Automated quantitative morphometry of vertebral heights on spinal radiographs: comparison of a clinical workflow tool with standard 6-point morphometry.

A workflow tool for measurements of vertebral heights on lateral spine radiographs based on automated placements of 6 points per vertebra was evaluated. The tool helps to standardize point placement among operators. Its success rate is very good in normal vertebrae but lower in vertebrae with more severe fractures. Manual corrections were required in 192 of 1257 analyzed vertebrae. INTRODUCTION: To evaluate a new workflow tool (SA) for the automated measurements of vertebral heights on lateral spine radiographs. METHODOLOGY: Lateral radiographs from 200 postmenopausal women were evaluated at two visits. Genant's semi-quantitative fracture assessment (SQ) and manual quantitative morphometry (QM) results were available from prior analyses. Vertebral heights from point placements using SA were compared with manual 6-point placement QM. Differences were quantified as RMS coefficient of variations (rmsCV) and standard deviations (rmsSD). RESULTS AND CONCLUSIONS: SA required manual corrections in 192 of 1257 vertebrae. SA heights were larger than QM ones by 2.2-3.6%. Correlations (r2 > 0.92) between SA and QM were very high. Differences between QM and SA were higher for fractured (SQ = 2; rmsCV% 14.5%) than for unfractured vertebrae (rmsCV% 4.2-4.7%). rmsCV% for QM varied between 3 and 6% and for SA between 2.5 and 7.5%. For SA, highest rmsCV% was obtained for T4 and L4. Manual correction mostly affected the end vertebrae T4 and L4. SA helps to standardize point placement among operators. The algorithm success rate is very good in normal vertebrae but lower in vertebrae with more severe fractures, which are of greater clinical interest but are more readily recognized without morphometric measurements.

Short-term in vivo precision of BMD and parameters of trabecular architecture at the distal forearm and tibia.

UNLABELLED: In vivo hr-pQCT precision was determined in 42 postmenopausal women using double baseline measurements from a multicenter trial of odanacatib. Errors, e.g., at the radius below 1.3% for BMD and below 6.3% for trabecular structure, were comparable to single-center results. Motion artifacts remain a challenge, particularly at the forearm. INTRODUCTION: The short-term in vivo precision of BMD, trabecular bone structure, cortical thickness and porosity of the forearm and tibia was measured by hr-pQCT. Also the effect of image quality on precision was evaluated. METHODS: In 42 postmenopausal women (age 64.4 ± 6.8 years) out of 214 subjects enrolled in a multi center advanced imaging phase III study of odanacatib (DXA spine or hip T-scores between -1.5 and -3.5), double baseline hr-pQCT (XtremeCT) measurements with repositioning were performed. The standard ultradistal location and a second, more proximally located VOI were measured at the radius and tibia to better assess cortical thickness and porosity. Image analysis and quality grading (grades: perfect, slight artifacts, pronounced artifacts, unacceptable) were performed centrally. RESULTS: At the radius RMS%CV values varied from 0.7% to 1.3% for BMD and BV/TV and from 5.6% to 6.3% for Tb.Sp, Tb.Th, Tb.N, and cortical porosity. Numerically at the tibia, precision errors were approx. 0.5% lower for BMD and 1% to 2% lower for structural parameters although most differences were insignificant. In the radius but not in the tibia, precision errors for cortical thickness were smaller at the distal compared to the ultradistal location (1% versus 2%). CONCLUSIONS: BMD precision errors were lower than those for trabecular architecture and cortical porosity. Motion artifacts remain a challenge, particularly at the forearm. Quality grading remains subjective, and more objective evaluation methods are needed. Precision in the context of a multicenter clinical trial, with centralized training and scan analysis, was comparable to single-center results previously reported.

Glucocorticosteroid-induced osteoporosis in adult primiparous Göttingen miniature pigs: effects on bone mineral and mineral metabolism.

Information on the pathophysiology of glucocorticoid-induced osteoporosis (GIO) is limited, since its clinical picture often reflects a combined effect of glucocorticoids (GC) and the treated systemic disease (i.e., inflammation and immobility). In 50 healthy adult (30-mo-old) primiparous Göttingen minipigs, we studied the short-term (8 mo, n = 30) and long-term (15 mo, n = 10) effect of GC on bone and mineral metabolism longitudinally and cross-sectionally compared with a control group (n = 10). All animals on GC treatment received prednisolone orally at a dose of 1.0 mg x kg body wt(-1) x day(-1) for 8 wk and thereafter at 0.5 mg/kg body wt(-1) x day(-1). In the short term, GC reduced bone mineral density (BMD) at the lumbar spine by -47.5 +/- 5.1 mg/cm(3) from baseline (P < 0.001), which was greater (P < 0.05) than the loss [not significant (NS)] in the control group of -11.8 +/- 12.6 mg/cm(3). Calcium absorption decreased from baseline by -2,488 +/- 688 mg/7 days (P < 0.001) compared with -1,380 +/- 1,297 mg/7 days (NS) in the control group. Plasma bone alkaline phosphatase (BAP) decreased from baseline by -17.8 +/- 2.2 U/l (P < 0.000), which was significantly different (P < 0.05) from the value of the control group of -1.43 +/- 4.8 U/l. In the long term, the loss of BMD became more pronounced and bone mineral content (BMC), trabecular thickness, mechanical stability, calcium absorption, 25-hydroxyvitamin D(3), 1,25-dihydroxyvitamin D(3), and parathyroid hormone tended to be lower compared with the control group. There was a negative association between the cumulative dose of GC and BMD, which was associated with impaired osteoblastogenesis. In conclusion, the main outcomes after GC treatment are comparable to symptoms of GC-induced osteoporosis in human subjects. Thus the adult Göttingen miniature pig appears to be a valuable animal model for GC-induced osteoporosis.

Ibandronate treatment reverses glucocorticoid-induced loss of bone mineral density and strength in minipigs.

The Göttingen minipig is one of the few large animal models that show glucocorticoid (GC)-induced bone loss. We investigated whether GC-induced loss of bone mineral density (BMD) and bone strength in minipigs can be recovered by treatment with the bisphosphonate ibandronate (IBN). 40 primiparous sows were allocated to 4 groups when they were 30 months old: GC treatment for 8 months (GC8), for 15 months (GC15), GC treatment for 15 months plus IBN treatment for months 8-15 (GC&IBN), and a control group without GC treatment. Prednisolone was given at a daily oral dose of 1 mg/kg body weight for 8 weeks and thereafter 0.5 mg/kg body weight. IBN was administered intramuscularly and intermittently with an integral dose of 2.0 mg/kg body weight. BMD of the lumbar spine (L1-3) was assessed in vivo by Quantitative Computed Tomography (QCT) at months 0, 8, and 15. Blood and urine samples were obtained every 2-3 months. After sacrificing the animals lumbar vertebrae L4 were tested mechanically (Young's modulus and ultimate stress). Histomorphometry was performed on L2 and mineral content determined in ashed specimens of T12 and L4. In the GC&IBN group, the GC associated losses in BMD of -10.5%+/-1.9% (mean+/-standard error of the mean, p<0.001) during the first 8 months were more than recovered during the following 7 months of IBN treatment (+14.8%+/-1.2%, p<0.0001). This increase was significantly larger (p<0.0001) than the insignificant +2.1%+/-1.2% change in group GC15. At month 15, the difference between groups GC&IBN and GC15 was 22% (p<0.01) for BMD, 48% (p<0.05) for Young's modulus, and 31% (p<0.14) for ultimate stress; bone-specific alkaline phosphatase showed trends to lower values (p<0.2) while deoxypyridinoline was comparable. This minipig study demonstrates that GC-induced impairment of bone strength can be effectively and consistently treated by IBN. GC&IBN associated alterations in BMD and bone turnover markers can be monitored in vivo using QCT of the spine and by biochemical analyses, reflecting the changes in bone strength.

Assessment of the geometry of human finger phalanges using quantitative ultrasound in vivo.

Quantitative Ultrasound (QUS) methods have been shown to be useful in the assessment of bone status. Nevertheless, ultrasound transmission depends on a variety of skeletal parameters, and a detailed understanding of ultrasound propagation through bone is important for the accurate interpretation of QUS results. In this study we wanted to elucidate the pathways of an ultrasound wave through finger phalanges and determine correlations between geometric and QUS parameters. Phalanges of a subject group were measured using QUS and magnetic resonance imaging (MRI). MRI was used for the derivation of the geometric parameters. Similar assessments were performed on cylindrical tubes and with a simulation program. New parameters related to speed of sound (SOS) and amplitude of the wave (A2P) were calculated. Strong correlations between QUS parameters and morphologic cross-sectional areas were observed in vivo and in phantoms. Similar correlations could be found in the calculations using the simulation software. Cross-sectional cortical area, medullary canal area and relative cortical area could be calculated from the QUS parameters (subjects: R2 = 0.71 for cortical area, R2 = 0.45 for medullary canal area and R2 = 0.61 for relative cortical area; phantoms: R2 = 0.98 for cortical area, R2 = 0.78 for medullary canal area and R2 = 0.77 for relative cortical area). In vivo, phantom and simulation results consistently showed that SOS was correlated with cortical area but not with medullary canal area while the opposite was found for A2P. Pathways of the ultrasound wave through solid cortical bone and the medullary canal could be identified and the propagation of the wave could be depicted. These results help to interpret QUS findings and provide information that may be helpful in improving the performance of QUS.