Dean Inglis

Sex-specific developmental changes in muscle size and bone geometry at the femoral shaft

INTRODUCTION When expressed as a percentage of the average result in young adults, bone mineral content lags behind bone length before puberty. Even though this observation has led to speculation about bone fragility in children, such relationships could simply be due to scaling effects when measures with different geometrical dimensions are compared. METHODS The study population comprised 145 healthy subjects (6-25 years, 94 females). Magnetic resonance imaging and dual-energy X-ray absorptiometry were used to determine femur length, bone mineral content, cortical bone mineral density, cross-sectional bone geometry (bone diameter; cortical thickness; total, cortical and medullary areas; cross-sectional and polar moments of area; bone strength index) and muscle area at the proximal one-third site of the femur. Results were dimensionally scaled by raising two-, three- and four-dimensional variables to the power of 1/2, 1/3 and 1/4, respectively. Sex-differences were also assessed before and after functionally adjusting variables for femur length and weight or muscle size. RESULTS In prepubertal children, unscaled results expressed as percentages of adult values were lowest for variables with the highest dimensions (e.g., moments of area<bone mineral content<cross-sectional areas<femur length). However, when dimensionally scaled, results in children represented similar percentages of the respective average adult values, even after functional adjustments. Before puberty, there was no sex-difference in adjusted bone or muscle variables. After puberty, males had greater total and cortical bone area, bone diameter, moments of area, bone strength index and muscle area than women, both in absolute terms as well as adjusted for femur length and weight. The largest sex-difference was found for muscle area. When compared relative to muscle size, young adult women attained greater total and cortical bone area than men. CONCLUSIONS Growth in femoral length, diameter, mass and strength appears well coordinated before puberty. Postpubertal females have narrower femora, less bone strength and muscle size than males. However, when muscle size is taken into account, females have a larger femoral bone cross-section and more cortical bone. These sex-differences likely result from a combination of mechanical and hormonal effects occurring during puberty.

Longitudinal changes in intermuscular fat volume and quadriceps muscle volume in the thighs of women with knee osteoarthritis

To quantify rates of change in quadriceps muscle (QM) and intermuscular fat (IMF) volumes over 2 years in women in the Osteoarthritis Initiative (OAI) study and examine group differences between those with radiographic osteoarthritis (ROA) and those without ROA.

Association of larger holes in the trabecular bone at the distal radius in postmenopausal women with type 2 diabetes mellitus compared to controls.

Adults with type 2 diabetes mellitus (DM) have an elevated fracture risk despite normal areal bone mineral density (aBMD). The study objective was to compare trabecular bone microarchitecture of postmenopausal women with type 2 DM and women without type 2 DM.

Quantitative analysis of subchondral sclerosis of the tibia by bone texture parameters in knee radiographs: site-specific relationships with joint space width

OBJECTIVES To determine the ability of radiographic bone texture (BTX) parameters to quantify subchondral tibia sclerosis and to examine clinical relevance for assessing osteoarthritis (OA) progression. We examined the relationship between BTX parameters and each of (1) location-specific joint space width (JSW) [JSW(x)] and minimum JSW (mJSW) of the affected compartment, and (2) knee alignment (KA) angle in knee radiographs of participants undergoing total knee arthroplasty (TKA). DESIGN Digitized fixed-flexion knee radiographs were analyzed for run-length and topological BTX parameters in a subchondral region using an algorithm. Medial JSW(x) was computed at x=0.200, 0.225, 0.250 and 0.275 according to a coordinate system defined by anatomic landmarks. mJSW was determined for medial and lateral compartment lesions. KA angles were determined from radiographs using an anatomic landmark-guided algorithm. JSW measures and the magnitude of knee malalignment were each correlated with BTX parameters. Reproducibility of BTX parameters was measured by root-mean square coefficients of variation (RMSCV%). RESULTS Run-length BTX parameters were highly reproducible (RMSCV%<1%) while topological parameters showed poorer reproducibility (>5%). In TKA participants (17 women, 13 men; age: 66+/-9 years; body mass index (BMI): 31+/-6 kg m(-2); WOMAC: 41.5+/-16.1; Kellgren-Lawrence score mode: 4), reduced trabecular spacing (Tb.Sp) and increased free ends (FE) were correlated with decreased JSW after accounting for BMI, gender and knee malalignment. These relationships were dependent on site of JSW measurement. CONCLUSION High reproducibility in quantifying bone sclerosis using Tb.Sp and its significant relationship with JSW demonstrated potential for assessing OA progression. Increased trabecular FE and reduced porosity observed with smaller JSW suggest collapsing subchondral bone or trabecular plate perforation in advanced knee OA.

Changes in trabecular bone microarchitecture in postmenopausal women with and without type 2 diabetes: a two year longitudinal study

BackgroundThe risk of experiencing an osteoporotic fracture is greater for adults with type 2 diabetes despite higher than normal bone mineral density (BMD). In addition to BMD, trabecular bone microarchitecture contributes to bone strength, but is not assessed using conventional BMD measurement by dual x-ray absorptiometry (DXA). The aim of this study was to compare two year changes in trabecular bone microarchitecture in women with and without type 2 diabetes.MethodsWe used a 1 Tesla magnetic resonance imaging (MRI) scanner to acquire axial images (resolution 195 μm × 195 μm × 1000 μm) of the distal radius. We report the change in the number and size of trabecular bone holes, bone volume fraction (BVTV), trabecular thickness (Tb.Th), number (Tb.N) and separation (Tb.Sp), endosteal area, nodal and branch density for each group. Lumbar spine and proximal femur BMD were measured with DXA (Hologic, Discovery QDR4500A) at baseline and follow-up. Using a multivariable linear regression model, we evaluated whether the percent change in the trabecular bone microarchitecture variables differed between women with and without type 2 diabetes.ResultsOf the 54 participants at baseline with valid MRI image sets, 37 participants (baseline mean [SD] age, 70.8 [4.4] years) returned for follow-up assessment after 25.4 [1.9] months. Lumbar spine BMD was greater for women with diabetes compared to without diabetes at both baseline and follow-up. After adjustment for ethnicity, women with diabetes had a higher percent increase in number of trabecular bone holes compared to controls (10[1] % versus −7 [2]%, p=0.010), however results were no longer significant after adjustment for multiple comparisons (p=0.090). There were no differences in the change in other trabecular bone microarchitecture variables between groups.ConclusionThere were no differences in percent change in trabecular bone microarchitecture variables over two years in women with type 2 diabetes compared to women without diabetes. This study provides feasibility data, which will inform future trials assessing change in trabecular bone microarchitecture in women with type 2 diabetes. Larger studies using higher resolution imaging modalities that can assess change in trabecular and cortical bone compartments in women with type 2 diabetes are needed.

Reproducibility of computer-assisted joint alignment measurement in OA knee radiographs

OBJECTIVES (1) To investigate the reproducibility of computer-assisted measurements of knee alignment angle (KA) from digitized radiographs of osteoarthritis (OA) participants requiring total knee arthroplasty (TKA) and (2) to determine whether landmark choice affects the precision of KA measurements on radiographs. METHODS Using a custom algorithm, femoral, central, and tibial measurement-guiding rules were interactively placed on digitized posteroanterior fixed-flexion knee radiographs by mouse control and positioned according to different anatomic landmarks. The angle subtended by lines connecting these guiding rules was measured by three readers to assess interobserver, intraobserver and experience-inexperience reproducibility. Test-retest reproducibility was evaluated with duplicate radiographs from a healthy cohort. Reproducibility was assessed using root-mean square coefficients of variation (RMSCV%). The Bland-Altman method was performed on data obtained from varying anatomic landmarks (confidence interval, CI= 95%). RESULTS From 16 healthy and 30 TKA participants, reproducibility analyses revealed a high degree of intraobserver (n=38, RMSCV=0.56%), interobserver (n=38, RMSCV=0.72%), test-retest (n=16, RMSCV=0.87%) and experience-inexperience (n=38, RMSCV=0.73%) reproducibility with variances below 1%. Varying the orientation of tibial and femoral rules according to anatomic landmarks produced a difference that exceeded an a priori limit of agreement of -1.11 degrees to +1.67 degrees. CONCLUSION Our custom-designed software provides a robust method for measuring KAs within digitized knee radiographs. Although test-retest analyses were only performed in a healthy cohort, we anticipate a similar degree of reproducibility in an OA sample. A standardized set of anatomic landmarks employed for KA measurement is recommended since arbitrary selection of landmarks resulted in imprecise KA measurement even with a computer-assisted technique.

Measuring Apparent Trabecular Structure With pQCT: A Comparison With HR-pQCT

We evaluated how comparable peripheral quantitative computed tomography (pQCT) measurements of cortical thickness, density, and apparent trabecular structure at the ultradistal tibia were with those measured with high-resolution pQCT (HR-pQCT). We also examined whether the accuracy of the pQCT-based trabecular and cortical measurements improved with reductions in slice thickness from the standard 2.2mm to 1.1 and 0.6mm. We immersed 15 dry tibia specimens in saline in a sealed cylinder and scanned 22.5mm from the distal tibia plateau using pQCT and HR-pQCT. pQCT underestimated cortical thickness by Stratec (CThStratec) and trabecular spacing (Tb.Sp) by 21.4% and 72.9%, whereas bone volume to total volume (BV/TV) and cortical density (CDen) were overestimated by 265.8% and 13.1%, respectively. Measurements of trabecular volumetric bone mineral density, trabecular area, total area, cortical thickness by custom software were comparable, but for CThStratec, Tb.Sp, BV/TV, and CDen, the differences between imaging devices varied with magnitude of the estimate. We recommend that researchers or clinicians interested in using pQCT to measure apparent trabecular structure or cortical thickness at the epiphyses, or in comparing findings from different devices, be aware of the differences between HR-pQCT and pQCT.

Comparison of pQCT-Based Measures of Radial Bone Geometry and Apparent Trabecular Bone Structure Using Manufacturer and In-House-Developed Algorithms

Peripheral quantitative computed tomography (pQCT) provides noninvasive densitometric and morphometric measures of total, trabecular, and cortical bone compartments. Skeletal changes over time can be determined by repeated measurements. Image thickness of 2.5mm is thought to be advantageous with respect to test-retest reliability through interrogation of a significant tissue volume. However, the error associated with slight shifts in image location is unknown. The primary purpose of this study was to determine the effects of positional variability around the 4% site on radial bone measures. The secondary objective was to compare different software algorithms for estimating the same bone characteristics. Eight left cadaveric forearms (aged 65-88 yr) were imaged at 0.5-mm intervals around the 4% site of the radial bone using pQCT (10 slices; in-plane resolution: 0.2 × 0.2mm; thickness: 2.5mm; Stratec XCT2000L. We used the manufacturers software (Stratec v6.0B) to determine the total bone mineral density (BD_tot), total bone mineral content (BMC_tot), total bone area (Area_tot), trabecular bone mineral density (BD_trab), trabecular bone mineral content (BMC_trab), and trabecular bone area (Area_trab) from each image. For comparison, in-house-developed software was also used to analyze Area_tot and Area_trab at the 4% site. The in-house software also produced measures of apparent trabecular structure, including number (App.Tb.N), thickness (App.Tb.Th), and spacing (App.Tb.Sp), quantified using 2 different stereological approaches: the parallel-plate method using trabecular perimeter lengths and mean intercept length analysis. The effect of slice position was assessed using a 1-way repeated-measures analysis of variance (ANOVA). Reliability of nonsignificant slice distances around the 4% site was determined using intraclass correlation coefficients (ICCs). One-way repeated-measures ANOVA was used to compare measures of similar bone characteristics at the 4% site. Bland-Altman plots were created to assess the level of agreement between pairs of algorithms quantifying comparable apparent trabecular structure. Area_tot and Area_trab differed significantly at greater than or equal to 1.0mm proximal and greater than or equal to 0.5mm distal to the 4% site. BMC_tot and BMC_trab differ significantly greater than or equal to 1.5mm proximally (for both) and greater than or equal to 2.0 and 1.0mm distally, respectively. BD_tot differed significantly at greater than or equal to 1mm proximal and distal to the 4% site. BD_trab did not differ among the 10 slices. For images acquired at the 4% site, and 0.5mm more proximally, reliability was excellent (ICC=0.98 to 0.99). Although the in-house software yielded a higher value for Area_tot and Area_trab at the 4% site (p<0.05), no systematic bias was observed. The parallel-plate method yielded higher values for App.Tb.N and lower values for App.Tb.Th (p<0.05), with no systematic bias. App.Tb.Sp values were smaller using the parallel-plate method, and the difference in methods increased as App.Tb.Sp values increased. Statistically, tolerance for repositioning around the 4% site of the radial bone is least for measures of bone area and greatest for BD_trab. On repeated measures, a proximal shift of 0.5mm will not influence the results.

Multiplanar reconstruction recovers morphological cartilage assessment reproducibility from maloriented coronal MRI scans

The studys purpose was to assess the effect of multiplanar reconstruction on precision of weight‐bearing medial and lateral femoral cartilage (cMF, cLF) morphometry in maloriented coronal MR images. Twenty knees were scanned four times with a 1.0 Tesla extremity imager using a fat‐suppressed T1‐weighted three‐dimensional spoiled gradient recalled echo sequence; twice with “best as” double bulls‐eye orientation of the femoral condyles, and once each with 5° internal and external rotation. Multiplanar reconstruction was applied to maloriented scans to recover double bulls‐eye orientation. Medial and lateral femoral cartilages were segmented and precision of bone area, cartilage volume and thickness (ThCtAB) evaluated for all scans. Test‐retest precision (RMSCV%) of the double bulls‐eye scans was 1.1% for total bone area and 4.1% for cartilage volume. Differences in precision between double bulls‐eye and maloriented images were assessed. Higher precision errors were observed in malorientated images for all outcomes (1.7–4.8% for internally rotation scans; 1.7–4.8% for external rotation scans). Precision generally improved with multiplanar reconstruction correction (1.7–5.6% for internally rotated scans; 1.2–3.5% for external rotation scans). Precision of femoral cartilage morphometry is generally reduced when maloriented images are acquired. Multiplanar reconstruction can correct malorientated scans and recover precision losses. Measurements are affected in a rotationally and compartmentally dependent manner. Magn Reson Med, 2011.

Magnetic resonance imaging, X-ray and dual X-ray absorptiometry techniques for assessment and monitoring of knee osteoarthritis

Health needs assessment of musculoskeletal conditions: an international bone and joint burden of disease study N Khaltaev1, B Pfleger1, AD Woolf2, K Åkesson3, JM Hazes4, D Symmons5, and the Bone and Joint Monitor Group 1Management of Noncommunicable Diseases, World Health Organization, Geneva, Switzerland; 2Duke of Cornwall Rheumatology Department, Royal Cornwall Hospital, Truro, UK; 3Department of Orthopaedic Surgery, Malmö University Hospital, Malmö, Sweden; 4Department of Rheumatology, University Hospital of Rotterdam, The Netherlands; 5Epidemiology Research Unit, University of Manchester, UK Arthritis Res Ther 2004, 6(Suppl 3):103 (DOI 10.1186/ar1334)