolutional neural network framework (anduin.bonescreen.de). Mean vBMD was calculated for levels T5-8, T9-12, and L1-5. VFs were identified by an expert in spine imaging. Odds ratios (ORs) for prevalent and incident VFs were calculated for vBMD (per standard deviation decrease) at each level, for baseline VF prevalence (yes/no), and for baseline VF count (n) using logistic regression models, adjusted for age and sex. Models were compared using Akaike's and Bayesian information criteria (AIC & BIC). 420 patients (mean age, 63 years ± 9, 276 males) were included in this study. 40 (25 female) had prevalent and 24 (13 female) had incident VFs. Individuals with lower vBMD at any spine level had higher odds for VFs (L1-5, prevalent VF: OR,95%-CI,p: 2.2, 1.4-3.5,p=0.001; incident VF: 3.5, 1.8-6.9,p<0.001). In contrast, VF status (2.15, 0.72-6.43,p=0.170) and count (1.38, 0.89-2.12,p=0.147) performed worse in incident VF prediction. Information criteria revealed best fit for vBMD-based models (AIC vBMD=165.2; VF status=181.0; count=180.7). VF prediction based on automatically extracted vBMD from routine clinical MDCT outperforms prediction models based on VF status and count. These findings underline the importance of opportunistic quantitative osteoporosis screening in clinical routine MDCT data.

Alteration of Volumetric Bone Mineral Density Parameters in Men with Spinal Cord Injury.

Spinal cord injury (SCI) induces severe losses of trabecular and cortical volumetric bone mineral density (vBMD), which cannot be discriminated with conventional dual-energy X-ray absorptiometry (DXA) analysis. The objectives were to: (i) determine the effects of SCI on areal BMD (aBMD) and vBMD determined by advanced 3D-DXA-based methods at various femoral regions and (ii) model the profiles of 3D-DXA-derived parameters with the time since injury. Eighty adult males with SCI and 25 age-matched able-bodied (AB) controls were enrolled in this study. Trabecular and cortical vBMD, cortical thickness and derived strength parameters were assessed by 3D-SHAPER® software at various femoral subregions. Individuals with SCI had significantly lower integral vBMD, trabecular vBMD, cortical vBMD, cortical thickness and derived bone strength parameters (p < 0.001 for all) in total proximal femur compared with AB controls. These alterations were approximately to the same degree for all three femoral subregions, and the difference between the two groups tended to be greater for cortical vBMD than trabecular vBMD. There were minor differences according to the lesion level (paraplegics vs tetraplegics) for all 3D-DXA-derived parameters. For total proximal femur, the decreasing bone parameters tended to reach a new steady state after 5.1years for integral vBMD, 7.4years for trabecular vBMD and 9.2years for cortical vBMD following SCI. At proximal femur, lower vBMD (integral, cortical and trabecular) and cortical thickness resulted in low estimated bone strength in individuals with SCI. It remains to be demonstrated whether these new parameters are more closely associated with fragility fracture than aBMD.

Bone microstructure and volumetric bone mineral density in patients with global sagittal malalignment.

Sagittal spinal malalignment often leads to surgical realignment, which is associated with major complications. Low bone mineral density (BMD) and impaired bone microstructure are risk factors for instrumentation failure. This study aims to demonstrate differences in volumetric BMD and bone microstructure between normal and pathological sagittal alignment and to determine the relationships among vBMD, microstructure, sagittal spinal and spinopelvic alignment. A retrospective, cross-sectional study of patients who underwent lumbar fusion for degeneration was conducted. The vBMD of the lumbar spine was assessed by quantitative computed tomography. Bone biopsies were evaluated using microcomputed tomography (μCT). C7-S1 sagittal vertical axis (SVA; ≥ 50mm malalignment) and spinopelvic alignment were measured. Univariate and multivariable linear regression analysis evaluated associations among the alignment, vBMD and μCT parameters. A total of 172 patients (55.8% female, 63.3years, BMI 29.7kg/m2, 43.0% with malalignment) including N = 106 bone biopsies were analyzed. The vBMD at levels L1, L2, L3 and L4 and the trabecular bone (BV) and total volume (TV) were significantly lower in the malalignment group. SVA was significantly correlated with vBMD at L1-L4 (ρ = -0.300, p < 0.001), BV (ρ = - 0.319, p = 0.006) and TV (ρ = - 0.276, p = 0.018). Significant associations were found between PT and L1-L4 vBMD (ρ = - 0.171, p = 0.029), PT and trabecular number (ρ = - 0.249, p = 0.032), PT and trabecular separation (ρ = 0.291, p = 0.012), and LL and trabecular thickness (ρ = 0.240, p = 0.017). In the multivariable analysis, a higher SVA was associated with lower vBMD (β = - 0.269; p = 0.002). Sagittal malalignment is associated with lower lumbar vBMD and trabecular microstructure. Lumbar vBMD was significantly lower in patients with malalignment. These findings warrant attention, as malalignment patients may be at a higher risk of surgery-related complications due to impaired bone. Standardized preoperative assessment of vBMD may be advisable.

Differences in spine volumetric bone mineral density between grade 1 vertebral fracture and non-fractured participants in the China action on spine and hip status study

This study evaluated the prevalence of vertebral fractures (VF) in middle-aged and elderly Chinese men and women and explored the differences in lumbar spine volumetric bone mineral density (vBMD) derived from quantitative CT (QCT) between those with a grade 1 vertebral fracture and non-fractured individuals. 3,457 participants were enrolled in the China Action on Spine and Hip Status (CASH) study and had upper abdominal CT examinations. Vertebral fractures were identified by Genant's semi-quantitative method from lateral CT scout views or CT sagittal views. L1-3 vBMD was measured by Mindways QCT Pro v5.0 software. The characteristics of different fracture severity groups were compared using one-way ANOVA, independent-samples t-tests, and Kruskal-Wallis H-tests. 1267 males (aged 62.77 ± 9.20 years) and 2170 females (aged 61.41 ± 9.01 years) were included in the analysis. In men, the prevalence of VF increased from 14.7% at age&lt;50 years to 23.2% at age ≥70 years, and in women from 5.1% at age&lt;50 years to 33.0% at age ≥70 years. Differences in mean age and vBMD were found between the different fracture grade groups. After age stratification, vBMD differences in men aged &lt; 50 years old disappeared (p = 0.162) but remained in the older age bands. There was no significant difference in mean vBMD between those with multiple mild fractures and those with a single mild fracture. In women, the prevalence of VF increased rapidly after age 50, while it grew more slowly in men. In general, with the exception of men &lt;50 years old, participants with a grade 1 VF had lower vBMD than non-fractured individuals. The majority of women younger than 50 with a grade 1 VF had normal bone mass. We recommend that a vertebral height reduction ratio of &lt;25% be diagnosed as a deformity rather than a fracture in people under the age of 50. The presence of multiple mild fractured vertebrae does not imply lower BMD.

Greater bone marrow fat and myosteatosis are associated with lower vBMD but not asymptomatic vertebral fracture.

Organ fat may affect bone metabolism and be associated with vertebral fracture (VF). This study aimed to explore relationships between VF, adiposity indexes measured by MRI, and volumetric BMD (vBMD) measured by quantitative CT (QCT). Four hundred volunteers, ranging in age from 22 to 83 years, were recruited and underwent same-day abdominal QCT and chemical shift-encoded (CSE) MRI. We used MRI to quantify the fat content of bone marrow (BMF), psoas major and paraspinal muscles, and the liver. Abdominal fat, VF, and vBMD of the lumbar spine were measured by QCT. For VF discrimination analysis, we examined both the whole cohort (60 VF cases in 30 men and 30 women) and a restricted subgroup of those aged over 50 years (50 VF cases in 23 men and 27 women). Amongst the men, a 1 SD increase in BMF was associated with a 27.67 (95% CI, -32.71 to -22.62) mg/cm3 decrease in vBMD after adjusting for age and BMI. Amongst women, all adiposity indexes except for liver fat were significantly associated with vBMD, with BMF having the strongest association (β, -24.00; 95% CI, -28.54 to -19.46 mg/cm3). Similar findings were also observed in participants aged over 50 years. The associations of adiposity indexes with vertebral fracture were not significant after adjusting for age in both sexes aged over 50 years. In both sexes, higher bone marrow fat was associated with lower vBMD at the spine. However, marrow fat and other adipose tissues were not associated with radiographic-based prevalent vertebral fractures. • In both sexes, higher bone marrow fat was associated with lower vBMD at the spine. • Among women, all adiposity indexes except for liver fat content were significantly associated with vBMD, with bone marrow fat having the strongest association. • Marrow fat and other adipose tissues were not associated with radiographic-based asymptomatic vertebral fractures.

Level-Specific Volumetric BMD Threshold Values for the Prediction of Incident Vertebral Fractures Using Opportunistic QCT: A Case-Control Study.

PurposeTo establish and evaluate the diagnostic accuracy of volumetric bone mineral density (vBMD) threshold values at different spinal levels, derived from opportunistic quantitative computed tomography (QCT), for the prediction of incident vertebral fractures (VF).Materials and MethodsIn this case-control study, 35 incident VF cases (23 women, 12 men; mean age: 67 years) and 70 sex- and age-matched controls were included, based on routine multi detector CT (MDCT) scans of the thoracolumbar spine. Trabecular vBMD was measured from routine baseline CT scans of the thoracolumbar spine using an automated pipeline including vertebral segmentation, asynchronous calibration for HU-to-vBMD conversion, and correction of intravenous contrast medium (https://anduin.bonescreen.de). Threshold values at T1-L5 were calculated for the optimal operating point according to the Youden index and for fixed sensitivities (60 – 85%) in receiver operating characteristic (ROC) curves.ResultsvBMD at each single level of the thoracolumbar spine was significantly associated with incident VFs (odds ratio per SD decrease [OR], 95% confidence interval [CI] at T1-T4: 3.28, 1.66–6.49; at T5-T8: 3.28, 1.72–6.26; at T9-T12: 3.37, 1.78–6.36; and at L1-L4: 3.98, 1.97–8.06), independent of adjustment for age, sex, and prevalent VF. AUC showed no significant difference between vertebral levels and was highest at the thoracolumbar junction (AUC = 0.75, 95%-CI = 0.63 - 0.85 for T11-L2). Optimal threshold values increased from lumbar (L1-L4: 52.0 mg/cm³) to upper thoracic spine (T1-T4: 69.3 mg/cm³). At T11-L2, T12-L3 and L1-L4, a threshold of 80.0 mg/cm³ showed sensitivities of 85 - 88%, and specificities of 41 - 49%. To achieve comparable sensitivity (85%) at more superior spinal levels, resulting thresholds were higher: 114.1 mg/cm³ (T1-T4), 92.0 mg/cm³ (T5-T8), 88.2 mg/cm³ (T9-T12).ConclusionsAt all levels of the thoracolumbar spine, lower vBMD was associated with incident VFs in an elderly, predominantly oncologic patient population. Automated opportunistic osteoporosis screening of vBMD along the entire thoracolumbar spine allows for risk assessment of imminent VFs. We propose level-specific vBMD threshold at the thoracolumbar spine to identify individuals at high fracture risk.

Muscle fat infiltration but not muscle cross-sectional area is independently associated with bone mineral density at the lumbar spine.

Although sarcopenia and osteoporosis are inter-related conditions that are common with advancing age, few studies have explored relationships between muscle quality and bone mineral density (BMD). We investigated age- and sex-specific paraspinal muscle fat infiltration (MFI), muscle cross-sectional area (CSA), and spine volumetric BMD (vBMD) in healthy Chinese adults. 605 healthy adults aged 20-59 years (340 women, mean age 39.2 years; 265 men, mean age 38.8 years) had axial T2WI MRI imaging of the lumbar spine and CSA (cm2) and MFI (%) were measured in the psoas and multifidus and erector spinae (MF-ES) muscles (L3-L4). MFI measurements were calibrated against a region of interest in an adjacent area of subcutaneous pure fat. L2-L4 vBMD was measured by quantitative CT. Age- and sex-specific subgroups were compared using the Mann-Whitney test. Multiple regression was used to test independent associations of MFI and CSA with vBMD. Females had lower CSA and higher MFI than males in both the psoas and MF-ES muscles (p < 0.001). In females and males, MF-ES MFI increased with age (p < 0.001) and in females age-related increases were observed for the psoas muscles (p < 0.05). Greater fat infiltration of the MS-ES muscle unit was associated with lower vBMD in both sexes (p < 0.001) but not with CSA. Following adjustment for demographic variables and CSA, MS-ES MFI remained predictive of vBMD (β = -0.408 to -0.157, p < 0.001). We have demonstrated that, independent of CSA and demographic variables, MFI of the MF-ES muscles is predictive of lower lumbar spine vBMD in both sexes. This is the first study to demonstrate that, independent of muscle size and demographic variables, MFI of the paraspinal MF-ES muscles is predictive of lower lumbar spine vBMD in both sexes.

The Role of Sex Hormones on Bone Mineral Density, Marrow Adiposity, and Muscle Adiposity in Middle-Aged and Older Men.

PurposeThe etiology of age-related bone loss is less clear in men. This study is aimed to observe the variations of endogenous sex hormone concentrations with increasing of age in men, and investigate their relations to bone mass, marrow adiposity, and muscle adiposity.MethodsA total of 199 community-dwelling Chinese men (aged 41 to 82 years) were included and measured of serum total estradiol, total testosterone, and follicle-stimulating hormone (FSH) concentrations by enzyme-linked immunosorbent assay (ELISA). Vertebral trabecular volumetric bone mineral density (vBMD) was measured by quantitative computed tomography for all participants, and vertebral marrow fat content and erector muscle fat content were quantified by Chemistry-shift-encoding magnetic resonance imaging in 62 participants.ResultsIn this population, FSH concentration increased (p < 0.001) gradually with aging. Lower vBMD was independently associated with higher FSH concentration (β = -0.216, p < 0.001), but not with total estradiol or total testosterone. For each standard deviation increase in FSH there was a 50% higher risk of an individual having osteopenia or osteoporosis (vBMD < 120 mg/cm3). Marrow fat content and erector muscle fat content were greater in osteopenic and osteoporotic men, but there were no associations with sex hormones concentrations.ConclusionIn summary, FSH but not total estradiol or total testosterone is related to vertebral trabecular vBMD in middle-aged and older Chinese men. Neither marrow adiposity nor muscle adiposity is associated with sex hormones.

Hyperglycemia Is Not Associated With Higher Volumetric BMD in a Chinese Health Check-up Cohort.

Background and PurposeType 2 diabetes mellitus patients have an increased fracture risk despite having higher areal bone mineral density (aBMD) measured by DXA. This apparent paradox might be explained by the overestimation of BMD by DXA due to the higher fat mass in type 2 diabetes mellitus patients. Volumetric BMD (vBMD) as assessed by quantitative CT (QCT) is not influenced by fat mass. We assessed the association of vBMD and fasting plasma glucose in a large cohort of Chinese subjects and compared the vBMD in healthy and diabetic subjects. In addition, we compared the relation between aBMD, vBMD, glucose and fat mass in a subset of this cohort.Materials and Methods10309 participants from the China Biobank project underwent QCT based on chest low dose CT to compute vBMD of L1 and L2 vertebrae and FPG measurements between 2018 and 2019. Among them, 1037 subjects also had spine DXA scans. Data was analyzed using linear regression models.ResultsIn the total cohort (5889 men and 4420 women, mean age 53 years, range 30-96), there was no significant association between vBMD and FPG after adjustment for age (women: p=0.774; men: p=0.149). 291 women and 606 men fitted the diagnostic criteria of diabetes. Both women and men with diabetes had lower vBMD compared to non-diabetic subjects, but this became non-significant after adjusting for age in the total cohort (women: p=0.817; men: p=0.288) and after propensity score matching based on age (women: p=0.678; men: p=0.135). In the DXA subcohort, aBMD was significantly higher in men with diabetes after adjusting for age and this difference disappeared after further adjusting for total fat area (p=0.064).ConclusionWe did not find any effect of fasting plasma glucose or diabetes on the volumetric BMD measured with QCT after adjustment for age. Therefore, vBMD measured with QCT might be a more reliable measurement to diagnose osteoporosis and assess fracture risk than aBMD measured with DXA in diabetic patients.

Human Immunodeficiency Virus (HIV) and Menopause Are Independently Associated With Lower Bone Mineral Density: Results From the Women's Interagency HIV Study.

We previously reported lower bone mineral density (BMD) among premenopausal women with HIV (WWH) compared to women without HIV (HIV-). Rate of bone loss may be even greater for WWH during the menopausal transition. Pre-, peri- and postmenopausal women in the Women\'s Interagency HIV Study (WIHS) underwent whole body DXA and central quantitative computed tomography to measure areal BMD (aBMD) and volumetric BMD (vBMD), respectively. Multivariable regression models with covariates associated with low aBMD (T score < -1.0) in univariate analyses (P≤.05) and known risk factors for low BMD assessed contributions of HIV and menopausal stage to the prediction of aBMD. Compared to HIV- women, in unadjusted analyses, WWH had 5-9% lower aBMD at the lumbar spine (P=.001), femoral neck (P=.04), total hip (P=.003) and the ultradistal radius (P=.004), and higher osteoporosis prevalence (T score<-2.5) at the ultradistal radius only (13.5% vs 0%, P=.0003). WWH also had lower vBMD at the spine and hip. In fully adjusted models, HIV independently predicted reduced aBMD at the lumbar spine, total hip, femoral neck, and ultradistal radius; menopausal stage remained a significant predictor of lumbar spine and ultradistal radius aBMD. HIV infection and menopausal stage were independent predictors of lower BMD, and had an additive effect on lumbar spine and total hip BMD. Additional research is needed to better understand underlying mechanisms by which HIV impacts BMD as women age and transition through menopause, and develop strategies to mitigate osteoporosis and fracture risk in this growing population.

Microarchitectural parameters and bone mineral density in patients with tumour-induced osteomalacia by HR-pQCT and DXA.

Tumour-induced osteomalacia (TIO) is a rare paraneoplastic condition characterised by decreased tubular phosphate reabsorption. The purpose of this study is to evaluate bone mineral density (BMD) and microarchitecture in six TIO patients, compared with 18 healthy controls. Volumetric BMD and microarchitecture were evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT), and areal BMD by dual-energy X-ray absorptiometry (DXA). Differences between groups were significant for p < .05. All TIO subjects were healthy until the development of diffuse bone pain and multiple skeletal fractures and deformities. At baseline, sPi and TmPi/GFR were low and patients were on vitamin D and phosphate replacement at the study. Compared with controls, TIO patients had lower aBMD at lumbar spine and hip, and lower vBMD at trabecular, cortical and entire bone, at distal radius (R) and distal tibia (T): trabecular vBMD (R = 118.3 × 177.1; T = 72.3 × 161.3 gHA/cm3 ); cortical vBMD (R = 782.3 × 866.5; T = 789.1 × 900.9 gHA/cm3 ); total region vBMD (R = 234.5 × 317; T = 167.1 × 295.8 gHA/cm3 ). Bone microarchitecture was very heterogeneous among patients and significantly different from controls: lower cortical thickness (R = 0.59 × 0.80; T = 0.90 × 1.31 mm), bone volume-to-total volume ratio (R = 0.09 × 0.14; T = 0.06 × 0.13) and Tb.N (R = 1.46 × 2.10; T = 0.93 × 1.96 mm-1 ) and also higher Tb.Sp (R = 0.70 × 0.41; T = 1.28 × 0.45 mm) and Tb.1/N.SD(R = 0.42 × 0.18; T = 0.87 × 0.20 mm). In this original study of TIO patients, DXA and HR-pQCT evaluation identified lower areal and volumetric BMD and severely impaired microarchitecture at cortical and trabecular bones, which probably contribute to bone fragility and fractures.

Patients with abnormal microarchitecture have an increased risk of early complications after spinal fusion surgery.

Spine fusion is one of the most common orthopedic surgeries, with more than 400,000 cases performed annually. While these procedures correct debilitating pain and deformities, complications occur in up to 45%. As successful fusion rests upon early stability of hardware in bone, patients with structural skeletal deficits may be at particular risk for complications. Few studies have investigated this relationship, and none have used higher order imaging to evaluate microstructural mechanisms for complications. Standard DXA measurements are subject to artifact in patients with spinal disease and therefore provide limited information. The goal of this prospective study was to investigate pre-operative bone quality as a risk factor for early post-operative complications using high resolution peripheral QCT (HR-pQCT) measurements of volumetric BMD (vBMD) and microarchitecture. We hypothesized that patients with low vBMD and abnormal microarchitecture at baseline would have more skeletal complications post-operatively. Conversely, we hypothesized that pre-operative DXA measurements would not be predictive of complications. Fifty-four subjects (mean age 63years, BMI 27kg/m2) were enrolled pre-operatively and followed for 6months after multi-level lumbar spine fusion. Skeletal complications occurred in 14 patients. Patients who developed complications were of similar age and BMI to those who did not. Baseline areal BMD and Trabecular Bone Score by DXA did not differ. In contrast, HR-pQCT revealed that patients who developed complications had lower trabecular vBMD, fewer and thinner trabeculae at both the radius and tibia, and thinner tibial cortices. In summary, abnormalities of both trabecular and cortical microarchitecture were associated the development of complications within the first six months following spine fusion surgery. Our results suggest a mechanism for early skeletal complications after fusion. Given the burgeoning number of fusion surgeries, further studies are necessary to investigate strategies that may improve bone quality and lower the risk of post-operative complications.

207. Postmenopausal women presenting for spinal fusion surgery have abnormal microarchitecture despite normal DXA

BACKGROUND CONTEXT More than 400,000 spinal fusion surgeries are performed annually in the US, with related health care costs exceeding $287 billion. As spinal fusion involves extensive instrumentation of the vertebrae, patients with skeletal abnormalities may be at increased risk for complications. However, preoperative identification of high-risk patients remains a challenge. Due to skeletal effects of aging and estrogen deficiency, postmenopausal (PM) women may be at particular risk. Dual energy x-ray absorptiometry (DXA) measurements of areal BMD are subject to artifact in patients with spinal pathology, and may be limited as screening tests. PURPOSE This prospective study investigated skeletal health in postmenopausal women having lumbar spine fusion and matched controls using DXA and high resolution peripheral QCT (HRpQCT) measurements of volumetric BMD (vBMD) and microarchitecture. We aimed to determine if HRpQCT would reveal additional abnormalities in vBMD and microarchitecture in fusion patients compared to DXA. STUDY DESIGN/SETTING Prospective, single center study. PATIENT SAMPLE A total of 60 patients were included in this study. PM women undergoing lumbar fusion were prospectively enrolled and compared to PM controls. OUTCOME MEASURES HRpQCT measurements of cortical and trabecular vBMD and microarchitecture, DXA, age and BMI. METHODS PM women undergoing lumbar fusion (n=20) were matched 1:2 by age with PM controls (n=40) who had no history of spine surgery or secondary osteoporosis. Subjects had assessments by standard DXA and high resolution peripheral QCT (HRpQCT) to measure cortical (Ct) and trabecular (Tb) vBMD and microarchitecture of the distal radius and tibia. RESULTS Mean age of subjects was 66+/-6 years, BMI (28+/-6 kg/m2) without any significant differences between groups. By DXA, T-scores in fusion patients were normal at the lumbar spine (mean 0.0) and osteopenic at the total hip (-1.2), femoral neck (-1.5) and 1/3 radius (-1.5). T- Scores did not differ significantly from controls at any site. In contrast, HRpQCT revealed low vBMD (total, Ct, Tb) in fusion patients compared to controls at both radius and tibia, with total vBMD 21-30% lower, Ct density ∼7% and Tb density ∼25% lower. Fusion patients had microarchitectural abnormalities, significantly fewer, thinner and more widely spaced trabeculae. Specifically, Tb number was 9% lower, Tb thickness 6% lower, and Tb separation 23% greater at the radius with similar differences at the tibia. CONCLUSIONS In summary, PM women presenting for spine fusion surgery had low volumetric BMD and abnormal trabecular microarchitecture, despite DXA values that were normal or slightly low. Our results suggest that additional techniques may be necessary for detection of bone quality deficits in patients presenting for spinal fusion. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Low volumetric bone density is a risk factor for early complications after spine fusion surgery

Lumbar spine (LS) fusion surgery is increasingly performed worldwide. Complications after fusion result in significant morbidity and healthcare costs. Multiple factors, including osteoporosis, have been suggested to contribute to risk of complications and re-operation. However, most studies have used DXA, which is subject to artifact in patients with spine pathology, and none have investigated the relationship between BMD and timing of post-operative complications. This study aims to investigate LS volumetric bone density (vBMD) as a risk factor for complications (pseudoarthrosis, instrumentation failure, adjacent fractures), re-operation, and time to complication after fusion. We evaluated a cohort of 359 patients who had initial LS fusion surgery at our institution, had pre-operative LS CTs and post-operative imaging available for review. Demographic factors, smoking status, vBMD, and details of surgical procedure were related to likelihood and timing of post-operative complications. Mean age was 60 ± 14years, vBMD 122 ± 37g/cm3. Median follow-up was 11months. Skeletal complications occurred in 47 patients (13%); 34 patients (10%) required re-operation. Low vBMD (directly measured and estimated using HU) and smoking were associated with increased risk of skeletal complications. Each increase in baseline vBMD of 10g/cm3 decreased the complication hazard and increased the complication-free duration in time-to-event analysis (hazard ratio 0.91, 95% CI 0.83-0.98, p < 0.02). Low vBMD was a significant risk factor for early post-operative complications in patients undergoing LS fusion. Prospective studies are needed to confirm these findings and to elucidate the optimal timing for follow-up and strategies for prevention of post-operative complications in this population.