Long-term leisure-time physical activity has a positive effect on bone mass gain in girls.

The purpose of this 7-year prospective longitudinal study was to examine whether the level and consistency of leisure-time physical activity (LTPA) during adolescence affected the bone mineral content (BMC) and bone mineral density (BMD) attained at early adulthood. The study subjects were 202 Finnish girls who were 10 to 13 years of age at baseline. Bone area (BA), BMC, and BMD of the total body (TB), total femur (TF), and lumbar spine (L(2)-L(4)) were assessed by dual-energy X-ray absorptiometry (DXA). Scores of LTPA were obtained by questionnaire. Girls were divided into four groups: consistently low physical activity (G(LL)), consistently high (G(HH)), and changed from low to high (G(LH)) and from high to low (G(HL)) during 7 years of follow-up. At baseline, no differences were found in BA, BMC, and BMD among the groups in any of the bone sites. Compared with the G(LL) group, the G(HH) group had higher BMC (11.7% in the TF, p < .05) and BMD at the TB (4.5%) and the TF (12.2%, all p < .05) at age 18. Those in the G(LH) group also had higher a BMC at each site (8.5% to 9.4%, p < .05) and a higher BMD in the TB (5.4%) and the TF (8.9%) than that of G(LL) (all p < 0.05) at the age 18. Our results suggest that long-term leisure-time physical activity has a positive effect on bone mass gain of multiple bone sites in girls during the transition from prepuberty to early adulthood. In addition, girls whose physical activity increases during adolescence also benefit from bone mass gain.

Low volumetric BMD is linked to upper-limb fracture in pubertal girls and persists into adulthood: a seven-year cohort study.

The aetiology of increased incidence of fracture during puberty is unclear. This study aimed to determine whether low volumetric bone mineral density (vBMD) in the distal radius is associated with upper-limb fractures in growing girls, and whether any such vBMD deficit persists into adulthood. Fracture history from birth to 20 years was obtained and verified by medical records in 1034 Finnish girls aged 10-13 years. Bone density and geometry at distal radius, biomarkers and lifestyle/behavioural factors were assessed in a subset of 396 girls with a 7.5-year follow-up. We found that fracture incidence peaked during puberty (relative risk 3.1 at age of 8-14 years compared to outside this age window), and 38% of fractures were in the upper-limb. Compared to the non-fracture cohort, girls who sustained upper-limb fracture at ages 8-14 years had lower distal radial vBMD at baseline (258.9+/-37.5 vs. 287.5+/-34.1 mg/cm(3), p=0.001), 1-year (252.0+/-29.3 vs. 282.6+/-33.5 mg/cm(3), p=0.001), 2-year (258.9+/-32.2 vs. 289.9+/-40.1 mg/cm(3), p=0.003), and 7-year follow-ups (early adulthood, 307.6+/-35.9 vs. 343.6+/-40.9 mg/cm(3), p=0.002). There was a consistent trend towards larger bone cross-sectional area in the fracture cohort compared to non-fracture. In a logistic regression model, lower vBMD (p=0.001) was the only significant predictor of upper-limb fracture during the period of 8-14 years. Our results indicate that low BMD is an important factor underlying elevated upper-limb fracture risk during puberty, and that low BMD in pubertal girls with fracture persists into adulthood. Hence low vBMD during childhood is not a transient deficit. Methods to monitor vBMD and to maximise bone mineral accrual and reduce risks of falling in childhood should be developed.

Monitoring bone growth using quantitative ultrasound in comparison with DXA and pQCT.

Quantitative ultrasound (QUS) is a safe, inexpensive, and nonradiation method for bone density assessment. QUS correlates with, and predicts fragility fractures comparable to, dual-energy X-ray absorptiometry (DXA)-derived bone mineral density (BMD) in postmenopausal women. However, its validity in monitoring bone growth in children is not well understood. Two hundred and fifty-eight 10-13 yr pubertal girls and 9 37-43 yr adults without diseases or history of medications known to affect bone metabolism were included in the 2-yr prospective study. Calcaneal broadband ultrasound attenuation (cBUA) was assessed using QUS-2 (Quidel, Santa Clara, CA), speed of sound of tibial shaft (tSOS) using Omnisense (Sunlight Technologies, Israel), apparent volumetric BMD (vBMD) of tibial shaft using peripheral quantitative computed tomography (pQCT; XCT2000, Stratec), and femoral neck (FN) and lumbar spine 2-4 (LS) areal BMD (aBMD) using DXA (Prodigy, GE). Over the 2 yr in girls, FN and LS aBMD showed the largest increases (17+/-8% and 20+/-8%, respectively), followed by tibial vBMD and cBUA (10+/-5% and 9+/-9%, respectively). There was no apparent change in tSOS (2+/-3%). The increase in FN and LS aBMD attenuated 48% and 40%, respectively, after adjustment of the change in body size. The change of cBUA correlated significantly with change in tibial vBMD and FN and LS aBMD (r=0.24-0.40). At the matched location, tSOS correlated only with cortical vBMD, not with cortical thickness, apparent vBMD, or bone size. The long-term reproducibility, assessed using the concordance correlation coefficient of young adults' pre-post measurements, was substantially lower in tSOS than cBUA, tibial vBMD, FN, and LS aBMD (0.65 vs 0.97, 0.95, 0.98, and 0.96; p<0.05). The transverse transmission method-derived calcaneal BUA, but not the axial transmission method-derived SOS, is comparable to DXA and pQCT for monitoring bone densitometric change in pubertal girls. The role of QUS in fracture-risk prediction in children and adolescents needs further investigation.

Ultrasonically determined thickness of long cortical bones: two-dimensional simulations of in vitro experiments.

Previously it has been demonstrated that cortical bone thickness can be estimated from ultrasonic guided-wave measurements, in an axial transmission configuration, together with an appropriate analytical model. This study considers the impact of bone thickness variation within the measurement region on the ultrasonically determined thickness (UTh). To this end, wave velocities and UTh were determined from experiments and from time-domain finite-difference simulations of wave propagation, both performed on a set of ten human radius specimens (29 measurement sites). A two-dimensional numerical bone model was developed with tunable material properties and individualized geometry based on x-ray computed-tomography reconstructions of human radius. Cortical thickness (CTh) was determined from the latter. UTh data for simulations were indeed in a excellent accordance (root-mean-square error was 0.26 mm; r2=0.94, p<0.001) with average CTh within the measurement region. These results indicate that despite variations in cortical thickness along the propagation path, the measured phase velocity can be satisfactorily modeled by a simple analytical model (the A(0) plate mode in this case). Most of the variability (up to 85% when sites were carefully matched) observed in the in vitro ultrasound data was explained through simulations by variability in the cortical thickness alone.

Ultrasonically determined thickness of long cortical bones: Three-dimensional simulations of in vitro experiments.

It was reported in a previous study that simulated guided wave axial transmission velocities on two-dimensional (2D) numerically reproduced geometry of long bones predicted moderately real in vitro ultrasound data on the same bone samples. It was also shown that fitting of ultrasound velocity with simple analytical model yielded a precise estimate (UTh) for true cortical bone thickness. This current study expands the 2D bone model into three dimensions (3D). To this end, wave velocities and UTh were determined from experiments and from time-domain finite-difference simulations of wave propagation, both performed on a collection of 10 human radii (29 measurement sites). A 3D numerical bone model was developed with tuneable fixed material properties and individualized geometry based on X-ray computed tomography reconstructions of real bones. Simulated UTh data were in good accordance (root-mean-square error was 0.40 mm; r(2)=0.79, p<0.001) with true cortical thickness, and hence the measured phase velocity can be well estimated by using a simple analytical inversion model also in 3D. Prediction of in vitro data was improved significantly (by 10% units) and the upgraded bone model thus explained most of the variability (up to 95% when sites were carefully matched) observed in in vitro ultrasound data.

Assessment of the cortical bone thickness using ultrasonic guided waves: modelling and in vitro study.

Determination of cortical bone thickness is warranted, e.g., for assessing the level of endosteal resorption in osteoporosis or other bone pathologies. We have shown previously that the velocity of the fundamental antisymmetric (or flexural) guided wave, measured for bone phantoms and bones in vitro, correlates with the cortical thickness significantly better than those by other axial ultrasound methods. In addition, we have introduced an inversion scheme based on guided wave theory, group velocity filtering and 2-D fast Fourier transform, for determination of cortical thickness from the measured velocity of guided waves. In this study, the method was validated for tubular structures by using numerical simulations and experimental measurements on tube samples. In addition, 40 fresh human radius specimens were measured. For tubes with a thin wall, plate theory could be used to determine the wall thickness with a precision of 4%. For tubes with a wall thicker than 1/5 of the outer radius, tube theory provided the wall thickness with similar accuracy. For the radius bone specimens, tube theory was used and the ultrasonically-determined cortical thickness was found to be U-Th = 2.47 mm +/- 0.66 mm. It correlated strongly (r(2) = 0.73, p < 0.001) with the average cortical thickness, C-Th = 2.68 +/- 0.53 mm, and the local cortical thickness (r(2) = 0.81, p < 0.001), measured using peripheral quantitative computed tomography. We can conclude that the guided-wave inversion scheme introduced here is a feasible method for assessing cortical bone thickness.

Differential effects of sex hormones on peri- and endocortical bone surfaces in pubertal girls.

CONTEXT: The role of sex steroids in bone growth in pubertal girls is not yet clear. Bone biomarkers are indicators of bone metabolic activity, but their value in predicting bone quality has not been studied in growing girls. OBJECTIVE: This study examines the association of sex hormones and bone markers with bone geometry and density in pubertal girls. DESIGN: The study was designed as a 2-yr longitudinal study in pubertal girls. Measurements were performed at baseline and at 1- and 2-yr follow-ups. SETTING: The study was conducted in a university laboratory. PARTICIPANTS: A total of 258 10- to 13-yr-old healthy girls at the baseline participated. METHODS: Peripheral quantitative computed tomography was used to scan the left tibial shaft. Serum 17beta-estradiol (E2), testosterone (T), SHBG, osteocalcin (OC), bone-specific alkaline phosphatase, and tartrate-resistant acid phosphatase isoform 5b were assessed. Data were analyzed using hierarchical linear models with random effect. RESULTS: E2 was a positive predictor for total bone mineral density (BMD), cortical thickness, and a negative predictor for endocortical circumference but had no predictive value for total bone cross-sectional area or periosteal circumference. T was a positive predictor for total cross-sectional area and periosteal circumference as well as endocortical circumference, and a negative predictor for total BMD. OC was negatively correlated with cortical BMD (R2 = 0.325; P < 0.001). CONCLUSIONS: In pubertal girls, E2 and T have different influences on bone properties at the long bone shaft. The results suggest that, at the endocortical surface, E2 inhibits bone resorption during rapid growth, and later, after menarche, acts at higher concentrations to promote bone formation. At the periosteal surface, T promotes bone formation, whereas E2 does not affect it. In addition, OC might be used as a predictor of cortical BMD.

Effects of calcium, dairy product, and vitamin D supplementation on bone mass accrual and body composition in 10-12-y-old girls: a 2-y randomized trial.

BACKGROUND: Little is known about the relative effectiveness of calcium supplementation from food or pills with or without vitamin D supplementation for bone mass accrual during the rapid growth period. OBJECTIVE: The purpose was to examine the effects of both food-based and pill supplements of calcium and vitamin D on bone mass and body composition in girls aged 10-12 y. DESIGN: This placebo-controlled intervention trial randomly assigned 195 healthy girls at Tanner stage I-II, aged 10-12 y, with dietary calcium intakes <900 mg/d to 1 of 4 groups: calcium (1000 mg) + vitamin D3 (200 IU), calcium (1000 mg), cheese (1000 mg calcium), and placebo. Primary outcomes were bone indexes of the hip, spine, and whole body by dual-energy X-ray absorptiometry and of the radius and tibia by peripheral quantitative computed tomography. RESULTS: With the use of intention-to-treat or efficacy analysis, calcium supplementation with cheese resulted in a higher percentage change in cortical thickness of the tibia than did placebo, calcium, or calcium + vitamin D treatment (P = 0.01, 0.038, and 0.004, respectively) and in higher whole-body bone mineral density than did placebo treatment (P = 0.044) when compliance was >50%. With the use of a hierarchical linear model with random effects to control for growth velocity, these differences disappeared. CONCLUSIONS: Increasing calcium intake by consuming cheese appears to be more beneficial for cortical bone mass accrual than the consumption of tablets containing a similar amount of calcium. Diverse patterns of growth velocity may mask the efficacy of supplementation in a short-term trial of children transiting through puberty.

Differences in estimates of change of bone accrual and body composition in children because of scan mode selection with the prodigy densitometer.

Girls of age 10-13 yr with Tanner stage I-III maturation status (n = 155) were measured using the Prodigy (GE Lunar) densitometer. Bone area (BA), bone mineral content (BMC), and bone mineral density (BMD) were assessed for the whole body, lumbar spine, and proximal femur using the Thin (T) and Standard (S) scan modes at years 1 and 3 of the study. The differences obtained between the T and S mode at year 1 were 1-2% for the lumbar spine and proximal femur and 5-11% for the whole body. For those girls whose default mode changed from T at year 1 to S mode at year 3, the estimated gain in BA, BMC, and BMD was 3.4%, 7.6%, and 3.1% respectively, lower than that obtained when scanning with the T mode at both times for the whole body. Small changes in magnitude but large intersubject variability were noted in BA, BMC, and BMD of the lumbar spine and proximal femur when scanned with the default mode of T at year 1 and S at year 3 compared to T or S at both years. Errors of this size are comparable to the changes expected with longitudinal intervention studies and are, therefore, clinically relevant.

Thickness sensitivity of ultrasound velocity in long bone phantoms.

One approach to bone disease diagnosis such as osteoporosis is to measure the velocity of ultrasound propagating axially along long bones. In this study, the variation in velocity as a function of radial position was assessed using two polyvinyl chloride (PVC) bone phantoms with cross-sectional geometry similar to the human tibia but differing in medullary cavity diameter. Two ultrasonometers were used: these were a commercial device operating at a relatively high frequency (HF) of 1.25 MHz and a prototype low frequency (LF) device operating at approximately 200 kHz. The LF measurements showed a larger variation with radial position, with changes in velocity of up to 20% occurring around the phantom compared with changes of only 4% at most for HF. The LF velocity correlated strongly with local thickness (r(2) = 0.81) but HF velocity did not. The results demonstrate that LF measurements have a greatly enhanced thickness sensitivity. Using LF, it may therefore be possible to assess bone thickness as a function of radial position and hence to determine the distribution of bone around the long axis.

Relationship of sex hormones to bone geometric properties and mineral density in early pubertal girls.

This study aimed to evaluate the associations among serum 17beta-estradiol (E2), testosterone (T), sex hormone-binding globulin (SHBG), bone geometric properties, and mineral density in 248 healthy girls between the ages of 10 and 13 yr old. The left tibial shaft was measured by peripheral quantitative computed tomography (Stratec XCT-2000; Stratec Medizintechnik, GmbH, Pforzheim, Germany). The cortical bone and marrow cavity areas were expressed as proportions of the total tibial cross-sectional area (CSA). Cortical thickness and total volumetric bone mineral density (vBMD) were also determined. These tibial geometric and densitometric measures were correlated against the serum sex hormone concentrations after controlling for age and body size. The results showed that E2 was negatively associated with marrow cavity proportion (r = -0.19, P = 0.003) and positively associated with cortical proportion and thickness and with total vBMD (r = 0.26, P < 0.001; r = 0.25, P < 0.001; and r = 0.23, P < 0.001, respectively). However, T was not associated with these bone variables. On the other hand, SHBG was positively associated with marrow cavity proportion (r = 0.17, P = 0.007) and negatively associated with cortical proportion and thickness and with total vBMD (r = -0.14, P = 0.029; r = -0.16, P = 0.010; and r = -0.18, P = 0.005, respectively). Total bone CSA did not correlate with E2, T, or SHBG. These results suggest that E2 has a positive effect on bone geometric and densitometric development by suppressing bone turnover at the endocortical surface during the early pubertal period, that SHBG plays an opposite role to E2, and that T has no detectable effect.

Guided ultrasonic waves in long bones: modelling, experiment and in vivo application.

Existing ultrasound devices for assessing the human tibia are based on detecting the first arriving signal, corresponding to a wave propagating at, or close to, the bulk longitudinal velocity in bone. However, human long bones are effectively irregular hollow tubes and should theoretically support the propagation of more complex guided modes similar to Lamb waves in plates. Guided waves are attractive because they propagate throughout the bone thickness and can potentially yield more information on bone material properties and architecture. In this study, Lamb wave theory and numerical simulations of wave propagation were used to gain insights into the expected behaviour of guided waves in bone. Experimental measurements in acrylic plates, using a prototype low-frequency axial pulse transmission device, confirmed the presence of two distinct propagating waves: the first arriving wave propagating at, or close to, the longitudinal velocity, and a slower second wave whose behaviour was consistent with the lowest order Lamb antisymmetrical (A0) mode. In a pilot study of healthy and osteoporotic subjects, the velocity of the second wave differed significantly between the two groups, whereas the first arriving wave velocity did not, suggesting the former to be a more sensitive indicator of osteoporosis. We conclude that guided wave measurements may offer an enhanced approach to the ultrasonic characterization of long bones.

Bone marrow influences quantitative ultrasound measurements in human cancellous bone.

Quantitative ultrasound (QUS) transmission and backscatter measurements were made in 46 human cancellous bone specimens from the calcaneus. All QUS measurements were made at 35 degrees C, initially with marrow filling the pores and then repeated after substituting water for marrow. Bone mineral density (BMD) was determined using x-ray absorptiometry. Marrow significantly decreased ultrasound (US) velocity, but increased attenuation, attenuation slope and backscatter (p < 0.001 for all) compared to the water-saturated state. The impact of marrow on QUS measurements was greater at lower BMD values (p < 0.05), and was greater in women than in men (p < 0.05). QUS measurements in marrow-saturated specimens correlated less strongly with BMD than did corresponding measurements in water-saturated specimens (p < 0.05), consistent with interspecimen marrow heterogeneity. These data indicate that the potential impact of marrow should be considered when interpreting clinical QUS measurements. Understanding and exploiting these effects could lead to novel approaches for ultrasonic characterisation of both bone and marrow.