Peripheral Quantitative Computed Tomography (pQCT) Measures Contribute to the Understanding of Bone Fragility in Older Patients With Low-trauma Fracture

Dual-energy X-ray absorptiometry (DXA) as currently used has limitations in identifying patients with osteoporosis and predicting occurrence of fracture. We aimed to express peripheral quantitative computed tomography (pQCT) variables of patients with low-trauma fracture as T-scores by using T-score scales obtained from healthy young women, and to evaluate the potential clinical utility of pQCT for the assessment of bone fragility. Fracture patients were recruited from a fracture liaison service at the Royal Melbourne Hospital. Reference pQCT data were obtained from studies on women's health conducted by our group. A study visit was arranged with fracture patients, during which DXA and pQCT were applied to measure their bone strength. A total of 59 fracture patients were recruited, and reference data were obtained from 78 healthy young females. All DXA variables and most pQCT variables were significantly different between healthy young females and fracture patients (p?<?0.05), except polar stress-strain index (p?=?0.34) and cortical bone density (p?=?0.19). Fracture patients were divided into osteoporosis and non-osteoporosis groups according to their DXA T-scores. Significant differences were observed in most pQCT variables (p?<?0.05), except trabecular area and cortical density (p?>?0.9 and p?=?0.5, respectively). By applying pQCT T-scores, 11 (27%) of patients who were classified as having low or medium risk of osteoporosis on DXA T-scores alone were reclassified as high risk. Results of logistic regression suggested trabecular bone density as an independent predictor of osteoporosis status. More patients can be identified with osteoporosis by applying pQCT T-score variables in older people with low-trauma fracture. Peripheral QCT T-scores contribute to the understanding of bone fragility in this population.     

Assessment of Bone and Muscle Measurements by Peripheral Quantitative Computed Tomography in Geriatric Patients

The loss of bone and muscle mass increases the risk of osteoporotic fractures. Dual energy X-ray absorptiometry (DXA) loses sensitivity in older age. The purpose of this study was to evaluate bone and muscle measurements of peripheral quantitative computed tomography (pQCT) in a geriatric cohort with osteoporosis. Bone mineral density and muscle area of 168 patients aged 65 years and older (76.3 ± 6.5) were measured with pQCT at distal forearm additionally to an osteoporosis assessment consisting of anamnesis, blood test and DXA of lumbar spine and hip. Prior fractures were categorized in minor and major osteoporotic fractures. Logistic regression was used to show the association of bone mineral density and muscle area with major fractures. 54.8% of the participants had at least one major fracture. Bone mineral density measured with pQCT and muscle area were significantly associated with these fractures (total and trabecular bone mineral density OR 2.243 and 2.195, p < 0.01; muscle area OR 2.378, p < 0.05), whereas DXA bone mineral density showed no significant association. These associations remained after adjustment for age, sex, BMI, physical activity and other factors. In all models for patients >75 years only muscle area was significantly associated (OR 5.354, p < 0.05) with major fractures. Measurement of bone mineral density and muscle area with pQCT seems to have advantage over DXA in fracture association in geriatric patients. Measuring muscle area also adds useful information to estimate the presence of osteosarcopenia.     

Changes in trabecular bone density in incident pediatric Crohn’s disease: a comparison of imaging methods

Summary

This study of changes in dual energy x-ray absorptiometry (DXA) spine BMD following diagnosis and treatment for childhood Crohn’s disease demonstrated that changes in conventional posteroanterior BMD results were confounded by impaired growth, and suggested that lateral spine measurements and strategies to estimate volumetric BMD were more sensitive to disease and treatment effects.

Introduction

We previously reported significant increases in peripheral quantitative CT (pQCT) measures of trabecular volumetric bone mineral density (vBMD) following diagnosis and treatment of pediatric Crohn’s disease (CD). The objective of this study was to compare pQCT trabecular vBMD and three DXA measures of spine BMD in this cohort: (1) conventional posteroanterior BMD (PA-BMD), (2) PA-BMD adjusted for height Z (PA-BMD_HtZ), and (3) width-adjusted volumetric BMD (WA-BMD) estimated from PA and lateral scans.

Methods

Spine DXA [lumbar (L1–4) for posteroanterior and L3 for lateral] and tibia pQCT scans were obtained in 65 CD subjects (ages 7–18 years) at diagnosis and 12 months later. BMD results were converted to sex, race, and age-specific Z-scores based on reference data in >650 children (ages 5–21 years). Multivariable linear regression models identified factors associated with BMD Z-scores.

Results

At CD diagnosis, all BMD Z-scores were lower compared with the reference children (all p values <0.01). The pQCT vBMD Z-scores (?1.46?±?1.30) were lower compared with DXA PA-BMD (?0.75?±?0.98), PA-BMD_HtZ (?0.53?±?0.87), and WA-BMD (?0.61?±?1.10) among CD participants. Only PA-BMD Z-scores were correlated with height Z-scores at baseline (R?=?0.47, p?<?0.0001). pQCT and WA-BMD Z-scores increased significantly over 12 months to ?1.04?±?1.26 and ?0.20?±?1.14, respectively. Changes in all four BMD Z-scores were positively associated with changes in height Z-scores (p?<?0.05). Glucocorticoid doses were inversely associated with changes in WA-BMD (p?<?0.01) only.

Conclusions

Conventional and height Z-score-adjusted PA DXA methods did not demonstrate the significant increases in trabecular vBMD noted on pQCT and WA-BMD scans. WA-BMD captured glucocorticoid effects, potentially due to isolation of the vertebral body on the lateral projection. Future studies are needed to identify the BMD measure that provides greatest fracture discrimination in CD.     

Discrimination of fractures by low-frequency axial transmission ultrasound in postmenopausal females

Summary

In this cross-sectional study, 95 postmenopausal women, with and without fracture history, were measured by low-frequency axial transmission ultrasound. The measured ultrasound velocity discriminated the fractured subjects from the nonfractured ones equally or better than peripheral quantitative computed tomography (pQCT) and dual energy x-ray absorptiometry (DXA). These results suggest that low-frequency ultrasound is suitable for bone fragility assessment.

Introduction

Quantitative low-frequency axial transmission ultrasound is a promising modality for assessing mineral density and geometrical properties of long bones such as radius and tibia. The aim of the current study was to evaluate the ability of low-frequency axial transmission ultrasound to discriminate fractures retrospectively in postmenopausal women.

Methods

A cross-sectional study involved 95 female subjects aged 45–88 years, whose fracture information was gathered retrospectively. The fracture group was defined as subjects with one or more low-/moderate-energy fractures. The radius and tibial shaft were measured with a custom-made ultrasonometer to assess the velocity of the low-frequency first-arriving signal (V _LF). Site-matched pQCT was used to measure volumetric cortical and subcortical bone mineral density (sBMD), and cortical thickness (CTh). Areal BMD (aBMD) was measured using DXA for the whole body (WB), lumbar spine, and hip.

Results

The majority (19/32; 59 %) of the fractures were in the upper limb. V _LF in the radius, but not in the tibia, discriminated fractures with an age- and BMI-adjusted odds ratio (OR) of 2.06 (95 % CI 1.21–3.50, p?<?0.01). In the radius, CTh and cortical BMD (CBMD) significantly discriminated fractures, as did the total, cortical, and sBMD in the tibia (adjusted OR 1.35–2.15, p?<?0.05). Sensitivity and specificity were similar among all the measurements (area under the receiver operating characteristic curve 0.74–0.81, p?<?0.001).

Conclusions

Low-frequency axial transmission ultrasound in the radius was able to discriminate fractured subjects from the nonfractured ones. This suggests that low-frequency axial transmission ultrasound has the potential to assess bone fragility in postmenopausal women.     

The Assessment of Skeletal Muscle and Cortical Bone by Second-generation HR-pQCT at the Tibial Midshaft

Background: Peripheral quantitative computed tomography (pQCT) is the current densitometric gold-standard for assessing skeletal muscle at the 66% proximal tibia site. High resolution peripheral quantitative computed tomography (HR-pQCT) is a leading technology for quantifying bone microarchitecture at the distal extremities, and with the second-generation HR-pQCT it is possible to measure proximal limb sites. Therefore, the objectives of this study were to: (1) assess the feasibility of using HR-pQCT to assess skeletal muscle parameters at the 66% proximal tibia site, and (2) test HR-pQCT skeletal muscle measurement reproducibility at this site. Methods: Adult participants (9 males; 7 females; ages 31–75) received 1 pQCT scan and 2 HR-pQCT scans at the 66% proximal site of the nondominant tibia. Participants were repositioned between HR-pQCT scans to test reproducibility. HR-pQCT and pQCT scans were analyzed to quantify muscle cross-sectional area (CSA) and muscle density. Coefficients of determination and Bland-Altman plots compared muscle parameters between pQCT and HR-pQCT. For short-term reproducibility, root-mean-square of coefficient of variance and least significant change were calculated. Results: HR-pQCT and pQCT measured muscle density and muscle CSA were positively correlated (R² = 0.66, R² = 0.95, p < 0.001, respectively). Muscle density was equivalent between HR-pQCT and pQCT; however, there was systematic and directional bias for muscle CSA, such that muscle CSA was 11% lower with HR-pQCT and bias increased with larger muscle CSA. Root-mean-square of coefficient of variance was 0.67% and 0.92% for HR-pQCT measured muscle density and muscle CSA, respectively, while least significant change was 1.4 mg/cm³ and 174.0 mm² for muscle density and muscle CSA, respectively. Conclusion: HR-pQCT is capable of assessing skeletal muscle at the 66% site of the tibia with good precision. Measures of muscle density are comparable between HR-pQCT and pQCT.     

Lean Soft Tissue Mass Measured Using Dual-Energy X-Ray Absorptiometry Is an Effective Index for Assessing Change in Leg Skeletal Muscle Mass Following Exercise Training

It is difficult to precisely and easily estimate the changes in skeletal muscle mass (SMM) following exercise training. We aimed to assess whether the change in lean soft tissue mass measured using dual-energy X-ray absorptiometry (DXA) reflects the change in SMM measured using magnetic resonance imaging (MRI) following exercise training in both the leg and trunk regions. Anthropometry, DXA, and MRI measurements of the trunk and leg regions were obtained in 10 male college sumo wrestlers before and after exercise training (mean duration between measurements: ~2?yr). Contiguous magnetic resonance images with 1-cm slice thickness and without gap were obtained from the first cervical vertebra to the ankle joints as reference data. Skeletal muscle volume was calculated from the summation of the digitized cross-sectional areas. The volume measurements were converted into mass by using an assumed skeletal muscle density (1.041?g/cm³). Trunk and leg areas, using DXA regional computer-generated lines, were adjusted to coincide with each discrete region by using MRI. Although the change in the DXA-measured lean soft tissue mass in the trunk region was significantly different from that of the MRI-measured SMM (Cohen's d?=??1.3145, concordance correlation coefficient?=?0.26, p?<?0.01), the changes were similar in the leg region (Cohen's d?=?0.07, concordance correlation coefficient?=?0.87, p?=?0.88). The exercise training-induced change in lean soft tissue mass significantly correlated with that in SMM, both in the leg (r?=?0.88, p?<?0.01) and trunk (r?=?0.64, p?<?0.05) regions. Bland–Altman analysis did not indicate a bias for the changes in leg lean soft tissue mass and SMM following exercise training. These results suggest that lean soft tissue mass measured using DXA is an effective index for assessing change in leg SMM following exercise training.     

Fracture risk in children with a forearm injury is associated with volumetric bone density and cortical area (by peripheral QCT) and areal bone density (by DXA)

Summary

Children who sustain a forearm fracture when injured have lower bone density throughout their skeleton, and have a smaller cortical area and a lower strength index in their radius. Odds ratios per SD decrease in bone characteristics measured by peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA) were similar (1.28 to 1.41).

Introduction

Forearm fractures are common in children. Bone strength is affected by bone mineral density (BMD) and bone geometry, including cross-sectional dimensions and distribution of mineral. Our objective was to identify bone characteristics that differed between children who sustained a forearm fracture compared to those who did not fracture when injured.

Methods

Children (5–16 years) with a forearm fracture (cases, n?=?224) and injured controls without fracture (n?=?200) were enrolled 28?±?8 days following injury. Peripheral QCT scans of the radius (4% and 20% sites) were obtained to measure volumetric BMD (vBMD) of total, trabecular and cortical bone compartments, and bone geometry (area, cortical thickness, and strength strain index [SSI]). DXA scans (forearm, spine, and hip) were obtained to measure areal BMD (aBMD) and bone area. Receiver operating characteristic (ROC) analyses were used to assess screening performance of bone measurements.

Results

At the 4% pQCT site, total vBMD, but not trabecular vBMD or bone area, was lower (?3.4%; p?=?0.02) in cases than controls. At the 20% site, cases had lower cortical vBMD (?0.9%), cortical area (?2.8%), and SSI (?4.6%) (p?<?0.05). aBMD, but not bone area, at the 1/3 radius, spine, and hip were 2.7–3.3% lower for cases (p?<?0.01). Odds ratios per 1 SD decrease in bone measures (1.28–1.41) and areas under the ROC curves (0.56–0.59) were similar for all bone measures.

Conclusions

Low vBMD, aBMD, cortical area, and SSI of the distal radius were associated with an increased fracture risk. Interventions to increase these characteristics are needed to help reduce forearm fracture occurrence.     

Age-related changes in proximal humerus bone health in healthy, white males

Summary

The proximal humerus is a common site for osteoporotic fracture. The current study demonstrates the rate of age-related decline in proximal humerus bone health. The data suggest aging is associated with considerable loss of bone mass, structural deterioration and reduced bone strength at the proximal humerus.

Introduction

The proximal humerus is relatively under investigated despite being the fourth most common site for osteoporotic fracture.

Methods

A cross-sectional study was performed to assess age-related changes in dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) properties of the proximal humerus in a cohort of 170 healthy, white males.

Results

Regression models estimated considerable age-related loss of DXA measured bone quantity at the proximal humerus, with areal bone mineral density modeled to decline by 29% (95% confidence interval [CI], 17.5–35.0%) in the 50?years between ages 30 and 80?years (p?<?0.001). pQCT measures indicated aging was associated with progressive periosteal and endosteal expansion, with the later occurring more rapidly as indicated by age-related declines in cortical bone mass, area and thickness (all p?<?0.01). The net result of the density, mass and structural changes was a 26% (95% CI, 13.5–38.0%) decline in pQCT estimated proximal humerus bone strength in the 50?years between ages 30 and 80?years (p?<?0.001).

Conclusion

Aging is associated with considerable declines in proximal humeral bone health which, when coupled with a traumatic event such as a fall, may contribute to osteoporotic fracture at this site.     

Abnormal microarchitecture and reduced stiffness at the radius and tibia in postmenopausal women with fractures

Measurement of areal bone mineral density (aBMD) by dual‐energy x‐ray absorptiometry (DXA) has been shown to predict fracture risk. High‐resolution peripheral quantitative computed tomography (HR‐pQCT) yields additional information about volumetric BMD (vBMD), microarchitecture, and strength that may increase understanding of fracture susceptibility. Women with (n = 68) and without (n = 101) a history of postmenopausal fragility fracture had aBMD measured by DXA and trabecular and cortical vBMD and trabecular microarchitecture of the radius and tibia measured by HR‐pQCT. Finite‐element analysis (FEA) of HR‐pQCT scans was performed to estimate bone stiffness. DXA T‐scores were similar in women with and without fracture at the spine, hip, and one‐third radius but lower in patients with fracture at the ultradistal radius (p < .01). At the radius fracture, patients had lower total density, cortical thickness, trabecular density, number, thickness, higher trabecular separation and network heterogeneity (p < .0001 to .04). At the tibia, total, cortical, and trabecular density and cortical and trabecular thickness were lower in fracture patients (p < .0001 to .03). The differences between groups were greater at the radius than at the tibia for inner trabecular density, number, trabecular separation, and network heterogeneity (p < .01 to .05). Stiffness was reduced in fracture patients, more markedly at the radius (41% to 44%) than at the tibia (15% to 20%). Women with fractures had reduced vBMD, microarchitectural deterioration, and decreased strength. These differences were more prominent at the radius than at the tibia. HR‐pQCT and FEA measurements of peripheral sites are associated with fracture prevalence and may increase understanding of the role of microarchitectural deterioration in fracture susceptibility. © 2010 American Society for Bone and Mineral Research.     

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

Summary

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.