DXA-based Bone Mineral Density Research Articles

Bone density in postmenopausal women with scoliosis is associated with markers of degenerative joint disease.

Bone mineral density (BMD) measured with dual x-ray absorptiometry (DXA) is the clinical standard for the diagnosis of osteoporosis and prediction of bone fracture risk. In the aging skeleton, osteoporosis is often concomitantly present with degenerative joint disease (DJD). In this study, we evaluated tissue-level changes in the differentially loaded concave (CC) and convex (CV) sides of the lumbar spine in a sample of postmenopausal women with scoliosis. We used a cumulative degeneration score to assess osteophyte formation, the severity of sclerotic morphology, and marrow changes as markers of DJD in the lumbar spine and examined the correlation between markers of DJD and BMD. More severe osteophyte growth and sclerosis were present on the CC side of the spine. The degenerative score (DS) was higher on the CC side of the lumbar spine compared with the CV side. While CC BMD was positively correlated with CC DS and marrow, CV DS was not correlated with CV BMD. Marrow changes were correlated with DS on the CC lumbar spine. These results highlight the importance of mechanoadaptive as well as broader inflammatory processes in the manifestation of degenerative changes and local mineral deposition at the lumbar spine. DXA-based BMD measurement of osteoporosis need to be contextualized within the biomechanical and degenerative conditions of a joint rather than using a strict threshold cutoff.

A243 BONE MINERAL DENSITY AND DIETARY BONE NUTRIENTS DIFFER IN PATIENTS WITH CROHN'S DISEASE STRICTURES

Abstract Background Crohn’s disease (CD) phenotypes include inflammatory (non-stricture) and stricture behaviours. Strictures are bowel narrowing’s that may lead to obstructions and subsequent dietary restrictions to prevent blockages. Bone mineral density (BMD) in CD is affected by many factors including corticosteroid use, CD itself, but also dietary changes. Clinical gold standard for measuring BMD is by dual x-ray absorptiometry (DXA) scans. High-resolution peripheral quantitative computed tomography (HR-pQCT), a more precise imaging modality assesses volumetric BMD, bone geometry and bone microarchitecture. We aim to compare dietary intake, and bone quality in both stricture and non-stricture CD. Aims To identify nutritional patterns, bone quality differences and deficiencies between two subtypes of CD; including energy intake, dietary components and/or micronutrients Methods Individuals (≥55 years old) with ileal CD strictures (fixed, angulated bowel or thickened bowel with pre-stenotic dilation on diagnostic imaging), or inflammatory CD were prospectively recruited. Patients with short gut, celiac disease, dysphagia history were excluded. All patients completed DXA hip and spine scans and HR-pQCT radius and tibia scans. Dietary assessment questionnaires (Automated Self-Administered 24-hour Dietary Assessment Tool (ASA24), and Diet History Questionnaire III for food frequency over the past year were completed. Results 56 (27 inflammatory (48% female, mean age 64.2, BMI 28.7, 16 years CD duration) and 29 strictures (45% female, mean age 65.9, BMI 27.3, 25 years CD duration, 15 (51.7%) prior bowel resection) were included. 31/56 (55.4%) patients were on biologics and 11 (19.5%) had past corticosteroid exposure. DXA-based BMD for stricture versus non-stricture CD patients was not significantly different at the hip or spine. However, HR-pQCT-based radial total BMD (p=0.03), cortical thickness (p=0.01) and cortical area (p=0.04) were lower in stricture than non-stricture patients.11 (7 stricture, 4 inflammatory) patients with past steroids consumed more dairy (p=0.01), vitamin D (p = 0.04), and calcium (p=0.03) than other CD patients. Stricture patients had significantly less consumption of vitamin K (p=0.001), vegetables (p=0.02), calcium (p=0.03), and dairy (p=0.03). Conclusions Patients with CD strictures have lower BMD and cortical bone quality at the radius than those without strictures. Patients with CD strictures also consume significantly less vitamin K, calcium, and dairy, all vital dietary components to prevent OP, compared to non-stricture patients. Overall, the skeletal fracture risk is likely much greater in CD patients with strictures than without, due to greater inherent bone fragility, and less consumption of key nutrition building blocks of bones. Funding Agencies Koopmans Memorial Research Fund

Opportunistic CT-Based Hounsfield Units Strongly Correlate with Biomechanical CT Measurements in the Thoracolumbar Spine.

Retrospective cohort study. Hounsfield units (HUs) are known to correlate with clinical outcomes, but no study has evaluated how they correlate with biomechanical computed tomography (BCT) and dual-energy x-ray absorptiometry (DXA) measurements. Low bone mineral density (BMD) represents a major risk factor for fracture and poor outcomes following spine surgery. DXA can provide regional BMD measurements but has limitations. Opportunistic HUs provide targeted BMD estimates; however, they are not formally accepted for diagnosing osteoporosis in current guidelines. More recently, BCT analysis has emerged as a new modality endorsed by the International Society for Clinical Densitometry for assessing bone strength. Consecutive cases from 2017 to 2022 at a single institution were reviewed for patients who underwent BCT in the thoracolumbar spine. BCT-measured vertebral strength, trabecular BMD, and the corresponding American College of Radiology Classification were recorded. DXA studies within three months of the BCT were reviewed. Pearson Correlation Coefficients were calculated, and receiver-operating characteristic curves were constructed to assess the predictive capacity of HUs. Threshold analysis was performed to identify optimal HU values for identifying osteoporosis and low BMD. Correlation analysis of 114 cases revealed a strong relationship between HUs and BCT vertebral strength ( r =0.69; P <0.0001; R2 =0.47) and trabecular BMD ( r =0.76; P <0.0001; R2 =0.58). However, DXA poorly correlated with opportunistic HUs and BCT measurements. HUs accurately predicted osteoporosis and low BMD (Osteoporosis: C =0.95, 95% CI 0.89-1.00; Low BMD: C =0.87, 95% CI 0.79-0.96). Threshold analysis revealed that 106 and 122 HUs represent optimal thresholds for detecting osteoporosis and low BMD. Opportunistic HUs strongly correlated with BCT-based measures, while neither correlated strongly with DXA-based BMD measures in the thoracolumbar spine. HUs are easy to perform at no additional cost and provide accurate BMD estimates at noninstrumented vertebral levels across all American College of Radiology-designated BMD categories.

Prediction of proximal femur fracture risk from DXA images based on novel fracture indexes

ABSTRACT Background: Osteoporosis is the degradation of bone microstructure that increase proximal femur risk of fracture. Current fracture prediction methods are based on the analysis of bone mineral density (BMD). Nevertheless, it has been shown that BMD alone cannot predict with certainty who will have a future hip fracture. The aim of this study was to develop a novel proximal femur fracture index approach including patient-specific geometrical and mechanical properties data to assess the femoral neck fracture risk. Methods: The patient-specific femoral neck geometry and data for the analysis were obtained from DXA scans. The fracture index was built based on a mechanical description of the fracture occurrence under a side fall impact. Results: The current approach predicts with a very good accuracy the fracture risk (TPR = 78%, TNR = 81%) and provided a good agreement with the experimental data, while the DXA-based BMD was less accurate (TPR = 60%, TNR = 56). Our predicted results showed that the proposed bone fracture index, may provide an enhanced diagnostic of proximal fracture risk diagnostic. Conclusions: The index developed here may be used in clinical applications as an enhanced tool to predict fracture risk and contribute to osteoporosis diagnosis based on DXA.

MRI-Based Quantitative Osteoporosis Imaging at the Spine and Femur.

Osteoporosis is a systemic skeletal disease with a high prevalence worldwide, characterized by low bone mass and microarchitectural deterioration, predisposing an individual to fragility fractures. Dual-energy X-ray absorptiometry (DXA) has been the clinical reference standard for diagnosing osteoporosis and for assessing fracture risk for decades. However, other imaging modalities are of increasing importance to investigate the etiology, treatment, and fracture risk. The purpose of this work is to review the available literature on quantitative magnetic resonance imaging (MRI) methods and related findings in osteoporosis at the spine and proximal femur as the clinically most important fracture sites. Trabecular bone microstructure analysis at the proximal femur based on high-resolution MRI allows for a better prediction of osteoporotic fracture risk than DXA-based bone mineral density (BMD) alone. In the 1990s, T2 * mapping was shown to correlate with the density and orientation of the trabecular bone. Recently, quantitative susceptibility mapping (QSM), which overcomes some of the limitations of T2 * mapping, has been applied for trabecular bone quantifications at the spine, whereas ultrashort echo time (UTE) imaging provides valuable surrogate markers of cortical bone quantity and quality. Magnetic resonance spectroscopy (MRS) and chemical shift encoding-based water-fat MRI (CSE-MRI) enable the quantitative assessment of the nonmineralized bone compartment through extraction of the bone marrow fat fraction (BMFF). Furthermore, CSE-MRI allows for the differentiation of osteoporotic vs. pathologic fractures, which is of high clinical relevance. Lastly, advanced postprocessing and image analysis tools, particularly considering statistical parametric mapping and region-specific BMFF distributions, have high potential to further improve MRI-based fracture risk assessments at the spine and hip. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY STAGE: 2.

A new corrective model to evaluate TBS in obese post-menopausal women: a cross-sectional study

The relationship between post-menopausal osteoporosis and obesity has been mainly investigated using bone mineral density (BMD) as marker of bone health. Since BMD does not reflect bone microarchitecture, another analytical tool, the Trabecular Bone Score (TBS), has been recently developed for this purpose. In this study, we intended to investigate the validity of TBS as marker of bone quality in obese post-menopausal women. Three hundred fifty-two post-menopausal women were consecutively enrolled in the study and underwent anthropometric and dual-energy X-ray absorptiometry (DXA) examination. DXA-based BMD was used to classify subjects into osteoporotic (9%), osteopenic (58%), and controls (33%) categories. As TBS is sometimes sensitive to the effects of increased image noise with higher BMI, a corrected version of the TBS (TBS*) was also used to assess bone microarchitecture quality in this cohort. As expected, BMI was positively and negatively related to total BMD (r = 0.22, p < 0.0001) and TBS (r = - 0.12, p < 0.05), respectively. TBS* was found positively and significantly correlated with femoral neck BMD (r = 0.40, p < 0.001), total hip (r = 0.33, p < 0.001) and lumbar spine BMD (r = 0.50, p < 0.001). TBS, once removed the effect of BMI, can serve as a good surrogate maker of bone microarchitecture in obese post-menopausal women in addition to BMD.

Use of Bioelectrical Impedance Analysis for the Measurement of Appendicular Skeletal Muscle Mass/Whole Fat Mass and Its Relevance in Assessing Osteoporosis among Patients with Low Back Pain: A Comparative Analysis Using Dual X-ray Absorptiometry.

Study DesignCross-sectional observational study.PurposeTo compare measurements of appendicular skeletal muscle mass (ASMM) and whole fat mass (WFM) obtained using dualenergy X-ray absorptiometry (DXA) and bioelectrical impedance analysis (BIA) among patients with low back pain (LBP). Moreover, the study investigated the correlation between BIA-based ASMM and DXA-based bone mineral density (BMD).Overview of the LiteratureIf reliable, BIA may be a useful alternative to DXA as a screening tool for sarcopenia and osteoporosis among patients with LBP.MethodsMeasurements were performed in 130 patients, including BMD of the lumbar spine and femoral neck. The correlation between DXA and BIA as well as between BIA-ASMM and BMD were evaluated.ResultsBIA and DXA were highly correlated in both male and female patients (r =0.73–0.90, p <0.0001). However, BIA consistently overestimated ASMM by 1.5–2.5 kg on an average (p <0.0001) and underestimated WFM (−4.0 to −2.7 kg) on an average (p <0.0001). BIA-based ASMM correlated with BMD of the lumbar spine in both male and female patients (r =0.28–0.37, p ≤0.02) and that of the femoral neck (r =0.34–0.51, p ≤0.005). Regarding the calculated skeletal muscle index (SMI: ASMM/height [m2]) used as a criterion for sarcopenia, BIA-based SMI correlated with BMD of the lumbar spine in male patients (r =0.44, p =0.0004) and that of the femoral neck in female patients (r =0.33, p =0.009).ConclusionsBIA may be a favorable alternative to DXA as a screening tool for sarcopenia and osteoporosis among patients with LBP. Considering the overestimation of BIA-based ASMM and SMI, we recommend using the cutoff values for sarcopenia of 7.9 kg/m2 for males and 6.1 kg/m2 for females.

Bone Mineral Density Utilization in Patients with Newly Diagnosed Multiple Myeloma: A Single Center Experience

Introduction: Bone disease is a major cause for morbidity in multiple myeloma (MM), mainly manifested by osteolytic lesions. Bone mineral loss is another aspect of bone involvement, although osteoporosis (with or without compression fractures) in the absence of osteolytic lesions is no more a criterion for treatment initiation in MM.Methods: We performed a retrospective study to evaluate the use of bone mineral density (BMD) exams by dual-energy X-ray absorptiometry (DXA) among MM patients in a tertiary medical care facility. We included 173 patients with symptomatic MM diagnosed between January 2007 and September 2014 who underwent BMD exam at diagnosis. The T-scores of lumbar spine (LS), left femur neck (FN) and left total hip (TH) were obtained and analyzed. In addition, we have specified the lowest T-score at each site. In patients with follow-up exam, we calculated the relative difference between the baseline and follow-up exams as the percentage change in absolute BMD value expressed in g/cm2 as follows: [(BMD at follow-up) - (BMD at baseline)/(BMD at baseline)]*100.Results: The mean lumbar spine T-score was (-1.3), while the low lumbar spine T-score was (-2.0). At the femur level, the mean FN T-score was (-1.5), while the mean TH T-score was (-1.1) and the mean low femur T-score was (-2.2). There was a strong correlation between spine and femur T-scores (r=0.56-0.61, p<0.0001). Nevertheless, on a multivariate regression analysis, different parameters correlated with the T-scores of the LS and the femur sites. The following variables were encountered as significantly associated with the mean T-score value at the lumbar spine: sex (β coefficient= (-0.17), p=0.05), BMI (β coefficient=0.21, p=0.02) and vertebral fracture(s) (β coefficient= (-0.23), p=0.01). Conversely, the following variables were found to be independent predictors of the FN T-score: age (β coefficient= (-0.37), p<0.0001) and vertebral fracture (s) (β coefficient= (-0.25), p=0.005), whereas vitamin D showed a strong trend towards significance (β coefficient= (-0.15), p=0.08). Patients with light chain only disease had lower T-score values compared with patients with IgG myeloma, reaching significance at the femur sites [FN T-score (-1.7) vs. (-1.3), p=0.06; TH T-score (-1.3) vs. (-0.9), p=0.02; femur low T-score (-2.4) vs. (-1.8), p=0.008]. Patients with vertebral fracture(s) had significantly lower T-scores of the spine compared to patients without vertebral fractures. Sixty-three patients (36.4% of all patients) had a follow-up DXA exam at a median of 25 months from the baseline test (range, 12-82 months). Basically, LS T-scores increased, while femur sites' T-scores decreased during follow-up. This did not include patients who achieved complete response (CR) and/or retained it during follow-up, who had improved BMD results at the femur sites as well (Table).Conclusion: DXA-based BMD assessment of myeloma bone disease is a valuable tool that illustrates a differential myeloma-induced bone mineral loss regarding the lumbar spine and femur. TableVariables associated with change of bone mineral density values at follow-up DXA exam in relation to exam at diagnosisVariable mean [range]Mean change at lumbar spine (LS)Mean change at femur neck (FN)Mean change at total hip (TH)Time interval between tests12-24 months (n=31)4.1% [(-10%) - 25.2%]-4.3% [(-24.8%) - 10.6%]-0.1% [(-17.4%) - 10.4%]Time interval >24 months (n=32)4.8% [(-3.8) - 16.4%]-1.7%[(-19.5%) - 27.2%]-0.1%[(-18.8%) - 14.9%]P value0.500.220.96Autologous stem cell transplantationYes (n=35)4.5% [(-7.6%) - 25.2%]-3.4%[(-24.8%) - 27.2%]-1.1%[(-18.8%) - 14.9%]No (n=28)4.3% [(-10.8) - 19.4%]-2.7%[(-18.3%) - 11.1%]-0.1%[(-17.9%) - 10.4%]P value0.890.760.77Response to first line treatmentCR/sCR (n=22)4.3%[(-10.8%) - 18.1%]0.1%[(-12%) - 18.1%]2.1%[(-10.6%) - 10.4%]Less than CR (n=41)4.5%[(-5.5) - 25.2%]-5%[(-24.8%) - 8.6%]-2.5%[(-18.8%) - 14.9%]P value0.910.010.01Disease status at FU testCR/sCR (n=15)3.9% [(-10.8%) - 19.4%]-1.2%[(-24.8%) - 27.2%]2.4%[(-10%) - 10.4%]Less than CR* (n=48)4.6% [(-5.5%) - 19.4%]-3.6%[(-10%) - 10.9%]-1.9%[(-18.8%) - 14.9%]P value0.80.350.03* All patients with partial response or very good partial response DisclosuresRaanani:Pfizer: Other: Advisory Board; Novartis: Other: Advisory Board, Research Funding; BMS: Other: Advisory Board; Ariad: Other: Advisory Board.

Dual-Energy CT–based Phantomless in Vivo Three-dimensional Bone Mineral Density Assessment of the Lumbar Spine

To evaluate the feasibility of phantomless in vivo dual-energy computed tomography (CT)-based three-dimensional (3D) bone mineral density (BMD) assessment in comparison with dual x-ray absorptiometry (DXA). This retrospective study was approved by the institutional review board, and the requirement to obtain informed consent was waived. Data from clinically indicated dual-energy CT and DXA examinations within 2 months, comprising the lumbar spine of 40 patients, were included. By using automated dedicated postprocessing dual-energy CT software, the trabecular bone of lumbar vertebrae L1-L4 were analyzed and segmented. A mixed-effects model was used to assess the correlations between BMD values derived from dual-energy CT and DXA. One hundred sixty lumbar vertebrae were analyzed in 40 patients (mean age, 57.1 years; range, 24-85 years), 21 male (mean age, 54.3 years; range, 24-85 years) and 19 female (mean age, 58.5 years; range, 31-80 years). Mean BMD of L1-L4 determined with DXA was 0.995 g/cm(2), and 18 patients (45%) showed an osteoporotic BMD (T score less than -2.5) of at least two vertebrae. Mean dual-energy CT-based BMD of L1-L4 was 0.254 g/cm(3). Bland-Altman analysis with mixed effects demonstrated a lack of correlation between dual-energy CT-based and DXA-based BMD values, with a mean difference of 0.7441 and 95% limits of agreement of 0.7441 ± 0.4080. Dedicated postprocessing of dual-energy CT data allows for phantomless in vivo BMD assessment of the trabecular bone of lumbar vertebrae and enables freely rotatable color-coded 3D visualization of intravertebral BMD distribution.

Microstructural, Densitometric and Metabolic Variations in Bones from Rats with Normal or Altered Skeletal States

BackgroundHigh resolution μCT, and combined μPET/CT have emerged as non-invasive techniques to enhance or even replace dual energy X-ray absorptiometry (DXA) as the current preferred approach for fragility fracture risk assessment. The aim of this study was to assess the ability of µPET/CT imaging to differentiate changes in rat bone tissue density and microstructure induced by metabolic bone diseases more accurately than current available methods.MethodsThirty three rats were divided into three groups of control, ovariectomy and vitamin-D deficiency. At the conclusion of the study, animals were subjected to glucose (18FDG) and sodium fluoride (Na18F) PET/CT scanning. Then, specimens were subjected to µCT imaging and tensile mechanical testing. ResultsCompared to control, those allocated to ovariectomy and vitamin D deficiency groups showed 4% and 22% (significant) increase in 18FDG uptake values, respectively. DXA-based bone mineral density was higher in the vitamin D deficiency group when compared to the other groups (cortical bone), yet μCT-based apparent and mineral density results were not different between groups. DXA-based bone mineral density was lower in the ovariectomy group when compared to the other groups (cancellous bone); yet μCT-based mineral density results were not different between groups, and the μCT-based apparent density results were lower in the ovariectomy group compared to the other groups. ConclusionPET and micro-CT provide an accurate three-dimensional measurement of the changes in bone tissue mineral density, as well as microstructure for cortical and cancellous bone and metabolic activity. As osteomalacia is characterized by impaired bone mineralization, the use of densitometric analyses may lead to misinterpretation of the condition as osteoporosis. In contrast, µCT alone and in combination with the PET component certainly provides an accurate three-dimensional measurement of the changes in both bone tissue mineral density, as well as microstructure for cortical and cancellous bone and metabolic activity.

Standard Radiography: Untapped Potential in the Assessment of Osteoporotic Fracture Risk

Assessment of osteoporotic fracture risk is based primarily on bone mineral density (BMD) measurements using dual X-ray absorptiometry (DXA). However, recent evidence indicates that the method is insufficient for accurate individual risk assessment; in addition to methodological inaccuracies related to DXA, the mechanical strength of bone is influenced not only by low BMD but also by other factors that are not captured by DXA. DXA-based BMD can provide information on the amount of bone but does not elucidate bone structure, which is significant for bone mechanical strength and for fracture risk. In order to achieve more a comprehensive assessment of fracture risk, recent efforts have been directed toward imaging techniques by which bone structural changes can be observed. In addition to novel three-dimensional imaging techniques, analysis of plain radiographs has also been investigated with promising results. As plain radiographs are cheap and widely available, it was considered of interest to discover how well plain radiography could be utilised for the assessment of bone mechanical competence and fracture risk. In this article, we review studies related to radiographic assessment of fracture risk in order to show the potential of this conventional methodology for screening subjects at risk. • Conventional radiography has sufficient theoretical requirements for assessment of bone structure. • Bone geometry and trabecular structure can be depicted by and evaluated from standard radiographs. • Texture-based analysis of radiographs discriminates postmenopausal women with and without fractures. • Such analysis can also predict fractures in individuals without frank osteoprosis. • Imaging and subsequent analysis should become more standardised to allow structural quantification.

Dual-energy digital radiography in the assessment of bone mechanical properties

At present, bone fragility and fracture risk are estimated with bone mineral density (BMD), measured by dual-energy x-ray absorptiometry (DXA). It is known that DXA-based BMD (BMDDXA) has a relationship with mechanical characteristics of bone. Dual-energy digital radiography (DEDR) has also been shown to be a potential method to determine BMD, but the ability of DEDR-based BMD (BMDDEDR) to predict bone mechanical properties is not yet known. In this study, we investigated the ability of BMDDEDR to predict the mechanical characteristics of bone. Reindeer femora (N = 50) were imaged at two different energies (79 and 100 kVp) using a clinical digital radiography system. BMD was determined in four regions from these images using the DXA calculation principle. Femora were mechanically tested using axial loading configuration. Mechanical parameters were correlated with the BMDDEDR and BMDDXA of the femoral neck (FNBMDDEDR and FNBMDDXA). FNBMDDEDR and FNBMDDXA both correlated moderately with mechanical parameters. The highest correlations were found with maximal load (r = 0.53 and r = 0.65, p < 0.01, respectively). No statistically significant differences were found between the correlation coefficients when comparing the FNBMDDEDR or FNBMDDXA values and mechanical parameters. The correlation coefficient between BMDDEDR and BMDDXA varied between r = 0.56 and 0.86 (p < 0.01) in different regions of the upper femur. In conclusion, BMDDEDR predicts the mechanical parameters of reindeer bone with similar accuracy as BMDDXA.

Effects of intravenous zoledronic acid plus subcutaneous teriparatide [rhPTH(1–34)] in postmenopausal osteoporosis

Clinical data suggest concomitant therapy with bisphosphonates and parathyroid hormone (PTH) may blunt the anabolic effect of PTH; rodent models suggest that infrequently administered bisphosphonates may interact differently. To evaluate the effects of combination therapy with an intravenous infusion of zoledronic acid 5 mg and daily subcutaneous recombinant human (rh)PTH(1-34) (teriparatide) 20 µg versus either agent alone on bone mineral density (BMD) and bone turnover markers, we conducted a 1-year multicenter, multinational, randomized, partial double-blinded, controlled trial. 412 postmenopausal women with osteoporosis (mean age 65 ± 9 years) were randomized to a single infusion of zoledronic acid 5 mg plus daily subcutaneous teriparatide 20 µg (n = 137), zoledronic acid alone (n = 137), or teriparatide alone (n = 138). The primary endpoint was percentage increase in lumbar spine BMD (assessed by dual-energy X-ray absorptiometry [DXA]) at 52 weeks versus baseline. Secondary endpoints included change in BMD at the spine at earlier time points and at the total hip, trochanter, and femoral neck at all time points. At week 52, lumbar spine BMD had increased 7.5%, 7.0%, and 4.4% in the combination, teriparatide, and zoledronic acid groups, respectively (p < .001 for combination and teriparatide versus zoledronic acid). In the combination group, spine BMD increased more rapidly than with either agent alone (p < .001 versus both teriparatide and zoledronic acid at 13 and 26 weeks). Combination therapy increased total-hip BMD more than teriparatide alone at all times (all p < .01) and more than zoledronic acid at 13 weeks (p < .05), with final 52-week increments of 2.3%, 1.1%, and 2.2% in the combination, teriparatide, and zoledronic acid groups, respectively. With combination therapy, bone formation (assessed by serum N-terminal propeptide of type I collagen [PINP]) increased from 0 to 4 weeks, declined minimally from 4 to 8 weeks, and then rose throughout the trial, with levels above baseline from 6 to 12 months. Bone resorption (assessed by serum β-C-telopeptide of type I collagen [β-CTX]) was markedly reduced with combination therapy from 0 to 8 weeks (a reduction of similar magnitude to that seen with zoledronic acid alone), followed by a gradual increase after week 8, with levels remaining above baseline for the latter half of the year. Levels for both markers were significantly lower with combination therapy versus teriparatide alone (p < .002). Limitations of the study included its short duration, lack of endpoints beyond DXA-based BMD (e.g., quantitative computed tomography and finite-element modeling for bone strength), lack of teriparatide placebo, and insufficient power for fracture outcomes. We conclude that while teriparatide increases spine BMD more than zoledronic acid and zoledronic acid increases hip BMD more than teriparatide, combination therapy provides the largest, most rapid increments when both spine and hip sites are considered.

Assessment of the bilateral asymmetry of human femurs based on physical, densitometric, and structural rigidity characteristics

The purpose of this study was to perform a comprehensive geometric, densitometric, biomechanical, and statistical analysis of paired femurs for an adult population over a wide age range using three imaging modalities to quantify the departure from symmetry in size, bone mineral density, and cross-sectional structural rigidities. Femur measurements were obtained from 20 pairs of cadaveric femurs. Dimensions of these anatomic sites were measured using calipers directly on the bone and plain radiographs. Dual energy X-ray absorptiometry was used to measure bone mineral density. Bone mineral content and axial and bending rigidities were determined from the CT imaging. No differences were observed between the geometric measurements, DXA based bone mineral density and axial and bending rigidities of left and right femurs ( P>0.05 for all cases). Left and right proximal femurs are not significantly different based on geometric, densitometric, and structural rigidity measurements. However, absolute left–right differences for individual patients can be substantial. When using the contralateral femur as a control, the number of femur pairs required to assess significant changes in anatomic dimensions and structural properties induced by a tumor, infection, fracture, or implanted device can range from 3 to 165 pairs depending on the desired effect size or sensitivity (5% or 10% difference). This information is important both for femoral arthroplasty implant design and the use of the contralateral femur as an intra-subject control for clinical assessment and research studies. In addition, our statistical analysis provides sample size estimates for planning future orthopedic research studies.

Dual-energy digital radiography for the assessment of bone mineral density

Bone mineral density (BMD) is usually determined by dual-energy X-ray absorptiometry (DXA). Digital radiography (DR) has enabled the application of dual-energy techniques for separating bone and soft tissue, but it is not clear yet whether BMD information can reliably be obtained using DR. To determine the ability of dual-energy digital radiography (DEDR) to predict BMD as determined by DXA. Reindeer femora (n=15) were imaged in a water bath at a typical clinical imaging voltage of 79 kVp and additionally at 100 kVp on a DR system. BMD was determined in four segmented regions (femoral neck, trochanter, inter-trochanter, Ward's triangle) from these images using the DXA calculation principle. BMD results as determined by DEDR were compared with BMD values as determined by DXA. Significant moderate to high linear correlations (0.66-0.76) were observed at the femoral neck, Ward's triangle, and trochanter between BMD values as determined by the two techniques. The coefficient of variation (CV(RMS)) ranged between 2.2 and 4.7% and 0.2 and 1.8% for DEDR and DXA analyses, respectively. DXA-based BMD information can be obtained with moderate precision and accuracy using DEDR. In future, combining BMD measurements using DEDR with structural and geometrical information available on digital radiographs could enable a more comprehensive assessment of bone.