Injectable calcium phosphate cement for augmentation around cancellous bone screws. In vivo biomechanical studies

In lower cancellous apparent bone density, it can be difficult to achieve adequate screw fixation and hence stable fracture fixation. Different strategies have been proposed, one of them is through augmentation using calcium phosphate cement in the region at or close to the screw thread itself. To support the hypothesis of an improved screw fixation technique by augmentation of the bone surrounding the implanted screw, in vivo biomechanical and densitometric studies are performed on rabbit specimen where normal and simulated weak bone quality are considered. In particular, the evolution of screw stability till 12 weeks following the implantation is quantified. A statistical significance in the pull out force for augmented versus non-augmented screws was found for the shorter time periods tested of ≤ 5 days whilst the pull out force was found to increase with time for both augmented and non-augmented screws during the 12 week course of the study. The results of the study demonstrate that the use of an injectable calcium phosphate cement which sets in vivo can significantly improve screw pull out strength at and after implantation for normal and simulated weak bone quality.     

Material changes in osteoporotic human cancellous bone following infiltration with acrylic bone cement for a vertebral cement augmentation

Bone cement infiltration can be effective at mechanically augmenting osteoporotic vertebrae. While most published literature describes the gain in mechanical strength of augmented vertebrae, we report the first measurements of viscoelastic material changes of cancellous bone due to cement infiltration. We infiltrated cancellous core specimen harvested from osteoporotic cadaveric spines with acrylic bone cement. Bone specimen before and after cement infiltration were subjected to identical quasi-static and relaxation loading in confined and free compression. Testing data were fitted to a linear viscoelastic model of compressible material and the model parameters for cement, native cancellous bone, and cancellous bone infiltrated (composite) with cement were identified. The fitting demonstrated that the linear viscoelastic model presented in this paper accurately describes the mechanical behaviour of cement and bone, before and after infiltration. Although the composite specimen did not completely adopt the properties of bulk bone cement, the stiffening of cancellous bone due to cement infiltration is considerable. The composite was, for example, 8.5 times stiffer than native bone. The local stiffening of cancellous bone in patients may alter the load transfer of the augmented motion segment and may be the cause of subsequent fractures in the vertebrae adjacent to the ones infiltrated with cement. The material model and parameters in this paper, together with an adequate finite-element model, can be helpful to investigate the load shift, the mechanism for subsequent fractures, and filling patterns for ideal cement infiltration.     

An approximate model for cancellous bone screw fixation

This paper presents a finite element (FE) model to identify parameters that affect the performance of an improved cancellous bone screw fixation technique, and hence potentially improve fracture treatment. In cancellous bone of low apparent density, it can be difficult to achieve adequate screw fixation and hence provide stable fracture fixation that enables bone healing. Data from predictive FE models indicate that cements can have a significant potential to improve screw holding power in cancellous bone. These FE models are used to demonstrate the key parameters that determine pull-out strength in a variety of screw, bone and cement set-ups, and to compare the effectiveness of different configurations. The paper concludes that significant advantages, up to an order of magnitude, in screw pull-out strength in cancellous bone might be gained by the appropriate use of a currently approved calcium phosphate cement.     

A CAAX motif can compensate for the PH domain of Num1 for cortical dynein attachment

During mitosis in budding yeast, cortically anchored dynein exerts pulling forces on cytoplasmic microtubules, moving the mitotic spindle into the mother-bud neck. Anchoring of dynein requires the cortical patch protein Num1, which is hypothesized to interact with PI(4,5)P₂ via its C-terminal pleckstrin homology (PH) domain. Here we show that the PH domain and PI(4,5)P₂ are required for the cortical localization of Num1, but are not sufficient to mediate the cortical assembly of Num1 patches. A GFP fusion to the PH domain localizes to the cortex in foci containing ~2 molecules, whereas patches of full-length Num1-GFP contain ~14 molecules. A membrane targeting sequence containing the CAAX motif from the yeast Ras2 protein can compensate for the PH domain to target Num1 to the plasma membrane as discrete patches. The CAAX-targeted Num1 exhibits overlapping but largely distinct localization from wild-type Num1. However, it is fully functional in the dynein pathway. More importantly, cortical PI(4,5)P₂ is dispensable for the localization and function of the CAAX-targeted Num1. Together, these results demonstrate that cortical assembly of Num1 into functional dynein-anchoring patches is independent of its interaction with PI(4,5)P₂.     

The effects of growth hormone on cortical and cancellous bone

Growth hormone (GH) has profound effects on linear bone growth, bone metabolism and bone mass. The GH receptor is found on the cell surface of osteoblasts and osteoclasts, but not on mature osteocytes. In vitro, GH stimulates proliferation, differentiation and extracellular matrix production in osteoblast-like cell lines. GH also stimulates recruitment and bone resorption activity in osteoclast-like cells. GH promotes autocrine/paracrine insulin-like growth factor 1 (IGF-I) production and endocrine (liver-derived) IGF-I production. Some of the GH-induced effects on bone cells can be blocked by IGF-I antibodies, while others cannot. In animal experiments, GH administration increases bone formation and resorption, and enhances cortical bone mass and mechanical strength. When GH induces linear growth, increased cancellous bone volume is seen, but an unaffected cancellous bone volume is found in the absence of linear growth. Patients with acromegaly have increased bone formation and resorption markers. Bone mass results are conflicting because many acromegalics have hypogonadism, but in acromegalics without hypogonadism, increased bone mineral density (BMD) is seen in predominantly cortical bone, and normal BMD in predominantly cancellous bone. Adult patients with growth hormone deficiency have decreased bone mineral content and BMD. GH therapy rapidly increases bone formation and resorption markers. During the first 6-12 months of therapy, declined or unchanged BMD is found in the femoral neck and lumbar spine. All GH trials with a duration of two years or more show enhanced femoral neck and lumbar spine BMD. In osteoporotic patients, GH treatment quickly increases markers for bone formation and resorption. During the first year of treatment, unchanged or decreased BMD values are found, whereas longer treatment periods report enhanced or unchanged BMD values. However, existing trials comprising relatively few patients and limited treatment periods do not allow final conclusions to be drawn regarding the effects of GH on osteoporosis during long-term treatment.     

Elastic constants of composites formed from PMMA bone cement and anisotropic bovine tibial cancellous bone

An ultrasonic pulse-transit time technique is used to determine the nine orthotropic engineering constants of 32 cement-cancellous bone composites as a function of volume fractions of bone ranging from 0.0 to 0.4. The composites are manufactured using well-aligned bovine cancellous bone from the proximal end of the tibia and low viscosity bone cement. Selected composites are also subjected to mechanical compression tests to compare with the ultrasonic results. There is excellent correlation between the dynamic or ultrasonically determined moduli and the static or mechanically determined moduli; the dynamic moduli are approximately twice the static moduli and this difference is thought to be due to the effect of strain rate. An orthotropic model is assumed requiring nine independent elastic constants to be determined. The dynamic Young's modulus in the direction of major trabecular alignment, E1, increases linearly from 4.9 to 10.4 GPa as bone volume fraction increases from 0 to 0.4; dynamic E2 and E3 values increase from 4.9 to 7 GPa as bone volume fractions increase from 0 to 0.4, with E2 being slightly higher than E3. The dynamic shear modulus, G12, increases from 1.8 to 3.0 GPa, and G31 and G23 increase slightly from 1.8 to 2.2 GPa as bone volume fractions increase from 0 to 0.4. The Poisson's ratios are more sensitive than the Young's moduli and shear moduli to experimental error in the velocity measurements. The mechanically tested modulus (static modulus) in the direction of major trabecular alignment, E1, increases with volume fraction of bone from 2.4 to 4.4 GPa as the bone volume fraction increases from 0 to 0.25; static E2 and E3 values are either equal to or lower than that of pure PMMA.     

Experimental and theoretical investigation of directional permeability of human vertebral cancellous bone for cement infiltration

The use of acrylic polymers in infiltrating the porous bone structure is an emerging procedure for the augmentation of osteoporotic vertebrae. Although this procedure is employed frequently, it is performed based on empirical knowledge, and therefore, does not take into consideration the porosity-dependent permeability of human vertebral cancellous bone. The purpose of this study was to: (a). experimentally and theoretically investigate interdependence of the vertebral cancellous bone permeability and porosity, and (b). examine if the bone permeability of spinal cancellous bone can be predicted using bone mineral density measurements. If these relations can be established, they can be useful in optimizing the injection conditions for predicable cement infiltration. To determine the porosity-dependent and directional permeability, 34 bone cores-20 samples in the superior-inferior (SI) direction and 14 in the anterior-posterior (AP) direction-were cut from 20 lumbar vertebrae and infiltrated with silicone oil with a viscosity matching that of PMMA. The permeability of the cores was determined based on Darcy's law. The mean permeability of SI and AP cores was 4.45+/-1.72 x 10(-8) and 3.44+/-1.26 x 10(-8)m(2), respectively. An interesting finding of this study was that the permeability of the AP cores was approximately 78% of that of SI cores, though the porosity of the SI and AP cores taken from the same vertebra was approximately equal. In addition, we provided a theoretical model for the porosity-dependent permeability that accurately described non-linear dependency of the bone permeability and porosity in both directions. Although the relation of the bone permeability and porosity was established, bone mineral density was a weak predictor of the bone permeability. The experimental and theoretical results of this study can be used to understand polymer flow in cement infiltration procedures.     

Normal vision can compensate for the loss of the circadian clock

Circadian clocks are thought to be essential for timing the daily activity of animals, and consequently increase fitness. This view was recently challenged for clock-less fruit flies and mice that exhibited astonishingly normal activity rhythms under outdoor conditions. Compensatory mechanisms appear to enable even clock mutants to live a normal life in nature. Here, we show that gradual daily increases/decreases of light in the laboratory suffice to provoke normally timed sharp morning (M) and evening (E) activity peaks in clock-less flies. We also show that the compound eyes, but not Cryptochrome (CRY), mediate the precise timing of M and E peaks under natural-like conditions, as CRY-less flies do and eyeless flies do not show these sharp peaks independently of a functional clock. Nevertheless, the circadian clock appears critical for anticipating dusk, as well as for inhibiting sharp activity peaks during midnight. Clock-less flies only increase E activity after dusk and not before the beginning of dusk, and respond strongly to twilight exposure in the middle of the night. Furthermore, the circadian clock responds to natural-like light cycles, by slightly broadening Timeless (TIM) abundance in the clock neurons, and this effect is mediated by CRY.     

Impacted morselized cancellous bone: mechanical effects of defatting and augmentation with fine hydroxyapatite particles

Geotechnical engineering testing techniques were used to study the mechanical properties of morselized cancellous bone (MCB) and the effects of defatting and augmentation with fine hydroxyapatite (HA) particles. Bovine and human cancellous bone was morselized, rinsed, and manually squeezed to remove excess fluid, producing a standard surgical MCB sample that was also used as a control. Some of the MCB was defatted with heat and detergent and mixed with HA particles in ratios ranging from 0% to 100% HA. Compaction tests were used to determine the effects of moisture content and the amount of MCB that can be packed into a confined space. One-dimensional consolidation tests were used to determine the uniaxial strain behavior, confined modulus, and steady-state creep rate. The compaction tests demonstrated that defatting and adding HA particles significantly increased density. The one-dimensional consolidation tests showed that strain was decreased, modulus was increased and the creep rate was decreased by defatting and adding HA.     

N-cofilin can compensate for the loss of ADF in excitatory synapses

Actin plays important roles in a number of synaptic processes, including synaptic vesicle organization and exocytosis, mobility of postsynaptic receptors, and synaptic plasticity. However, little is known about the mechanisms that control actin at synapses. Actin dynamics crucially depend on LIM kinase 1 (LIMK1) that controls the activity of the actin depolymerizing proteins of the ADF/cofilin family. While analyses of mouse mutants revealed the importance of LIMK1 for both pre- and postsynaptic mechanisms, the ADF/cofilin family member n-cofilin appears to be relevant merely for postsynaptic plasticity, and not for presynaptic physiology. By means of immunogold electron microscopy and immunocytochemistry, we here demonstrate the presence of ADF (actin depolymerizing factor), a close homolog of n-cofilin, in excitatory synapses, where it is particularly enriched in presynaptic terminals. Surprisingly, genetic ablation of ADF in mice had no adverse effects on synapse structure or density as assessed by electron microscopy and by the morphological analysis of Golgi-stained hippocampal pyramidal cells. Moreover, a series of electrophysiological recordings in acute hippocampal slices revealed that presynaptic recruitment and exocytosis of synaptic vesicles as well as postsynaptic plasticity were unchanged in ADF mutant mice. The lack of synaptic defects may be explained by the elevated n-cofilin levels observed in synaptic structures of ADF mutants. Indeed, synaptic actin regulation was impaired in compound mutants lacking both ADF and n-cofilin, but not in ADF single mutants. From our results we conclude that n-cofilin can compensate for the loss of ADF in excitatory synapses. Further, our data suggest that ADF and n-cofilin cooperate in controlling synaptic actin content.     

Anisotropy and inhomogeneity of the trabecular structure can describe the mechanical strength of osteoarthritic cancellous bone

Osteoarthritic cancellous bone was studied to investigate the development of this pathology, and the functional changes it induces in the bone. In order to predict how the morphological alterations of the tissue induced by the pathology can change the mechanical properties of the structure, two different strategies have been used in the literature: (1) emphasising the influence of structural anisotropy; (2) stressing the highly inhomogeneous characteristics of cancellous bone. The aim of the present study was to verify the theory that mechanical strength of osteoarthritic cancellous bone depends both on tissue anisotropy and inhomogeneity.Twenty-five specimens were extracted from osteoarthritic femoral heads, along selected directions, and analysed by means of a microtomograph. The same specimens were mechanically tested in compression to determine the mechanical strength. The most representative structural parameters, confirmed by a stepwise analysis, were used to define four models to describe the measured mechanical strength. The models were applied neglecting (global analysis) or considering (local analysis) tissue inhomogeneities to verify whether the correlation with ultimate stress could be improved.The coefficient of determination increased from 0.53, considering only bone volume fraction, up to 0.88, combining it with off-axis angle and normalised eigenvalue. A further improvement was found performing a local analysis (R²=0.90), which corresponded to a decrease of 17% in the residual error.The proposed approach of considering both tissue anisotropy and inhomogeneity improved the accuracy in predicting the mechanical behaviour of cancellous bone tissue and should be suitable for more general loading conditions.     

Effect of resistance exercise training on cortical and cancellous bone in mature male rats

Westerlind, Kim C., James D. Fluckey, Scott E. Gordon,William J. Kraemer, Peter A. Farrell, and Russell T. Turner.Effect of resistance exercise training on cortical and cancellousbone in mature male rats. J. Appl.Physiol. 84(2): 459-464, 1998.The effect ofresistance training on tibial cancellous and cortical bone wasevaluated in rats by using static histomorphometry and Northernanalysis. Five-month-old male Sprague-Dawley rats were randomlyassigned to exercise (Ex; n = 8) orcontrol (Con; n = 4) groups. Animalswere operantly conditioned to press two levers, facilitating fullextension and flexion of the hindlimbs ("squats"), while wearingan unweighted vest. After an 8-wk familiarization period, Ex animalsperformed 3 sessions/wk for 17-19 sessions with progressivelyincreased amounts of weight applied to the vest. Con rats completed thesame exercise protocol without applied resistance. No difference incross-sectional, medullary, or cortical bone area was observed betweenEx and Con rats in the tibial diaphysis. In contrast, the cancellousbone area in the proximal tibial metaphysis was significantly larger intrained rats. Trabecular number, trabecular thickness, and thepercentage of cancellous bone covered by osteoid were significantlygreater in the Ex animals compared with Con animals. In addition,steady-state mRNA levels for osteocalcin for the Ex group were 456%those expressed in the Con group. The data demonstrate that resistancetraining increases cancellous bone area in sexually mature male ratsand suggest that it does so, in part, by stimulating bone formation.

     

Variability of tissue mineral density can determine physiological creep of human vertebral cancellous bone

Creep is a time-dependent viscoelastic deformation observed under a constant prolonged load. It has been indicated that progressive vertebral deformation due to creep may increase the risk of vertebral fracture in the long-term. The objective of this study was to examine the relationships of creep with trabecular architecture and tissue mineral density (TMD) parameters in human vertebral cancellous bone at a physiological static strain level. Architecture and TMD parameters of cancellous bone were analyzed using microcomputerized tomography (micro-CT) in specimens cored out of human vertebrae. Then, creep and residual strains of the specimens were measured after a two-hour physiological compressive constant static loading and unloading cycle. Creep developed (3877 ± 2158 με) resulting in substantial levels of non-recoverable post-creep residual strain (1797 ± 1391 με). A strong positive linear correlation was found between creep and residual strain (r = 0.94, p < 0.001). The current results showed that smaller thickness, larger surface area, greater connectivity of trabeculae, less mean tissue mineral density (TMD, represented by gray levels) and higher variability of TMD are associated with increasing logarithmic creep rate. The TMD variability (GL(COV)) was the strongest correlate of creep rate (r = 0.79, p < 0.001). This result suggests that TMD variability may be a useful parameter for estimating the long-term deformation of a whole vertebral body. The results further suggest that the changes in TMD variability resulting from bone remodeling are of importance and may provide an insight into the understanding of the mechanisms underlying progressive failure of vertebral bodies and development of a clinical fracture.     

Use of the cylinder osteotome for cancellous bone grafting

An instrument is described for removing iliac crest cancellous bone grafts under local anesthesia. The device has widespread applications for plastic and orthopedic surgery. The convenience of obtaining bone grafts with this device broadens the use of bone-grafting techniques in patients in whom the need for bone graft is unexpected.     

万古霉素骨水泥用于骨折内固定术后髓内感染的临床价值分析

目的探讨万古霉素骨水泥用于骨折内固定术后髓内感染的临床价值。方法回顾性分析2013年1月至2014年6月通海骨伤医院收治的28例应用万古霉素骨水泥治疗骨折术后髓内感染患者的临床资料;彻底清创扩髓后植入万古霉素骨水泥;术后按药敏结果给予抗菌药物治疗,记录患者感染控制时间及复发情况。结果所有患者均获得随访,平均随访时间14个月。其中26例患者感染均得到控制,治疗时间为3~6个月,平均治疗时间为(4.1±0.7)个月。1例因局部反复有渗出,感染未控制,1例患者感染复发,均经再次清创万古霉素骨水泥置入,感染得到控制;按临床疗效结果判定,本研究优23例,良3例,差2例,优良率为92.9%。结论采用万古霉素骨水泥填塞法治疗骨折内固定术后髓内感染安全有效,可减少感染复发,临床价值高值得推广。     

Comparative effects of alendronate and alfacalcidol on cancellous and cortical bone mass and bone mechanical properties in ovariectomized rats.

The purpose of the present study was to compare the effects of alendronate and alfacalcidol on cancellous and cortical bone mass and bone mechanical properties in ovariectomized rats. Twenty-six female Sprague-Dawley rats, 7 months of age, were randomized by the stratified weight method into four groups: the sham-operated control (Sham) group and the three ovariectomy (OVX) groups, namely, OVX + vehicle, OVX + alendronate (2.5 mg/kg, p.o., daily), and OVX + alfacalcidol (0.5 mug/kg, p.o., daily). At the end of the 8-week experimental period, bone histomorphometric analyses of cancellous bone at the proximal tibial metaphysis and cortical bone at the tibial diaphysis were performed, and the mechanical properties of the femoral distal metaphysis and femoral diaphysis were evaluated. OVX decreased cancellous bone volume per total tissue volume (BV/TV), and the maximum load of the femoral distal metaphysis, as a result of increases in serum osteocalcin (OC) levels, and also the number of osteoclasts (N.Oc), osteoclast surface (OcS) and bone formation rate (BFR) per bone surface (BS), and BFR/BV, without any effect on cortical area (Ct Ar), or maximum load of the femoral diaphysis. Alendronate prevented this decrease in cancellous BV/TV by suppressing increases in N.Oc/BS, OcS/BS, BFR/BS, and BFR/BV, without any apparent effect on Ct Ar, or maximum load of the femoral distal metaphysis and femoral diaphysis. On the other hand, alfacalcidol increased cancellous BV/TV, Ct Ar, and the maximum load of the femoral distal metaphysis and femoral diaphysis, by mildly decreasing trabecular BFR/BV, maintaining trabecular mineral apposition rate and osteoblast surface per BS, increasing periosteal and endocortical BFR/BS, and preventing an increase in endocortical eroded surface per BS. The present study clearly showed the differential skeletal effects of alendronate and alfacalcidol in ovariectomized rats. Alendronate prevented OVX-induced cancellous bone loss by suppressing bone turnover, while alfacalcidol improved cancellous and cortical bone mass and bone strength by suppressing bone resorption and maintaining or even increasing bone formation.     

Continuous infusion of PGE2 is catabolic with a negative bone balance on both cancellous and cortical bone in rats

It is well documented that intermittent PGE(2) treatment increases both trabecular and cortical bone mass. However, the effects of continuous PGE(2) administration remain undocumented. The aim of the study was to investigate the effects of continuous prostaglandin E(2) (PGE(2)) on different bone sites in skeletally mature rats. Six-month-old Sprague Dawley rats were treated with PGE(2) at 1 or 3 mg/kg/d continuously via infusion pump for 21 days. Two other groups of rats received PGE(2) at the same doses by intermittent (daily) subcutaneous injections and served as positive controls. Histomorphometry was performed on cancellous bone of the proximal tibial metaphysis and cortical bone of the tibial shaft. As expected, intermittent PGE(2) treatment increased both cancellous and cortical bone mass by stimulating bone formation at the cancellous, periosteal and endocortical bone surfaces. In contrast, continuous PGE(2) treatment decreased cancellous bone mass with bone resorption exceeding bone formation. In addition, continuous PGE(2) treatment increased endocortical and intracortical bone remodeling, inducing bone loss which was partially offset by stimulating periosteal expansion. We conclude that continuous PGE(2) treatment induces overall catabolic effects on both cancellous and cortical bone envelopes, which differs from intermittent PGE(2) treatment that is anabolic. Lastly, we speculate that superior bone mass may be achieved by co-treatment of continuous PGE(2) in combination with an anti-catabolic agent.     

hSMUG1 can functionally compensate for Ung1 in the yeast Saccharomyces cerevisiae

There are at least four distinct families of enzymes that recognize and remove uracil from DNA. Family-3 (SMUG1) enzymes have recently been identified and have a preference for uracil in single-stranded DNA when assayed in vitro. Here we investigate the in vivo function of SMUG1 using the yeast Saccharomyces cerevisiae as a model system. These organisms lack a SMUG1 homologue and use a single enzyme, Ung1 to carry out uracil-repair. When a wild-type strain is treated with antifolate agents to induce uracil misincorporation into DNA, S-phase arrest and cellular toxicity occurs. The arrest is characteristic of checkpoint activation due to single-strand breaks caused by continuous uracil removal and self-defeating DNA repair. When uracil-DNA glycosylase is deleted (deltaung1), cells continue through S-phase and arrest at G(2)/M, presumably due to the effects of stable uracil misincorporation in DNA. Pulsed field gel electrophoresis (PFGE) demonstrates that cells are able to complete DNA replication with uracil-substituted DNA and do not experience the extensive strand breakage attributed to uracil-DNA glycosylase-mediated repair. As a result, these cells experience early protection from antifolate-induced cytotoxicity. When either UNG1 or SMUG1 functions are reintroduced back into the null strain and then subjected to antifolate treatment, the cells revert back to the wild-type phenotype as shown by a restored sensitivity to drug and S-phase arrest. The arrest is accompanied by the accumulation of replication intermediates as determined by PFGE. Collectively, these data indicate that SMUG1 can act as a functional homolog of the family-1 uracil-DNA glycosylase enzymes.     

Intracellular Ca can compensate for the lack of NADPH oxidase-derived ROS in endothelial cells

The aim of the present study is to determine the role of intracellular Ca²⁺ in VEGF signaling. We demonstrate that reduction in Ca²⁺ by chelating compound BAPTA-AM or by IP₃-endoplasmic reticulum blocker 2-APB selectively inhibited VEGF-induced activation of c-Src-PI3K-Akt but not ERK1/2 in human coronary artery endothelial cells (HCAEC). We also show that the selective inhibitory effects of NADPH oxidase knockdown on VEGF-mediated activation of c-Src-PI3K-Akt signaling and cell proliferation in HCAEC can be reversed by increase in intracellular Ca²⁺. These results suggest an essential role for Ca²⁺ in redox-dependent selective activation of c-Src-PI3K-Akt and endothelial cell proliferation.