Heather M. Macdonald

Postmenopausal women with osteopenia have higher cortical porosity and thinner cortices at the distal radius and tibia than women with normal aBMD: an in vivo HR-pQCT study

Increases in cortical porosity (Ct.Po) and decreases in cortical thickness (Ct.Th) are associated with increased bone fragility. The purpose of this study was to validate an autosegmentation method for high‐resolution peripheral quantitative computed tomography (HR‐pQCT) scans to measure Ct.Po and Ct.Th and use it to compare Ct.Po and Ct.Th between pre‐ and postmenopausal women with normal, osteopenic, and osteoporotic areal bone mineral density (aBMD). The Ct.Po and Ct.Th measurements were validated using cadaver forearms (n = 10) and micro‐computed tomography (µCT) as the gold standard. The analysis was applied to distal radius and tibia HR‐pQCT scans from a subset of participants from the Calgary, Alberta, cohort of the Canadian Multicentre Osteoporosis Study (n = 280, 18 to 90 years). Analysis of covariance compared Ct.Po and Ct.Th outcomes between 63 normal premenopausal (dual‐energy X‐ray absorptiometry femoral neck T‐score > −1), 87 normal postmenopausal, 121 osteopenic postmenopausal, and 9 osteoporotic postmenopausal women. Linear regression analysis and Bland‐Altman plots were used to assess the agreement between the HR‐pQCT and µCT measurements, resulting in r2 values of 0.80 for Ct.Po and 0.98 for Ct.Th. At both sites, Ct.Po was higher in postmenopausal (all groups) than in premenopausal women (3.2% to 12.9%, p < .001). Ct.Th was not significantly different between normal premenopausal and postmenopausal women at either site; however, both osteopenic and osteoporotic women had thinner (−12.8% to −30.3%, p < .01), more porous (2.1% to 8.1%, p < .001) cortices than normal postmenopausal women. Our method offers promise as a valuable tool to measure Ct.Po and Ct.Th in vivo and investigate associations among cortical bone structure, age, and disease status.

Age-related patterns of trabecular and cortical bone loss differ between sexes and skeletal sites: a population-based HR-pQCT study.

In this cross‐sectional study, we aimed to predict age‐related changes in bone microarchitecture and strength at the distal radius (DR) and distal tibia (DT) in 644 Canadian adults (n = 442 women and 202 men) aged 20 to 99 years. We performed a standard morphologic analysis of the DR and DT with high‐resolution peripheral quantitative computed tomography (pQCT) and used finite‐element analysis (FEA) to estimate bone strength (failure load) and the load distribution. We also calculated a DR load‐to‐strength ratio as an estimate of forearm fracture risk. Total bone area, which was 33% larger in young men at both sites, changed similarly with age in women and men at the DT but increased 17% more in men than in women at the DR (p < .001). Trabecular number and thickness (Tb.Th) were 7% to 20% higher in young men than in young women at both sites, and with the exception of Tb.Th at the DR, which declined more with age in men (−16%) than in women (−2%, p < .01), the age‐related decline in these outcomes was similar in women and in men. In the cortex, porosity (Ct.Po) was 31% to 44% lower in young women than in young men but increased 92% to 176% more with age in women than in men (p < .001). The DR cortex carried 14% more load in young women than in young men, and the percentage of load carried by the DR cortex did not change with age in women but declined by 17% in men (p < .01). FEA‐estimated bone strength was 34% to 47% greater in young men, but the predicted change with age was similar in both sexes. In contrast, the load‐to‐strength ratio increased 27% more in women than in men with age (p < .01). These results highlight important site‐ and sex‐specific differences in patterns of age‐related bone loss. In particular, the trends for less periosteal expansion, more porous cortices, and a greater percentage of load carried by the DR cortex in women may underpin sex differences in forearm fracture risk.

Is a School‐Based Physical Activity Intervention Effective for Increasing Tibial Bone Strength in Boys and Girls?

This 16‐month randomized, controlled school‐based study compared change in tibial bone strength between 281 boys and girls participating in a daily program of physical activity (Action Schools! BC) and 129 same‐sex controls. The simple, pragmatic intervention increased distal tibia bone strength in prepubertal boys; it had no effect in early pubertal boys or pre or early pubertal girls.

Bone Structure and Volumetric BMD in Overweight Children: A Longitudinal Study†

The effect of excess body fat on bone strength accrual is not well understood. Therefore, we assessed bone measures in healthy weight (HW) and overweight (OW) children. Children (9–11 yr) were classified as HW (n = 302) or OW (n = 143) based on body mass index. We assessed total (ToD) and cortical (CoD) volumetric BMD and bone area, estimates of bone strength (bone strength index [BSI]; stress‐strain index [SSIp]), and muscle cross‐sectional area (CSA) at the distal (8%), midshaft (50%), and proximal (66%) tibia by pQCT. We used analysis of covariance to compare bone outcomes at baseline and change over 16 mo. At baseline, all bone measures were significantly greater in OW compared with HW children (+4–15%; p ≤ 0.001), with the exception of CoD at the 50% and 66% sites. Over 16 mo, ToA increased more in the OW children, whereas there was no difference for change in BSI or ToD between groups at the distal tibia. At the tibial midshaft, SSIp was similar between groups at baseline when adjusted for muscle CSA, but low when adjusted for body fat in the OW group. At both sites, bone strength increased more in OW because of a greater increase in bone area. Changes in SSIp were associated with changes in lean mass (r = 0.70, p < 0.001) but not fat mass. In conclusion, although OW children seem to be at an advantage in terms of absolute bone strength, bone strength did not adapt to excess body fat. Rather, bone strength was adapted to the greater muscle area in OW children.

An active school model to promote physical activity in elementary schools: Action schools! BC

Objective: To assess the impact of an active school model on children’s physical activity (PA). Design: 16-month cluster randomised controlled trial. Setting: 10 elementary schools in Greater Vancouver, BC. Participants: 515 children aged 9–11 years. Intervention: Action Schools! BC (AS! BC) is an active school model that provided schools with training and resources to increase children’s PA. Schools implemented AS! BC with support from either external liaisons (liaison schools, LS; four schools) or internal champions (champion schools, CS; three schools). Outcomes were compared with usual practice (UP) schools (three schools). Main outcome measurements: PA was measured four times during the study using pedometers (step count, steps/day). Results: Boys in the LS group took 1175 more steps per day, on average, than boys in the UP group (95% CI: 97 to 2253). Boys in the CS group also tended to have a higher step count than boys in the UP group (+804 steps/day; 95% CI: −341 to 1949). There was no difference in girls’ step counts across groups. Conclusions: The positive effect of the AS! BC model on boys’ PA is important in light of the current global trend of decreased PA.

Cortical porosity is higher in boys compared with girls at the distal radius and distal tibia during pubertal growth: An HR-pQCT study

The aim of this study was to determine the sex‐ and maturity‐related differences in bone microstructure and estimated bone strength at the distal radius and distal tibia in children and adolescents. We used high‐resolution pQCT to measure standard morphological parameters in addition to cortical porosity (Ct.Po) and estimated bone strength by finite element analysis. Participants ranged in age from 9 to 22 years (n = 212 girls and n = 186 boys) who were scanned annually for either one (11%) or two (89%) years at the radius and for one (15%), two (39%), or three (46%) years at the tibia. Participants were grouped by the method of Tanner into prepubertal, early pubertal, peripubertal, and postpubertal groups. At the radius, peri‐ and postpubertal girls had higher cortical density (Ct.BMD; 9.4% and 7.4%, respectively) and lower Ct.Po (–118% and–56%, respectively) compared with peri‐ and postpubertal boys (all p < 0.001). Peri‐ and postpubertal boys had higher trabecular bone volume ratios (p < 0.001) and larger cortical cross‐sectional areas (p < 0.05, p < 0.001) when compared with girls. Based upon the load‐to‐strength ratio (failure load/estimated fall force), boys had lower risk of fracture than girls at every stage except during early puberty. Trends at the tibia were similar to the radius with differences between boys and girls in Ct.Po (p < 0.01) and failure load (p < 0.01) at early puberty. Across pubertal groups, within sex, the most mature girls and boys had higher Ct.BMD and lower Ct.Po than their less mature peers (prepuberty) at both the radius and tibia. Girls in early, peri‐, and postpubertal groups and boys in peri‐ and postpubertal groups had higher estimates of bone strength compared with their same‐sex prepubertal peers (p < 0.001). These results provide insight into the sex‐ and maturity‐related differences in bone microstructure and estimated bone strength.

Peripheral quantitative computed tomography in children and adolescents: the 2007 ISCD Pediatric Official Positions.

Peripheral quantitative computed tomography (pQCT) has mainly been used as a research tool in children. To evaluate the clinical utility of pQCT and formulate recommendations for its use in children, the International Society of Clinical Densitometry (ISCD) convened a task force to review the literature and propose areas of consensus and future research. The types of pQCT technology available, the clinical application of pQCT for bone health assessment in children, the important elements to be included in a pQCT report, and quality control monitoring techniques were evaluated. The review revealed a lack of standardization of pQCT techniques, and a paucity of data regarding differences between pQCT manufacturers, models and software versions and their impact in pediatric assessment. Measurement sites varied across studies. Adequate reference data, a critical element for interpretation of pQCT results, were entirely lacking, although some comparative data on healthy children were available. The elements of the pQCT clinical report and quality control procedures are similar to those recommended for dual-energy X-ray absorptiometry. Future research is needed to establish evidence-based criteria for the selection of the measurement site, scan acquisition and analysis parameters, and outcome measures. Reference data that sufficiently characterize the normal range of variability in the population also need to be established.

Examining Bone Surfaces Across Puberty: A 20-Month pQCT Trial†

This follow‐up study assessed sex differences in cortical bone growth at the tibial midshaft across puberty. In both sexes, periosteal apposition dominated over endosteal resorption. Boys had a greater magnitude of change at both surfaces, and thus, a greater increase in bone size across puberty. Relative increase in cortical bone area was similar between sexes.

Women with previous fragility fractures can be classified based on bone microarchitecture and finite element analysis measured with HR-pQCT

SummaryHigh-resolution peripheral quantitative computed tomography (HR-pQCT) measurements of distal radius and tibia bone microarchitecture and finite element (FE) estimates of bone strength performed well at classifying postmenopausal women with and without previous fracture. The HR-pQCT measurements outperformed dual energy x-ray absorptiometry (DXA) at classifying forearm fractures and fractures at other skeletal sites.IntroductionAreal bone mineral density (aBMD) is the primary measurement used to assess osteoporosis and fracture risk; however, it does not take into account bone microarchitecture, which also contributes to bone strength. Thus, our objective was to determine if bone microarchitecture measured with HR-pQCT and FE estimates of bone strength could classify women with and without low-trauma fractures.MethodsWe used HR-pQCT to assess bone microarchitecture at the distal radius and tibia in 44 postmenopausal women with a history of low-trauma fracture and 88 age-matched controls from the Calgary cohort of the Canadian Multicentre Osteoporosis Study (CaMos) study. We estimated bone strength using FE analysis and simulated distal radius aBMD from the HR-pQCT scans. Femoral neck (FN) and lumbar spine (LS) aBMD were measured with DXA. We used support vector machines (SVM) and a tenfold cross-validation to classify the fracture cases and controls and to determine accuracy.ResultsThe combination of HR-pQCT measures of microarchitecture and FE estimates of bone strength had the highest area under the receiver operating characteristic (ROC) curve of 0.82 when classifying forearm fractures compared to an area under the curve (AUC) of 0.71 from DXA-derived aBMD of the forearm and 0.63 from FN and spine DXA. For all fracture types, FE estimates of bone strength at the forearm alone resulted in an AUC of 0.69.ConclusionModels based on HR-pQCT measurements of bone microarchitecture and estimates of bone strength performed better than DXA-derived aBMD at classifying women with and without prior fracture. In future, these models may improve prediction of individuals at risk of low-trauma fracture.

Enhancing a somatic maturity prediction model

PURPOSE Assessing biological maturity in studies of children is challenging. Sex-specific regression equations developed using anthropometric measures are widely used to predict somatic maturity. However, prediction accuracy was not established in external samples. Thus, we aimed to evaluate the fit of these equations, assess for overfitting (adjusting as necessary), and calibrate using external samples. METHODS We evaluated potential overfitting using the original Pediatric Bone Mineral Accrual Study (PBMAS; 79 boys and 72 girls; 7.5-17.5 yr). We assessed change in R and standard error of the estimate (SEE) with the addition of predictor variables. We determined the effect of within-subject correlation using cluster-robust variance and fivefold random splitting followed by forward-stepwise regression. We used dominant predictors from these splits to assess predictive abilities of various models. We calibrated using participants from the Healthy Bones Study III (HBS-III; 42 boys and 39 girls; 8.9-18.9 yr) and Harpenden Growth Study (HGS; 38 boys and 32 girls; 6.5-19.1 yr). RESULTS Change in R and SEE was negligible when later predictors were added during step-by-step refitting of the original equations, suggesting overfitting. After redevelopment, new models included age × sitting height for boys (R, 0.91; SEE, 0.51) and age × height for girls (R, 0.90; SEE, 0.52). These models calibrated well in external samples; HBS boys: b0, 0.04 (0.05); b1, 0.98 (0.03); RMSE, 0.89; HBS girls: b0, 0.35 (0.04); b1, 1.01 (0.02); RMSE, 0.65; HGS boys: b0, -0.20 (0.02); b1, 1.02 (0.01); RMSE, 0.85; HGS girls: b0, -0.02 (0.03); b1, 0.97 (0.02); RMSE, 0.70; where b0 equals calibration intercept (standard error (SE)) and b1 equals calibration slope (SE), and RMSE equals root mean squared error (of prediction). We subsequently developed an age × height alternate for boys, allowing for predictions without sitting height. CONCLUSION Our equations provided good fits in external samples and provide an alternative to commonly used models. Original prediction equations were simplified with no meaningful increase in estimation error.