Muscle and Myotendinous Tissue Properties at the Distal Tibia as Assessed by High-Resolution Peripheral Quantitative Computed Tomography.

High-resolution peripheral quantitative computed tomography (HR-pQCT) quantifies bone microstructure and density at the distal tibia where there is also a sizable amount of myotendinous (muscle and tendon) tissue (MT); however, there is no method for the quantification of MT. This study aimed (1) to assess the feasibility of using HR-pQCT distal tibia scans to estimate MT properties using a custom algorithm, and (2) to determine the relationship between MT properties at the distal tibia and mid-leg muscle density (MD) obtained from pQCT. Postmenopausal women from the Hamilton cohort of the Canadian Multicenter Osteoporosis Study had a single-slice (2.3 ± 0.5 mm) 66% site pQCT scan measuring muscle cross-sectional area (MCSA) and MD. A standard HR-pQCT scan was acquired at the distal tibia. HR-pQCT-derived MT cross-sectional area (MTCSA) and MT density (MTD) were calculated using a custom algorithm in which thresholds (34.22-194.32 mg HA/cm3) identified muscle seed volumes and were iteratively expanded. Pearson and Bland-Altman plots were used to assess correlations and systematic differences between pQCT- and HR-pQCT-derived muscle properties. Among 45 women (mean age: 74.6 ± 8.5 years, body mass index: 25.9 ± 4.3 kg/m2), MTD was moderately correlated with mid-leg MD across the 2 modalities (r = 0.69-0.70, p < 0.01). Bland-Altman analyses revealed no evidence of directional bias for MTD-MD. HR-pQCT and pQCT measures of MTCSA and MCSA were moderately correlated (r = 0.44, p < 0.01). Bland-Altman plots for MTCSA revealed that larger MCSAs related to larger discrepancy between the distal and the mid-leg locations. This is the first study to assess the ability of HR-pQCT to measure MT size, density, and morphometry. HR-pQCT-derived MTD was moderately correlated with mid-leg MD from pQCT. This relationship suggests that distal MT may share common properties with muscle throughout the length of the leg. Future studies will assess the value of HR-pQCT-derived MT properties in the context of falls, mobility, and balance.

Operator variability in scan positioning is a major component of HR-pQCT precision error and is reduced by standardized training.

In this study, we determined that operator positioning precision contributes significant measurement error in high-resolution peripheral quantitative computed tomography (HR-pQCT). Moreover, we developed software to quantify intra- and inter-operator variability and demonstrated that standard positioning training (now available as a web-based application) can significantly reduce inter-operator variability. INTRODUCTION: HR-pQCT is increasingly used to assess bone quality, fracture risk, and anti-fracture interventions. The contribution of the operator has not been adequately accounted in measurement precision. Operators acquire a 2D projection ("scout view image") and define the region to be scanned by positioning a "reference line" on a standard anatomical landmark. In this study, we (i) evaluated the contribution of positioning variability to in vivo measurement precision, (ii) measured intra- and inter-operator positioning variability, and (iii) tested if custom training software led to superior reproducibility in new operators compared to experienced operators. METHODS: To evaluate the operator in vivo measurement precision, we compared precision errors calculated in 64 co-registered and non-co-registered scan-rescan images. To quantify operator variability, we developed software that simulates the positioning process of the scanner's software. Eight experienced operators positioned reference lines on scout view images designed to test intra- and inter-operator reproducibility. Finally, we developed modules for training and evaluation of reference line positioning. We enrolled six new operators to participate in a common training, followed by the same reproducibility experiments performed by the experienced group. RESULTS: In vivo precision errors were up to threefold greater (Tt.BMD and Ct.Th) when variability in scan positioning was included. The inter-operator precision errors were significantly greater than the short-term intra-operator precision (p < 0.001). New trained operators achieved comparable intra-operator reproducibility to experienced operators and lower inter-operator reproducibility (p < 0.001). Precision errors were significantly greater for the radius than for the tibia. CONCLUSION: Operator reference line positioning contributes significantly to in vivo measurement precision and is significantly greater for multi-operator datasets. Inter-operator variability can be significantly reduced using a systematic training platform, now available online ( http://webapps.radiology.ucsf.edu/refline/ ).

Trabecular bone score improves fracture risk prediction in non-osteoporotic women: the OFELY study.

UNLABELLED: The use of areal bone mineral density (aBMD) for fracture prediction may be enhanced by considering bone microarchitectural deterioration. Trabecular bone score (TBS) helped in redefining a significant subset of non-osteoporotic women as a higher risk group. INTRODUCTION: TBS is an index of bone microarchitecture. Our goal was to assess the ability of TBS to predict incident fracture. METHODS: TBS was assessed in 560 postmenopausal women from the Os des Femmes de Lyon cohort, who had a lumbar spine (LS) DXA scan (QDR 4500A, Hologic) between years 2000 and 2001. During a mean follow-up of 7.8 ± 1.3 years, 94 women sustained 112 fragility fractures. RESULTS: At the time of baseline DXA scan, women with incident fracture were significantly older (70 ± 9 vs. 65 ± 8 years) and had a lower LS_aBMD and LS_TBS (both -0.4SD, p < 0.001) than women without fracture. The magnitude of fracture prediction was similar for LS_aBMD and LS_TBS (odds ratio [95 % confidence interval] = 1.4 [1.2;1.7] and 1.6 [1.2;2.0]). After adjustment for age and prevalent fracture, LS_TBS remained predictive of an increased risk of fracture. Yet, its addition to age, prevalent fracture, and LS_aBMD did not reach the level of significance to improve the fracture prediction. When using the WHO classification, 39 % of fractures occurred in osteoporotic women, 46 % in osteopenic women, and 15 % in women with T-score > -1. Thirty-seven percent of fractures occurred in the lowest quartile of LS_TBS, regardless of BMD. Moreover, 35 % of fractures that occurred in osteopenic women were classified below this LS_TBS threshold. CONCLUSION: In conclusion, LS_aBMD and LS_TBS predicted fractures equally well. In our cohort, the addition of LS_TBS to age and LS_aBMD added only limited information on fracture risk prediction. However, using the lowest quartile of LS_TBS helped in redefining a significant subset of non-osteoporotic women as a higher risk group which is important for patient management.

Impaired trabecular and cortical microarchitecture in daughters of women with osteoporotic fracture: the MODAM study.

UNLABELLED: We investigated the familial resemblance of bone microarchitecture parameters between postmenopausal mothers with fragility fracture and their premenopausal daughters using high-resolution peripheral quantitative computed tomography (HR-pQCT). We found that daughters of women with fracture have lower total volumetric bone mineral density (vBMD), thinner cortices, and impaired trabecular microarchitecture at the distal radius and tibia, compared to controls. INTRODUCTION: Familial resemblance of areal bone mineral density (aBMD) in mothers and daughters has been widely studied, but not its morphological basis, including microarchitecture. METHODS: We compared aBMD, vBMD, bone size, and bone microarchitecture at the distal radius and tibia assessed by HR-pQCT in mothers and their premenopausal daughters. We included 115 women aged 43 ± 8 years whose mothers had sustained a fragility fracture and 206 women aged 39 ± 9 years whose mothers had never sustained a fragility fracture. RESULTS: Women whose mothers had fracture had significantly (p < 0.05) lower aBMD at the lumbar spine, total hip, femoral neck, mid-distal radius, and ultradistal radius compared to controls. In similar multivariable models, women whose mothers had a fracture had lower total vBMD at the distal radius (-5 %, 0.3 standard deviation [SD]; p < 0.005) and distal tibia (-7 %, 0.4 SD; p < 0.005). They also had lower cortical thickness and area at the distal radius (-5 %, 0.3 SD and -4 %, 0.2 SD, respectively; p < 0.005) and at the distal tibia (-6 %, 0.3 SD and -4 %, 0.3SD, respectively; p < 0.005). Trabecular vBMD was lower at the distal radius (-5 %, 0.3 SD; p < 0.05) and tibia (-8 %, 0.4 SD; p < 0.005), with a more spaced and heterogeneous trabecular network (4 and 7 % at the radius and 5 and 9 %, at the tibia, p < 0.05, for Tb.Sp and Tb.Sp.SD, respectively). CONCLUSION: Premenopausal daughters of women who had sustained fragility fracture have lower total and trabecular vBMD, thinner cortices, as well as impaired trabecular microarchitecture at the distal radius and tibia, compared with premenopausal daughters of women without fracture.

Local topological analysis at the distal radius by HR-pQCT: Application to in vivo bone microarchitecture and fracture assessment in the OFELY study.

High-resolution peripheral quantitative computed tomography (HR-pQCT) is an in-vivo technique used to analyze the distal radius and tibia. It provides a voxel size of 82µm. In addition to providing the usual microarchitecture parameters, local topological analysis (LTA) depicting rod- and plate-like trabeculae may improve prediction of bone fragility. Thirty-three women with prevalent wrist fractures from the OFELY cohort were compared with age-matched controls. Bone microarchitecture, including the structural model index (SMI), was assessed by HR-pQCT, and micro-finite element analysis (µFE) was computed on trabecular bone images of the distal radius (XtremeCT, Scanco Medical AG). A new LTA method was applied to label each bone voxel as a rod, plate or node. Then the bone volume fraction (BV/TV*), the rod, plate and node ratios over bone volume (RV/BV*, PV/BV*, NV/BV*) or total volume (RV/TV*, PV/TV*, NV/TV*) and the rod to plate ratio (RV/PV*) were calculated. Associations between LTA parameters and wrist fractures were computed in a conditional logistic regression model. Multivariate models were tested to predict the µFE-derived trabecular bone stiffness. RV/TV* (OR=4.41 [1.05-18.62]) and BV/TV* (OR=6.45 [1.06-39.3]), were significantly associated with prevalent wrist fracture, after adjustment for ultra distal radius aBMD. Multivariate linear models including PV/TV* or BV/TV*+RV/PV* predicted trabecular stiffness with the same magnitude as those including SMI. Conversion from plates into rods was significantly associated with bone fragility, with a negative correlation between RV/PV* and trabecular bone stiffness (r=-0.63, p<0.0001). We conclude that our local topological analysis is feasible for a voxel size of 82µm. After further validation, it may improve bone fragility description.

Poor trabecular microarchitecture at the distal radius in older men with increased concentration of high-sensitivity C-reactive protein--the STRAMBO study.

Low-grade inflammation, assessed by serum high-sensitivity C-reactive protein (hsCRP) concentration, is associated with higher fracture risk irrespective of areal bone mineral density (aBMD). We assessed the association of hsCRP with bone microarchitecture (measured by high-resolution pQCT) at the distal radius and tibia in 1,149 men, aged 19-87 years. hsCRP concentration increased with age until the age of 72, then remained stable. aBMD was not correlated with hsCRP level. After adjustment for confounders, bone microarchitecture was not associated with hsCRP level in men aged <72. After the age of 72, hsCRP >5 mg/L was associated with lower trabecular density, lower trabecular number, higher trabecular spacing, and more heterogeneous trabecular distribution (p < 0.05-0.005) at the distal radius versus hsCRP ≤ 5 mg/L. Similar differences were found for the fourth hsCRP quartile (>3.69 mg/L) versus the three lower quartiles combined. Cortical parameters of distal radius and microarchitectural parameters of distal tibia did not vary according to hsCRP concentration in men aged ≥ 72. Fracture prevalence increased with increasing hsCRP level. After adjustment for confounders (including aBMD), odds for fracture were higher in men with hsCRP >5 mg/L compared to hsCRP <1 mg/L (OR = 2.22, 95 % CI 1.29-3.82) and did not change after additional adjustment for microarchitectural parameters. The association between hsCRP level and bone microarchitecture was observed only for trabecular parameters at the radius in men aged ≥72. Impaired bone microarchitecture does not seem to explain the association between elevated CRP level and higher risk of fracture.

Poor bone microarchitecture in older men with impaired physical performance--the STRAMBO study.

UNLABELLED: In 810 men ≥ 60 years, poor physical performance of lower limbs was associated with lower areal bone mineral density (aBMD) of total hip and poor bone microarchitecture at the distal tibia (assessed by HR-pQCT). Men who reported falls had lower hip aBMD and lower cortical density at the distal tibia. INTRODUCTION: The aim of this study was to assess the association between bone microarchitecture and physical performance in older men. METHODS: Volumetric bone mineral density (vBMD) and bone microarchitecture were assessed in 810 men ≥ 60 years at the distal radius and tibia by high resolution pQCT. aBMD was measured at the spine, hip, whole body, and distal radius by dual energy X-ray absorptiometry. Clinical tests included chair stands and tests of static and dynamic balance. We calculated a composite score summarizing abilities and time required to perform the tests. RESULTS: In multivariable models, men who failed in ≥ one test had lower total hip aBMD than men who accomplished all the tests. They had lower total vBMD (Tt.vBMD), cortical thickness (Ct.Th), trabecular vBMD (Tb.vBMD), and more heterogenous trabecular distribution (Tb.Sp.SD) at the distal tibia (p < 0.05). Men who failed in ≥ two tests had lower aBMD at the total hip, femoral neck, and trochanter as well as lower Tt.vBMD, cortical vBMD (Ct.vBMD), Ct.Th and trabecular number (Tb.N), and higher Tb.Sp.SD at the distal tibia (p < 0.05). Men in the lowest quartile of the composite score had lower aBMD (total hip, distal radius), lower Tb.vBMD and Tb.N at the distal radius, and lower Tt.vBMD, Ct.vBMD, Ct.Th, Tb.vBMD, and Tb.N, and higher Tb.Sp.SD at the distal tibia compared with the highest quartile. In multivariables models, men reporting falls had lower total hip aBMD and lower distal tibia Ct.vBMD (p < 0.01). CONCLUSION: In older men, poor physical performance is associated with lower hip aBMD and poor bone microarchitecture (mainly at the distal tibia).

Cortical bone status is associated with serum osteoprotegerin concentration in men: the STRAMBO study.

CONTEXT: Osteoprotegerin (OPG) is an inhibitor of bone resorption, but its relationship to bone microarchitecture remains unclear. OBJECTIVE: Our objective was to study the relationship between OPG concentration and bone microarchitecture in men. DESIGN, SETTING, AND PARTICIPANTS: We conducted a cross-sectional study of a population-based cohort of 1149 men aged 20-87 yr. INTERVENTIONS: We assessed bone microarchitecture at the distal radius and tibia by high-resolution peripheral quantitative computed tomography (XtremeCT Scanco) and measured serum OPG concentration and bone turnover markers: osteocalcin, bone-specific alkaline phosphatase, N-terminal extension type I collagen propeptide, C-terminal type 1 collagen telopeptide, and urinary deoxypyridinoline. MAIN OUTCOME MEASURES: Differences were assessed in bone microarchitectural parameters across the OPG quartiles in the models adjusted for age, weight, height, physical activity, ischemic heart disease, diabetes mellitus, calcium intake, serum levels of free testosterone, bioavailable 17ß-estradiol, PTH, 25-hydroxycholecalciferol, and creatinine. RESULTS: After adjustment for the confounders, men in the highest (fourth) quartile of OPG levels (>4.55 pmol/liter) had higher total cross-sectional area and trabecular area at the distal radius and distal tibia (3.3-6.0%, P < 0.05). At both skeletal sites, the highest OPG quartile was associated with lower cortical thickness (8.2%, P < 0.001, and 3.7%, P < 0.05) and volumetric bone mineral density (vBMD, 2.7%, P < 0.001, and 1.6%, P < 0.005) compared with the three lower quartiles combined. Associations of OPG level with trabecular vBMD, number, thickness, and distribution were not significant. Men in the fourth OPG quartile had higher levels of bone resorption markers (11.8-13.1%, P < 0.01-0.001). CONCLUSIONS: Men with higher serum OPG concentration had lower cortical thickness and vBMD, probably due to accelerated endo- and intracortical bone turnover, but higher cross-sectional area possibly due to periosteal apposition.

Association of bone microarchitecture with parathyroid hormone concentration and calcium intake in men: the STRAMBO study.

UNLABELLED: OBJECTVIE: In the elderly, vitamin D deficit, low calcium intake, and impaired bone microarchitecture are associated with higher risk of hip fracture. We assessed the association of bone microarchitecture with calcium intake and serum concentrations of 25-hydroxycholecalciferol (25OHD) and parathyroid hormone (PTH) in men. DESIGN: Cross-sectional analysis was performed in 1064 men aged 20-87 years not taking vitamin D or calcium supplements. METHODS: Daily calcium intake was assessed using a food frequency questionnaire. Bone microarchitecture was assessed at distal radius and tibia by high-resolution peripheral quantitative computed tomography. We measured serum and urinary levels of biochemical bone turnover markers (BTMs). Statistical models were adjusted for age, weight, height, and glomerular filtration rate. RESULTS: In 500 men aged <65 years, lower 25OHD levels and low calcium intake were associated with lower trabecular volumetric bone mineral density (Dtrab) at the distal tibia, due to lower trabecular number (Tb.N). Low calcium intake was associated with lower cortical thickness (Ct.Th). Higher PTH level was associated with higher BTM levels. In 563 men aged ≥65 years, the highest PTH quartile was associated with lower Ct.Th (tibia), lower Dtrab (both sites), and lower Tb.N (radius) compared with the lowest quartile. Low calcium intake was associated with lower Tb.N and more heterogenous trabecular distribution. BTM positively correlated with the PTH concentration. CONCLUSION: In older men, elevated PTH concentration is associated with high bone turnover, poor trabecular microarchitecture (radius and tibia), and, at the distal tibia, lower Ct.Th. Low calcium intake is associated with lower Tb.N and more heterogenous trabecular distribution.

[Bone quality evaluation in allograft hand transplant]. / Évaluation de la qualité de l'os dans les allogreffes de main.

Five bilateral forearms allograft have been performed between January 2000 and July 2009 in Lyon (France). The first four patients (three males, one female) have been the subject of an assessment of the bone quality of those allografts. The techniques selected for this study were: radioclinical analysis, bone scintigraphy, MRI, bone densitometry and High Resolution peripheral Quantitative Computed Tomography (HR-PQCT). Histology has been performed only on the first patient unilaterally grafted in 1998 who did not take part in this clinical research protocol, after amputation of his rejected graft. On the clinical, radiological and scintigraphical aspects, donor bone integration in hands allograft are good on a macroscopic point of view considering the healing and the general reaction of the bone in situation of fractures, infection and growth. The scintigraphy does not show important variations compared to the ones we can observe on contact with osteosynthesis material or during bone autografts. MRI found neither focal nor periosteal anomaly on grafted bone. The bone densitometry did not show significant difference with secondary osteoporosis one can observe in other grafted patients under immunosuppressive treatment. The HR-PQCT showed for the three males patients, a higher loss in volumetric density, for grafted bone than in the recipient patient control skeleton. Due to the few patients of this series, and the discrepancies in follow-up duration, the presented data have to be confirmed with further studies.