Bone Quality Measured Using Calcaneal Quantitative Ultrasonography Is Reduced Among Children with HIV in Johannesburg, South Africa.

We evaluated bone quality among South African children with HIV over a 2-year period by quantitative ultrasound (QUS). Children with HIV have persistently lower bone quality compared with controls reflecting increased porosity, reduced strength, and possibly an increased short- and long-term risk of fracture.

Comparison of quantitative ultrasonography and dual X-ray absorptiometry for bone status assessment in South African children living with HIV.

Children living with HIV (CLHIV) have decreased bone mineral content (BMC) and density (BMD), increasing risk for fracture and future osteoporosis. While DXA is the gold-standard for bone assessments, it lacks availability in resource-constrained settings (RCS). Quantitative ultrasound (QUS) offers an alternative owing to its portability, low cost, ease of handling, and lack of ionizing radiation. While QUS has detected reduced bone quality in CLHIV, the relationship between QUS and DXA in this population remains unexplored. At baseline and 12 months, BMC and BMD of the whole body, lumbar spine, and radius were measured by DXA in a longitudinal cohort of CLHIV in Johannesburg, South Africa. Calcaneal speed of sound (SOS) and broadband ultrasound attenuation (BUA) and radius SOS were obtained by QUS, and calcaneal stiffness index (SI) was calculated. Spearman correlations, with and without HIV stratification, were performed between QUS and DXA measurements at each visit and for absolute difference in measurements between visits. At baseline and 12-months, calcaneal BUA and SI displayed strong positive correlations with DXA, with only modest correlations between radial QUS and DXA at baseline. Longitudinal measures of QUS did not correlate with DXA. At both baseline and 12-months, individuals with DXA whole-body BMD z-score < -1 displayed significantly lower calcaneal BUA and SI. Cross-sectionally, calcaneal QUS correlates strongly with whole body DXA and may represent a viable diagnostic alternative in RCS. Longitudinally, the two methods do not correlate well, possibly reflecting that each method assesses distinct aspects of bone architecture.

Ultrasound simulation in the distal radius using clinical high-resolution peripheral-CT images.

The overall objective of this research is to develop an ultrasonic method for noninvasive assessment of the distal radius. The specific objective of this study was to examine the propagation of ultrasound through the distal radius and determine the relationships between bone mass and architecture and ultrasound parameters. Twenty-six high-resolution peripheral-CT clinical images were obtained from a set of subjects that were part of a larger study on secondary osteoporosis. A single midsection binary slice from each image was selected and used in the two-dimensional (2D) simulation of an ultrasound wave propagating from the anterior to the posterior surfaces of each radius. Mass and architectural parameters associated with each radius, including total (trabecular and cortical) bone mass, trabecular volume fraction, trabecular number and trabecular thickness were computed. Ultrasound parameters, including net time delay (NTD), broadband ultrasound attenuation (BUA) and ultrasound velocity (UV) were also evaluated. Significant correlations were found between NTD and total bone mass (R2 = 0.92, p < 0.001), BUA and trabecular number (R2 = 0.78, p < 0.01) and UV and trabecular bone volume fraction (R2 = 0.82, p < 0.01). There was only weak, statistically insignificant correlation (R2 < 0.14, p = 0.21) found between trabecular thickness and any of the ultrasound parameters. The study shows that ultrasound measurements are correlated with bone mass and architecture at the distal radius and, thus, ultrasound may prove useful as a method for noninvasive assessment of osteoporosis and fracture risk.

Quantitative ultrasound in the management of osteoporosis: the 2007 ISCD Official Positions.

Dual-energy X-ray absorptiometry (DXA) is commonly used in the care of patients for diagnostic classification of osteoporosis, low bone mass (osteopenia), or normal bone density; assessment of fracture risk; and monitoring changes in bone density over time. The development of other technologies for the evaluation of skeletal health has been associated with uncertainties regarding their applications in clinical practice. Quantitative ultrasound (QUS), a technology for measuring properties of bone at peripheral skeletal sites, is more portable and less expensive than DXA, without the use of ionizing radiation. The proliferation of QUS devices that are technologically diverse, measuring and reporting variable bone parameters in different ways, examining different skeletal sites, and having differing levels of validating data for association with DXA-measured bone density and fracture risk, has created many challenges in applying QUS for use in clinical practice. The International Society for Clinical Densitometry (ISCD) 2007 Position Development Conference (PDC) addressed clinical applications of QUS for fracture risk assessment, diagnosis of osteoporosis, treatment initiation, monitoring of treatment, and quality assurance/quality control. The ISCD Official Positions on QUS resulting from this PDC, the rationale for their establishment, and recommendations for further study are presented here.

A portable real-time ultrasonic bone densitometer.

The objectives of this study were to develop a novel ultrasound device to estimate bone mineral density (BMD) at the calcaneus. The device is entirely self-contained, portable (or=0.9), effectively making the former parameter a proxy for the latter. In conclusion, although X-ray methods are effective in bone mass assessment, osteoporosis remains one of the largest undiagnosed and under-diagnosed diseases in the world today. The research described here, in conjunction with the fact that the devices are designed to be manufactured at very low cost (approximately $400 USD), should enable the significant expansion of diagnosis and monitoring of osteoporosis.

Unusually High Calcaneal Speed of Sound Measurements in Children with Small Foot Size.

The purpose of this clinical note is to describe the performance of the Lunar Achilles Insight device in assessing bone quality at the calcaneus in 142 children between the ages of 5 and 11 y accessing healthcare in Johannesburg, South Africa. We observed an asymmetric bimodal distribution in speed of sound (SOS). The minor mode consisted of unusually high SOS values (≥1625 m/s), which were primarily observed among children with foot size <19 cm and height <119 cm. Cortical regions of the bone may have been inadvertently included in the region of interest for smaller feet, causing unusually high SOS values. The unusually high SOS values indicate that the validity of SOS in this device, as it is currently used for measuring bone quality in young children, is questionable. Future studies using this device in young children should develop new methodology to account for smaller foot size.

Efavirenz is associated with higher bone mass in South African children with HIV.

BACKGROUND: We investigate if switching from a ritonavir-boosted lopinavir (LPV/r)-based to an efavirenz-based antiretroviral therapy (ART) regimen is associated with beneficial bone development. METHODS: The CHANGES Bone Study follows HIV-infected children who participated in a noninferiority randomized trial in Johannesburg, South Africa evaluating the safety and efficacy of preemptive switching to efavirenz (n = 106) compared with remaining on LPV/r (n = 113). HIV-uninfected children were also recruited. Whole-body and lumbar spine bone mineral content (BMC) were assessed by dual-energy X-ray absorptiometry at a cross-sectional visit. BMC Z-scores adjusted for sex, age, and height were generated. Physical activity and dietary intake were assessed. CD4 percentage and viral load were measured. We compared bone indices of HIV-infected with HIV-uninfected children and LPV/r with efavirenz by intent-to-treat. RESULTS: The 219 HIV-infected (52% boys) and 219 HIV-uninfected (55% boys) children were 6.4 and 7.0 years of age, respectively. Mean ART duration for HIV-infected children was 5.7 years. Whole-body BMC Z-score was 0.17 lower for HIV-infected children compared with HIV-uninfected children after adjustment for physical activity, dietary vitamin D and calcium (P = 0.03). Whole-body BMC Z-score was 0.55 higher for HIV-infected children switched to efavirenz compared with those remaining on LPV/r after adjustment for physical activity, dietary vitamin D and calcium, CD4 percentage, and viral load (P < 0.0001). CONCLUSION: South African HIV-infected children receiving ART have lower bone mass compared with HIV-uninfected controls. Accrued bone mass is positively associated with switching to efavirenz-based ART compared with remaining on LPV/r, providing additional rationale for limiting LPV/r exposure once viral suppression has been achieved.

Clinical assessment of the 1/3 radius using a new desktop ultrasonic bone densitometer.

The objectives of this study were to evaluate the capability of a novel ultrasound device to clinically estimate bone mineral density (BMD) at the 1/3 radius. The device rests on a desktop and is portable, and permits real-time evaluation of the radial BMD. The device measures two net time delay (NTD) parameters, NTD(DW) and NTD(CW). NTD(DW) is defined as the difference between the transit time of an ultrasound pulse to travel through soft-tissue, cortex and medullary cavity, and the transit time through soft tissue only of equal overall distance. NTD(CW) is defined as the difference between the transit time of an ultrasound pulse to travel through soft-tissue and cortex only, and the transit time through soft tissue only again of equal overall distance. The square root of the product of these two parameters is a measure of the radial BMD at the 1/3 location as measured by dual-energy X-ray absorptiometry (DXA). A clinical IRB-approved study measured ultrasonically 60 adults at the 1/3 radius. BMD was also measured at the same anatomic site and time using DXA. A linear regression using NTD produced a linear correlation coefficient of 0.93 (p < 0.001). These results are consistent with previously reported simulation and in vitro studies. In conclusion, although X-ray methods are effective in bone mass assessment, osteoporosis remains one of the largest undiagnosed and under-diagnosed diseases in the world today. The research described here should enable significant expansion of diagnosis and monitoring of osteoporosis through a desktop device that ultrasonically assesses bone mass at the 1/3 radius.

A poisson process model for hip fracture risk.

The primary method for assessing fracture risk in osteoporosis relies primarily on measurement of bone mass. Estimation of fracture risk is most often evaluated using logistic or proportional hazards models. Notwithstanding the success of these models, there is still much uncertainty as to who will or will not suffer a fracture. This has led to a search for other components besides mass that affect bone strength. The purpose of this paper is to introduce a new mechanistic stochastic model that characterizes the risk of hip fracture in an individual. A Poisson process is used to model the occurrence of falls, which are assumed to occur at a rate, lambda. The load induced by a fall is assumed to be a random variable that has a Weibull probability distribution. The combination of falls together with loads leads to a compound Poisson process. By retaining only those occurrences of the compound Poisson process that result in a hip fracture, a thinned Poisson process is defined that itself is a Poisson process. The fall rate is modeled as an affine function of age, and hip strength is modeled as a power law function of bone mineral density (BMD). The risk of hip fracture can then be computed as a function of age and BMD. By extending the analysis to a Bayesian framework, the conditional densities of BMD given a prior fracture and no prior fracture can be computed and shown to be consistent with clinical observations. In addition, the conditional probabilities of fracture given a prior fracture and no prior fracture can also be computed, and also demonstrate results similar to clinical data. The model elucidates the fact that the hip fracture process is inherently random and improvements in hip strength estimation over and above that provided by BMD operate in a highly "noisy" environment and may therefore have little ability to impact clinical practice.

Ultrasound simulation in bone.

The manner in which ultrasound interacts with bone is of key interest in therapy and diagnosis alike. These may include applications directly to bone, as, for example, in treatment to accelerate the healing of bone fractures and in assessment of bone density in osteoporosis, or indirectly in diagnostic imaging of soft tissue with interest in assessing exposure levels to nearby bone. Because of the lack of analytic solutions to virtually every "practical problem" encountered clinically, ultrasound simulation has become a widely used technique for evaluating ultrasound interactions in bone. This paper provides an overview of the use of ultrasound simulation in bone. A brief description of the mathematical model used to characterize ultrasound propagation in bone is first provided. A number of simulation examples are then presented that explain how simulation may be utilized in a variety of practical configurations. The focus of this paper in terms of examples presented is on diagnostic applications in bone, and, in particular, for assessment of osteoporosis. However, the use of simulation in other areas of interest can easily be extrapolated from the examples presented. In conclusion, this paper describes the use of ultrasound simulation in bone and demonstrates the power of computational methods for ultrasound research in general and tissue and bone applications in particular.

Ultrasonic assessment of the radius in vitro.

The overall objective of this research is to develop an ultrasonic system for noninvasive assessment of the distal radius. The specific objective of this study was to examine the relationship between geometrical features of cortical bone and ultrasound measurements in vitro. Nineteen radii were measured in through transmission in a water bath. A 3.5 MHz rectangular (1 cm x 4.8 cm) single element transducer served as the source and a 3.5 MHz rectangular (1 cm x 4.8 cm) linear array transducer served as the receiver. The linear array consisted of 64 elements with a pitch of 0.75 mm. Ultrasound measurements were carried out at a location that was 1/3rdrd of the length from the distal end of each radius and two net time delay parameters, tau(NetDW) and tau(NetCW), associated with a direct wave (DW) and a circumferential wave (CW), respectively, were evaluated. The cortical thickness (CT), medullar thickness (MT) and cross-sectional area (CSA) of each radius was also evaluated based on a digital image of the cross-section at the 1/3rd location. The linear correlations between CT and tau(NetDW) was r = 0.91 (p < 0.001) and between MT and tau(NetCW) - tau(NetDW) was r = 0.63 (p < 0.05). The linear correlation between CSA and a nonlinear combination of the two net time delays, tau(NetDW) and tau(NetCW), was r = 0.95 (p < 0.001). The study shows that ultrasound measurements can be used to noninvasively assess cortical bone geometrical features in vitro as represented by cortical thickness, medullar thickness and cross-sectional area.

Caracterizaçäo ultra-sônica de osso trabecular humano e animal: um estudo comparativo / Human and animal ultrasonic characterization of human trabecular bone: a comparative study

Este trabalho investigou se o osso trabecular bovino é um bom modelo para se investigar a caracterização ultra-sônica de osso trabecular humano.

This study assess if bovine trabecular bone is a good model to investigate the ultrasonic characterization of human trabecular bone.