DXA-derived Bone Mineral Density Research Articles

Heel Ultrasound Can Assess Maintenance of Bone Mass in Women With Breast Cancer

Postmenopausal women with early stage breast cancer are at increased risk for bone loss and fractures. Bisphosphonates can prevent bone loss, but little data are available on changes in bone mass assessed by heel quantitative ultrasound (QUS). Our objectives were to determine if (1) heel QUS would provide a reliable and accessible method for evaluation of changes in bone mass in women with breast cancer when compared with the current standard of bone mass measurement, dual-energy X-ray absorptiometry (DXA) and (2) oral risedronate could affect these changes. Eighty-six newly postmenopausal (up to 8yr) women with nonmetastatic breast cancer were randomized to risedronate, 35mg once weekly or placebo. Outcomes were changes in heel QUS bone mass measurements and conventional DXA-derived bone mineral density (BMD). Over 2yr, bone mass assessed by heel QUS remained stable in women on risedronate, whereas women on placebo had a 5.2% decrease (p≤0.05) in heel QUS bone mass. Both total hip BMD and femoral neck BMD assessed by DXA decreased by 1.6% (p≤0.05) in the placebo group and remained stable with risedronate. Spine BMD remained stable in both groups. Heel QUS was moderately associated with BMD measured by DXA at the total hip (r=0.50), femoral neck (r=0.40), and spine (r=0.46) at baseline (all p≤0.001). In conclusion, risedronate helps to maintain skeletal integrity as assessed by heel QUS for women with early stage breast cancer. Heel QUS is associated with DXA-derived BMD at other major axial sites and may be used to follow skeletal health and bone mass changes in these women.

Body composition and its components in preterm and term newborns: A cross‐sectional, multimodal investigation

A prospective, cross-sectional, observational study in preterm and term infants was performed to compare multimodal measurements of body composition, namely, limb ultrasound, bone quantitative ultrasound, and dual X-ray absorptiometry (DXA). One hundred and two preterm and term infants appropriate for gestational age were enrolled from the newborn nursery and neonatal intensive care unit. Infants were included when they were medically stable, in an open crib, on full enteral feeds and within 1 week of anticipated discharge. Correlations among the various measurements of body composition were performed using standard techniques. A comparison between preterm infant (born at 28-32 weeks) reaching term to term-born infants was performed. Limb ultrasound estimates of cross-sectional areas of lean and fat tissue in a region of tissue (i.e., the leg) were remarkably correlated with regional and whole-body estimates of fat-free mass and fat obtained from DXA suggesting the potential usefulness of muscle ultrasound as an investigative tool for studying aspects of body composition in this fragile population. There was a weak but significant correlation between quantitative ultrasound measurements of bone strength and DXA-derived bone mineral density (BMD). Preterm infants reaching term had significantly lower body weight, length, head circumference, muscle and fat cross-sectional area, bone speed of sound, whole-body and regional lean body mass, fat mass, and BMD compared to term-born infants. Current postnatal care and nutritional support in preterm infants is still unable to match the in-utero environment for optimal growth and bone development. The use of relatively simple bedside, noninvasive body composition measurements may assist in understanding how changes in different components of body composition early in life affect later growth and development.

Evaluation of trabecular mechanical and microstructural properties in human calcaneal bone of advanced age using mechanical testing, μCT, and DXA

Early detection of fracture risk is important for initiating treatment and improving outcomes from both physiologic and pathologic causes of bone loss. While bone mineral density (a quantity measure) has traditionally been used for this purpose, alternative structural imaging parameters (quality measures) are proposed to better predict bone's true mechanical properties. To further elucidate this, trabecular bone from cadaveric human calcanei were used to evaluate the interrelationship of mechanical and structural parameters using mechanical testing, dual energy X-ray absorptiometry (DXA) scanning, and micro computed tomography (μCT) imaging. Directional specific structural properties were assessed in three-dimensional (3-D) and correlated to mechanical testing and DXA. The results demonstrated that μCT-derived indices of bone quality (i.e., volume fraction and structural model index) are better than DXA-derived bone mineral density for the prediction of the mechanical parameters of bone (i.e., elastic modulus, yield stress, and ultimate stress). Diagnostically, this implies that future work on the early prediction of fracture risk should focus as much on bone quality as on quantity. Furthermore, the results of this study show that a loss of bone primarily affects the connectedness and overall number of trabeculae. Ultimate stress, however, is better correlated with trabecular number than thickness. As such, primary prevention of osteoporosis may be more important than later countermeasures for bone loss.

Pediatric bone density and fracture

As children grow, they accumulate bone mineral, which serves as a "bone bank" for the future. Any condition that interferes with normal bone mineral accrual during childhood has the potential to reduce peak bone mass and subsequently increase future risk for fracture. In contrast to adults, for whom dual-energy x-ray absorptiometry (DXA) has become the standard clinical instrument for assessing bone mineral density and criteria have been developed to define osteopenia and osteoporosis, information for children is still limited. Numerous issues confound the interpretation of DXA-derived bone mineral density measurements in children, and clinicians often find themselves caught between the limitations of these methods and the practical issue of taking care of their pediatric patient. The explosion of treatment options for postmenopausal osteoporosis has resulted in new options for the treatment of children and adolescents. However, most of these agents have not been sufficiently well studied in children to permit the development of standardized treatment guidelines.

A phase II report of longitudinal bone marker time trends in racially diverse prostate cancer patients receiving zoledronic acid with androgen deprivation

14568 Background: Evidence for preventing androgen deprivation (AD) induced osteoporosis with bisphosphonate therapy in prostate cancer patients has emerged largely from trials conducted in caucasian patients. Osteoporosis related skeletal event incidence in African Americans (AA) receiving AD is significantly lower than caucasians and the effect of bisphosphonates therapy uncertain. We conducted a prospective study to evaluate the efficacy of zoledronic acid in preventing osteoporosis in racially diverse population receiving AD. Methods: Asymptomatic, prostate cancer patients (16 caucasians and 6 AA) with normal renal function undergoing AD, started within the last 9 months were randomized to receive (Arm A) CaCO3/vitamin D (500 mg/200U TID) or (Arm B) CaCO3/vitamin D and zoledronic acid (4 mg IV every 3 months for a year). Bone turnover markers including urine N-telopeptide, serum osteocalcin, serum bone specific alkaline phosphatase(BsAP) were serially measured every 3 months and bone mineral density (BMD) measured by DXA at hip, femur, spine and ward’s triangle at 0, 6 and 15 month intervals. Primary endpoint was to obtain BMD changes and bone turnover rates for each treatment arm. Nonparametric methods for analyzing longitudinal data were used to compare DXA-derived BMD measures and bone turnover rate markers in patients receiving zoledronic acid to the control group. Results: Data is presented for 16/22 patients who have completed 15- month follow up. Time trend analysis of bone formation (BsAP, osteocalcin) and resorption (N-telopeptide) markers and DXA measurements of BMD (spine and hip) are shown in the table. Conclusions: This study suggests that zoledronic acid preserves BMD at spine in racially diverse patients and, likewise provides preliminary estimates of BMD changes that occur over 15 months in patients receiving zoledronic acid and placebo. Larger AA cohorts are needed for prospective validation of the observed effect with zoledronic acid. [Table: see text] [Table: see text]

In vivo short-term precision of hip structure analysis variables in comparison with bone mineral density using paired dual-energy X-ray absorptiometry scans from multi-center clinical trials

Hip structural analysis (HSA) is a technique for extracting strength-related structural dimensions of bone cross-sections from two-dimensional hip scan images acquired by dual energy X-ray absorptiometry (DXA) scanners. Heretofore the precision of the method has not been thoroughly tested in the clinical setting. Using paired scans from two large clinical trials involving a range of different DXA machines, this study reports the first precision analysis of HSA variables, in comparison with that of conventional bone mineral density (BMD) on the same scans. A key HSA variable, section modulus ( Z), biomechanically indicative of bone strength during bending, had a short-term precision percentage coefficient of variation (CV%) in the femoral neck of 3.4–10.1%, depending on the manufacturer or model of the DXA equipment. Cross-sectional area (CSA), a determinant of bone strength during axial loading and closely aligned with conventional DXA bone mineral content, had a range of CV% from 2.8% to 7.9%. Poorer precision was associated with inadequate inclusion of the femoral shaft or femoral head in the DXA-scanned hip region. Precision of HSA-derived BMD varied between 2.4% and 6.4%. Precision of DXA manufacturer-derived BMD varied between 1.9% and 3.4%, arising from the larger analysis region of interest (ROI). The precision of HSA variables was not generally dependent on magnitude, subject height, weight, or conventional femoral neck densitometric variables. The generally poorer precision of key HSA variables in comparison with conventional DXA-derived BMD highlights the critical roles played by correct limb repositioning and choice of an adequate and appropriately positioned ROI.

Evaluation of Bone Mineral Density in Children with Sickle Cell Anemia.

Background : Reduced bone mineral density (BMD) has been reported in adults and children with sickle cell anemia (SCA). Dual energy x-ray absorptiometry (DXA) is routinely used for measuring BMD because of less radiation exposure and lower cost. However, changes in vertebral body shape, marrow hyperplasia and bone infarction due to SCA may affect the evaluation of BMD with DXA. Hence, we compared DXA with quantitative computerized tomography (QCT), which measures true volumetric density, and may be less influenced by bone changes.Methods : The study enrolled children between 9–19 years of age with SCA, and one or more severe manifestations: >2 hospital admissions/year, growth failure, avascular necrosis, or regular red cell transfusions for sickle cell-related complications. BMD of lumbar spine was determined by performing DXA of lumbar spine (Hologic Delphi-A, Bedford, MA). The apparent volumetric bone mineral density (BMAD) was calculated from bone mineral content, and compared to age, sex and ethnicity-matched reference data. BMD of the lumbar spine was also measured by QCT (Mindways Software, San Francisco, CA), and compared to age and sex-appropriate reference data.Results : The study has enrolled 25 patients (13 females and 12 males), of which 16 were younger than 14 years. In 6 children the height was <10th centile for age. Thirteen patients were on regular transfusions for >6 months, including 10 who had been transfused for >2 years. Calcium intake, assessed by a standardized questionnaire, was less than recommended dietary allowance in 13 patients.The z-score for BMAD determined by DXA was > −1.0 in 8, between −1.0 and −2.0 in 5, and < −2.0 in 12 patients. The z-score for lumbar spine by QCT was > −1.0 in 20, between −1.0 and −2.0 in 1 and < −2.0 in 4 patients. DXA-derived BMD (areal density) and BMAD (apparent volumetric density) z-scores did not differ significantly (p=0.16). On the other hand, the paired values of z-scores by DXA (BMAD) and QCT were significantly different (p=.002). When z-scores were categorized as greater or less than −1.0, the results were concordant in 13 (both DXA and QCT normal in 8, and both DXA and QCT abnormal in 5), and discordant in 12 cases (abnormal DXA with normal QCT in every case). Among patients in discordant group, 9/12 had been on regular red cell transfusions for >6 months, compared to 4/13 with concordant results (p=.047). There was no difference in the serum ferritin values between the two groups (p=.685).No significant difference in the prevalence of low BMAD z-scores was detected between groups based upon age, calcium intake, or growth failure. Five out of the 12 patients with BMAD z-score < −2.0 were not on regular transfusion program.Conclusions : Almost half of the children with SCA had BMD below −2 standard deviations compared to age-matched controls. Low BMD was observed in chronically transfused as well as non-transfused children. In comparison, 16% of the patients were classified as low BMD (z < −2.0) by QCT. The paired DXA/QCT results were discordant in half of the sample, with patients on regular transfusions for >6 months more likely to have normal QCT results. It is likely that the reduction in marrow hyperplasia following initiation of regular transfusions may disproportionately affect the trabecular BMD measured by QCT. Longitudinal evaluation of BMD in patients starting on transfusion program could help to define the effect of transfusions on measures of BMD in SCA.

Abnormal bone collagen morphology and decreased bone strength in growth hormone-deficient rats

Patients with growth hormone deficiency (GHD) have an increased risk of bone fractures. In these patients, the well-described decrease in bone mineral density (BMD) and content (BMC) may, however, not alone explain the increase in fracture rate. Accordingly, the aim of this study was to evaluate collagen morphology and bone mineralisation in cortical bone as well as bone strength in GHD rats to try to clarify the explanation for the increased fracture rate. The Dw-4 rat was used as a model for GHD. This strain of rats has an autosomal recessive disorder, reducing GH synthesis to approximately 10% and growth rate to approximately 40–50% when compared to normal control rats. Five male Dw-4 rats were examined at age 12 weeks and five healthy Lewis rats served as age-matched controls. The animals were examined for (1) bone mineral status by dual energy X-ray absorptometry (DXA) and ash weight/bone volume, (2) biomechanical properties, (3) serum insulin-like growth factor I (IGF-I) and IGF binding protein 3 (IGFBP-3), and (4) collagen morphology of cortical bone from the right femurs was examined by scanning and transmission electron microscopy. A significant decrease was found in serum IGF-I, IGFBP-3 and biomechanical properties in GHD rats compared to controls ( P < 0.009). While DXA-derived BMD was decreased, no significant difference was found in ash weight/bone volume. Electron microscopy showed a significant decrease in the number and a significant increase in the diameter of collagen microfibrils in GHD rats as compared to their controls ( P < 0.009). In conclusion, we report for the first time that collagen morphology in bone is markedly altered in rats with isolated GHD. Whether similar conditions are present in GHD patients need further investigations. The changes described, however, may provide a co-explanation for the increased fracture rate in GHD.

Inaccuracies inherent in dual-energy X-ray absorptiometry in vivo bone mineral densitometry may flaw osteopenic/osteoporotic interpretations and mislead assessment of antiresorptive therapy effectiveness

New, anatomically realistic simulation studies based on a cadaveric lumbar vertebra and a broad range of soft tissue anthropometric representations have quantitatively delineated inaccuracies inherent in dual-energy X-ray absorptiometry (DXA) in vivo bone mineral density (BMD) methodology. It is found that systematic inaccuracies in DXA BMD measurements may readily exceed ±20% at typical in vivo lumbar vertebral sites, especially for osteopenic/osteoporotic, postmenopausal, and elderly patients. These findings are quantitatively compared with extensive clinical evidence of strong, positive correlations between soft tissue anthropometrics and DXA in vivo BMD upon which prior significant bone biology interpretations and implications have been based. The agreement is found to be both qualitatively and quantitatively excellent. Moreover, recent extensive multicenter clinical studies have also exposed new facets of strong linkages between body mass/percent body fat/body mass index (BMI) and DXA-measured BMD that are particularly relevant to osteopenia/osteoporosis and remedial effectiveness of antiresorptive drug therapy. These seemingly disparate and unrelated diagnostic and prognostic aspects of clinically observed associations between soft tissue anthropometrics and measured vertebral BMD are, in this study, self-consistently shown to share the common origin of being manifestations of systematic inherent inaccuracies in DXA in vivo BMD methodology, without the need to invoke any underlying biologically causal mechanism(s). These inaccuracies arise principally from absorptiometric disparities between the intra- and extraosseous soft tissues within the DXA scan region of interest. The present evaluative comparisons are based exclusively on an incisive and diverse body of clinical data that appears difficult to dismiss or discount. Previous invocations of biologically causal mechanisms responsible for this broad range of observations linking body mass, percent body fat, and/or BMI to measured BMD now appear questionable. This doubtful status has also been extended in the present work to previously reported relationships between antiresorptive therapies and observed changes in DXA-derived BMD. These findings strongly indicate that critical and insightful reassessments of diagnostic/prognostic imputations underpinned by DXA in vivo BMD measurements are warranted. It is suggested that a good deal of what is known of bone fragility, bone densitometry, antiresorptive drug efficacy, and/or other therapeutic regimens, if based on patient-specific in vivo DXA methodology, may prove to be equivocal and tenuous.

Analytic and quantitative exposition of patient-specific systematic inaccuracies inherent in planar DXA-derived in vivo BMD measurements.

An extensive analytic exposition is developed of systematic inaccuracies inherent in planar dual-energy x-ray absorptiometry (DXA) in vivo bone mineral density (BMD) measurements arising directly from the dual-energy facet of this methodology. Generalized and specific criteria governing these BMD inaccuracies are derived for the presence of relevant absorptiometrically distinguishable extra- and intra-osseous soft tissues (lean muscle tissue, interposed adipose, marrow, and cerebrospinal fluid). These analytic findings are utilized in comprehensive quantitative simulation studies which evaluate the magnitude and stipulate the direction (under- or over-estimate) of such systematic errors for typical, realistic DXA in vivo lumbar vertebral BMD scans over the ranges of soft tissue parameters and trabecular bone volumes (TBV) encountered clinically. It is shown that inherent systematic inaccuracies as high as +/- approximately 20% may be anticipated in typical patient-specific planar DXA vertebral BMD scans, particularly so for older, osteoporotic-prone, and osteoporotic individuals. These inaccuracies exceed considerably the DXA precision error and may mask or exaggerate clinically significant true changes in BMD. Both the scale and trends of patient-specific inaccuracies found to pertain in the present work are in keeping with those observed by recent investigators in actual specimen-specific in situ and in vitro DXA scans of given cadaveric bones. Insofar as the range of BMD inaccuracies found here is comparable to that of variations in the DXA-measured interpatient, age-moderated BMD of normal individuals, the intrinsic specificity of planar DXA for screening/diagnostic purposes is examined critically. It is shown that these inherent inaccuracies may prompt erroneous diagnoses, assessments, and interpretations of DXA-derived BMD measurements undertaken to screen, monitor, and help evaluate patient-specific predictive bone fragility, and to assess the efficacy of drug and other therapeutic regimens.