Ankle flexor torque, size and density are differential determinants of distal tibia trabecular plate-rod morphometry and bone strength: The Ankle Quality Study.

HYPOTHESIS: Greater peak torque and higher myotendinous density at the ankle are associated with a more plate-like architecture at the distal tibia. METHODS: In this cross-sectional study, women and men ≥ 50 years old with no metal implants, reconstructive surgery, muscular dystrophies, or tendinopathies in any leg were recruited by convenience. Isometric ankle dorsi-plantar flexion and inversion-eversion peak torques were measured using dynamometry. HR-pQCT distal tibia scans were completed. Both assessments were completed on the same day on the non-dominant leg. Integral and trabecular vBMD were derived from standard analyses, failure load (FL) was obtained from finite element analysis, plate-specific parameters were computed from individual trabecula segmentation (ITS) analysis, myotendinous density (MyD) and volume fraction (MyV/TV) were computed from soft tissue analysis. pQCT scans of the 66 % mid-leg were performed (500 µm at 15 mm/s) to obtain muscle density (MD) and muscle cross-sectional area (MCSA). STATISTICAL ANALYSIS: General linear models estimated how ankle muscle group torque and muscle size and density differentially related, both separately and together, to whole-bone properties (integral vBMD, FL) and trabecular morphometry (ITS plate parameters). Models were adjusted for age, sex, BMI, use of glucocorticoids, current osteoarthritis, and participation in moderate to vigorous recreational or sport activities. RESULTS: Among 105 participants (77 % female, mean age: 63 (10) years, BMI: 25.8 (5.4) kg/m2, 25 % with OA, 17 % fracture history, 42 % falls history), all torque measures, particularly ankle dorsiflexion and eversion, were correlates of plate-plate/rod junction density and failure load. However, muscle size and density measures were further associated with vBMD. The effect of greater ankle flexor-extensor torque on more connected bone was stronger when MyD was higher (interaction p < 0.001). CONCLUSION: Strength of muscles around the ankle are correlates of plate-like trabeculae at the distal tibia, while leaner muscle and myotendinous tissues facilitates better quality bone for stronger ankle muscle torque.

Validation of High-Resolution peripheral Quantitative Computed Tomography-Derived Achilles Tendon Properties Against Diagnostic Ultrasound.

OBJECTIVES: 1) To assess the precision of high resolution peripheral quantitative computed tomography (HR-pQCT)-derived Achilles tendon (AT) cross-sectional area (HR AT-CSA) and density, and 2) to validate HR AT-CSA against ultrasound-derived AT-CSA (US AT-CSA). METHODS: Women and men (≥50 years) had HR-pQCT (0.082mm isotropic) and US scans (B-mode) performed on the non-dominant ankle. Linear regression and Bland-Altman analyses assessed systematic differences between HR-pQCT and US-derived AT-CSA. Precision measured by % root mean square coefficients of variation (%RMSCV) and agreement by type 2,1 intraclass correlation coefficients (ICC2,1), were determined for test-retest US AT-CSA scans, and analysis-reanalysis of 30 HR-pQCT and US images. RESULTS: Among 44 participants, HR and US AT-CSA were strongly correlated (R2=0.84, p<0.01, B=1.05[0.90-1.19]), with no differences between modalities (p=0.37). Bland-Altman analysis revealed minimal systematic bias (-0.7mm2[-10.7-9.3]; 1.3%) between HR-pQCT and US-derived AT-CSA with smaller AT-CSA values showing larger inter-modality differences (R2=0.098, B=-0.137 [-0.268--0.008], p=0.039). US AT-CSA demonstrated excellent test-retest precision (ICC2,1=0.998, %RMSCV=1.04%). Analysis-reanalysis of HR-pQCT AT-density and both HR-pQCT and US AT-CSA displayed ICC2,1 above 0.95 and %RMSCV within 3%. CONCLUSION: HR-pQCT can examine AT-morphometry with acceptable analytical precision. Future studies should explore these metrics' association with functional outcomes and ankle-bone structural and mechanical properties.

A Valid and Precise Semiautomated Method for Quantifying Intermuscular Fat Intramuscular Fat in Lower Leg Magnetic Resonance Images.

The accumulation of INTERmuscular fat and INTRAmuscular fat (IMF) has been a hallmark of individuals with diabetes, those with mobility impairments such as spinal cord injuries and is known to increase with aging. An elevated amount of IMF has been associated with fractures and frailty, but the imprecision of IMF measurement has so far limited the ability to observe more consistent clinical associations. Magnetic resonance imaging has been recognized as the gold standard for portraying these features, yet reliable methods for quantifying IMF on magnetic resonance imaging is far from standardized. Previous investigators used manual segmentation guided by histogram-based region-growing, but these techniques are subjective and have not demonstrated reliability. Others applied fuzzy classification, machine learning, and atlas-based segmentation methods, but each is limited by the complexity of implementation or by the need for a learning set, which must be established each time a new disease cohort is examined. In this paper, a simple convergent iterative threshold-optimizing algorithm was explored. The goal of the algorithm is to enable IMF quantification from plain fast spin echo (FSE) T1-weighted MR images or from water-saturated images. The algorithm can be programmed into Matlab easily, and is semiautomated, thus minimizing the subjectivity of threshold-selection. In 110 participants from 3 cohort studies, IMF area measurement demonstrated a high degree of reproducibility with errors well within the 5% benchmark for intraobserver, interobserver, and test-retest analyses; in contrast to manual segmentation which already yielded over 20% error for intraobserver analysis. This algorithm showed validity against manual segmentations (r > 0.85). The simplicity of this technique lends itself to be applied to fast spin echo images commonly ordered as part of standard of care and does not require more advanced fat-water separated images.

Measuring Marrow Density and Area Using Peripheral Quantitative Computed Tomography at the Tibia: Precision in Young and Older Adults and Individuals With Spinal Cord Injury.

The objective of this study was to compare the test-retest precision error for peripheral quantitative computed tomography (pQCT)-derived marrow density and marrow area segmentation at the tibia using 3 software packages. A secondary analysis of pQCT data in young adults (n = 18, mean ± standard deviation 25.4 ± 3.2 yr), older adults (n = 47, 71.8 ± 8.2 yr), and individuals with spinal cord injury (C1-T12 American Spinal Injury Association Impairment Scale, classes A-C; n = 19, 43.5 ± 8.6 yr) was conducted. Repeat scans of the tibial shaft (66%) were performed using pQCT (Stratec XCT2000). Test-retest precision errors (root mean square standard deviation and root mean square coefficient of variation [RMSCV%]) for marrow density (mg/cm3) and marrow area (mm2) were reported for the watershed-guided manual segmentation method (SliceOmatic version 4.3 [Sliceo-WS]) and the 2 threshold-based edge detection methods (Stratec version 6.0 [Stratec-TB] and BoneJ version 1.3.14 [BoneJ-TB]). Bland-Altman plots and 95% limits of agreement were computed to evaluate test-retest discrepancies within and between methods of analysis and subgroups. RMSCV% for marrow density segmentation was >5% for all methods across subgroups (Stratec-TB: 12.2%-28.5%, BoneJ-TB: 14.5%-25.2%, and Sliceo-WS: 10.9%-23.0%). RMSCV% for marrow area segmentation was within 5% for all methods across subgroups (Stratec-TB: 1.9%-4.4%, BoneJ-TB: 2.6%-5.1%, and Sliceo-WS: 2.4%-4.5%), except using BoneJ-TB in older adults. Intermethod discrepancies in marrow density appeared to be present across the range of marrow density values and did not differ by subgroup. Intermethod discrepancies varied to a greater extent for marrow area and were found to be more frequently at mid- to higher-range values for those with spinal cord injury. Precision error for pQCT-derived marrow density segmentation exceeded 5% for all methods of analysis across a range of bone mineral densities and fat infiltration, whereas precision error for marrow area segmentation ranged from 2% to 5%. Further investigation is necessary to determine alternative acquisition and analysis methods for pQCT-derived marrow segmentation.

Appendicular and whole body lean mass outcomes are associated with finite element analysis-derived bone strength at the distal radius and tibia in adults aged 40years and older.

PURPOSE: The purpose of this cross-sectional study was to determine how appendicular lean mass index (ALMI), and whole body lean (LMI) and fat mass indices (FMI) associate with estimated bone strength outcomes at the distal radius and tibia in adults aged 40 years and older. METHODS: Dual energy X-ray absorptiometry (DXA) scans were performed to determine body composition, including whole body lean and fat mass, and appendicular lean mass. ALMI (appendicular lean mass/height2), LMI (lean tissue mass/height2) and FMI (fat mass/height2) were calculated. High-resolution peripheral quantitative computed tomography (HRpQCT) scans were performed to assess bone structural properties at the distal radius and tibia. Using finite element analysis, failure load (N), stiffness (N/mm), ultimate stress (MPa), and cortical-to-trabecular load ratio were estimated from HRpQCT scans. The associations between body composition (ALMI, LMI, FMI) and estimated bone strength were examined using bivariate and multivariable linear regression analyses adjusting for age, sex, and other confounding variables. RESULTS: In 197 participants (127 women; mean±SD, age: 69.5±10.3y, body mass index: 27.95±4.95kg/m2, ALMI: 7.31±1.31kg/m2), ALMI and LMI were significantly associated with failure load at the distal radius and tibia (explained 39%-48% of the variance) and remained significant after adjusting for confounding variables and multiple testing (R2=0.586-0.645, p<0.001). ALMI, LMI, and FMI did not have significant associations with ultimate stress in our multivariable models. FMI was significantly associated with cortical-to-trabecular load ratio at the distal radius and tibia (explained 6%-12% of the variance) and remained significant after adjusting for confounders and multiple testing (R2=0.208-0.243, p<0.001). FMI was no longer significantly associated with failure load after adjusting for confounders. CONCLUSION: These findings suggest that ALMI and LMI are important determinants of estimated bone strength, particularly failure load, at the distal radius and tibia, and may contribute to preservation of bone strength in middle-to-late adulthood.

Modifying the Phenotypic Frailty Model in Predicting Risk of Major Osteoporotic Fracture in the Elderly.

INTRODUCTION: The phenotypic frailty (PF) model (including slow walking, low physical activity, exhaustion, weakness, and unintentional weight loss) has been widely used to quantify the degree of frailty and predict risks of adverse health outcomes for the elderly. However, evidence has shown that not all the components included in the PF model contribute equally, and low predictive accuracy of the PF model has been reported in predicting risks of outcomes. We aimed to improve predictive accuracy of the PF model in risk of major osteoporotic fracture (MOF) in the elderly by modifying its weighting of individual components. METHODS: Data from the Global Longitudinal Study of Osteoporosis in Women (GLOW) 3-year Hamilton cohort were used for this study. We used the multivariable Cox regression model to identify the updated weighting for components in the original PF model. The goodness of fit and discrimination were assessed for model performances. RESULTS: There were 3985 women included for analyses (mean age: 69.4 years). In the modified PF model, the updated weighting was 3 points for slowness and weakness, 2 points for weight loss, 1 point for poor endurance and exhaustion, and 1 point for low physical activity, respectively. The modified PF model could capture and categorize the future risk of MOF more accurately than the original model. Significant relationship between risks of MOF, falls, and death and the modified PF model was found. Compared with the original model, the modified PF model was a better fit to the data and with improved predictive accuracy. CONCLUSION: Based on a simple and practical rescoring and recategorizing algorithm, the modified PF model could predict risks of adverse outcomes more accurately than the original model, reflecting a cost-effective way. More evidence is needed to validate the modified PF model and support its application in geriatric practice.

Bone lead (Pb) content at the tibia is associated with thinner distal tibia cortices and lower volumetric bone density in postmenopausal women.

Conflicting evidence suggests that bone lead or blood lead may reduce areal bone mineral density (BMD). Little is known about how lead at either compartment affects bone structure. This study examined postmenopausal women (N=38, mean age 76 ± 8, body mass index (BMI): 26.74 ± 4.26 kg/m(2)) within the Hamilton cohort of the Canadian Multicentre Osteoporosis Study (CaMos), measuring bone lead at 66% of the non-dominant leg and at the calcaneus using (109)Cadmium X-ray fluorescence. Volumetric BMD and structural parameters were obtained from peripheral quantitative computed tomography images (200 µm in-plane resolution, 2.3 ± 0.5mm slice thickness) of the same 66% site and of the distal 4% site of the tibia length. Blood lead was measured using atomic absorption spectrometry and blood-to-bone lead partition coefficients (PBB, log ratio) were computed. Multivariable linear regression examined each of bone lead at the 66% tibia, calcaneus, blood lead and PBB as related to each of volumetric BMD and structural parameters, adjusting for age and BMI, diabetes or antiresorptive therapy. Regression coefficients were reported along with 95% confidence intervals. Higher amounts of bone lead at the tibia were associated with thinner distal tibia cortices (-0.972 (-1.882, -0.061) per 100 µg Pb/g of bone mineral) and integral volumetric BMD (-3.05 (-6.05, -0.05) per µg Pb/g of bone mineral). A higher PBB was associated with larger trabecular separation (0.115 (0.053, 0.178)), lower trabecular volumetric BMD (-26.83 (-50.37, -3.29)) and trabecular number (-0.08 (-0.14, -0.02)), per 100 µg Pb/g of bone mineral after adjusting for age and BMI, and remained significant while accounting for diabetes or use of antiresorptives. Total lead exposure activities related to bone lead at the calcaneus (8.29 (0.11, 16.48)) and remained significant after age and antiresorptives-adjustment. Lead accumulated in bone can have a mild insult on bone structure; but greater partitioning of lead in blood versus bone revealed more dramatic effects on both microstructure and volumetric BMD.

A Trimodality Comparison of Volumetric Bone Imaging Technologies. Part III: SD, SEE, LSC Association With Fragility Fractures.

Part II of this 3-part series demonstrated 1-yr precision, standard error of the estimate, and 1-yr least significant change for volumetric bone outcomes determined using peripheral (p) quantitative computed tomography (QCT) and peripheral magnetic resonance imaging (pMRI) modalities in vivo. However, no clinically relevant outcomes have been linked to these measures of change. This study examined 97 women with mean age of 75 ± 9 yr and body mass index of 26.84 ± 4.77 kg/m(2), demonstrating a lack of association between fragility fractures and standard deviation, least significant change and standard error of the estimate-based unit differences in volumetric bone outcomes derived from both pMRI and pQCT. Only cortical volumetric bone mineral density and cortical thickness derived from high-resolution pQCT images were associated with an increased odds for fractures. The same measures obtained by pQCT erred toward significance. Despite the smaller 1-yr and short-term precision error for measures at the tibia vs the radius, the associations with fractures observed at the radius were larger than at the tibia for high-resolution pQCT. Unit differences in cortical thickness and cortical volumetric bone mineral density able to yield a 50% increase in odds for fractures were quantified here and suggested as a reference for future power computations.

A trimodality comparison of volumetric bone imaging technologies. Part I: Short-term precision and validity.

In vivo peripheral quantitative computed tomography (pQCT) and peripheral magnetic resonance imaging (pMRI) modalities can measure apparent bone microstructure at resolutions 200 µm or higher. However, validity and in vivo test-retest reproducibility of apparent bone microstructure have yet to be determined on 1.0 T pMRI (196 µm) and pQCT (200 µm). This study examined 67 women with a mean age of 74±9 yr and body mass index of 27.65±5.74 kg/m2, demonstrating validity for trabecular separation from pMRI, cortical thickness, and bone volume fraction from pQCT images compared with high-resolution pQCT (hr-pQCT), with slopes close to unity. However, because of partial volume effects, cortical and trabecular thickness of bone derived from pMRI and pQCT images matched hr-pQCT more only when values were small. Short-term reproducibility of bone outcomes was highest for bone volume fraction (BV/TV) and densitometric variables and lowest for trabecular outcomes measuring microstructure. Measurements at the tibia for pQCT images were more precise than at the radius. In part I of this 3-part series focused on trimodality comparisons of precision and validity, it is shown that pQCT images can yield valid and reproducible apparent bone structural outcomes, but because of longer scan time and potential for more motion, the pMRI protocol examined here remains limited in achieving reliable values.

A Trimodality Comparison of Volumetric Bone Imaging Technologies. Part II: 1-Yr Change, Long-Term Precision, and Least Significant Change.

The previous article in this 3-part series demonstrated short-term precision and validity for volumetric bone outcome quantification using in vivo peripheral (p) quantitative computed tomography (pQCT) and magnetic resonance imaging (MRI) modalities at resolutions 200 µm or higher. However, 1-yr precision error and clinically significant references are yet to be reported for these modalities. This study examined 59 women with mean age of 75 ± 9 yr and body mass index of 26.84 ± 4.77 kg/m², demonstrating the lowest 1-yr precision error, standard errors of the estimate, and least significant change values for high-resolution (hr) pQCT followed by pQCT, and 1.0-T pMRI for all volumetric bone outcomes except trabecular number. Like short-term precision, 1-yr statistics for trabecular separation were similar across modalities. Excluding individuals with a previous history of fragility fractures, or who were current users of antiresorptives reduced 1-yr change for bone outcomes derived from pQCT and pMR images, but not hr-pQCT images. In Part II of this 3-part series focused on trimodality comparisons of 1-yr changes, hr-pQCT was recommended to be the prime candidate for quantifying change where smaller effect sizes are expected, but pQCT was identified as a feasible alternative for studies expecting larger changes.

Assessing adherence to teriparatide therapy, causes of nonadherence and effect of adherence on bone mineral density measurements in osteoporotic patients at high risk for fracture.

OBJECTIVES: To determine (a) adherence rates at 6, 9 and 18 months amongst patients receiving teriparatide treatment for severe osteoporosis and (b) causes of therapy discontinuation and the effect of teriparatide on bone mineral density (BMD) in adherent and nonadherent patients at different time intervals. METHODS: A retrospective chart review of 111 patients receiving teriparatide from September 2004 to June 2007 was performed. Patients self-reports were used to record adherence and causes of nonadherence at 6, 9 and 18 months. BMDs for all patients were measured using the same DXA scanner at baseline and follow up. RESULTS: Of 111 participants, 17 were male (mean age 60 years) and 94 were female (mean age 69 years). Of these, 12 did not initiate therapy and 4 were lost to follow up. Reported adherence was 89.6% at 6 months, 87.6% at 9 months and 74.7% at 18 months. Causes of nonadherence included cost (n = 4), no benefit (n = 1) and adverse events (n = 8). Common adverse events were leg cramps (n = 9), headache (n = 5) and myalgia (n = 4). Mean spine and femur BMD changes were 3.30% and 0.67% at 4-9 months respectively, and 5.39% and 0.77% at 10-18 months respectively. CONCLUSION: Adherence to teriparatide was almost 90% at 9 months and decreased to 75% at 18 months. Adverse events led to nonadherence in 20% of patients. Those who were nonadherent had lower baseline BMD values than those who were adherent. Changes in BMD at the lumbar spine were greater than changes observed at the femoral neck.