P. H. F. Nicholson

University of Jyväskylä, Jyväskylä, Province of Western Finland, Finland

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Publications (79)263.84 Total impact

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    Qin Wang · Decai Chen · Patrick Nicholson · Shumei Cheng · Markku Alen · Lijian Mao · Sulin Cheng
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    ABSTRACT: Context Serotonin plays a potential role in bone metabolism, but the nature and extent of this relationship is unclear and human studies directly addressing the skeletal effect of circulating serotonin are rare. Objective The study aimed to investigate the associations between serum serotonin and bone traits at multiple skeletal sites in women and men. Subjects and Methods Subjects were part of the CALEX-family study and comprised 235 young women, 121 premenopausal women, 124 postmenopausal women, and 168 men. Body composition was assessed using DXA, as was areal bone mineral density (aBMD) of spine, femur and whole body. In addition, pQCT was used to determine bone properties at tibial midshaft and distal radius. Fasting serum serotonin concentration was assessed using a competitive enzyme-linked immunosorbent assay. Results Serum serotonin declined with advancing age both in females and males (all p<0.01). Serotonin was negatively correlated with weight, BMI, lean and fat mass in women (r = −0.22 to −0.39, all p<0.001), but positively with height and lean mass in men (all p<0.01). In the premenopausal women, serotonin was negatively correlated with lumbar spine aBMD (r = −0.23, p<0.05) but the statistical significance disappeared after adjustment for weight. Conversely, in postmenopausal women, serotonin was positively correlated with whole body and femur aBMD, as well as with distal radius bone mineral content and volumetric BMD (r = 0.20 to 0.30, all p<0.05), and these associations remained significant after adjustment for weight. In men, no significant associations were found between serotonin and bone traits. Conclusion Serum serotonin is positively associated with bone traits in postmenopausal women, but not in premenopausal women or men. This partially supports the idea of circulating serotonin playing a role in the regulation of bone metabolism, but also indicates the importance of gender and age specific factors.
    Full-text · Article · Oct 2014 · PLoS ONE
  • Qin Wang · Decai Chen · Shu Mei Cheng · Patrick Nicholson · Markku Alen · Sulin Cheng
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    ABSTRACT: Osteoporotic hip fracture is a serious clinical event associated with high morbidity and mortality. Understanding femoral growth patterns is important for promoting bone health in the young and preventing fractures in later life. In this study, growth patterns of areal bone mineral density (aBMD) and geometric properties of the proximal femur were measured by dual-energy X-ray absorptiometry. They were studied in 251 girls from premenarche (11.2±0.7 years) to late adolescence (18.3±1.1 years) and compared with their premenopausal mothers (n=128, aged 44.9±4.1 years) and postmenopausal grandmothers (n=128, aged 70.0±6.3 years). Hip axis length (HAL) was the first to reach peak growth velocity (10.5 months before menarche), followed by neck diameter (ND) and neck cross-sectional area (CSA), (7.1 and 4.1 months before menarche, respectively). Both neck-shaft angle (NSA) and aBMD of neck and total hip peaked at menarche. At 18 years (7-year follow-up), girls already had higher femoral neck aBMD but similar HAL and NSA compared with their mothers. Grandmothers had the longest HAL, narrowest NSA, widest ND but lowest aBMD and CSA. Hip strength index (HSI), an index of femoral neck strength during a fall, dropped rapidly after menarche in girls but thereafter remained relatively constant. Grandmothers had lower HSI than either mothers or girls. In conclusion, differences in proximal femoral bone mass and structure in adulthood are largely established before menarche, indicating that heritable factors are responsible for most of the individual variance. The development of geometric properties precedes aBMD in puberty, resulting in relatively constant hip strength after menarche. This asynchronous growth leads to adaptation of bone strength to the imposed loads, avoiding fractures in a biologically efficient manner. Both deterioration of aBMD and inadequate compensatory change in bone geometry after menopause contribute to the increased fracture risk later in life.
    No preview · Article · Sep 2014 · Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research
  • P Moilanen · M Määttä · V Kilappa · L Xu · P H F Nicholson · M Alén · J Timonen · T Jämsä · S Cheng
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    ABSTRACT: In this cross-sectional study, 95 postmenopausal women, with and without fracture history, were measured by low-frequency axial transmission ultrasound. The measured ultrasound velocity discriminated the fractured subjects from the nonfractured ones equally or better than peripheral quantitative computed tomography (pQCT) and dual energy x-ray absorptiometry (DXA). These results suggest that low-frequency ultrasound is suitable for bone fragility assessment. Introduction Quantitative low-frequency axial transmission ultrasound is a promising modality for assessing mineral density and geometrical properties of long bones such as radius and tibia. The aim of the current study was to evaluate the ability of low-frequency axial transmission ultrasound to discriminate fractures retrospectively in postmenopausal women. Methods A cross-sectional study involved 95 female subjects aged 45–88 years, whose fracture information was gathered retrospectively. The fracture group was defined as subjects with one or more low-/moderate-energy fractures. The radius and tibial shaft were measured with a custom-made ultrasonometer to assess the velocity of the low-frequency first-arriving signal (V LF). Site-matched pQCT was used to measure volumetric cortical and subcortical bone mineral density (sBMD), and cortical thickness (CTh). Areal BMD (aBMD) was measured using DXA for the whole body (WB), lumbar spine, and hip. Results The majority (19/32; 59 %) of the fractures were in the upper limb. V LF in the radius, but not in the tibia, discriminated fractures with an age- and BMI-adjusted odds ratio (OR) of 2.06 (95 % CI 1.21–3.50, p < 0.01). In the radius, CTh and cortical BMD (CBMD) significantly discriminated fractures, as did the total, cortical, and sBMD in the tibia (adjusted OR 1.35–2.15, p < 0.05). Sensitivity and specificity were similar among all the measurements (area under the receiver operating characteristic curve 0.74–0.81, p < 0.001). Conclusions Low-frequency axial transmission ultrasound in the radius was able to discriminate fractured subjects from the nonfractured ones. This suggests that low-frequency axial transmission ultrasound has the potential to assess bone fragility in postmenopausal women.
    No preview · Article · May 2012 · Osteoporosis International
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    ABSTRACT: 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. © 2011 American Society for Bone and Mineral Research
    Full-text · Article · Sep 2011 · Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research
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    ABSTRACT: Bone adapts to mechanical loads applied on it. During aging, loads decrease to a greater extent at those skeletal sites where loads increase most in earlier life. Thus, the loss of bone may occur preferentially at sites where most bone has been deposited previously; ie, bone loss could be the directional reversal of accrual. To test this hypothesis, we compared the bone mass distribution at weight-bearing (tibia) and non-weight-bearing (radius) bones among 18-year-old girls, their premenopausal mothers, and their postmenopausal maternal grandmothers. Bone and muscle properties were measured by pQCT, and polar distribution of bone mass was obtained in 55 girl-mother-maternal grandmother trios. Site-matched differences in bone mass were compared among three generations. The differences between girls and mothers and between mothers and grandmothers were used to represent the patterns of bone mass accrual from early adulthood to middle age and bone loss from middle to old age, respectively. Compared to the mothers, 18-year old girls had less bone mass in the anterior and medial-posterior regions of the tibial shaft, while the grandmothers had less bone in the anterior and posterior regions. In contrast, the bone mass differences in the radial shaft between girls and mothers and mothers and grandmothers were relatively uniform. We conclude that both bone accrual and loss are direction-specific in weight-bearing bones but relatively uniform in non-weight-bearing bones. Bone loss in old age is largely, but not completely, a reversal of the preferential deposition of bone in the most highly loaded regions during early life.
    Full-text · Article · May 2011 · Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research
  • V Kilappa · P Moilanen · L Xu · P H F Nicholson · J Timonen · S Cheng
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    ABSTRACT: Axial transmission velocity of a low-frequency first arriving signal (V (LF)) was assessed in the radius and tibia of 254 females, and compared to site-matched pQCT measurements. V (LF) best correlated with cortical BMD, but significantly also with subcortical BMD and cortical thickness. Correlations were strongest for the radius in postmenopausal females. Ultrasonic low-frequency (LF; 0.2-0.4 MHz) axial transmission, based on the first arriving signal (FAS), provides enhanced sensitivity to thickness and endosteal properties of cortical wall of the radius and tibia compared to using higher frequencies (e.g., 1 MHz). This improved sensitivity of the LF approach has not yet been clearly confirmed by an in vivo study on adult subjects. The aims of the present study were to evaluate the extent to which LF measurements reflect cortical thickness and bone mineral density, and to assess whether an individual LF measurement can provide a useful estimate for these bone properties. Velocity of the LF FAS (V (LF)) was assessed in the radius and tibia shaft by a new ultrasonometer (CV(RMS) = 0.5%) in a cross-sectional study involving 159 premenopausal (20-58 years) and 95 postmenopausal females (45-88 years). Site-matched volumetric total bone mineral density (BMD), cortical bone mineral density (CBMD), subcortical bone mineral density (ScBMD) and cortical thickness (CTh) were assessed using pQCT. For the postmenopausal females, V (LF) correlated best with CBMD in the radius (R = 0.850, p < 0.001), but significantly also with ScBMD and CTh (R = 0.759 and R = 0.761, respectively; p < 0.001). Similar trends but weaker correlations were observed for the tibia and for the premenopausal women. The LF assessment, with an optimal excitation frequency, thus provided good prediction of both cortical thickness and subcortical bone material properties. These results suggest that the LF approach does indeed have enhanced sensitivity for detecting osteoporotic changes that occur deep in the endosteal bone.
    No preview · Article · Apr 2011 · Osteoporosis International
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    Leiting Xu · Patrick Nicholson · Qing-Ju Wang · Qin Wang · Markku Alén · Sulin Cheng
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    ABSTRACT: 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.
    Full-text · Article · Nov 2010 · Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research
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    Full-text · Article · Mar 2010 · Bone
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    ABSTRACT: 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.
    Full-text · Article · Nov 2009 · Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research
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    ABSTRACT: 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.
    No preview · Article · Jun 2009 · Bone
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    Leiting Xu · Patrick Nicholson · Qingju Wang · Markku Alén · Sulin Cheng
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    ABSTRACT: 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 girl's 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.
    Full-text · Article · May 2009 · Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research
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    ABSTRACT: 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 (R2 = 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. (E-mail: [email protected] /* */).
    No preview · Article · Feb 2009 · Ultrasound in medicine & biology
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    ABSTRACT: Recent in vitro and simulation studies have shown that guided waves measured at low ultrasound frequencies (f=200 kHz) can characterize both material properties and geometry of the cortical bone wall. In particular, a method for an accurate cortical thickness estimation from ultrasound velocity data has been presented. The clinical application remains, however, a challenge as the impact of a layer of soft tissue on top of the bone is not yet well established, and this layer is expected to affect the dispersion and relative intensities of guided modes. The present study is focused on the theoretical modeling of the impact of an overlying soft tissue. A semianalytical method and finite-difference time domain simulations were used. The models developed were shown to predict consistently real in vivo data on human radii. As a conclusion, clinical guided wave data are not consistent with in vitro data or related in vitro models, but use of an adequate in vivo model, such as the one introduced here, is necessary. A theoretical model that accounts for the impact of an overlying soft tissue could thus be used in clinical applications.
    No preview · Article · Nov 2008 · The Journal of the Acoustical Society of America
  • Patrick H F Nicholson
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    ABSTRACT: Ultrasound is a mechanical wave and consequently has a unique potential to characterize the mechanical properties of bone. In some applications, such as determination of the anisotropic elastic constants of cortical bone specimens, this potential has been realized. In other applications, including the hugely important field of clinical measurements, current ultrasonic techniques struggle to provide information directly relating to mechanical properties. This article reviews the successes and shortcomings of ultrasound as a tool for determination of bone mechanical properties and highlights those new developments likely to bring progress in the future.
    No preview · Article · Aug 2008 · IEEE transactions on ultrasonics, ferroelectrics, and frequency control
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    ABSTRACT: 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.
    No preview · Article · Apr 2008 · Journal of Clinical Densitometry

  • No preview · Article · Dec 2007
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    ABSTRACT: 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.
    No preview · Article · Nov 2007 · The Journal of the Acoustical Society of America
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    ABSTRACT: 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.
    No preview · Article · Sep 2007 · The Journal of the Acoustical Society of America
  • P.H.F. Nicholson · R Alkalay
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    ABSTRACT: Quantitative ultrasound is in widespread clinical use for assessment of bone quality at peripheral skeletal sites, but has not yet been applied to those sites in the axial skeleton, such as the spine and hip, where osteoporotic fractures are common. Ultrasound measurements were made in 11 cadaveric vertebrae and relationships with bone mineral density and failure load were investigated. An ultrasonic imaging system was used to measure speed of sound, broadband ultrasonic attenuation, and attenuation at a single frequency, through the vertebral body in the sagittal plane. Ultrasonic measurements were averaged over a region of interest centrally within the vertebral body, and were calculated with and without normalization for bone size. Vertebral bone mineral density was measured in antero-posterior and lateral projections using dual energy X-ray absorptiometry. Compressive mechanical testing was performed to determine vertebral failure load. Bone mineral density correlated with failure load (r=0.74-0.78, all P<0.01), and with quantitative ultrasound (r=0.63-0.82, P=0.038-0.004), in line with previous studies. Of the ultrasonic measurements, those parameters not normalized for bone size gave the highest correlations with failure load, ranging from r=0.71 (P=0.021) for speed of sound to r=0.93 (P<0.001) for attenuation. When ultrasonic measurements were normalized for bone size, the correlations with both failure load and bone mineral density were lower. These results confirm the feasibility of vertebral quantitative ultrasound in vitro, and indicate that ultrasound does provide information on both bone mineral density and failure load. The predictive performance of ultrasonic measurements for failure load was comparable to or greater than that of bone mineral density, suggesting that ultrasound has the potential to be at least as useful as mineral density in the assessment of vertebral bone. Normalizing ultrasonic measurements for bone size reduced the strength of correlations because both bone mineral density and bone strength reflect bone size to a certain extent.
    No preview · Article · Jul 2007 · Clinical Biomechanics
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    ABSTRACT: The mechanical environment is considered to be the most important determinant of bone strength. Local muscle force, in turn, is regarded as the largest source of loading applied to bones. However, the effect of weight-bearing on bone mineral accrual is unclear. Comparing the relationship between muscle force and bone mineral content (BMC) in the upper and lower limbs provides a means of investigating this issue. The study group comprised 258 healthy girls aged 10-13 years old at baseline. BMC, lean body mass (LM) and fat body mass (FM) of total body were assessed by dual-energy X-ray absorptiometry at baseline and 2 years after. The maximal isometric voluntary contraction (MVC) of left elbow flexors and knee extensors was evaluated by a dynamometer. A hierarchical linear statistical model with random effects was used to analyze the relationship between BMC and limb-matched MVC. Fisher's z-transformation was used to compare the correlation coefficients between arms and legs. The ratio of BMC to MVC (BMC/MVC) in upper and lower limbs was compared using Student's t-test. BMC was highly correlated with MVC in arms and legs (r(2)=0.54 and 0.50, respectively), and the correlation coefficients did not differ between upper and lower limbs. On the other hand, BMC/MVC was significantly (30%) higher in leg than in arm. The results indicate that local muscle contraction and weight-bearing exert an additive effect on bone mass accretion in the lower limbs. Exercise regimes combining resistance and impact training should provide larger bone response than either one of them alone in growing children.
    Full-text · Article · Jun 2007 · Bone

Publication Stats

3k Citations
263.84 Total Impact Points


  • 2002-2014
    • University of Jyväskylä
      • • Department of Health Sciences
      • • Department of Physics
      Jyväskylä, Province of Western Finland, Finland
  • 2006
    • University of Turku
      • Institute of Biomedicine
      Turku, Varsinais-Suomi, Finland
  • 1998-2002
    • Beth Israel Deaconess Medical Center
      Boston, Massachusetts, United States
  • 1996-1999
    • University of Leuven
      • Department of Mechanical Engineering
      Louvain, Flanders, Belgium
    • Universitair Ziekenhuis Leuven
      • Department of Radiology
      Louvain, Flanders, Belgium
  • 1993-1994
    • Robert Jones and Agnes Hunt Orthopaedic and District Hospital NHS Trust
      Oswestry, England, United Kingdom