Trabecular Volumetric Bone Mineral Density Research Articles

Effects of Abaloparatide on Bone Mineral Density in Proximal Femoral Regions Corresponding to Arthroplasty Gruen Zones: A Study of Postmenopausal Women with Osteoporosis.

Low hip bone mineral density (BMD) in patients who undergo total hip arthroplasty (THA) increases the risk of periprosthetic fractures, implant instability, and other complications. Recently, emphasis has been placed on bone health optimization: treating low BMD prior to a planned orthopaedic implant procedure in an effort to normalize BMD and reduce the potential risk of future complications. Abaloparatide is a U.S. Food and Drug Administration-approved osteoanabolic agent for men and postmenopausal women with osteoporosis and a candidate drug for bone health optimization that, in addition to benefits at the spine, increases hip BMD and reduces nonvertebral fracture risk. We hypothesized that abaloparatide would improve BMD in proximal femoral regions surrounding a virtual THA stem. This post hoc analysis obtained dual x-ray absorptiometry (DXA) hip scans from 500 randomly selected postmenopausal women with osteoporosis from the Phase-3 Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE, NCT01343004) study after 0, 6, and 18 months of abaloparatide (250 patients) or placebo (250 patients). Hip DXA scans underwent 3-dimensional (3D) modeling via 3D-Shaper, followed by virtual resection of the proximal femur and simulated placement of a tapered, flat-wedge hip stem that guided delineation of the Gruen zones that were fully (zones 1 and 7) or largely (zones 2 and 6) captured in the scanning region. Integral, cortical, and trabecular volumetric BMD, cortical thickness, and cortical surface BMD (the product of cortical volumetric BMD and cortical thickness) were determined for each zone. Compared with placebo, the abaloparatide group showed greater increases in integral volumetric BMD in all zones at months 6 and 18; cortical surface BMD in zones 1, 6, and 7 at month 6; cortical thickness, cortical volumetric BMD, and cortical surface BMD in all zones at month 18; and trabecular volumetric BMD in zones 1 and 7 at months 6 and 18. Abaloparatide increases BMD in proximal femoral regions that interact with and support femoral stems, suggesting that abaloparatide may have value for preoperative or potentially perioperative bone health optimization in patients with osteoporosis undergoing THA. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Increase in lumbar spine but not distal radius bone mineral density in adults after pancreas kidney transplantation

Osteoporosis occurs in every third individual after simultaneous pancreas kidney transplantation (SPKT). Currently used bone measures insufficiently predict their fracture risk. Lumbar spine Trabecular bone score (TBS) and distal radius areal and volumetric bone mineral density (BMD) were monitored for the first time in patients with type 1 diabetes and chronic renal failure after SPKT with steroid-sparing protocol. In 33 subjects (mean age 43.4 ± 9.8 years), dual-energy X-ray absorptiometry and peripheral quantitative computed tomography were performed just after SPKT (baseline) and one and three years later. While TBS Z-scores increased (−1.1 ± 1.2 and −0.3 ± 1.0; p˂0.001, at baseline and year three, respectively), trabecular volumetric BMD Z-scores at distal radius metaphysis did not change during the study (−1.3 ± 1.3 and −1.3 ± 1.0; p = 0.38). Similarly, areal BMD Z-scores increased at lumbar spine, total hip and femoral neck (all p < 0.01), but not at the distal radius. SPKT induced bone measures' improvement at lumbar spine and hip but not at distal radius. Before suggesting changes in current clinical care, predictive value of individual bone measures or its combination for fracture risk assessment remains to be elucidated.

Associations of global biomarkers of oxidative stress with osteoporosis, bone microstructure and bone turnover: Evidence from human and animal studies

PurposeHuman evidence on the association between oxidative stress and osteoporosis is inconsistent. Fluorescent Oxidation Products (FlOPs) are global biomarkers of oxidative stress. We examined the associations of FlOPs (excitation/emission wavelengths 320/420 nm for FlOP_320, 360/420 nm for FlOP_360, and 400/475 nm for FlOP_400) with osteoporosis, bone microstructure, and bone turnover markers in humans and rats. MethodsIn humans, we conducted a 1:2 age, sex, hospital, and specimen-matched case-control study to test the association between FlOPs and osteoporosis diagnosed from dual-energy X-ray absorptiometry. In eight-week-old male Wistar rats, we administrated D-galactose and 0.9 % saline for 90 days in treatment and control groups (n = 8/group); micro-CT was used to determine bone microstructure. ResultsIn humans, higher levels of FlOP_320 (OR for per 1 SD increase = 1.49, 95 % CI: 1.01–2.20) and FlOP_360 (OR for per 1 SD increase = 1.59, 95 % CI: 1.07–2.37) were associated with increased odds of osteoporosis. FlOP_400 were not associated with osteoporosis. D-galactose treated rats, as compared with control rats, showed higher levels of FlOP_320 and MDA, and lower P1NP levels during 90 days of experiment (all P < 0.05). The D-galactose group had lower trabecular bone volume fraction (0.07 ± 0.03 vs. 0.13 ± 0.05; P = 0.008) and volumetric BMD (225.4 ± 13.8 vs. 279.1 ± 33.2 mg HA/cm3; P = 0.001) than the control group. ConclusionIn conclusion, higher FlOP_320 levels were associated with increased odds of osteoporosis, impaired bone microstructure and decreased bone formation.

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.

Primary Hyperparathyroidism: Assessment of the Effects of Parathyroidectomy Using Dual X-Ray Absorptiometry, Trabecular Bone Score, and Dual X-Ray Absorptiometry–Based Three-Dimensional Modeling

ObjectiveThis study aimed to evaluate the bone microstructure to determine whether curative surgery of primary hyperparathyroidism produces changes in bone mineral density (BMD), trabecular bone score (TBS), and three-dimensional (3D) dual x-ray absorptiometry (DXA) parameters and whether these changes are comparable. MethodsWe retrospectively studied 85 patients (60 women and 25 men, 60.4 ± 12.5 years) diagnosed with primary hyperparathyroidism and undergoing parathyroidectomy. Mean percent changes in BMD (lumbar spine [LS], femoral neck [FN], total hip [TH], and 1/3 radius), TBS and 3D-DXA parameters (trabecular volumetric BMD (vBMD), cortical vBMD, integral vBMD, cortical surface density (sBMD), and cortical thickness at TH) after surgery (12, 24, and/or 36 months) were calculated and compared, and we sought the determinants of these changes. ResultsAfter parathyroidectomy, BMD presented statistically significant mean increases in LS, FN, and TH during the first 3 years after surgery (P < .001), accompanied by an improvement in all 3D-DXA parameters, but there were no significant changes in 1/3 radius BMD or TBS. Cortical sBMD, trabecular vBMD, and integral vBMD reached mean increases of similar magnitude to those of FN and TH BMD. Age and preoperative serum levels of parathyroid hormone and carboxy-terminal telopeptide of type 1 collagen were significantly associated with percent changes after surgery. ConclusionWe found a benefit of parathyroidectomy for bone, with significant percent increases in LS, FN, and TH BMD up to the third year after surgery, and a qualitative benefit for the hip in both its trabecular and cortical compartments and bone strength.

Bone mineral density in young adults 5 to 11 years after adolescent metabolic and bariatric surgery for severe obesity compared to peers.

Metabolic and bariatric surgery (MBS) is associated with decreased bone mineral density (BMD) in adults. The long-term impact of MBS during adolescence on BMD is unknown. We report bone health status 5 to 11 years after Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) from the Teen-LABS study cohort. Between 2016 and 2022, BMD was measured by dual energy x-ray absorptiometry (DXA) in 106 young adults who had undergone MBS as adolescents. Volumetric BMD by peripheral quantitative computed tomography was measured on a subset. Ninety-one controls who had not undergone MBS were recruited for comparison. In cases (RYGB: mean age 26.8 ± 1.9 years, mean BMI 42.1 ± 9.9 kg/m2, VSG: mean age 25.1 ± 2.1 years, mean BMI 37.1 ± 8.4 kg/m2), compared to controls (mean age 26.5 ± 2.7 years, mean BMI 40.2 ± 8.7 kg/m2) (age p < 0.001, BMI p = 0.02), adjusted mean DXA-BMD (g/cm2) of the RYGB (n = 58) and VSG (n = 48) groups were lower at the hip (-10.0% and -6.3%), femoral neck (-9.6% and -5.7%) and ultra-distal radius (-7.9% and -7.0%; all p < 0.001), respectively. DXA-BMD did not differ between RYGB and VSG groups. Trabecular volumetric BMD at the radius and tibia were lower in the RYGB (-30% and -26%) and VSG (-15% and -14%) groups compared to the control group (p < 0.001). Greater time since MBS was associated with lower BMD Z-scores at the hip (p = 0.05) and femoral neck (p = 0.045). Percent change in body mass index (BMI) from baseline or in the first year after MBS were not associated with bone measures at a median of 9.3 years post MBS. BMD, especially of the hip and femoral neck, was lower in young adults who underwent MBS during adolescence compared to matched peers who had not undergone MBS. BMD Z-scores of the femoral neck were inversely associated with time since MBS but were not associated with BMI change.

Cortical Endplate Bone Density Measured by Novel Phantomless Quantitative Computed Tomography May Predict Cage Subsidence more Conveniently and Accurately.

Previous studies have shown that bone mineral density (BMD) is a predictor of cage subsidence. Phantom-less quantitative computed tomography (PL-QCT) can measure volumetric bone mineral density (vBMD) of lumbar trabecular and cortical bone. The study of endplate vBMD (EP-vBMD) is important in predicting cage settlement after extreme lateral interbody fusion (XLIF). This study aimed to determine the risk factors for postoperative cage subsidence after XLIF, particularly focusing on the relationship between vBMD measured by automatic PL-QCT and cage subsidence. Patients who underwent XLIF surgery from January 2018 to October 2020 with a minimum of 6 months of follow-up were retrospectively included. Cage subsidence was defined as >2 mm cage sinking on the adjacent endplate in follow-up imaging evaluation. Outcome measures were localized vBMDs included EP-vBMDs with different region of interest (ROI) heights measured by PL-QCT based on a customized muscle-fat algorithm. Shapiro-Wilk test, one-way ANOVA, Mann-Whitney test, Fisher exact test, univariable and multivariable logistic regression and receiver operating characteristic (ROC) curve analysis were executed in this study. One hundred and thirteen levels of 78 patients were included in the analysis. The mean age was 65 ± 7.9 years for 11 males and 67 females. Cage subsidence occurred on 45 (39.8%) surgical levels. There was no significant difference in demographics, fused levels, or preoperative radiographic parameters. 1.25-mm EP-vBMD (0.991 [0.985,0.997], p = 0.004) and P-TB-vBMD (cage-positioned trabecular volumetric bone mineral density) (0.988 [0.977-0.999], p = 0.026) were cage-subsidence relevant according to univariate analysis. Low 1.25-mm EP-vBMD (0.992 [0.985, 0.999], p = 0.029) was an independent risk factor according to multifactorial analysis. Preoperative low EP-vBMD was an independent risk factor for postoperative cage subsidence after XLIF. EP-vBMD measured by most cortex-occupied ROI may be the optimal vBMD parameter for cage subsidence prediction.

THU419 Comprehensive Evaluation Of Osteoporosis And Impaired Bone Micro Architecture In Patients With Transfusion Dependent Beta Thalassemia

Abstract Disclosure: P. Dutta: None. comprehensive evaluation of osteoporosis and impaired bone micro architecture in patients with transfusion dependent beta thalassemia Authors: Pinaki Dutta, Liza Das, Alka Khadwal, Pankaj Malhotra, Sanjay Kumar Bhadada, Vandana Dhiman, Vivek Sharma, Raman Introduction: Thalassemia-related bone disease is an entity that includes low bone mass, fractures and impaired bone microarchitecture. The current study was designed to evaluate the prevalence and determinants of low bone mass, osteoporosis and microarchitectural parameters using high-resolution peripheral quantitative computed tomography (HR-pQCT) in patients with transfusion-dependent thalassemia (TDT). Patients and Methods TDT patients (n=42) and age- and BMI-matched controls (n=40) were recruited. Demographic, biochemical and hormonal parameters were assessed. Bone mineral density (BMD), T- and Z- scores were measured by DEXA using the HOLOGIC Discovery A Viewer 6 machine. Bone microarchitecture was estimated by HR-pQCT (XtremeCT II, Scanco Medical AG, Switzerland). Results: The mean age of thalassemia patients at recruitment was 26.9 ± 6.5 years and that of controls was 28.9 ± 7.9 years. The mean age of transfusion initiation was 7 months (IQR 3-18) and the median number of transfusions required was 24 (15-25) annually. Serum calcium in cases (8.87 ± 0.67mg/dl) was significantly lower than the controls (9.40 ± 0.45mg/dl), with 9 patients having hypocalcemia and 7 of these having hypoparathyroidism. Hypogonadism was present in 40.4% patients. Bone turnover markers (P1NP, β-CTX) were not significantly different between cases and controls, except alkaline phosphatase (ALP) which was higher in the cases (102.6 ± 60.7 U/l) as opposed to controls (78.2 ± 32.1 U/l). There was a significant correlation between ALP and liver dysfunction (alanine transaminase exceeding the upper normal limit) (r = 0.36, p=0.01) and 63.6% of those with elevated ALP had liver dysfunction. Low bone mass (Z ≤−2) was present in significantly greater proportion of patients versus controls at femoral neck (29.3% vs 2.4%) and at lumbar spine (52.4% vs 14.7%). Total, cortical and trabecular volumetric bone mineral density were significantly lower in cases as compared to controls(p&amp;lt;0.05). The trabecular number was significantly lower (p&amp;lt;0.0001) and trabecular separation significantly higher at radius and tibia (p&amp;lt;0.001). Cortical thickness at radius and tibia were also significantly lower in cases than controls (p&amp;lt;0.0001). Conclusion: Patients with transfusion-dependent thalassemia have significantly lower areal and volumetric BMD (both cortical and trabecular). The bone microarchitecture is also significantly impaired in terms of lower number and wider spacing of trabeculae as well as lower cortical thickness at both radius and tibia. Presentation: Thursday, June 15, 2023

OR13-03 Assessment Of Skeletal Health Including Bone Density, Turnover, Microarchitecture And Osteoporosis In Patients With Sheehan’s Syndrome: A Prospective, Multicentric Study In Asian Indians

Abstract Disclosure: L. Das: None. B. Laway: None. J. Sahoo: None. S.K. Bhadada: None. P. Dutta: None. Introduction: Sheehan’s syndrome (SS) is a rare cause of hypopituitarism. Evidence on skeletal health in patients with this condition is limited, and data on bone geometry, structure and volumetric bone mineral density (BMD) are lacking. We aimed to comprehensively explore skeletal fragility in a multicentric cohort of treated SS. Patients and Methods: Patients with SS were recruited for analysis of demographic, clinico-biochemical and hormonal profile including bone turnover markers. Areal BMD, T- and Z-scores and trabecular bone score (TBS) were evaluated using DXA. In a subset of patients (n=29) as well as age-and BMI-matched controls (n=34), high-resolution peripheral quantitative computed tomography (HRpQCT, XtremeCT II, Scanco Medical AG, Switzerland) was performed to assess bone geometry and microarchitecture. Results: There were a total of 105 patients with SS with a mean age 45.2 ± 10.5 years and a lag of 7.4 ± 5.5 years from disease onset to diagnosis. Regular levothyroxine replacement was ongoing in 91.2% and glucocorticoid replacement in 86.1% of the cohort. Past HRT replacement was done in 66.7% patients. Bone turnover markers (P1NP, CTX) were not significantly different between cases and controls. The T- score [-2.3 (-3.0 to -1.6) vs -1.5 (-3.0 to -0.7)] and Z-score [-1.4 (-2.1 to -1.2) vs -0.6 (-2.1 to -0.1)] at the lumbar spine (LS) and the T- score [-1.8 (-2.3 to -1.3) vs -0.8 (-2.1 to -0.1)] and Z-score [-1.1 (-1.7 to -0.4) vs -0.4 (-1.0 to 0.2)] at the femoral neck (FN) were lower in cases as compared to controls (trend towards significance). Osteopenia or osteoporosis was prevalent in significantly greater proportion of the cases as compared to controls, at LS (96.3% vs 64.7%), FN (91.7% vs 47%) and ultradistal radius (65.2% vs 11.8%). Bone microarchitectural assessment showed no significant differences between TBS, or bone geometry. However, trabecular volumetric bone mineral density was higher at both tibia (p&amp;lt;0.05) and radius (p&amp;gt;0.05) in cases as opposed to age-and BMI-matched controls. There was a weak negative correlation between glucocorticoid and levothyroxine replacement duration and BMD at both LS and FN (p&amp;lt;0.05), but not with replacement dose. Conclusion: Osteopenia-osteoporosis is highly prevalent in SS. BMD at both LS and FN is negatively correlated with duration of glucocorticoid and levothyroxine exposure. There are no significant differences in bone microarchitecture or geometry but tibial trabecular volumetric BMD is greater in treated SS. Presentation: Friday, June 16, 2023

THU603 Bone Fragility In Mild Autonomous Cortisol Secretion: A Cross-Sectional Cohort Study

Abstract Disclosure: C.D. Zhang: None. S. Singh: None. J. Saini: None. M. Suresh: None. K. Thangamuthu: None. R. Nathani: None. A.L. Ebbehøj: None. V. Fell: None. S.J. Achenbach: None. E.J. Atkinson: None. S. Khosla: None. I. Bancos: None. Background: Patients with mild autonomous cortisol secretion (MACS) have higher rates of fractures compared to patients with non-functioning adrenal nodules, but bone mass is typically only modestly reduced. We hypothesized that chronic exposure to mild levels of cortisol excess may lead to a deterioration in bone quality. Objective: To characterize the effect of MACS on bone metabolism and bone microarchitecture, as measured by high-resolution peripheral quantitative computed tomography (HR-pQCT). Methods: In this cross-sectional single-center study, patients with MACS were matched by age, sex, and gonadal status to referent subjects without adrenal nodules. MACS was defined as serum cortisol concentration &amp;gt;1.8 mcg/dL after the 1 mg overnight dexamethasone suppression test (1-mg DST), in the absence of a classic Cushingoid phenotype. Those with other known secondary causes of osteoporosis and/or on pharmacologic treatment for low bone mass were excluded. All study participants underwent a bone health interview, blood draw for bone turnover markers, dual-energy x-ray absorptiometry (DXA) scan with trabecular bone score (TBS), and HR-pQCT of the non-dominant radius and tibia. Participants with a recent fracture within 12 months were excluded from the analysis of bone turnover markers. The Kruskal-Wallis test was used to compare measurements between groups. Results: A total of 82 patients with MACS and 82 referent subjects were prospectively enrolled between 1/2019 and 7/2022. The median age of study participants at the time of enrolment was 57 years (interquartile range [IQR], 47-65), and 57 (70%) were women. In the MACS cohort, the median cortisol following 1-mg DST was 3.2 mcg/dL (IQR, 2.3-6.5) with median ACTH of 8.7 pg/mL (IQR, 6.0-14.0) and median DHEA-S of 42.0 mcg/dL (IQR 23.0-68.0). While no differences in bone mineral density (BMD) were observed at any site (lumbar spine, total hip, femoral neck, or distal radius) between the two groups, patients with MACS had decreased TBS (1.374 vs 1.467, P &amp;lt;0.001) and lower osteocalcin concentrations (16.9 vs. 19.7 ng/mL, P = 0.005) than referent subjects without adrenal nodules. On HR-pQCT at the tibia, patients with MACS had significantly reduced trabecular volumetric BMD (151.6 vs 167.4 mg hydroxyapatite/cm3, P = 0.002), trabecular bone volume/tissue volume ratio (0.219 vs 0.237, P = 0.011), and number of trabeculae (1.428 vs 1.506 1/mm, P = 0.045), while trabecular separation (0.707 vs 0.656, P = 0.023) was increased compared to referent subjects. Conclusions: Patients with MACS have altered bone metabolism and microstructural deterioration that is not evident on routine DXA BMD testing. These changes may mediate their increased fracture risk and could serve as biomarkers of cortisol-induced changes in the bone. Presentation: Thursday, June 15, 2023

Total Calcium Intake Is Associated With Trabecular Bone Density in Adolescent Girls With Type 1 Diabetes.

Type 1 diabetes (T1D) confers an increased risk of fracture and is associated with lower bone mineral density (BMD) and altered microarchitecture compared with controls. Adequate calcium (Ca) intake promotes bone mineralization, thereby increasing BMD. The objective of this analysis was to evaluate the associations of total daily Ca intake with bone outcomes among youth with T1D. This was a cross-sectional analysis of girls ages 10-16 years with (n = 62) and without (n = 60) T1D. We measured Ca intake with a validated food-frequency questionnaire and BMD, microarchitecture, and strength estimates with dual-energy X-ray absorptiometry and high-resolution peripheral quantitative computed tomography. Total daily Ca intake did not differ between groups (950 ± 488 in T1D versus 862 ± 461 mg/d in controls, p = 0.306). Serum 25OHD was lower in T1D (26.3 ± 7.6 versus 32.6 ± 9.0 ng/mL, p = <0.001), and parathyroid hormone (PTH) was higher in T1D (38.9 ± 11 versus 33.4 ± 9.7 pg/mL, p = 0.004). Trabecular volumetric BMD and thickness at the tibia were lower in T1D (p = 0.013, p = 0.030). Ca intake correlated with trabecular BMD at the radius and tibia among T1D participants (β = 0.27, p = 0.047, and β = 0.28, p = 0.027, β = 0.28, respectively) but not among controls (pinteraction = 0.009 at the radius, pinteraction = 0.010 at the tibia). Similarly, Ca intake was associated with estimated failure load at the tibia in T1D but not control participants (p = 0.038, β = 0.18; pinteraction = 0.051). We observed the expected negative association of Ca intake with parathyroid hormone in controls (p = 0.022, β = -0.29) but not in T1D participants (pinteraction = 0.022). Average glycemia as measured by hemoglobin A1c did not influence the relationship of Ca and PTH among participants with T1D (pinteraction = 0.138). These data suggest that youth with T1D may be particularly vulnerable to dietary Ca insufficiency. Increasing Ca intake may be an effective strategy to optimize bone health in this population. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Computed Tomography Provides Improved Quantification of Trabecular Lumbar Spine Bone Loss Compared to Dual-Energy X-Ray Absorptiometry in Ovariectomized Sheep.

Early detection of osteoporosis using advanced imaging is imperative to the successful treatment and prevention of high morbidity fractures in aging patients. In this preclinical study, we aimed to compare dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) to quantify bone mineral density (BMD) changes in the sheep lumbar spine. We also aimed to determine the relationship of BMD to microarchitecture in the same animals as an estimate of imaging modality precision. Osteoporosis was induced in 10 ewes via laparoscopic ovariectomy and administration of high-dose corticosteroids. We performed DXA and QCT imaging to measure areal BMD (aBMD) and trabecular volumetric BMD (Tb.vBMD)/cortical vBMD (Ct.vBMD), respectively, at baseline (before ovariectomy) and at 3, 6, 9, and 12 months after ovariectomy. Iliac crest bone biopsies were collected at each time point for micro-computed tomography (microCT) analysis; bone volume fraction (BV/TV), trabecular number (Tb.N), thickness (Tb.Th), and spacing (Tb.Sp) were reported. aBMD and Tb.vBMD both decreased significantly by 3 and 6 months (p < 0.05) compared with baseline, whereas no changes to Ct.vBMD were observed. Combined (Tb. and Ct.) vBMD was significantly correlated with aBMD at all time points (all p < 0.05). Additionally, greater significant correlations were found between BV/TV and Tb.vBMD at all five time points (R 2 = 0.54, 0.57, 0.66, 0.46, and 0.56, respectively) than with aBMD values (R 2 = 0.23, 0.55, 0.41, 0.20, and 0.19, respectively). The higher correlation of microCT values with QCT than with DXA indicates that QCT provides additional detailed information regarding bone mineral density changes in preclinical settings. Because trabecular bone is susceptible to rapid density loss and structural changes during osteoporosis, QCT can capture these subtle changes more precisely than DXA in a large animal preclinical model. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Comparison of volumetric and areal bone mineral density in CT and scout scans using spectral detector technology

BackgroundTo determine whether denoised areal bone mineral density (BMD) measurements from scout scans in spectral detector computed tomography (CT) correlate with volumetric trabecular BMD for opportunistic osteoporosis screening.MethodsA 64-slice single-source dual-layer spectral CT scanner was used to acquire scout scan data of 228 lumbar vertebral bodies within 57 patients. Scout scans in anterior–posterior (AP) view were performed with a dose of < 0.06 mSv and spectrally decomposed into areal BMD (aBMD) values. A spectral dictionary denoising algorithm was applied to increase the signal-to-noise ratio (SNR). Volumetric trabecular bone mineral density (vBMD) was determined via material decomposition. A 3D convolutional network for image segmentation and labeling was applied for automated vBMD quantification. Projected maps were used to compare the classification accuracy of AP and lateral scout scans.ResultsThe denoising algorithm led to the minimization of anticorrelated noise in spectral maps and an SNR increase from 5.23 to 13.4 (p < 0.002). Correlation analysis between vBMD and measured AP aBMD, projected AP, and lateral aBMD showed a Pearson correlation coefficient of 0.68, 0.81, and 0.90, respectively. The sensitivity and specificity for the osteoporosis classification task were higher in lateral projection images than in AP crystallizing in an increased area under the curve value of 0.99 versus 0.90.ConclusionDenoised material-specific aBMD maps show a positive correlation to vBMD, enabling spectral scout scans as an opportunistic predictor for osteoporotic patients. This could be applied routinely as a screening tool in patients undergoing a CT examination.Relevance statementScout-based DEXA could be applied routinely as a screening tool in patients undergoing a CT examination.Key points• Spectral scout scans can be used as a dual-energy x-ray absorptiometry-like screening tool.• Spectral dictionary denoising on projection images increases the signal-to-noise ratio.• Positive correlation between volumetric and areal bone mineral density is observed.• Lateral projections increase osteoporosis classification accuracy compared to anterior-posterior projections.Graphical

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.

Automated Opportunistic Trabecular Volumetric Bone Mineral Density Extraction Outperforms Manual Measurements for the Prediction of Vertebral Fractures in Routine CT

Opportunistic osteoporosis screening using multidetector CT-scans (MDCT) and convolutional neural network (CNN)-derived segmentations of the spine to generate volumetric bone mineral density (vBMD) bears the potential to improve incidental osteoporotic vertebral fracture (VF) prediction. However, the performance compared to the established manual opportunistic vBMD measures remains unclear. Hence, we investigated patients with a routine MDCT of the spine who had developed a new osteoporotic incidental VF and frequency matched to patients without incidental VFs as assessed on follow-up MDCT images after 1.5 years. Automated vBMD was generated using CNN-generated segmentation masks and asynchronous calibration. Additionally, manual vBMD was sampled by two radiologists. Automated vBMD measurements in patients with incidental VFs at 1.5-years follow-up (n = 53) were significantly lower compared to patients without incidental VFs (n = 104) (83.6 ± 29.4 mg/cm3 vs. 102.1 ± 27.7 mg/cm3, p &lt; 0.001). This comparison was not significant for manually assessed vBMD (99.2 ± 37.6 mg/cm3 vs. 107.9 ± 33.9 mg/cm3, p = 0.30). When adjusting for age and sex, both automated and manual vBMD measurements were significantly associated with incidental VFs at 1.5-year follow-up, however, the associations were stronger for automated measurements (β = −0.32; 95% confidence interval (CI): −20.10, 4.35; p &lt; 0.001) compared to manual measurements (β = −0.15; 95% CI: −11.16, 5.16; p &lt; 0.03). In conclusion, automated opportunistic measurements are feasible and can be useful for bone mineral density assessment in clinical routine.

Is There a Causal Relationship between Physical Activity and Bone Microarchitecture? A Study of Adult Female Twin Pairs.

The reasons for the association between physical activity (PA) and bone microarchitecture traits are unclear. We examined whether these associations were consistent with causation and/or with shared familial factors using a cross-sectional study of 47 dizygotic and 93 monozygotic female twin pairs aged 31-77 years. Images of the nondominant distal tibia were obtained using high-resolutionperipheral quantitative computed tomography. The bone microarchitecture was assessed using StrAx1.0 software. Based on a self-completed questionnaire, a PA index was calculated as a weighted sum of weekly hours of light (walking, light gardening), moderate (social tennis, golf, hiking), and vigorous activity (competitive active sports) = light + 2 * moderate + 3 * vigorous. We applied Inference about Causation through Examination of FAmiliaL CONfounding (ICE FALCON) to test whether cross-pair cross-trait associations changed after adjustment for within-individual associations. Within-individual distal tibia cortical cross-sectional area (CSA) and cortical thickness were positively associated with PA (regression coefficients [β] = 0.20 and 0.22), while the porosity of the inner transitional zone was negatively associated with PA (β = -0.17), all p < 0.05. Trabecular volumetric bone mineral density (vBMD) and trabecular thickness were positively associated with PA (β = 0.13 and 0.14), and medullary CSA was negatively associated with PA (β = -0.22), all p ≤ 0.01. Cross-pair cross-trait associations of cortical thickness, cortical CSA, and medullary CSA with PA attenuated after adjustment for the within-individual association (p = 0.048, p = 0.062, and p = 0.028 for changes). In conclusion, increasing PA was associated with thicker cortices, larger cortical area, lower porosity of the inner transitional zone, thicker trabeculae, and smaller medullary cavities. The attenuation of cross-pair cross-trait associations after accounting for the within-individual associations was consistent with PA having a causal effect on the improved cortical and trabecular microarchitecture of adult females, in addition to shared familial factors. © 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).

Shift in Calcium From Peripheral Bone to Axial Bone After Tumor Resection in Patients With Tumor-Induced Osteomalacia.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by excessive production of fibroblast growth factor 23 (FGF23) by a tumor. After successful tumor resection, patients can recover from hypophosphatemia quicky. However, data on the changes in bone mineral density (BMD) and microstructure in the short term after surgery remained unclear. This work aimed to investigate the postoperative changes in BMD and microstructure both in peripheral and axial bone in TIO patients. We evaluated BMD and microarchitecture in 22 TIO patients using high-resolution peripheral quantitative computed tomography (HR-pQCT) and dual-energy x-ray absorptiometry (DXA) before and 3 months after surgery in this retrospective study. In this study, a total of 22 TIO patients who had recovered serum phosphate levels postoperatively were enrolled. After surgery, areal BMD (aBMD) increased by 21.6% in the femoral neck, by 18.9% in the total hip, and by 29.5% in the lumbar spine. Moreover, TBS increased by 14.1% (all P < .001). In contrast, trabecular or cortical volumetric BMD (vBMD), and microstructure of trabecular bone (trabecular number, separation and bone volume ratio) and cortical bone (cortical thickness and porosity) at the distal radius or tibia were further deteriorated. Correlation analyses found that changes in femoral neck and total hip aBMD were both conversely associated with changes in trabecular vBMD and bone volume ratio, while positively correlated with change in trabecular separation at the distal radius. Although aBMD and microstructure in the axial bone were improved, vBMD and microstructure in the peripheral bone were further impaired shortly after surgery. Correlation of improvement of aBMD in the total hip and femoral neck with deterioration of vBMD and microstructure at the distal radius indicated a shift in calcium from the peripheral bone to the axial bone in the short term after tumor resection in TIO patients.

Development of musculoskeletal deficits in children with cystic fibrosis in later childhood.

Cystic fibrosis (CF) is a genetic condition primarily affecting the respiratory system, with the associated progressive lung damage and loss of function resulting in reduced lifespan. Bone health is also impaired in individuals with CF, leading to much higher fracture risk even in adolescence. However, the development of these deficits during growth and the relative contributions of puberty, body size and muscular loading remain somewhat unexplored. We therefore recruited 25 children with CF (10 girls, mean age 11.3±2.9y) and 147 children without CF (75 girls, mean age 12.4±2.6y). Bone characteristics were assessed using peripheral quantitative computed tomography (pQCT) at 4% and 66% distal-proximal tibia. Muscle cross-sectional area (CSA) and density (an indicator of muscle quality) were also assessed at the latter site. Tibial bone microstructure was assessed using high-resolution pQCT (HR-pQCT) at 8% distal-proximal tibial length. In addition, peak jump power and hop force were measured using jumping mechanography. Group-by-age interactions and group differences in bone and muscle characteristics were examined using multiple linear regression, adjusted for age, sex and pubertal status and in additional models, height and muscle force. In initial models group-by-age interactions were evident for distal tibial total bone mineral content (BMC) and trabecular volumetric bone mineral density (vBMD), with a lower rate of age-related accrual evident in children with CF. In assessments of distal tibial microstructure, similar patterns were observed for trabecular number and thickness, and cortical CSA. In the tibial shaft, group-by-age interactions indicating slower growth in CF were evident for total BMC and cortical CSA, whilst age-independent deficits in CF were observed for several other variables. Peak jump power and hop force also exhibited similar interactions. Group-by-age interactions for bone were partially attenuated at the distal tibia and fully attenuated at the tibial shaft by adjustment for muscle force. These results suggest that bone and muscle deficits in children with CF develop throughout later childhood, independent of differences in pubertal stage and body size. These diverging growth patterns appear to be mediated by differences in muscle function, particularly for bone characteristics in the tibial shaft. Given the high fracture risk in this population from childhood onwards, development of interventions to improve bone health would be of substantial clinical value.

Male Runners With Lower Energy Availability Have Impaired Skeletal Integrity Compared to Nonathletes.

Female athletes, particularly runners, with insufficient caloric intake for their energy expenditure [low energy availability (EA) or relative energy deficiency] are at risk for impaired skeletal integrity. Data are lacking in male runners. To determine whether male runners at risk for energy deficit have impaired bone mineral density (BMD), microarchitecture, and estimated strength. Cross-sectional. Clinical research center. 39 men (20 runners, 19 controls), ages 16-30 years. Areal BMD (dual-energy x-ray absorptiometry); tibia and radius volumetric BMD and microarchitecture (high-resolution peripheral quantitative computed tomography); failure load (microfinite element analysis); serum testosterone, estradiol, leptin; energy availability. Mean age (24.5 ± 3.8 y), lean mass, testosterone, and estradiol levels were similar; body mass index, percent fat mass, leptin, and lumbar spine BMD Z-score (-1.4 ± 0.8 vs -0.8 ± 0.8) lower (P < .05); and calcium intake and running mileage higher (P ≤ .01) in runners vs controls. Runners with EA <median had lower lumbar spine (-1.5 ± 0.7, P = .028), while runners with EA ≥median had higher hip (0.3 ± 0.7 vs -0.4 ± 0.5, P = .002), BMD Z-scores vs controls. After adjusting for calcium intake and running mileage, runners with EA <median had lower mean tibial total and trabecular volumetric BMD, trabecular bone volume fraction, cortical porosity, and apparent modulus vs controls (P < .05). Appendicular lean mass and serum estradiol (R ≥ 0.45, P ≤ .046), but not testosterone, were positively associated with tibial failure load among runners. Despite weight-bearing activity, skeletal integrity is impaired in male runners with lower caloric intake relative to exercise energy expenditure, which may increase bone stress injury risk. Lower estradiol and lean mass are associated with lower tibial strength in runners.