pQCT Data Research Articles

Peripheral quantitative computed tomography (pQCT) in 12- and 24-month-old children - Practical aspects and descriptive data.

Peripheral quantitative computed tomography (pQCT) is a useful tool to assess detailed bone characteristics. Its utility in infants is however limited due to lack of reference data and technical challenges. The purpose of this study was to provide data on length- and weight-adjusted pQCT values and to present a quality grading system for healthy children aged 12 and 24months. As a part of the Vitamin D intervention in Infants (VIDI) trial, we collected pQCT and anthropometric data from 855 children at 12months and from 784 children at 24months. Bone mineral content (BMC; mg/mm), volumetric bone mineral density (vBMD; mg/cm3), cross-sectional area (CSA; mm2), polar-moment of inertia (PMI; mm4), and periosteal circumference (PsC; mm) were assessed for total bone at 20% distal site of the left tibia using pQCT (Stratec XCT2000L). We evaluated the impact of scan quality on bone measures. Total bone parameters were assessed for boys and girls separately. The means of the bone parameters were also compared in relation to age. The associations between bone parameters and weight, length, sex and scan quality were analyzed. We included scans with sufficient quality (Grade 1-5) in the final analyses: 679/855 (79%) at 12months and 709/784 (90%) at 24months. Altogether 39% of the scans at 12months and 51% at 24months were of good or excellent quality (Grade 1-2). Scan quality had an impact on BMCs at 12 and 24months (p=0.001 and p=0.017, respectively) but not on other bone parameters. Boys presented greater total bone BMC, CSA, PMI and PsC values at 12 and 24months but vBMDs were similar. All bone parameters showed a significant increase between 12 and 24months for both sexes. When adjusting bone parameters for weight, length and scan quality, differences between sexes disappeared. Weight was the strongest modifier of BMC, CSA, PMI and PsS at 12 and 24months. This study increases our understanding on bone parameters in young children and demonstrates the suitability of pQCT in bone research in infants. The described pQCT data and scan quality grading system should prove useful in evaluating data reliability in research settings. NCT1723852.

Investigating in vivo knee volumetric bone mineral density and walking gait mechanics in healthy people.

The aim of this study was to investigate if the distribution of subchondral volumetric bone mineral density (vBMD) from peripheral quantitative computed tomography (pQCT) is related to estimates of knee joint loads calculated during walking gait in healthy young people. We recruited 19 young (age 18-40years) healthy people with no self-reported knee pain or pathology. For all participants we collected two forms of data: (1) pQCT data at 2% of tibia length (from the proximal joint line) using a Stratec XCT3000 scanner at 0.2×0.2mm in plane resolution; and (2) indices of joint loading, specifically external joint moment, at the indexed knee during walking gait. Joint moments were calculated from motion capture and ground reaction force data. pQCT scans were performed immediately prior to gait analysis. A sub-group of 9 participants attended a second scanning session to establish the reproducibility of the pQCT workflow. vBMD was extracted for four sub-regions (anteromedial, anterolateral, posteromedial and posterolateral). Reproducibility of the pQCT workflow was good to excellent (ICCs 0.832-0.985) with minimal detectable differences ranging from 2.3-39.5mg HA/cm3. Significant independent correlations were identified between the external rotation moment and the medial-to-lateral (r=0.517), posteromedial-to-posterolateral (r=0.627) and posteromedial-to-anterolateral (r=0.518) vBMD ratios, and between the knee adduction moment and the medial-to-lateral (r=-0.476) and posteromedial-to-posterolateral (r=-0.497) vBMD ratios. There appear to be significant relationships between measures of vBMD from pQCT and indices of joint loading in healthy people. These data are the first to combine imaging at the resolution available with pQCT and indices of joint loading in the same cohort.

Ethnic Differences in Peripheral Skeletal Development Among Urban South African Adolescents: A Ten-Year Longitudinal pQCT Study.

ABSTRACTThere are no longitudinal pQCT data of bone growth and development from sub‐Saharan Africa, where rapid environmental, societal, and economic transitions are occurring, and where fracture rates are predicted to rise. The aim of this study was to compare skeletal development in black and white South African adolescents using longitudinal data from the Birth to Twenty study. The Birth to Twenty Bone Health subcohort consisted of 543 adolescents (261 [178 black] girls, 282 [201 black] boys). Annual pQCT measurements of the radial and tibial metaphysis and diaphysis were obtained between ages 12 and 22 years (distal metaphysis: cross‐sectional area [CSA] and trabecular bone mineral density [BMD]; diaphysis: total and cortical CSA, cortical BMD, and polar stress‐strain index [SSIp]). Age at peak height velocity (APHV) was calculated to account for differences in maturational timing between ethnic groups and sexes. Mixed‐effects models were used to describe trajectories for each pQCT outcome. Likelihood‐ratio tests were used to summarize the overall difference in trajectories between black and white participants within each sex. APHV (mean ± SD years) was similar in black (11.8 ± 0.8) and white (12.2 ± 1.0) girls, but delayed in black (14.2 ± 1.0) relative to white boys (13.3 ± 0.8). By 4 years post‐APHV, white adolescents had significantly greater cortical CSA and SSIp than black adolescents at the radius. There were no significant differences at the radial metaphysis but there was some divergence, such that black adolescents had greater radial trabecular BMD by the end of follow‐up. At the tibia, white adolescents had lower diaphyseal CSA and SSIp, and greater metaphyseal CSA. There was no ethnic difference in tibial trabecular BMD. There are ethnic differences in bone growth and development, independent of maturation, in South African adolescents. This work gives new insights into the possible etiology of childhood fractures, which occur most commonly as peripheral sites. © 2017 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.

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.

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.

Bone Traits Seem to Develop Also During the Third Decade in Life—Normative Cross-Sectional Data on 1083 Men Aged 18–28 Years

By identifying individuals with low peak bone mass (PBM) at young age, early targeted interventions to reduce future fracture risk could be possible. Peripheral quantitative computed tomography (pQCT) is in many ways superior to the gold standard dual-energy X-ray absorptiometry (DXA), as cortical and trabecular compartments as well as the volumetric density and bone structure can be examined separately. Because each of these traits contributes independently to bone strength, it is probable that pQCT provides an even better fracture risk estimation than DXA. Currently, the clinical applications of pQCT are limited partly because comprehensive normative pQCT data, especially in young men, are not readily available. We therefore set up a study in young men with the following objectives: (1) to identify peak ages in pQCT bone traits with special reference to PBM and peak bone strength; and (2) to provide normative pQCT data. We measured volumetric bone mineral density and structural parameters at ultradistal (trabecular bone) and diaphyseal radius and tibia (cortical bone) by pQCT scans (Stratec XCT2000®; Stratec Medizintechnik GmbH, Pforzheim, Germany) in a population-based age-stratified sample of 1083 men aged 18–28 yr residing in greater Malmö, Sweden. Group differences in 1-yr classes were evaluated by analysis of variance. We found similar bone traits in age groups at ultradistal sites whereas most bone traits at diaphyseal sites were higher with higher ages, however with different increment patterns depending on the specific trait. In Swedish young adult men, we found that different bone traits continued to change after age 18, but at different rates, indicating that peak areal bone mineral density (as measured by DXA) and peak bone strength may be reached at different ages.

Fractures on bisphosphonates in osteoporosis pseudoglioma syndrome (OPPG): pQCT shows poor bone density and structure

Osteoporosis pseudoglioma syndrome (OPPG) is a rare autosomal recessive disorder of childhood osteoporosis and blindness due to inactivating mutations in LDL receptor-like protein 5 (LRP5). We and others have reported improvement in areal bone mineral density (aBMD) by DXA in OPPG on short term bisphosphonates. Long-term data on bisphosphonate use in OPPG and measures of volumetric BMD (vBMD) and cortical structure are not available. In addition, no long-term DXA data on untreated OPPG is available. The aims of this study were to: (1) record low trauma fractures and longitudinal aBMD by DXA in 5 OPPG patients on chronic bisphosphonate treatment, and in 4 OPPG patients never treated (2) to perform tibia peripheral quantitative CT (pQCT) to evaluate volumetric bone mineral density (vBMD), cortical structure and calf muscle area in 6 OPPG patients and 14 unaffected first degree family members. pQCT results were converted to sex-specific Z-scores for age and adjusted for tibia length based on data in >700 reference participants. We observed 4 fractures (3 femoral shafts) in 3 OPPG patients while on bisphosphonates, after each achieved significant improvement in aBMD. OPPG participants had significantly lower mean trabecular vBMD (−1.51 vs. 0.17, p=0.002), cortical area (−2.36 vs. 0.37; p<0.001) and periosteal circumference (−1.86 vs. −0.31, p=0.001) Z-scores, compared with unaffected participants and had a trend toward lower muscle area Z-score (−0.69 vs. 0.47, p=0.12). These data demonstrate substantial bone fragility despite improvements in aBMD. The pQCT data provide insight into the fragility with substantial deficits in trabecular vBMD and cortical dimensions, consistent with OPPG effects of bone formation. Treatment that improves bone quality is needed to reduce fractures in OPPG.

Bone loss patterns in cortical, subcortical, and trabecular compartments during simulated microgravity.

Disuse studies provide a useful model for bone adaptation. A direct comparison of these studies is, however, complicated by the different settings used for bone analysis. Through pooling and reanalysis of bone data from previous disuse studies, we determined bone loss and recovery in cortical, subcortical, and trabecular compartments and evaluated whether the study design modulated skeletal adaptation. Peripheral quantitative tomographic (pQCT) images from control groups of four disuse studies with a duration of 24, 35, 56, and 90 days were reanalyzed using a robust threshold-free segmentation algorithm. The pQCT data were available from 27 young healthy men at baseline, and at specified intervals over disuse and reambulation phases. The mean maximum absolute bone loss (mean ± 95% CI) was 6.1 ± 4.5 mg/mm in cortical, 2.4 ± 1.6 mg/mm in subcortical, and 9.8 ± 9.1 mg/mm in trabecular compartments, after 90 days of bed rest. The percentage changes in all bone compartments were, however, similar. During the first few weeks after onset of reambulation, the bone loss rate was systematically greater in the cortical than in the trabecular compartment (P < 0.002), and this was observed in all studies except for the longest study. We conclude that disuse-induced bone losses follow similar patterns irrespective of study design, and the largest mean absolute bone loss occurs in the cortical compartment, but apparently only during the first 60 days. With longer study duration, trabecular loss may become more prominent.

Evaluation of bone mineral density and bone/muscle geometry using pQCT in children after spinal cord injury

Spinal cord injury (SCI) is associated with a reduction in bone mineral density (BMD) and increasedbone fragility. This study aimed to quantify regional changes in bone mineral density and bone/muscle geometry in children following SCI using Peripheral Quantitative Computer Tomography (pQCT). A retrospective cohort study of 19 patients (10 males and 9 females) with SCI was undertaken. The group comprised 9 paraplegics (6 complete, 3 incomplete) and 10 tetraplegics (5 complete, 5 incomplete). The mean age at SCI was 6.6 years. pQCT assessment was performed at a mean of 5.7 years post SCI. A total of 7 patients also had serial scans performed: The first at a mean of 7.6 years and the second at a mean of 10.7 years post SCI. Reduced bone mass following SCI was regional. Lower limb involvement was universal and upper limb involvement was only seen in association with tetraplegia (Table ​(Table1).1). There was a significant loss of muscle cross sectional area in the calves.Analysis of serial pQCT data revealed a further reduction in trabecular volumetric bone mineral density (vBMD) Z-scores between 7.6 and 10.7 years post SCI, while cortical vBMD did not change.Incomplete paraplegics and tetraplegics, who were able to stand, had greater trabecular vBMD, cortical bone mineral content and cortical thickness tibial Z-scores than those with a complete SCI. Table 1 pQCT data of tibial and radial Z-scoresat 4% and 66% sites pQCT provides a valuable insight into the regional changes in bone and muscle development in children following SCI. Residual muscle function with the ability to weight bear, even if only in a frame, provides a significant benefit to bone development.

Imaging techniques enhance musculoskeletal safety and efficacy testing

The aim of this work was to establish in vivo imaging procedures to evaluate the effects of drugs on musculoskeletal development in non‐clinical studies with Sprague‐Dawley rats from preweaning to young adult using dual energy x‐ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT) and radiography. Radiographs were used to measure long bone (femur, tibia) and axial skeleton (L1–L6) length. DXA was used to measure bone area, bone mineral content (BMC) and bone mineral density (BMD) at the femur and spine, and lean/fat mass of the whole body. pQCT was used to measure BMC and BMD of trabecular and cortical bone, bone geometry, and lean/fat area at the proximal tibia. Reproducible DXA and pQCT data were obtained with coefficients of variation &lt;5% for most parameters. Radiographs and pQCT showed increases in bone length, diameter and BMC with age although increases in BMD were variable. Results indicate that radiography, DXA and pQCT provide safe, reproducible and repeated measures of musculoskeletal growth in rats at axial and appendicular sites and will serve as useful tools to enhance safety and efficacy testing in drug development.

Increased fat mass is associated with increased bone size but reduced volumetric density in pre pubertal children

Recent studies have shown that obesity is associated with an increased risk of fracture in both adults and children. It has been suggested that, despite greater bone size, obese individuals may have reduced true volumetric density; however this is difficult to assess using two dimensional techniques such as DXA. We evaluated the relationship between fat mass, and bone size and density, in a population cohort of children in whom DXA and pQCT measurements had been acquired.We recruited 530 children at 6years old from the Southampton Women's Survey. The children underwent measurement of bone mass at the whole body, lumbar spine and hip, together with body composition, by DXA (Hologic Discovery, Hologic Inc., Bedford, MA, USA). In addition 132 of these children underwent pQCT measurements at the tibia (Stratec XCT2000, Stratec Biomedical Systems, Birkenfeld, Germany).Significant positive associations were observed between total fat mass and both bone area (BA) and bone mineral content (BMC) at the whole body minus head, lumbar spine and hip sites (all p<0.0001). When true volumetric density was assessed using pQCT data from the tibia, fat mass (adjusted for lean mass) was negatively associated with both trabecular and cortical density (β=−14.6mg/mm3 per sd, p=0.003; β=−7.7mg/mm3 per sd, p=0.02 respectively).These results suggest that fat mass is negatively associated with volumetric bone density at 6years old, independent of lean mass, despite positive associations with bone size.This article is part of a Special Issue entitled: Interactions Between Bone, Adipose Tissue and Metabolism.

Determinants of bone size and strength in 13-year-old South African children: The influence of ethnicity, sex and pubertal maturation

We have previously shown ethnic differences in bone mass between pre-pubertal black and white children using DXA. To investigate these ethnic differences further, using pQCT, and to determine the influence of sex and pubertal development, we measured appendicular bone variables in 13-year-old children using pQCT.We collected pQCT data on a cohort of 471 black and white children at age 13years. Black boys and girls were shorter and had less lean mass than their white peers, and black boys were lighter than white boys at an earlier stage of pubertal development. Metaphyseal (4%) radial trabecular density was greater in the black girls than their white peers (239.5±49.5 vs. 222.7±34.2mg/cm3; p<0.05). Bone strength index was not different between the ethnic groups. All metaphyseal measures were 3–41% greater in boys than girls, after adjusting for height where appropriate. Diaphyseal (38%) tibial values, including total area, endosteal diameter, tibial diameter, periosteal circumference and polar strength-strain index were 4–22% greater in the black than white children and in boys than in girls. Cortical density was greater in black than white boys (1079.0±39.4 vs. 1058.7±34.5mg/mm3; p<0.001) and greater in the girls than boys (black: 1129.3±33.7 vs. 1079.0±39.4mg/mm3; p<0.001; white: 1126.8±28.3 vs. 1058.7±34.5mg/mm3; p<0.001). Cortical thickness was less in the black groups. Lower leg muscle cross-sectional area (MCSA) was higher in white than black children, and forearm MCSA was higher in white than black boys. There was no difference in fat cross-sectional area between the ethnic groups. In conclusion, ethnic and sex differences in both metaphyseal and diaphyseal bone parameters exist during puberty, which are not accounted for by differences in body size or skeletal maturity. South African black children have wider diaphyseal regions of appendicular bones with greater measures of bone strength.

A Computational Model for Cortical Endosteal Surface Remodeling Induced by Mechanical Disuse

In mechanical disuse conditions associated with immobilization and microgravity in spaceflight, cortical endosteal surface moved outward with periosteal surface moving slightly or unchanged, resulting in reduction of cortical thickness. Reduced thickness of the shaft cortex of long bone can be considered as an independent predictor of fractures. Accordingly, it is important to study the remodeling process at cortical endosteal surface. This paper presents a computer simulation of cortical endosteal remodeling induced by mechanical disuse at the Basic Multicellular Units level with cortical thickness as controlling variables. The remodeling analysis was performed on a representative rectangular slice of the cross section of cortical bone volume. The pQCT data showing the relationship between the duration of paralysis and bone structure of spinal cord injured patients by Eser et al. (2004) were used as an example of mechanical disuse to validate the model. Cortical thickness, BMU activation frequency, mechanical load and principal compressive strain for tibia and femur cortical models were simulated. The effects of varying the mechanical load and maximum BMU activation frequency were also investigated. The cortical thicknesses of femur and tibia models were both consistent with the clinical data. Varying the decreasing coefficient in mechanical load equation had little effect on the steady state values of cortical thickness and BMU activation frequency. However, it had much effect on the time to reach steady state. The maximum BMU activation frequency had effects on both the steady state value and the time to reach steady state for cortical thickness and BMU activation frequency. The computational model for cortical endosteal surface remodeling developed in this paper can be further used to quantify and predict the effects of mechanical factors and biological factors on cortical thickness and help us to better understand the relationship between bone morphology and mechanical as well as biological environment.

Reduced cortical bone density with normal trabecular bone density in girls with Turner syndrome

This study of 22 girls with Turner syndrome (TS) demonstrates a reduction in bone mineral apparent density (BMAD) at the femoral neck along with a reduction in cortical bone density at the radius (with sparing of trabecular bone). These findings may account for the increased fracture risk noted in this population. Increased fracture risk is a feature of TS; however, the reasons for this are unclear. Little is known regarding cortical and trabecular bone mineral density (BMD) in TS. We have addressed this by measurement of volumetric bone mineral density (vBMD) using peripheral quantitative computed tomography (pQCT). We studied 22 females with TS and 21 females without TS; mean ages 12.7 and 12.9 years, respectively. Bone mass measurements were made by dual-energy X-ray absorptiometry (DXA) of the lumbar spine and femur and pQCT of the radius. BMAD was calculated from DXA values. We utilized published reference data to generate Z-scores for both populations. The mean BMAD Z-score at the lumbar spine was not significantly different in individuals with TS compared to the controls. At the femoral neck, individuals with TS had a significantly lower BMAD Z-score compared to the controls (-1.32 vs. -0.14, p = 0.001). At the distal radius, total vBMD Z-score and trabecular vBMD Z-score were not significantly different between the TS group and controls. A significant reduction in cortical vBMD at the proximal radius was noted in the TS group however (-2.58 vs. -1.38, p = 0.02). There was also a trend towards reduced cortical thickness at this site in the TS group (Z-score -2.89 vs. -1.73, p = 0.08). TS is associated with reduced BMAD at the femoral neck; pQCT data suggests that cortical density is reduced with sparing of trabecular bone. This differential of cortical and trabecular BMD may predispose to fracture.

Knee loading accelerates bone healing in mice.

Knee loading is an anabolic loading modality that applies lateral loads to the knee. This study shows that loads applied to the proximal tibial epiphysis stimulate healing of surgically generated wounds in the tibial diaphysis. Wound healing is sensitive to mechanical stimulation such as various forms of stress and different magnitudes of strain. Knee loading has been shown to induce anabolic responses to murine tibias and femora when a strain of 10-20 mustrain is applied at the site of new bone formation. The object of this study was to address a question: does knee loading accelerate closure of open wounds in the tibia? Fifty-three C57/BL/6 female mice were used. A surgical wound (0.5 mm in diameter) was generated in the left tibia (loaded) and the right tibia (sham-loaded control). From the fourth postoperative day, knee loading was performed to the left knee with a custom-made piezoelectric loader for 3 min/d for 3 consecutive days. The peak-to-peak force was 0.5 N. Animals were killed 1, 2, or 3 wk after surgery, and the healing process was evaluated with muCT, pQCT, and bone histomorphometry with calcein labeling. The measured strain was <20 mustrain with 0.5-N force regardless of the presence or absence of surgical wounds. Compared with sham-loaded controls, the results showed load-driven acceleration of wound healing. First, muCT data revealed that knee loading reduced the size of surgical wounds by 13% (p < 0.01; 1 wk), 25% (p < 0.001; 2 wk), and 15% (p < 0.01; 3 wk). Second, pQCT data indicated that total BMD and BMC and cortical BMD and BMC were significantly increased in the third postoperative week. Last, bone histomorphometry revealed that bone formation was stimulated from the site proximal (close to the knee) to the wound. The reparative and remodeling phases of wound healing were enhanced by loads applied to the knee without inducing significant in situ strain at the site of wounds. Noninvasive knee loading might therefore be useful clinically to stimulate bone healing in the entire tibia along its length (including cast immobilized wounds).

Combined xeno/auto-grafting of a benign osteolytic lesion in a dog, using a novel bovine cancellous bone biomaterial

CASE HISTORY: A 4-year-old female Labrador Retriever was diagnosed with an osteolytic lesion of the right distal radius. CLINICAL FINDINGS: Radiographs indicated a well-circumscribed radiolucent area 18 × 15 × 8 mm, centred on the distal radial physeal scar. DIAGNOSIS: Histopathology, performed via Jamshidi needle biopsy and following surgical curettage, was inconclusive but suggested either an aneurysmal bone cyst or fibrous dysplasia. CLINICAL RELEVANCE: A novel processed cancellous bovine bone xenograft was used in conjunction with autogenous cancellous bone (at a ratio of approximately 4:1) to fill the curetted defect. There were no observed complications associated with the use of this new biomaterial. Osteointegration of the bone graft was followed using conventional radiographs and peripheral quantitative computed tomography (pQCT) for 10 months post-operatively. Radiographically, the osteolytic lesion modelled to resemble metaphyseal trabeculation. The cross-sectional area and the average bone density of the grafted lesion determined using pQCT data increased over time, suggesting healthy osteoconduction and native bone production.

A Densitometric and Morphometric Analysis of the Skeleton in Adults with Varying Degrees of Growth Hormone Deficiency

Low bone mass is a characteristic feature of the adult GH deficiency (GHD) syndrome, but recent dual-energy x-ray absorptiometry (DXA) studies in patients with GH-receptor and GHRH-receptor gene mutations suggest that the situation is more complex. The objective was to define bone areal and volumetric densities and morphometry in hypopituitary adults. The study was a cross-sectional case-controlled study performed between 1999 and 2001. The study was undertaken at an endocrine tertiary referral center. Thirty patients with GHD, 24 with GH insufficiency (GHI) [peak GH, 3-7 microg/liter (9-21 mU/liter)], and 30 age- and sex-matched controls were included for study. DXA and peripheral quantitative computed tomography (pQCT) derived bone density and morphometry were measured. No densitometric or morphometric abnormalities were detected in GHD patients who acquired their deficiency during adult life. GHD adults of childhood-onset (CO-GHD) showed decreased bone mineral density at the lumbar spine and hip on DXA. pQCT of the radius showed that CO-GHD patients have normal trabecular bone mineral density and only a 2% decrease in cortical density. Radial bone area was reduced 14.5%, cortical thickness 20%, and cortical cross-sectional area 23%, culminating in a reduction in cortical bone of 25%. The "apparent" low DXA bone density in CO-GHD adults therefore relates primarily to reduced cortical thickness and smaller bone area. DXA and pQCT data derived from adults with GHI revealed no evidence of densitometric or morphometric abnormalities. 1) Adult-onset GHD patients have normal bone density and size. 2) CO-GHD adults have marginally reduced cortical density but significantly reduced cortical bone as a result of reduced cortical thickness and bone size. 3) GHI has no measurable impact on the skeleton.

Determination of mechanical stiffness of bone by pQCT measurements: correlation with non-destructive mechanical four-point bending test data

Mechanical tests of bone provide valuable information about material and structural properties important for understanding bone pathology in both clinical and research settings, but no previous studies have produced applicable non-invasive, quantitative estimates of bending stiffness. The goal of this study was to evaluate the effectiveness of using peripheral quantitative computed tomography (pQCT) data to accurately compute the bending stiffness of bone. Normal rabbit humeri ( N=8) were scanned at their mid-diaphyses using pQCT. The average bone mineral densities and the cross-sectional moments of inertia were computed from the pQCT cross-sections. Bending stiffness was determined as a function of the elastic modulus of compact bone (based on the local bone mineral density), cross-sectional moment of inertia, and simulated quasistatic strain rate. The actual bending stiffness of the bones was determined using four-point bending tests. Comparison of the bending stiffness estimated from the pQCT data and the mechanical bending stiffness revealed excellent correlation ( R 2=0.96). The bending stiffness from the pQCT data was on average 103% of that obtained from the four-point bending tests. The results indicate that pQCT data can be used to accurately determine the bending stiffness of normal bone. Possible applications include temporal quantification of fracture healing and risk management of osteoporosis or other bone pathologies.

Cessation of Treatment: A Universal Achilles' Heel

To the Editor: We agree with Dr. Seeman that exercise during growth increases bone mass better than that in adulthood, and in fact, we were the first to show this with the baseline cross-sectional study of our Finnish female tennis players.1 The current 5-year follow-up of these players examined the effect of reduced training (not complete cessation of training) on exercise-induced bone gain.2 This separation is important because many physically active young people tend to maintain their activities at a reduced fitness level throughout their lives without complete retirement. Dr. Seeman noted that the bone mineral content (BMC) changes in the playing and nonplaying arms were not addressed in out paper. This is not correct because our statistical model (analysis of variance [ANOVA] with repeated measurements) used the absolute BMC values of both arms at both study points as the basis of the analysis, and the absolute BMC values can be found in Table 2 of our paper.2 Relative changes (%) were obtained through a log-transformation of the original variables in the analysis, and by using the antilog-transformation, the description of the results of the analysis was then given in percentages—for easy reading. The results showed indisputably that the exercise-induced bone gain was well maintained in the playing arm of the players during the 5-year follow-up despite decreased training; therefore, the title of our paper was—and still is—correct. Considering the length of the follow-up, we agree that 5 years is too short a period for final conclusions, but our study is one of the longest follow-up periods of a prospective exercise-cohort, and therefore, of salient value. Many other treatment modalities of bone do not provide any long-term follow-up data at all. Will the benefits of a bone intervention be eroded 30 to 50 years after the intervention? No study examining exercise, calcium, vitamin D, or a bone-specific drug has been able to show the long-term effects of such an intervention. In other words, little is known about what happens to bone and fracture risk when the intervention is stopped. The cross-sectional comparison of soccer players by Karlsson and colleagues3 did not provide a basis from which to estimate true secular trends in bone mass, and it was clearly too small to estimate the fracture risks in former players and controls and has therefore been criticized.4, 5 In general, the epidemiological evidence is strong and consistent for physical activity in prevention of osteoporotic fractures,6-11 which has led to exercise receiving a key position in recent recommendations for prevention of osteoporosis, falls, and fractures, such as the recent position statement of the Australian and New Zealand Bone and Mineral Society.12 Concerning our male player peripheral quantitative computed tomography (pQCT) study,13 these players underwent the pQCT measurements only once (at the 4-year follow-up), and thus it is impossible to say when and how the changes in the medullary area occurred (during the active years or the less active subsequent period). In the current female player study, the pQCT data were available at the 5-year follow-up point only, and thus the changes in bone size and volumetric density by time could not be assessed. Nevertheless, any benefit in bone size obtained during growth probably does not disappear—a large bone is likely to be a strong bone. With regard to the compliance issue, we see that compliance in any bone intervention is likely to be as problematic as that in exercise studies. It is true that complete cessation of exercise or any other intervention is likely to erode the bone benefit (whether achieved during growth or later on), whereas our current prospective follow-up shows that exercise-induced bone mass in the playing arm of the female racquet sports players can be well maintained with decreased training. We agree with Dr. Seeman that randomized trials are optimal to evaluate whether the reduced level of exercise maintains benefits obtained during growth. However, such trials with long enough follow-ups may never show up, and thus, carefully performed prospective cohort follow-ups are pertinent to receive the best possible answer to this ultimate question. The final answer of whether intense physical activity in growing years, followed by reduced but not stopped activity in adulthood, decreases the risk of fractures later in life may never been available, but the consistent evidence from the previous epidemiological studies and our current follow-ups speaks strongly for it. Moreover, of all the methods of fracture prevention, regular physical activity is the only one that provides other considerable health-related benefits.14 For these reasons, regular exercise can be recommended for both younger and older people.

Variation in bone biomechanical properties, microstructure, and density in BXH recombinant inbred mice.

To test the hypothesis that factors associated with bone strength (i.e., volumetric bone mineral density [vBMD], geometry, and microstructure) have heritable components, we exploited the 12 BXH recombinant inbred (RI) strains of mice derived from C57BL/6J (B6; low bone mass) and C3H/HeJ (C3H; high bone mass) progenitor strains. The femurs and lumbar vertebrae from each BXH RI strain were characterized for phenotypes of vBMD, microstructural, biomechanical, and geometrical properties. Methods included bending (femur) and compression (vertebra) testing, peripheral quantitative computed tomography (pQCT), and microcomputed tomography (microCT). Segregation patterns of femoral and vertebral biomechanical properties among the BXH RI strains suggested polygenic regulation. Femoral biomechanical properties were strongly associated with femoral width in the anteroposterior (AP) direction and cortical thickness--geometric properties with complex genetic regulation. Vertebral vBMD and biomechanical properties measured in BXH RI strains showed a greater variability than either B6 or C3H progenitors, suggesting both progenitor strains have independent subsets of genes that yield similar vBMD and strength. The microCT and pQCT data suggested that the distribution of vertebral mineral into cortical and trabecular compartments is regulated genetically. Although the B6 and C3H progenitors had similar vertebral strength, their vertebral structures were markedly different: B6 had good trabecular bone structure and modest cortical bone mineral content (BMC), whereas C3H had high cortical BMC combined with a deficiency in trabecular structure. These structural traits segregated independently in the BXH RI strains. Finally, vertebral strength was not correlated consistently with femoral strength among the BXH RI strains, suggesting genetic regulation of bone strength is site specific.