Marie Shea

Importance of bone mineral density in instrumented spine fusions.

The effect of equivalent mineral density on pedicular screw fixation strength was investigated. The equivalent mineral density of human vertebral bodies was correlated highly with the pullout force of Kluger screws (r2 = 0.61, P less than 0.02). A moderate to high correlation existed between density and vertical force (r2 = 0.42 for Kluger screws, r2 = 0.55 for Steffee screws, P less than 0.02). In calf vertebral bodies of higher density (146 +/- 14 mg/cc), the forces were significantly higher than in the human vertebral bodies (P less than 0.05). Human lumbosacral spines were instrumented with three different fixators: Steffee plates, AO fixateur interne, and Kluger fixateur interne. Of five specimens with a mean density of 88 +/- 11 mg/cc, one screw loosened. More than one screw loosened in six specimens with a mean density of 63 +/- 12 mg/cc, and no screw loosened in four specimens with a mean density of 114 +/- 38 mg/cc. Measurement of equivalent mineral density correlates with the fixation strength of the intrapedicular screws in vitro and should be considered in patients with signs of osteopenia before using pedicular screws for spinal fusions. It is also concluded that calf spines are a good model for testing implants because they tend to focus failure processes in the implant rather than in the implant-bone interface.

Effect of screw diameter, insertion technique, and bone cement augmentation of pedicular screw fixation strength.

This study investigated (1) the effect of screw diameter and insertion technique in lumbar vertebrae, and insertion site in the sacrum, on the axial pullout force and transverse bending stiffness of pedicle screws, and (2) the effect of bone cement augmentation using polymethylmethacrylate (PMMA) and the biodegradable composite, poly(propylene glycol-fumarate) on axial pullout force and transverse bending stiffness of pedicle screws inserted into lumbar vertebrae. The axial pullout force and transverse bending stiffness of a 6.25-mm Steffee screw and a 6-mm Kluger screw did not differ significantly in vertebral bodies of similar equivalent bone mineral density. The axial pullout force of Schanz screws was significantly increased with a 1-mm increase in screw diameter. However, there was no significant increase in transverse bending stiffness. In the sacrum, an approach through the S1 facet produced significantly higher axial pullout forces and transverse bending stiffness than the approach described by Harrington and Dickson. PMMA and a biodegradable composite bone cement poly(propylene glycol-fumarate) both increased the axial pullout force. PMMA also increased the transverse bending stiffness.

Bone density, strength, and formation in adult cathepsin K (-/-) mice

Cathepsin K (CatK) is a cysteine protease expressed predominantly in osteoclasts, that plays a prominent role in degrading Type I collagen. Growing CatK null mice have osteopetrosis associated with a reduced ability to degrade bone matrix. Bone strength and histomorphometric endpoints in young adult CatK null mice aged more than 10 weeks have not been studied. The purpose of this paper is to describe bone mass, strength, resorption, and formation in young adult CatK null mice. In male and female wild-type (WT), heterozygous, and homozygous CatK null mice (total N=50) aged 19 weeks, in-life double fluorochrome labeling was performed. Right femurs and lumbar vertebral bodies 1-3 (LV) were evaluated by dual-energy X-ray absorptiometry (DXA) for bone mineral content (BMC) and bone mineral density (BMD). The trabecular region of the femur and the cortical region of the tibia were evaluated by histomorphometry. The left femur and sixth lumbar vertebral body were tested biomechanically. CatK (-/-) mice show higher BMD at the central and distal femur. Central femur ultimate load was positively influenced by genotype, and was positively correlated with both cortical area and BMC. Lumbar vertebral body ultimate load was also positively correlated to BMC. Genotype did not influence the relationship of ultimate load to BMC in either the central femur or vertebral body. CatK (-/-) mice had less lamellar cortical bone than WT mice. Higher bone volume, trabecular thickness, and trabecular number were observed at the distal femur in CatK (-/-) mice. Smaller marrow cavities were also present at the central femur of CatK (-/-) mice. CatK (-/-) mice exhibited greater trabecular mineralizing surface, associated with normal volume-based formation of trabecular bone. Adult CatK (-/-) mice have higher bone mass in both cortical and cancellous regions than WT mice. Though no direct measures of bone resorption rate were made, the higher cortical bone quantity is associated with a smaller marrow cavity and increased retention of non-lamellar bone, signs of decreased endocortical resorption. The relationship of bone strength to BMC does not differ with genotype, indicating the presence of bone tissue of normal quality in the absence of CatK.

Mapping Quantitative Trait Loci That Influence Femoral Cross-sectional Area in Mice†

Size and shape are critical determinants of the mechanical properties of skeletal elements and can be anticipated to be highly heritable. Moreover, the genes responsible may be independent of those that regulate bone mineral density (BMD). To begin to identify the heritable determinants of skeletal geometry, we have examined femoral cross‐sectional area (FCSA) in male and female mice from two inbred strains of mice with divergent FCSA (C57BL/6 [B6] and DBA/2 [D2]), a large genetically heterogeneous population (n = 964) of B6D2F2 mice and 18 BXD recombinant inbred (RI) strains derived from their F2 cross. Femora were harvested from 16‐week‐old mice and FCSA (bone and marrow space enclosed within the periosteum) was measured at the midshaft by digital image analysis. In all mouse populations examined, FCSA was positively correlated with body weight and weight‐corrected FCSA (WC‐FCSA) values were normally distributed in the BXD‐RI and F2 populations, suggesting polygenic control of this trait. Genome‐wide quantitative trait locus (QTL) analysis of the B6D2F2 population revealed regions on four different chromosomes that were very strongly linked to WC‐FCSA (chromosomes 6, 8, 10, and X) in both genders. Evidence of gender‐specific genetic influences on femoral geometry was also identified at three other chromosomal sites (chromosomes 2, 7, and 12). Supporting evidence for the WC‐FCSA QTLs on chromosomes 2, 7, 8, 10, and 12 also was present in the RI strains. Interestingly, none of these WC‐FCSA QTLs were identified in our previous QTL analysis of whole body BMD in the same B6D2F2 population. Thus, the genetic determinants of bone size appear to be largely, if not entirely, distinct from those that regulate BMD attainment. The identification of the genes responsible for geometric differences in bone development should reveal fundamentally important processes in the control of skeletal integrity.

Compressive Strength of Autologous and Allogenous Bone Grafts for Thoracolumbar and Cervical Spine Fusion

The selection of the bone graft type for stabilization of spinal fusion depends on availability, the clinical situation, and the desired mechanical stability. The authors determined the potential immediate postoperative compressive strength of various types of bone grafts under axial compression on a material testing machine. The fibular strut graft (5,070 ± 3,250 N, mean ± standard deviation [SD]) was significantly stronger (P < 0.05) than the anterior (1,150 ± 487 N) and posterior (667 ± 311 N) iliac crest grafts, and the rib grafts (452 ± 192 N). Hydroxyapatite grafts with a pore size of 200 μ were significantly stronger (P < 0.05) than those with a pore size of 500 μ (1,420 ± 480 N versus 338 ± 78 N). Ethylenoxide sterilization had no significant effect on the immediate compressive strength. Bicortical and tricortical Bailey-Badgley and Cloward bone grafts also were compared. Results showed that all cervical graft types may be sufficiently strong to support sizable loads.

Pedicle screw placement in the thoracic spine: a comparison of image-guided and manual techniques in cadavers.

Study Design. A cadaveric study comparing image guidance technology to fluoroscopic guidance as a means of pedicle screw placement in the thoracic spine, using a unique starting point for screw placement. Objective. To assess accuracy of thoracic pedicle screw placement using image guidance versus fluoroscopic guidance for screw insertion. Summary of Background Data. While use of pedicle screws in the thoracic spine has been increasing, its adoption has been slower than for the lumbar spine, reflecting concern regarding possible vascular or spinal cord injury due to screw malplacement. Given these risks, efforts to improve the accuracy of thoracic pedicle screw placement remain appropriate. Stereotactic guidance has been applied in other aspects of spinal surgery to improve the accuracy of instrumentation placement. Methods. Pedicle screws were placed in the thoracic spines of eight cadavers, using either a stereotactic guidance or a manual, fluoroscopically guided technique. A slightly more superior and lateral starting point from prior descriptions was used. Each cadaver was instrumented with pedicle screws in the upper thoracic (T1–T2), middle thoracic (T4–T7), and lower thoracic (T9–T10) regions. In the upper and middle thoracic regions, screws with a 4.0-mm shank diameter were used while in the lower thoracic region a shank diameter of 4.5 mm was used. Postinstrumentation CT scans, followed by anatomic dissections, were used to evaluate screw exit rates and orientation relative to the pedicle axis. Exit rates for the two techniques and the effect of vertebral level on exit rate were compared using a &khgr;2 analysis. The effect of pedicle diameter was tested using a Pearson correlation coefficient. Results. No significant differences in the overall exit rates or orientation were found between the two techniques. There were significant differences in exit rates between the middle (47%), compared with the upper (9%) and lower (16%) thoracic regions, respectively (P < 0.001). A significant correlation between pedicle diameter and exit rate was also found (P < 0.0001). Conclusion. Our study showed no significant differences in the overall exit rates between the two techniques. Image guidance may increase confidence of surgeons with limited experience in thoracic pedicle screw placement. Successful placement of screws within the pedicle varies with the anatomic diameter of the pedicle itself. Concerns regarding accuracy of screw placement should be greatest in the middle thoracic vertebrae (T4–T7), where pedicle diameters are smallest and proximity of the great vessels is nearest.

A biomechanical study of the fatigue characteristics of thoracolumbar fixation implants in a calf spine model

Clinical failures of internal fixation implants for the treatment of the thoracolumbar spine are generally attributed to fatigue. Few studies, however, have characterized changes in fixation rigidity with time or subjected spine-implant fixation constructs to fatigue loading until failure. Fatigue characteristics of five dorsally applied spinal fixation implants were determined using lumbosacral calf spines, with an L3 vertebrectomy, loaded cyclically in combined compression (maximum 605 N) and flexion (maximum 16 Nm) for up to 100,000 cycles. Displacement transducers monitored motion at the site of instability and at the segment above the implants. Flexibility and strain at these segments were then calculated. A one-way analysis of variance showed that there were no significant differences in flexibility of the five fixation constructs (P > .05). A multiple Bonferroni test revealed that the AO and Kluger fixateur interne and Steffee plates, with fixation at L2 and L4, allowed significantly more strain (P < .01) across the site of instability than did Harrington rods and Luque plates with fixation at L1, L2, L4, and L5. There were no significant differences between fixation constructs in initial strain above the implants. After 10,000 cycles, however, there were significant increases in strain across the segment above the Luque and Harrington implants (P < .05). Failure of the AO Schanz screw occurred in three of six constructs at a mean of 73,300 cycles. The Steffee screws falled in four of five constructs at a mean of 20,800 cycles. The rods of the Kluger fixateur interne broke in four of five constructs at a mean of 47,800 cycles, and one screw slipped at 11,000 cycles. There were no metal failures in the Harrington or Luque implants. In these tests, longer implants allowed less strain across the destabllized site, and this can enhance the possibility of fusion with these implants. There was increased strain, however, across the segment above, which can be associated clinically with early degeneration and destabilization at this site. Short segmental fixation might therefore be preferable because fewer motion segments are immobilized and there is less strain across the adjacent segments. In vitro fatigue testing of spinal implants helps demonstrate potential design weaknesses so that improvements can be made before their clinical use in humans.

A comparison of the effects of automated percutaneous diskectomy and conventional diskectomy on intradiscal pressure, disk geometry, and stiffness.

Diskectomy, chemonucleolysis, percutaneous diskectomy, and laser ablation are used to treat patients with sciatica. The effects of percutaneous diskectomy on the intradiscal pressure of the human disk are not known. Our aims were to determine (a) whether removal of nucleus through automated percutaneous diskectomy significantly reduces intradiscal pressure without altering the disk geometry and stiffness, and if so, how much nucleus removal is required to achieve these goals; and (b) whether the effects of conventional diskectomy on these same parameters are equivalent to removal of nucleus through automated percutaneous diskectomy. Cyclic compressive loads of 20-900 N were applied to lumbar disks. Conventional diskectomy or automated percutaneous diskectomy (performed for 40 min with biomechanical measurements made four times at 10-min intervals) was then performed under zero load and the specimens retested under the same cyclic compressive loading. There were significant (p < 0.01) decreases in intradiscal pressure (by 7% under 900 N) after 10 min of automated percutaneous lumbar diskectomy. There were no further significant decreases in pressure during the next 30 min of percutaneous diskectomy. There were also significant decreases in pressure due to a puncture hole made with the Nucleotome trephine alone, without removal of disk material, and there was no difference in pressure after trephining alone and after percutaneous diskectomy. Decreases in disk height were significant, ranging from 5% at 10 min to 7% at 40 min of treatment. There were equivalent decreases in intradiscal pressure and disk height due to removal of similar amounts of nucleus during conventional diskectomy and during 40 min of percutaneous diskectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Phenotypic characterization of mice bred for high and low peak bone mass.

In humans, peak bone mineral density (BMD) is a highly heritable trait and a strong determinant of subsequent osteoporotic fracture risk. To identify the genetic factors responsible for variation in peak BMD, investigators have turned to animal models. In this study we examined the heritability of BMD acquisition and characterized differences in skeletal geometry, histomorphometry, and biomechanical competence between two lines of mice artificially selected for extremes of peak whole body BMD. F2 progeny from a cross between C57BL/6 and DBA/2 inbred strains was used as the foundation population to develop lines selected for either high or low BMD. Whole body BMD was measured by dual‐energy X‐ray absorptiometry (DXA). By the third generation of selection, highest‐scoring BMD (HiBMD) mice exhibited 14% greater peak BMD than lowest‐scoring BMD (LoBMD) mice. The mean realized heritability of peak BMD was 36%. Femoral shaft cortical area and thickness and vertebral cancellous bone volume (BV) were significantly greater (16–30%) in the HiBMD line compared with the LoBMD line. Mean cancellous bone formation rates (BFRs) were 35% lower in HiBMD mice compared with LoBMD mice. Failure load and stiffness in the femoral shaft, femoral neck, and L6 vertebrae were all substantially greater (by 25–190%) in HiBMD mice. Thus, these divergently selected murine lines serve to illustrate some of the means by which genetic mechanisms can affect skeletal structure and remodeling. Identification of the individual genes influencing peak BMD in this experimental system will likely reveal some of the genetic determinants of overall bone strength.

Cervical injuries under flexion and compression loading

Cervical spine segmental tests were performed to determine the specific patterns of initial cervical injury in response to loading just beyond the point of structural failure. Well-defined combinations of flexion rotation and compression translation were applied to segments with varying degrees of disc and facet degeneration. Twelve cervical spine specimens (from human cadavers ages 52-91 years), each consisting of three vertebrae (two motion segments) from the middle (C2-C5) or lower (C5-T1) regions, were subjected to pure flexion rotation (seven specimens) or to combined flexion rotation and axial compression translation (five specimens). Specimens were sectioned and dissected to determine the patterns of structural failure. Pure flexion, and combined flexion and compression produced similar patterns of injuries. The disc was the most commonly injured structure, with annular injuries noted in 8 of the 12 specimens, and with anterior herniation of the nucleus occurring in two specimens. Wedge fractures and posterior ligament injuries were noted in both specimen groups and with both modes of loading. We conclude that similar patterns of initial anterior bony compressive failure and posterior ligamentous failure can occur with both flexion and with combined flexion-compression, without axial or lateral rotation, at low rates of loading. Anterior cervical disc herniations were produced in both middle and lower cervical segments.