Volker Kuhn

Radius bone strength in bending, compression, and falling and its correlation with clinical densitometry at multiple sites.

This study comprehensively analyzes the ability of site‐specific and nonsite‐specific clinical densitometric techniques for predicting mechanical strength of the distal radius in different loading configurations. DXA of the distal forearm, spine, femur, and total body and peripheral quantitative computed tomography (pQCT) measurements of the distal radius (4, 20, and 33%) were obtained in situ (with soft tissues) in 129 cadavers, aged 80.16 ± 9.8 years. Spinal QCT and calcaneal quantitative ultrasound (QUS) were performed ex situ in degassed specimens. The left radius was tested in three‐point bending and axial compression, and the right forearm was tested in a fall configuration, respectively. Correlation coefficients with radius DXA were r = 0.89, 0.84, and 0.70 for failure in three‐point bending, axial compression, and the fall simulation, respectively. The correlation with pQCT (r = 0.75 for multiple regression models with the fall) was not significantly higher than for DXA. Nonsite‐specific measurements and calcaneal QUS displayed significantly (p < 0.01) lower correlation coefficients, and QUS did only contribute to the prediction of axial failure stress but not of failure load. We conclude that a combination of pQCT parameters involves only marginal improvement in predicting mechanical strength of the distal radius, nonsite‐specific measurements are less accurate for this purpose, and QUS adds only little independent information to site‐specific bone mass. Therefore, the noninvasive diagnosis of loss of strength at the distal radius should rely on site‐specific measurements with DXA or pQCT and may be the earliest chance to detect individuals at risk of osteoporotic fracture.

Sex Differences of Human Trabecular Bone Microstructure in Aging Are Site-Dependent†‡

In this study, we characterize bone microstructure, specifically sex differences, at multiple skeletal sites in 165 subjects >52 yr of age, using μCT technology in vitro. Significant sex differences are observed at the distal radius, femoral neck, and femoral trochanter, but not at the iliac crest, calcaneus, and lumbar vertebral body. Correlations in BV/TV between sites ranged from r = 0.13 to 0.56.

Bone Strength at Clinically Relevant Sites Displays Substantial Heterogeneity and Is Best Predicted From Site-Specific Bone Densitometry

In this study we test the hypotheses that mechanical bone strength in elderly individuals displays substantial heterogeneity among clinically relevant skeletal sites, that ex situ dual‐energy X‐ray absorptiometry (DXA) provides better estimates of bone strength than in situ DXA, but that a site‐specific approach of bone densitometry is nevertheless superior for optimal prediction of bone failure under in situ conditions. DXA measurements were obtained of the lumbar spine, the left femur, the left radius, and the total body in 110 human cadavers (age, 80.6 ± 10.5 years; 72 female, 38 male), including the skin and soft tissues. The bones were then excised, spinal and femoral DXA being repeated ex situ. Mechanical failure tests were performed on thoracic vertebra 10 and lumbar vertebra 3 (compressive loading of a functional unit), the left and right femur (side impact and vertical loading configuration), and the left and right distal radius (fall configuration, axial compression, and 3‐point‐bending). The failure loads displayed only very moderate correlation among sites (r = 0.39 to 0.63). Ex situ DXA displayed slightly higher correlations with failure loads compared with those of in situ DXA, but the differences were not significant and relatively small. Under in situ conditions, DXA predicted 50‐60% of the variability in bone failure loads at identical (or closely adjacent) sites, but only around 20‐35% at distant sites, advocating a site‐specific approach of densitometry. These data suggest that mechanical competence in the elderly is governed by strong regional variation, and that its loss in osteoporosis may not represent a strictly systemic process.

Mechanical strength of the thoracolumbar spine in the elderly: prediction from in situ dual-energy X-ray absorptiometry, quantitative computed tomography (QCT), upper and lower limb peripheral QCT, and quantitative ultrasound.

The objective of this study was to compare the ability of clinically available densitometric measurement techniques for evaluating vertebral strength in elderly individuals. Measurements were related to experimentally determined failure strength in the thoracic and lumbar spine. In 127 specimens (82 women and 45 men, age 80 +/- 10 years), dual-energy X-ray absorptiometry (DXA) was performed at the lumbar spine, femur, radius, and total body, and peripheral-quantitative computed tomography (pQCT) at the distal radius, tibia, and femur under in situ conditions with intact soft tissues. Spinal QCT and calcaneal ultrasound parameters were performed ex situ in degassed specimens. Mechanical failure loads of thoracic vertebrae 6 and 10 (T-6 and -10), and lumbar vertebra 3 (L-3) were determined in axial compression on functional three-segment units. In situ anteroposterior DXA and QCT of the lumbar spine explained approximately 65% of the variability of thoracolumbar failure. A combination of cortical and trabecular density (QCT) provided the best prediction in the lumbar spine. However, this was not the case in the thoracic spine, for which lumbar cortical density (QCT) and DXA provided significantly better estimates than trabecular density (QCT). pQCT was significantly less correlated with the strength of lumbar and thoracic vertebrae (r(2) = 40%), but was equivalent to femoral or radial DXA. pQCT measurements in the lower limb showed no advantage over those at the distal radius. Ultrasound explained approximately 25% of the variability of vertebral failure strength and added independent information to spinal QCT, but not to spinal DXA. These experimental results advocate site-specific assessment of vertebral strength by either spinal DXA or QCT.

Failure strengths in distal biceps tendon repair

Background Surgical repair is the most favored treatment for a rupture of the distal biceps tendon. A variety of techniques have been described for distal biceps tendon reattachment, including transosseous sutures, suture anchors, interference screws, and an EndoButton-based technique. Hypothesis EndoButton and suture anchor have initially stronger fixation strengths than do transosseous sutures, allowing early postoperative rehabilitation. Study Design Controlled laboratory study. Methods Single loads to failure and mode of failure of 13 different fixation techniques were determined using 130 human cadaveric elbows. Quantitative computer tomography was performed to exclude differences in bone mineral density as an affecting factor. Repeated-measures analysis of variance was used to assess differences in failure load between repair techniques. Results The EndoButton-based technique showed a significantly higher failure load (259 ± 28 N) than did all other techniques (P < .05). No significant differences were seen between the transosseous suture technique (210 ± 29 N) and most other techniques (P > .05). Failure loads of the TwinFix-QuickT (57 ± 29 N) and Biocuff screw (105 ± 28 N) were significantly lower than those of all other repairs (P < .05). Conclusion Significant differences exist in failure loads and modes of failure for the different repair techniques after rupture of the distal biceps tendon. Clinical Relevance The transosseous technique is still a sufficient and cost-saving procedure for repair of the distal biceps tendon. TwinFix-QuickT 5.0 mm and Biocuff screw 5.7 mm had significantly lower failure loads, which might affect early rehabilitation, particularly in patients with poor bone quality.

Ct-based finite element models can be used to estimate experimentally measured failure loads in the proximal femur

The objective of this experimental finite element (FE) study was to assess the accuracy of a simulation model estimate of the experimentally measured fracture load of the proximal femur in a sideways fall. Sixty-one formalin-fixed cadaver femora (41 female and 20 male) aged 55-100 years (an average of 80 years) were scanned with a multi-detector CT scanner and were mechanically tested for failure in a sideways fall loading configuration. Twenty-one of these femurs were used for training purposes, and 40 femurs were used for validation purposes. The training set FE models were used to establish the strain threshold for the element failure criteria. Bi-linear elastoplastic FE analysis was performed based on the CT images. The validation set was used to estimate the fracture loads. The Drucker-Prager criterion was applied to determine the yielding and the maximum principal stress criteria and the minimum principal strain criteria for element failure in tension and in compression, respectively. The estimated fracture load values were highly correlated with the experimental data (r=0.931; p<0.001). The slope was 0.929, with an intercept of 258 N, which was not significantly different from 1 and 0, respectively. The study shows that it is possible to estimate the fracture load with relatively high accuracy in a sideways fall configuration by using the CT-based FE method. This method may therefore be applied for studying the biomechanical mechanisms of hip fractures.

Reproducibility and Side Differences of Mechanical Tests for Determining the Structural Strength of the Proximal Femur

In this experimental study, we evaluated the reproducibility error of mechanical strength tests of the proximal femur when simulating a fall on the trochanter. Based on side differences in femoral failure loads in 55 pairs of femora, we estimated the upper limit of the precision error to be 15% for the side impact test, whereas the intersubject variability was >40%.

Spironolactone ameliorates PIT1-dependent vascular osteoinduction in klotho-hypomorphic mice

Klotho is a potent regulator of 1,25-hydroxyvitamin D3 [1,25(OH)2D3] formation and calcium-phosphate metabolism. Klotho-hypomorphic mice (kl/kl mice) suffer from severe growth deficits, rapid aging, hyperphosphatemia, hyperaldosteronism, and extensive vascular and soft tissue calcification. Sequelae of klotho deficiency are similar to those of end-stage renal disease. We show here that the mineralocorticoid receptor antagonist spironolactone reduced vascular and soft tissue calcification and increased the life span of kl/kl mice, without significant effects on 1,25(OH)2D3, FGF23, calcium, and phosphate plasma concentrations. Spironolactone also reduced the expression of osteoinductive Pit1 and Tnfa mRNA, osteogenic transcription factors, and alkaline phosphatase (Alpl) in calcified tissues of kl/kl mice. In human aortic smooth muscle cells (HAoSMCs), aldosterone dose-dependently increased PIT1 mRNA expression, an effect paralleled by increased expression of osteogenic transcription factors and enhanced ALP activity. The effects of aldosterone were reversed by both spironolactone treatment and PIT1 silencing and were mitigated by FGF23 cotreatment in HAoSMCs. In conclusion, aldosterone contributes to vascular and soft tissue calcification, an effect due, at least in part, to stimulation of spironolactone-sensitive, PIT1-dependent osteoinductive signaling.

Can Novel Clinical Densitometric Techniques Replace or Improve DXA in Predicting Bone Strength in Osteoporosis at the Hip and Other Skeletal Sites

New peripheral techniques are now available for the diagnosis of osteoporosis, but their value in the clinical management of the disease remains controversial. This study tests the hypothesis that peripheral quantitative computed tomography (pQCT) at the distal radius and/or quantitative ultrasound (QUS) at the calcaneus can serve as replacement or improvement of current methodology (QCT and DXA) for predicting bone strength at the hip and other sites. In 126 human cadavers (age, 80.2 ± 10.4 years), DXA of the femur, spine, and radius and pQCT of the radius were acquired with intact soft tissues. QCT (spine) and QUS (calcaneus) were performed ex situ in degassed specimens. Femoral failure loads were assessed in side impact and vertical loading. Failure loads of the thoracolumbar spine were determined at three levels in compression and those of the radius by simulating a fall. Site‐specific DXA explained approximately 55% of the variability in femoral strength, whereas pQCT and QUS displayed a lower association (15‐40%). QUS did not provide additional information on mechanical strength of the femur, spine, or radius. All techniques displayed similar capability in predicting a combined index of failure strength at these three sites, with only QUS exhibiting significantly lower associations than other methods. These experimental results suggest that clinical assessment of femoral fracture risk should preferably rely on femoral DXA, whereas DXA, QCT, and pQCT display similar capability of predicting a combined index of mechanical strength at the hip, spine, and radius.

Mechanical Strength of the Proximal Femur as Predicted From Geometric and Densitometric Bone Properties at the Lower Limb Versus the Distal Radius

This experimental study compares geometric and densitometric properties of cortical and trabecular bone at the lower limb and the distal radius with those at the femoral neck, and evaluates their ability to predict mechanical failure loads of the proximal femur. One hundred five cadavers were examined with peripheral quantitative computed tomography (LpQCT), with measurements being performed in situ at the distal radius (4%, 20%, 33%), at the distal and proximal tibia, at the tibial and femoral shaft, and at the distal femur. Ex situ measurements were obtained at the femoral neck and at the proximal femoral shaft. Pairs of femora were mechanically tested in a vertical loading and a side impact (fall) configuration. The total (cross-sectional) bone mineral content and trabecular density, but not the cortical properties, displayed a higher association between the femoral neck and the peripheral lower limb than between the neck and the distal radius. Approximately 50%-60% of the variability of femoral failure loads (and >80% of trochanteric side impact fractures) were predicted by in vitro measurements at the neck. Geometric cortical parameters and density contributed independently and significantly to femoral strength. Measurements at the peripheral skeleton explained, however, only 30%-45% of the variability of femoral failure, with no significant difference between the lower limb and the distal radius. At peripheral sites, a combination of geometric and densitometric variables was slightly superior to bone mineral content alone in predicting failure in vertical loading, but this was less evident for cervical side impact fractures. The results show that a stronger association of total bone mineral content and trabecular density between the femoral neck and the lower limb does not translate into improved prediction of femoral strength from measurements at the lower limb vs. those at the distal radius.