Patrick Nicholson

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.

Growth Patterns at Distal Radius and Tibial Shaft in Pubertal Girls: A 2-Year Longitudinal Study†

Bone changes, in terms of both size and BMD, were assessed longitudinally in pubertal girls. Before puberty, BMD at the distal radius declined, whereas bone size increased, suggesting that normal growing girls experience a transient period of increased bone fragility. This could explain the elevated low‐trauma forearm fracture rates reported in earlier studies.

Bone and muscle development during puberty in girls: a seven-year longitudinal study.

The growth of lean mass precedes that of bone mass, suggesting that muscle plays an important role in the growth of bone. However, to date, no study has directly followed the growth of bone and muscle size through puberty and into adulthood. This study aimed to test the hypothesis that the growth of muscle size precedes that of bone size (width and length) and mass during puberty. Bone and muscle properties were measured using pQCT and DXA in 258 healthy girls at baseline (mean age, 11.2 yr) and 1‐, 2‐, 3–4‐ and 7‐yr follow‐up. Growth trends as a function of time relative to menarche were determined from prepuberty to early adulthood for tibial length (TL), total cross‐sectional area (tCSA), cortical CSA (cCSA), total BMC (tBMC), cortical volumetric BMD (cBMD), and muscle CSA (mCSA) in hierarchical models. The timings of the peak growth velocities for these variables were calculated. Seventy premenopausal adults, comprising a subset of the girls mothers (mean age, 41.5 yr), were included for comparative purposes. In contrast to our hypothesis, the growth velocity of mCSA peaked 1 yr later than that of tibial outer dimensions (TL and tCSA) and slightly earlier than tBMC. Whereas TL ceased to increase 2 yr after menarche, tCSA, cCSA, tBMC, and mCSA continued to increase and were still significantly lower than adult values at the age of 18 yr (all p < 0.01). The results do not support the view that muscle force drives the growth of bone size during puberty.

Influence of physical activity and maturation status on bone mass and geometry in early pubertal girls1

This study aimed to evaluate the influence of leisure‐time physical activity on the development of bone mass and density in early pubertal girls. Scores of physical activity were obtained from 242 Finnish girls (10–12 years old within Tanner Stages I–II) using a questionnaire. Bone mass and density were assessed using different densitometric techniques. At Tanner Stage I, active girls had significantly higher bone mineral mass (BMC) and areal bone mineral density (aBMD) of the whole body and cortical volumetric BMD and thickness of the tibial shaft compared with sedentary girls (P<0.05). On the other hand, the active girls at Tanner Stage II showed significantly higher values only in BMC and aBMD at the lumbar spine (P=0.017 and P=0.007, respectively). These indicated that girls at Tanner Stage I with higher leisure‐time physical activity level benefited more from physical activity in terms of their bone development than their less active counterparts. Our results provide evidence that the most beneficial time for physical exercise to exhibit its effect on bone development is in the earlier pubertal period for normal school children, but the positive effect on the lumbar spine is also demonstrated in Tanner Stage II.

Ultrasonically determined thickness of long cortical bones: Three-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.

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.

Concerted actions of insulin-like growth factor 1, testosterone, and estradiol on peripubertal bone growth: a 7-year longitudinal study.

A better understanding of how bone growth is regulated during peripuberty is important for optimizing the attainment of peak bone mass and for the prevention of osteoporosis in later life. In this report we used hierarchical models to evaluate the associations of insulin‐like growth factor 1 (IGF‐1), estradiol (E2), and testosterone (T) with peripubertal bone growth in a 7‐year longitudinal study. Two‐hundred and fifty‐eight healthy girls were assessed at baseline (mean age 11.2 years) and at 1, 2, 3.5, and 7 years. Serum concentrations of IGF‐1, E2, and T were determined. Musculoskeletal properties in the left lower leg were measured using peripheral quantitative computed tomography (pQCT). Serum levels of IGF‐1, E2, and T increased dramatically before menarche, whereas they decreased, plateaued, or increased at a lower rate, respectively, after menarche. IGF‐1 level was positively associated with periosteal circumference (PC) and total bone mineral content (tBMC) throughout peripuberty but not after adjustment for muscle cross‐sectional area (mCSA). On the other hand, IGF‐1 was associated with tibial length (TL) independently of mCSA before menarche. T was positively associated with TL, PC, tBMC, and cortical volumetric bone mineral density, independent of mCSA, before menarche but not after. E2 was associated with TL positively before menarche but negatively after menarche. These findings suggest that during puberty, circulating IGF‐1 promotes bone periosteal apposition and mass accrual indirectly, probably through stimulating muscle growth, whereas the effects of sex steroids on bone growth differ before and after menarche, presenting a biphasic pattern. Hence the concerted actions of these hormones are essential for optimal bone development in peripuberty.

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 (L2–L4) 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 (GLL), consistently high (GHH), and changed from low to high (GLH) and from high to low (GHL) 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 GLL group, the GHH 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 GLH 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 GLL (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.

Fat Mass Accumulation Compromises Bone Adaptation to Load in Finnish Women: A Cross-Sectional Study Spanning Three Generations

Body weight and lean mass correlate with bone mass, but the relationship between fat mass and bone remains elusive. The study population consisted of 396 girls and 138 premenopausal mothers and 114 postmenopausal grandmothers of these girls. Body composition and tibial length were assessed using dual‐energy X‐ray absorptiometry (DXA), and bone traits were determined at the tibia using peripheral quantitative computed tomography (pQCT) in the girls at the ages of 11.2 ± 0.8, 13.2 ± 0.9, and 18.3 ± 1.0 years and in the mothers (44.7 ± 4.1 years) and grandmothers (70.7 ± 6.3 years). The values of relative bone strength index (RBSI), an index reflecting the ratio of bone strength to the load applied on the tibia, were correlated among family members (all p < .05). The mean values of RBSI were similar among 11‐ and 18‐year‐old girls and premenopausal women but significantly lower in 13‐year‐old girls and postmenopausal women. However, in each age group, subjects in the highest BMI tertiles had the lowest RBSI values (all p < .01). RBSI was inversely associated with body weight (all p < .01), indicating a deficit in bone strength relative to the applied load from greater body weight. RBSI was inversely associated with fat mass (all p < .001) across age groups and generations but remained relatively constant with increasing lean mass in girls and premenopausal women (all p > .05), indicating that the bone‐strength deficit was attributable to increased fat mass, not lean mass. Moreover, the adverse effect of fat mass was age‐dependent, with every unit increase in fat mass associated with a greater decrease in RBSI in pre‐ and postmenopausal women than in girls (all p < .001). This is largely due to the different capacity of young and adult bones to increase diaphyseal width by periosteal apposition in response to increased load. In summary, increasing body weight with fat accumulation is accompanied by an age‐dependent relative bone‐strength deficit in women because the beneficial effects of increased fat mass on bone, if any, do not compensate for the mechanical burden that it imposes.

Correlation of Tibial Low-Frequency Ultrasound Velocity with Femoral Radiographic Measurements and BMD in Elderly Women

The ultrasonic axial transmission technique has been proposed as a method for cortical bone characterization. Using a low enough center frequency, Lamb modes can be excited in long bones. Lamb waves propagate throughout the cortical bone layer, which makes them appealing for characterizing bone material and geometrical properties. In the present study, a prototype low-frequency quantitative ultrasonic axial transmission device was used on elderly women (n = 132) to investigate the relationships between upper femur geometry and bone mineral density (BMD) and tibial speed of sound. Ultrasonic velocities (V) were recorded using a two-directional measurement set-up on the midtibia and compared with dual-energy X-ray absorptiometry measurements and plain radiographs of the hip. Statistically significant, but weak, correlations were found between V and femoral shaft cortex thickness measured from radiographs (r = 0.20-0.26). V also correlated significantly with various BMD and bone mineral content parameters (r = 0.20-0.35). Femoral BMD and geometry were found to be significant independent predictors of V (R(2) = 0.07-0.16, p < 0.01). This study showed that femoral geometry and BMD affect significantly the axial ultrasound velocity measured at the tibia. In addition, the results confirmed, for the first time, a relationship between tibial ultrasound velocity and cortical bone thickness at the proximal femur.