Distal Radius Microstructure Research Articles

Dominant and nondominant distal radius microstructure: Predictors of asymmetry and effects of a unilateral mechanical loading intervention

Most information about distal radius microstructure is based on the non-dominant forearm, with little known about the factors that contribute to bilateral asymmetries in the general population, or what factors may influence bilateral changes over time. Here, we analyzed bilateral high resolution peripheral quantitative computed tomography (HRpQCT) data collected over a 12-month period as part of a clinical trial that prescribed a well-controlled, compressive loading task to the nondominant forearm. Baseline data from 102 women age 21–40, and longitudinal data from 66 women who completed the 12-month trial, were examined to determine factors responsible for side-to-side asymmetries in bone structure and change in structure over time. Cross-sectionally, the dominant radius had 2.4%–2.7% larger cross-sectional area, trabecular area, and bone mineral content than the nondominant radius, but no other differences were noted. Those who more strongly favored their dominant arm had significantly more, thinner, closely spaced trabecular struts in their dominant versus nondominant radius. Individuals assigned to a loading intervention had significant bilateral gains in total bone mineral density (2.0% and 1.2% in the nondominant versus dominant sides), and unilateral gains in the nondominant (loaded) cortical area (3.1%), thickness (3.0%), bone mineral density (1.7%) and inner trabecular density (1.3%). Each of these gains were significantly predicted by loading dose, a metric that included bone strain, number of cycles, and strain rate. Within individuals, change was negatively associated with age, meaning that women closer to age 40 experienced less of a gain in bone versus those closer to age 21. We believe that dominant/nondominant asymmetries in bone structure reflect differences in habitual loads during growth and past ability to adapt, while response to loading reflects current individual physiologic capacity to adapt.

Bone measurements at multiple skeletal sites in adolescent idiopathic scoliosis-an in vivo correlation study using DXA, HR-pQCT and QCT.

Low bone mass is an important feature of adolescent idiopathic scoliosis (AIS), which is a complex 3D spinal deformity that affects girls during puberty. However, no clinical imaging modality is suitable for regular monitoring on their spinal bone qualities in rapid growth period. Therefore, we investigated whether bone mineral density (BMD) and bone microstructure at non-spinal sites correlated with BMD and mechanical property in the spine in AIS patients. Thirty-two AIS girls (16.7 ± 3.5years old with mean Cobb angle of 67 ± 11°) who underwent pre-operative spine CT examination for navigation surgery were recruited. Volumetric BMD (vBMD) of lumbar spine (LS) was measured by quantitative computed tomography (QCT), vBMD and bone microstructure of distal radius (DR) by high-resolution peripheral QCT (HR-pQCT) and areal BMDs of total hip (TH) and femoral necks (FN) by dual-energy X-ray absorptiometry (DXA). Biomechanical properties of the DR and LS were estimated by finite element analysis (FEA). Pearson correlation was performed to study the correlation between bone parameters at these three sites. LS vBMD correlated significantly with both FN and TH aBMD (R = 0.663-0.725, both p< 0.01) and with DR microstructural parameters (R = 0.380-0.576, all p < 0.05). Mechanical properties of LS and DR were also correlated (R = 0.398, p= 0.039). Bone measurement at proximal femur and distal radius could provide an additional predictive power in estimating the bone changes at spine, which is the primary site of deformity in AIS patients. Our result indicated that DXA and HR-pQCT could provide a valid surrogate for spine bone measurements in AIS patients.

Is radius bone mineral density helpful for fracture risk assessment?

AbstractAlthough peripheral DXA is not recommended for the diagnosis of osteoporosis or to monitor osteoporotic treatments, its use for fracture risk assessment is supported by several studies. In addition, its potential interest is supported by the recent demonstration, in prospective cohorts, of the contribution of distal radius microstructure and strength, assessed by high-resolution peripheral QCT (HRpQCT), to predict incident fractures beyond the classical clinical tools (femoral neck BMD and FRAX). Indeed, areal BMD measured by DXA at the ultra-distal radius is highly correlated with bone strength derived from HRpQCT measurements at the same site. Ultra-distal radius areal BMD is therefore highly associated with fracture risk, with associations of higher magnitude than at the “classically recommended” one-third distal radius. Furthermore, ultra-distal radius areal BMD is also associated with incident fractures in non-osteoporotic women in women with T-score &gt; –2.5 SD on hip and spine DXA or women with FRAX score below the intervention threshold for age. Since more than half of low-trauma fractures occur in individuals not identified as being at high risk by BMD testing at the spine or hip, radius bone mineral density may help to refine fracture risk in patients with osteopenia defined by central DXA (spine or hip), or relatively few clinical risk factors.

Moderate-to-heavy smoking in women is potentially associated with compromised cortical porosity and stiffness at the distal radius.

Smokers have poor outcomes in the clinic after treatment for fractures. However, skeletal effects of smoking are still debated. Inconsistencies in published data are likely due to macro-scale variables used to characterize bone differences due to smoking. Therefore, our goal was to characterize distal radius microstructure and macrostructure differences between smokers and non-smokers, and determine the degree to which smoking is associated with compartment-specific mechanical differences resulting from compromised cortical-trabecular microstructure. Data were acquired from 46 female smokers (35 to 64years old), and 45 age- and body mass-matched female non-smokers. Distal radius microstructure and mechanical variables were determined from high-resolution peripheral quantitative computed tomography (HR-pQCT) images and multiscale finite element analysis. Distal radius macro-scale variables (bone volume, bone mineral content, volumetric bone mineral density [vBMD]) were determined from low-resolution images. Age- and body mass index-adjusted results showed that cortical porosity was 33% higher (p < 0.01), and that cortical vBMD and stiffness were 3% and 8% lower, respectively (p < 0.05), among smokers. We also observed unloading of the cortical compartment in smokers. There were no differences in the macro-scale variables. Average HR-pQCT-derived vBMD was 8% lower (p < 0.05) in smokers corresponding to 5years of postmenopausal loss. Skeletal effects of smoking become evident at the micron level through a structurally and mechanically compromised cortical compartment, which partially explains the inconsistent results observed at the macro-level, and the poor clinical outcomes. Smoking may also compound postmenopausal effects on bone potentially placing women having undergone menopause at a greater risk for fracture.

Distal radius microstructure and finite element bone strain are related to site-specific mechanical loading and areal bone mineral density in premenopausal women

While weight-bearing and resistive exercise modestly increases aBMD, the precise relationship between physical activity and bone microstructure, and strain in humans is not known. Previously, we established a voluntary upper-extremity loading model that assigns a person's target force based on their subject-specific, continuum FE-estimated radius bone strain. Here, our purpose was to quantify the inter-individual variability in radius microstructure and FE-estimated strain explained by site-specific mechanical loading history, and to determine whether variability in strain is captured by aBMD, a clinically relevant measure of bone density and fracture risk. Seventy-two women aged 21–40 were included in this cross-sectional analysis. High resolution peripheral quantitative computed tomography (HRpQCT) was used to measure macro- and micro-structure in the distal radius. Mean energy equivalent strain in the distal radius was calculated from continuum finite element models generated from clinical resolution CT images of the forearm. Areal BMD was used in a nonlinear regression model to predict FE strain. Hierarchical linear regression models were used to assess the predictive capability of intrinsic (age, height) and modifiable (body mass, grip strength, physical activity) predictors. Fifty-one percent of the variability in FE bone strain was explained by its relationship with aBMD, with higher density predicting lower strains. Age and height explained up to 31.6% of the variance in microstructural parameters. Body mass explained 9.1% and 10.0% of the variance in aBMD and bone strain, respectively, with higher body mass indicative of greater density. Overall, results suggest that meaningful differences in bone structure and strain can be predicted by subject characteristics.

Simplified boundary conditions alter cortical-trabecular load sharing at the distal radius; A multiscale finite element analysis

High-resolution peripheral quantitative computed tomography (HR-pQCT) derived micro-finite element (FE) modeling is used to evaluate mechanical behavior at the distal radius microstructure. However, these analyses typically simulate non-physiologic simplified platen-compression boundary conditions on a small section of the distal radius. Cortical and trabecular regions contribute uniquely to distal radius mechanical behavior, and various factors affect these regions distinctly. Generalized strength predictions from standardized platen-compression analyses may not adequately capture region specific responses in bone. Our goal was to compare load sharing within the cortical-trabecular compartments between the standardized platen-compression BC simulations, and physiologic BC simulations using a validated multiscale approach. Clinical- and high-resolution images were acquired from nine cadaveric forearm specimens using an HR-pQCT scanner. Multiscale FE models simulating physiologic BCs, and micro-FE only models simulating platen-compression BCs were created for each specimen. Cortical and trabecular loads (N) along the length of the distal radius micro-FE section were compared between BCs using correlations. Principal strain distributions were also compared quantitatively. Cortical and trabecular loads from the platen-compression BC simulations were strongly correlated to the physiologic BC simulations. However, a 30% difference in cortical loads distally, and a 53% difference in trabecular loads proximally was observed under platen BC simulations. Also, distribution of principal strains was clearly different. Our data indicated that platen-compression BC simulations alter cortical-trabecular load sharing. Therefore, results from these analyses should be interpreted in the appropriate mechanical context for clinical evaluations of normal and pathologic mechanical behavior at the distal radius.

Validation of a new multiscale finite element analysis approach at the distal radius

High-resolution peripheral computed tomography is commonly used to evaluate mechanical behavior of the distal radius microstructure using micro-finite element (FE) modeling. However, only a 9mm section is considered and boundary conditions (BCs) are usually simplified (platen-compression), and may not represent physiologic loading. Regardless, these methods are increasingly being used for clinical evaluations. Our goal was to develop and validate a novel multiscale solution that allows for physiologically relevant loading simulations (such as bracing during a fall), and show that mechanical behavior in the distal radius is different under platen BCs. Our approach incorporated bone microstructure together with organ-level radius geometry, by replacing matching continuum regions with micro-FE sections in user-defined regions of interest. Multiscale model predicted strains showed a strong correlation and a significant relationship with measured strains (r=0.836, p<0.001; slope=0.881, intercept=−12.17 µε, p<0.001). Interestingly, platen BC simulated strains were almost 50% lower than measured strains (r=0.835, p<0.001), and strain distributions were clearly different. Our multiscale method demonstrated excellent potential as a computationally efficient alternative for observing true mechanical environment within distal radius microstructure under physiologically accurate loading.

Serum 25-Hydroxyvitamin D Insufficiency in Search of a Bone Disease.

Vitamin D "insufficiency" and "deficiency" are defined as serum 25-hydroxyvitamin D [25(OH)D] levels <75 and <30 nmol/L, respectively. We aimed to determine whether these values signal hypocalcemia and hypophosphatemia, secondary hyperparathyroidism, high bone remodeling, low areal bone mineral density (aBMD), microstructural deterioration, or reduced matrix mineralization density (MMD) and so suggest whether bone fragility is present. Concentrations of 25(OH)D, calcium, phosphate, creatinine, and parathyroid hormone (PTH) were measured in 11,855 participants. Serum C-terminal telopeptide of type 1 collagen, procollagen type 1 N-terminal propeptide (P1NP), aBMD, and distal radius microstructure and MMD were measured in a second subset of 150 participants. A breakpoint for calcium, PTH, and alkaline phosphatase was identified at a threshold 25(OH)D level <30 nmol/L. There was no plateau beyond 75 nmol/L. In the subgroup with measurements of bone morphology, no associations were detectable between serum 25(OH)D concentration, aBMD, trabecular density, cortical porosity, or MMD. Among 1439 participants with serum 25(OH)D <30 nmol/L, 6.1% had low serum calcium, 3.4% had low serum phosphate, 6.1% had high alkaline phosphatase, and 34.2% had elevated PTH. Most participants did not have any abnormalities. At a 25(OH)D threshold of ≤30 nmol/L, abnormalities in biochemical features support the notion of a "deficiency" state predisposing to bone disease. However, no deleterious effects were found in participants within an insufficiency threshold of a 25(OH)D level of 30 to 75 nmol/L, which challenges the rationale justifying vitamin D supplementation in these individuals.

Carotid plaque and bone density and microarchitecture in psoriatic arthritis: the correlation with soluble ST2.

Psoriatic arthritis (PsA) patients have increased risk of both atherosclerosis and osteoporosis. Previous studies revealed that IL-33/ST2 axis may be related to both conditions; however, these associations were never evaluated in a single patients’ group. Here we explored the association among plasma levels of IL-33 and its decoy receptor soluble ST2 (sST2), carotid plaque determined by ultrasound, and volumetric bone mineral density (vBMD)/microstructure of distal radius measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) in 80 PsA patients (55% male; 53.0 ± 10.1 years). Plasma sST2 levels were significantly higher in 33 (41%) patients with carotid plaques (11.2 ± 4.5 vs 7.7 ± 3.7 ng/ml, P < 0.001). In multivariate analysis, sST2 was an independent explanatory variable associated with carotid plaques (OR = 1.296, 95% CI: [1.091,1.540]; P = 0.003). After adjustment for the osteoporotic risk factors, sST2 was significantly associated with higher cortical porosity (β = 0.184, [0.042,0.325]; P = 0.012) and cortical pore volume (2.247, [0.434,4.060]; P = 0.016); and had a trend to be associated with lower cortical vBMD (−2.918, [−6.111,0.275]; P = 0.073). IL-33 was not associated with carotid plaque or vBMD/microstructure. In conclusion, plasma sST2 levels were independently correlated with both carotid plaque and compromised cortical vBMD/microstructure in PsA patients. IL-33/ST2 axis may be a link between accelerated atherosclerosis and osteoporosis in PsA.

Fracture history of healthy premenopausal women is associated with a reduction of cortical microstructural components at the distal radius

ObjectivesThe objective of this study is to determine in healthy premenopausal women with a history of fracture which bone structural components of the distal radius are the most closely associated with a risk of fracture. Methods and participantsThe method was as follows: measurement of radial areal bone mineral density (aBMD) by DXA, microstructural components by high-resolution quantitative peripheral computerized tomography (HR-pQCT) and strength variables by micro Finite Element Analysis (μFEA) in 196 healthy premenopausal women aged 45.9±3.7 (±SD) years with (FX, n=96) and without (NO-FX, n=100) a history of fracture. We evaluated differences in T-scores between FX and NO-FX and risk of fracture by Odds ratios (OR with 95% confidence intervals, CI) per one SD decrease, using logistic regression analysis after adjustment for age, height, weight, menarcheal age, calcium and protein intakes, and physical activity. ResultsIn the whole group the mean radial metaphysis aBMD T-score was not significantly different from zero. In the FX as compared to the NO-FX group, the differences in T-scores were as follows: for radial metaphysis: aBMD, −0.24 (P=0.005); for distal radius microstructure components: cortical volumetric BMD, −0.38 (P=0.0009); cortical thickness, −0.37 (P=0.0001); cross-sectional area (CSA), +0.24 (P=0.034); and endosteal perimeter, +0.28 (P=0.032); and for strength estimates: stiffness, −0.15 (P=0.030); failure load, −0.14 (P=0.044); and apparent modulus, −0.28 (P=0.006). T-scores of trabecular volumetric BMD and thickness did not significantly differ between the FX and the NO-FX group. Accordingly, the risk of fracture (OR, 95% CI) for 1 SD decrease in radius bone parameters was as follows: radial metaphysis aBMD: 1.70 (1.18–2.44), P=0.004; cortical volumetric BMD: 1.86 (1.28–2.71), P=0.001; and cortical thickness: 2.36 (1.53–3.63), P=0.0001. The corresponding fracture risk for the strength estimates was as follows: stiffness: 1.66 (1.06–2.61), P=0.028; failure load: 1.59 (1.02–2.47), P=0.041; and apparent modulus: 1.76 (1.17–2.64), P=0.006. ConclusionsIn healthy premenopausal women, a history of fracture is associated with reduced T-scores in the distal radius, with the cortical components showing the greatest deficit. A reduction of one SD in cortical thickness is associated with a nearly three-fold increased risk of fracture. This finding strengthens the notion that, in healthy women, a certain degree of bone structural fragility contributes to fractures before the menopause and therefore should be taken into consideration in the individual prevention strategy of postmenopausal osteoporosis.