Vertebral Cortical Bone Research Articles

SIRT1 haplo-insufficiency results in reduced cortical bone thickness, increased porosity and decreased estrogen receptor alpha in bone in adult 129/Sv female mice.

Sirtuin 1 (SIRT1) is a key player in aging and metabolism and regulates bone mass and architecture. Sexual dimorphism in skeletal effects of SIRT1 has been reported, with an unfavorable phenotype primarily in female mice. To investigate the mechanisms of gender differences in SIRT1 skeletal effect, we investigated femoral and vertebral cortical and cancellous bone in global Sirt1 haplo-insufficient 129/Sv mice aged 2,7,12 months lacking Sirt1 exons 5,6,7 (Sirt1+/Δ ) and their wild type (WT) counterparts. In females, femoral bone mineral content, peak cortical thickness, and trabecular bone volume (BV/TV%), number and thickness were significantly lower in Sirt1+/Δ compared to WT mice. Increased femoral cortical porosity was observed in 7-month-old Sirt1+/Δ compared to WT female mice, accompanied by reduced biomechanical strength. No difference in vertebral indices was detected between Sirt1+/Δ and WT female mice. SIRT1 decreased with aging in WT female mice and was lower in vertebrae and femur in 18- and 30- versus 3-month-old 129/Sv and C57BL/6J female mice, respectively. Decreased bone estrogen receptor alpha (ERα) was observed in Sirt1+/Δ compared to WT female mice and was significantly higher in Sirt1 over-expressing C3HT101/2 murine mesenchymal stem cells. In males no difference in femoral indices was detected in Sirt1+/Δ versus WT mice, however vertebral BV/TV%, trabecular number and thickness were higher in Sirt1+/Δ vs. WT mice. No difference in androgen receptor (AR) was detected in bone in Sirt1+/Δ vs. WT male mice. Bone SIRT1 was significantly lower in male compared to female WT mice, suggesting that SIRT1 maybe more significant in female than male skeleton. These findings demonstrate that 50% reduction in SIRT1 is sufficient to induce the hallmarks of skeletal aging namely, decreased cortical thickness and increased porosity in female mice, highlighting the role of SIRT1 as a regulator of cortical bone quantity and quality. The effects of SIRT1 in cortical bone are likely mediated in part by its regulation of ERα. The age-associated decline in bone SIRT1 positions SIRT1 as a potential therapeutic target to ameliorate age-related cortical bone deterioration in females. The crosstalk between ERα, AR and SIRT1 in the bone microenvironment remains to be further investigated.

Computational modeling and analysis of thoracolumbar spine fractures in frontal crash reconstruction

Objective: This study aimed to reconstruct 11 motor vehicle crashes (6 with thoracolumbar fractures and 5 without thoracolumbar fractures) and analyze the fracture mechanism, fracture predictors, and associated parameters affecting thoracolumbar spine response.Methods: Eleven frontal crashes were reconstructed with a finite element simplified vehicle model (SVM). The SVM was tuned to each case vehicle and the Total HUman Model for Safety (THUMS) Ver. 4.01 was scaled and positioned in a baseline configuration to mimic the documented precrash driver posture. The event data recorder crash pulse was applied as a boundary condition. For the 6 thoracolumbar fracture cases, 120 simulations to quantify uncertainty and response variation were performed using a Latin hypercube design of experiments (DOE) to vary seat track position, seatback angle, steering column angle, steering column position, and D-ring height. Vertebral loads and bending moments were analyzed, and lumbar spine indices (unadjusted and age-adjusted) were developed to quantify the combined loading effect. Maximum principal strain and stress data were collected in the vertebral cortical and trabecular bone. DOE data were fit to regression models to examine occupant positioning and thoracolumbar response correlations.Results: Of the 11 cases, both the vertebral compression force and bending moment progressively increased from superior to inferior vertebrae. Two thoracic spine fracture cases had higher average compression force and bending moment across all thoracic vertebral levels, compared to 9 cases without thoracic spine fractures (force: 1,200.6 vs. 640.8 N; moment: 13.7 vs. 9.2 Nm). Though there was no apparent difference in bending moment at the L1–L2 vertebrae, lumbar fracture cases exhibited higher vertebral bending moments in L3–L4 (fracture/nonfracture: 45.7 vs. 33.8 Nm). The unadjusted lumbar spine index correctly predicted thoracolumbar fracture occurrence for 9 of the 11 cases (sensitivity = 1.0; specificity = 0.6). The age-adjusted lumbar spine index correctly predicted thoracolumbar fracture occurrence for 10 of the 11 cases (sensitivity = 1.0; specificity = 0.8). The age-adjusted principal stress in the trabecular bone was an excellent indicator of fracture occurrence (sensitivity = 1.0; specificity = 1.0). A rearward seat track position and reclined seatback increased the thoracic spine bending moment by 111–329%. A more reclined seatback increased the lumbar force and bending moment by 16–165% and 67–172%, respectively.Conclusions: This study provided a computational framework for assessing thoracolumbar fractures and also quantified the effect of precrash driver posture on thoracolumbar response. Results aid in the evaluation of motor vehicle crash–induced vertebral fractures and the understanding of factors contributing to fracture risk.

Global Disruption of α2A Adrenoceptor Barely Affects Bone Tissue but Minimizes the Detrimental Effects of Thyrotoxicosis on Cortical Bone.

Evidence shows that sympathetic nervous system (SNS) activation inhibits bone formation and activates bone resorption leading to bone loss. Because thyroid hormone (TH) interacts with the SNS to control several physiological processes, we raised the hypothesis that this interaction also controls bone remodeling. We have previously shown that mice with double-gene inactivation of α2A- and -adrenoceptors (α2A/2C-AR−/−) present high bone mass (HBM) phenotype and resistance to thyrotoxicosis-induced osteopenia, which supports a TH-SNS interaction to control bone mass and suggests that it involves α2-AR signaling. Accordingly, we detected expression of α2A-AR, α2B-AR and α2C-AR in the skeleton, and that triiodothyronine (T3) modulates α2C-AR mRNA expression in the bone. Later, we found that mice with single-gene inactivation of α2C-AR (α2C-AR−/−) present low bone mass in the femur and HBM in the vertebra, but that both skeletal sites are resistant to TH-induce osteopenia, showing that the SNS actions occur in a skeletal site-dependent manner, and that thyrotoxicosis depends on α2C-AR signaling to promote bone loss. To further dissect the specific roles of α2-AR subtypes, in this study, we evaluated the skeletal phenotype of mice with single-gene inactivation of α2A-AR (α2A-AR−/−), and the effect of daily treatment with a supraphysiological dose of T3, for 4 or 12 weeks, on bone microarchitecture and bone resistance to fracture. Micro-computed tomographic (μCT) analysis revealed normal trabecular and cortical bone structure in the femur and vertebra of euthyroid α2A-AR−/− mice. Thyrotoxicosis was more detrimental to femoral trabecular bone in α2A-AR−/− than in WT mice, whereas this bone compartment had been previously shown to present resistance to thyrotoxicosis in α2C-AR−/− mice. Altogether these findings reveal that TH excess depends on α2C-AR signaling to negatively affect femoral trabecular bone. In contrast, thyrotoxicosis was more deleterious to femoral and vertebral cortical bone in WT than in α2A-AR−/− mice, suggesting that α2A-AR signaling contributes to TH actions on cortical bone. These findings further support a TH-SNS interaction to control bone physiology, and suggest that α2A-AR and α2C-AR signaling pathways have key roles in the mechanisms through which thyrotoxicosis promotes its detrimental effects on bone remodeling, structure and resistance to fracture.

Effects of Low Bone Mineral Status on Biomechanical Characteristics in Idiopathic Scoliotic Spinal Deformity.

Low bone mass in patients with adolescent idiopathic scoliosis has been well reported. Poor bone quality was regarded as a new and unique prognostic factor in aggravating curve progression. However, the potential biomechanical correlation between them remains unclear. Three-dimensional finite element models of idiopathic scoliotic spine with different bone mineral status were created for axial loading simulation. An axial load of 3 different body weights was applied on different bone mineral mass models. The mechanical responses of the vertebral cortical and cancellous bone, facet joints, end plate, and intervertebral disc were analyzed. Accompanied with the low bone mineral status, thoracic scoliosis produced asymmetric and higher stress in the cortical bone, lumbar facet joints, and end plate at the concave side of the thoracic structure curve. Stress increased in the disc at the apex of the scoliosis, whereas it mildly decreased in the L4-5 and L5-S1 disc. Body weight gain increased the stress in scoliotic spine structures in all bone mineral statues. Biomechanical simulations indicated that low bone mineral mass might aggravate curve progression and induce more serious lumbar compensatory scoliosis in patients with adolescent idiopathic scoliosis. Weight gain was also a risk factor for curve progression.

Abstract 253: Mammary tumorigenesis causes bone loss and dietary selenium supplementation does not affect such bone loss in male MMTV-PyMT mice

Abstract Cancer progression is accompanied by wasting that eventually results in cachexia characterized by significant weight loss and multi-organ functional failures. Limited clinical trials indicate that bone is adversely affected by cancer-associated wasting. To determine the effects of breast cancer on skeletal health, we performed micro-computed tomographic analysis of femurs and vertebrae collected from a recently completed study showing that dietary supplementation with selenium (methylseleninic acid, 2.5 mg Se/kg) reduced male mammary tumorigenesis in MMTV-PyMT mice. Compared to age-matched non-tumor-bearing mice (MMTV-PyMT negative), the presence of mammary tumors significantly reduced bone volume fraction, trabecular thickness and bone mineral density and increased the structure model index (an indicator of the plate- and rod-like geometry of trabecular structure) in femoral trabecular bone. Mammary tumor development did not affect vertebral trabeculae nor femoral and vertebral cortical bone, except it significantly reduced cortical bone thickness of vertebrae. There were no differences in aforementioned measurements between groups with or without selenium supplementation. In conclusion, mammary tumorigenesis causes bone loss and dietary selenium supplementation at 2.5 mg Se/kg, which is antitumorigenic, does not affect mammary tumor-associated bone loss in this male MMTV-PyMT breast cancer model. Citation Format: Lin Yan. Mammary tumorigenesis causes bone loss and dietary selenium supplementation does not affect such bone loss in male MMTV-PyMT mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 253. doi:10.1158/1538-7445.AM2017-253

The effect of screw tunnels on the biomechanical stability of vertebral body after pedicle screws removal: a finite element analysis

Posterior reduction and pedicle screw fixation is a widely used procedure for thoracic and lumbar vertebrae fractures. Usually, the pedicle screws would be removed after the fracture healing and screw tunnels would be left. The aim of this study is to evaluate the effect of screw tunnels on the biomechanical stability of the lumbar vertebral body after pedicle screws removal by finite element analysis (FEA). First, the CT values of the screw tunnels wall in the fractured vertebral bodies were measured in patients whose pedicle screws were removed, and they were then compared with the values of vertebral cortical bone. Second, an adult patient was included and the CT images of the lumbar spine were harvested. Three dimensional finite element models of the L1 vertebra with unilateral or bilateral screw tunnels were created based on the CT images. Different compressive loads were vertically acted on the models. The maximum loads which the models sustained and the distribution of the force in the different parts of the models were recorded and compared with each other. The CT values of the tunnels wall and vertebral cortical bone were 387.126±62.342 and 399.204±53.612, which were not statistically different (P=0.149). The models of three dimensional tetrahedral mesh finite element of normal lumbar 1 vertebra were established with good geometric similarity and realistic appearance. After given the compressive loads, the cortical bone was the first one to reach its ultimate stress. The maximum loads which the bilateral screw tunnels model, unilateral screw tunnel model, and normal vertebral model can sustain were 3.97 Mpa, 3.83 Mpa, and 3.78 Mpa, respectively. For the diameter of the screw tunnels, the model with a diameter of 6.5 mm could sustain the largest load. In addition, the stress distributing on the outside of the cortical bone gradually decreased as the thickness of the tunnel wall increased. Based on the FEA, pedicle screw tunnels would not decrease the biomechanical stability and strength of the vertebral body. A large diameter of screw tunnel and thick tunnel wall were helpful for the biomechanical stability of the vertebral body.

Cement Leakage in Percutaneous Vertebral Augmentation for Osteoporotic Vertebral Compression Fractures: Analysis of Risk Factors.

The risk factors for cement leakage were retrospectively reviewed in 192 patients who underwent percutaneous vertebral augmentation (PVA). To discuss the factors related to the cement leakage in PVA procedure for the treatment of osteoporotic vertebral compression fractures. PVA is widely applied for the treatment of osteoporotic vertebral fractures. Cement leakage is a major complication of this procedure. The risk factors for cement leakage were controversial. A retrospective review of 192 patients who underwent PVA was conducted. The following data were recorded: age, sex, bone density, number of fractured vertebrae before surgery, number of treated vertebrae, severity of the treated vertebrae, operative approach, volume of injected bone cement, preoperative vertebral compression ratio, preoperative local kyphosis angle, intraosseous clefts, preoperative vertebral cortical bone defect, and ratio and type of cement leakage. To study the correlation between each factor and cement leakage ratio, bivariate regression analysis was employed to perform univariate analysis, whereas multivariate linear regression analysis was employed to perform multivariate analysis. The study included 192 patients (282 treated vertebrae), and cement leakage occurred in 100 vertebrae (35.46%). The vertebrae with preoperative cortical bone defects generally exhibited higher cement leakage ratio, and the leakage is typically type C. Vertebrae with intact cortical bones before the procedure tend to experience type S leakage. Univariate analysis showed that patient age, bone density, number of fractured vertebrae before surgery, and vertebral cortical bone were associated with cement leakage ratio (P<0.05). Multivariate analysis showed that the main factors influencing bone cement leakage are bone density and vertebral cortical bone defect, with standardized partial regression coefficients of -0.085 and 0.144, respectively. High bone density and vertebral cortical bone defect are independent risk factors associated with bone cement leakage.

Identification and Characterization of a Synthetic Osteogenic Peptide.

Osteoporosis is the most common metabolic bone disorder and its management represents a tremendous public health encumbrance. While several classes of therapeutics have been approved to treat this disease, all are associated with significant adverse effects. An algorithm was developed and utilized to discover potential bioactive peptides, which led to the identification of an osteogenic peptide that mapped to the C-terminal region of the calcitonin receptor and has been named calcitonin receptor fragment peptide (CRFP). In vitro treatment of human mesenchymal stem cells with CRFP resulted in dose-specific effects on both proliferation and osteoblastic differentiation. Similarly, in vitro treatment of rat RCJ3.1C5.18 cells led to dose- and species-specific effects on proliferation. A rat ovariectomy (OVX) model was used to assess the potential efficacy of CRFP in treating osteoporosis. MicroCT analysis of distal femoral samples showed that OVX rats treated with CRFP were significantly protected from losses of 55 % in trabecular bone volume fraction (BVF), 42 % in connectivity density, and 18 % in trabecular thickness in comparison to vehicle-treated controls. MicroCT analyses of vertebrae revealed CRFP to significantly prevent a 25 % reduction in BVF. MicroCT evaluation of femoral and vertebral cortical bone found a significant reduction of 2 % in vertebral bone mineral density. In summary, our in vitro studies indicate that CRFP is both bioactive and osteogenic and our in vivo studies indicate that CRFP is skeletally bioactive. These promising data indicate that further in vitro and in vivo evaluation of CRFP as a new treatment for osteoporosis is warranted.

Evaluation of crystallographic orientation of biological apatite in vertebral cortical bone in ovariectomized cynomolgus monkeys treated with minodronic acid and alendronate.

Quantitative analysis of the orientational distribution of biological apatite (BAp) crystals is proposed as a new index of bone quality. This study aimed to analyze BAp c-axis orientation in ovariectomized (OVX) monkeys treated with amino-bisphosphonates minodronic acid and alendronate as reference. Sixty female monkeys aged 9-17years were divided into five groups: one sham group and four OVX groups. The sham group and one OVX group were treated daily with vehicle for 17months. The other three groups were treated daily with minodronic acid at doses of 0.015 and 0.15mg/kg, and alendronate at 0.5mg/kg orally, respectively. The seventh lumbar vertebrae were subjected to analysis of the preferential BAp c-axis orientation in the ventral cortical bone. The BAp c-axis orientation along the craniocaudal axis was significantly increased in the OVX monkeys. The high dose of minodronic acid suppressed the OVX-induced increase in the BAp c-axis orientation, whereas alendronate showed a non-significant tendency to suppress the increase in the orientation. In analysis with other parameters, the BAp c-axis orientation was positively correlated with bone formation indices in biochemical markers and bone histomorphometry and negatively correlated with the increase in lumbar bone mineral density. On the other hand, the BAp c-axis orientation was not correlated with bone resorption indices, except for the eroded surface. These results indicate that the increase in BAp c-axis orientation was ameliorated by minodronic acid treatment in OVX monkeys, mainly by suppression of bone formation increase.

A Probabilistic Fracture Assessment of Vertebral Cortical Bone

A Probabilistic Fracture Assessment of Vertebral Cortical Bone

Relationship between human rib mechanical properties and cortical bone density measured by high-resolution quantitative computed tomography

Thoracic injuries are among the most serious injuries in vehicle crash accidents. To improve the safety of vehicle occupants, it is essential to have a better knowledge on biomechanical responses of human rib cage (Vezin and Berthet 2009). A better knowledge of the bone mechanical properties should be of great interest to take into account the inter-individual differences in the population. For such purpose, a non-invasive technique is requested. Quantitative computed tomography (QCT) is a clinical modality that can be used to measure bone density. A literature review by Helgason et al. (2008) demonstrated that bone density (measured by QCT) was a good predictor of bone mechanical properties. Kopperdahl et al. (2002) and Duchemin et al. (2008) showed the relationships between bone density assessed by QCT and mechanical properties on vertebral cancellous bone and femoral cortical bone respectively. In this context, the question is: do such relationships exist on human ribs? No study has demonstrated such relationships on this anatomical site. Thus, the goal of this study is to assess the relationship between human rib mechanical properties and the density.

Contribution of trabecular and cortical components to biomechanical behavior of human vertebrae: an ex vivo study.

Whereas there is clear evidence for a strong influence of bone quantity (i.e., bone mass or bone mineral density) on vertebral mechanical behavior, there are fewer data addressing the relative influence of cortical and trabecular bone microarchitecture. The aim of this study was to determine the relative contributions of bone mass, trabecular microarchitecture, and cortical thickness and curvature to the mechanical behavior of human lumbar vertebrae. Thirty-one L3 vertebrae (16 men, 15 women, aged 75 +/- 10 years and 76 +/- 10 years, respectively) were obtained. Bone mineral density (BMD) of the vertebral body was assessed by lateral dual energy X-ray absorptiometry (DXA), and 3D trabecular microarchitecture and anterior cortical thickness and curvature was assessed by micro-computed tomography (microCT). Then compressive stiffness, work to failure, and failure load were measured on the whole vertebral body. BMD was correlated with compressive stiffness (r = 0.60), failure load (r = 0.70), and work to failure (r = 0.55). Except for the degree of anisotropy, all trabecular and cortical parameters were correlated with mechanical behavior (r = 0.36 to 0.58, p = .05 to .001, and r = 0.36 to 0.61, p = .05 to .0001, respectively). Stepwise and multiple regression analyses indicated that the best predictor of (1) failure load was the combination of BMD, structural model index (SMI), and trabecular thickness (Tb.Th) (R = 0.80), (2) stiffness was the combination of BMD, Tb.Th, and curvature of the anterior cortex (R = 0.82), and (3) work to failure was the combination of anterior cortical thickness and BMD (R = 0.68). Our data imply that measurements of cortical thickness and curvature may enhance prediction of vertebral fragility and that therapies that improve both vertebral cortical and trabecular bone properties may provide a greater reduction in fracture risk.

Human versus sheep vertebral cortical bone strain and intervertebral disc mechanical properties

Human versus sheep vertebral cortical bone strain and intervertebral disc mechanical properties

Determinants of prevalent vertebral fractures and progressive bone loss in long-term hemodialysis patients

Skeletal fractures are common in hemodialysis (HD) patients. However, consensus regarding technique and site of bone examination has not been reached in HD patients. Seventy-two patients (44% females) aged 65 (1.4) years, treated with HD for 43 (4.6) months were examined with quantitative computed tomography and 53 of them re-examined after 1 year. Bone mineral density (BMD) of lumbar spine was established separately for cortical and trabecular bone, prevalent vertebral fractures were determined. Data are given as mean (standard error). At least one vertebral fracture was discovered in 15 (21%) patients. In a logistic regression model, fractures were best predicted by cortical BMD: OR 0.96 (CI 0.94, 0.99), p < 0.005. With a multiple regression analysis, time on dialysis was found to be independently correlated to cortical BMD (R = 0.35, p < 0.005). On follow-up, a decrease of BMD was detected, which occurred only in the cortical region and was significantly greater in females than in males: -7% (1.7) versus 1.2% (1.9), p < 0.005. A time-dependent loss of vertebral cortical bone occurs in HD patients, especially in females. This decrement may impose an increased risk of fractures on long-term dialysis patients.

Postcranial skeletal pneumaticity: a case study in the use of quantitative microCT to assess vertebral structure in birds

Limb elements in birds have been characterized as exhibiting a reduction in trabecular bone, thinner cortices and decreased bending strength when pneumatized, yet it is unclear if these characteristics generalize to the axial skeleton. Thin section techniques, the traditional gold standard for bone structure studies, have most commonly been applied to the study of avian bone. This destructive technique, however, makes it subsequently impossible to use the same samples in experimental testing systems that allow researchers to correlate structure with the mechanical properties of the bone. Micro-computed tomography (microCT), a non-destructive X-ray imaging technique, can be used to assess the effect of pneumatization on vertebral cortical and trabecular bone through virtual extraction and structural quantification of each tissue type. We conducted a preliminary investigation of the application of microCT methods to the study of cortical and trabecular bone structure in a small sample of pneumatic and apneumatic thoracic vertebrae. The sample consisted of two similar-sized anatids, Aix sponsa (n = 7) and Oxyura jamaicensis (n = 5). Volumes of interest were created that contoured (outlined) the boundaries of the ventral cortical bone shell, the trabecular compartment and the whole centrum (cortical bone + trabecular bone), and allowed independent structural analysis of each volume of interest. Results indicated that bone volume fraction of the whole centrum was significantly higher in the apneumatic O. jamaicensis than in the pneumatized A. sponsa (A. sponsa = 36%, O. jamaicensis = 48%, P < 0.05). In contrast, trabecular bone volume fraction was similar between the two species. The ventral cortical bone shell was approximately 23% thinner (P < 0.05) in A. sponsa (0.133 mm) compared with apneumatic O. jamaicensis (0.172 mm). This case study demonstrates that microCT is a powerful non-destructive imaging technique that may be applied to the three-dimensional study of avian bone. The preliminary results suggest that pneumatic and apneumatic vertebrae of comparably sized avian species differ in relative bone volume, with the largest difference apparent at the level of the cortex, and not within trabecular bone. The presence of relatively thin cortices in pneumatic vertebrae is consistent with previous studies contrasting diaphyseal cortical bone between pneumatic and apneumatic long bones. Methodological issues related to this and any comparative microCT study of bone structure are discussed.

Effects of cyclic vs. daily treatment with human parathyroid hormone (1–34) on murine bone structure and cellular activity

Previously, we demonstrated that the human parathyroid hormone (1–34) fragment (hPTH(1–34)) increased bone strength in proportion to its effects on BMD and cortical bone structure in the murine femur by comparing cyclic vs. daily administration of hPTH(1–34). Both cyclic and daily regimens increased vertebral BMD similarly at 7 weeks. Here, we have examined the effects of daily and cyclic PTH regimens on bone structure and cellular activity by static and dynamic histomorphometry. Twenty-week-old, intact female C57BL/J6 mice were treated with the following regimens ( n = 7 for each group): daily injection with vehicle for 7 weeks [control]; daily injection with hPTH(1–34) (40 μg/kg/day) for 7 weeks [daily PTH]; and daily injection with hPTH(1–34) (40 μg/kg/day) and vehicle alternating weekly for 7 weeks [cyclic PTH]. At days 9 and 10, and 2 and 3 prior to euthanasia, calcein (10 mg/kg) was injected subcutaneously. At the end of study, the lumbar vertebrae 1–3 and the left femora were excised, cleaned, and processed for histomorphometry. In the lumbar vertebrae, daily and cyclic PTH regimens significantly increased cancellous bone volume (BV/TV), trabecular number, trabecular osteoclast and osteoblast perimeters, trabecular mineral apposition rate (MAR) and bone formation rate (BFR), and periosteal MAR and BFR compared to control, with no significant difference between the two PTH-treated groups. Increased trabecular tunneling was observed in both PTH-treated groups. Both regimens tended to increase vertebral cortical bone formation parameters with the effects at the periosteum site being more marked than those at the endosteum site, resulting in a significant increase in cortical width. In the femur, the effects of cyclic PTH on BV/TV, trabecular width and number, trabecular and endocortical osteoblast and osteoclast perimeters, cortical width, and trabecular and periosteal BFR were less marked than those of daily PTH. A cyclic PTH regimen was as effective as a daily regimen in improving cancellous and cortical bone microarchitecture and cellular activity in the murine vertebra.

Parametric finite element model of lower cervical spine (C3–C7) in sagital plane

Cervical spine injuries could have life threatening consequences. This has made biomechanical studies on this region to be essentially needed. In this research a parametric 2D finite element model has been developed for lower cervical spine (C3-C7) in sagital plane. Being parametric, this model facilitates making changes in the geometrical sizes as well as omitting or modifying some parts of it in order to build a new model with special purposes. The first step of this research approach is to define 15 geometrical parameters for each vertebra. These parameters could be defined based on the anatomical similarities of the 3 rd to 7 th vertebra of cervical spine. The values differ from one vertebra to the other due to each one's morphology. Thus, parametric equations which describe the geometry of the model are derived. Then a Macro is programmed with Ansys Parametric Design Language (APDL), which runs under FEA software, ANSYSg.0. This model is made up of hard tissue (vertebral body, cortical and posterior elements bone) and soft tissue (intervertebral disks including nucleus, annulus and fibers, Ligaments with two interchangeably selected options of linear cable and nonlinear springs, and articular facets) which in spite of their integrity and continuity they preserve their independency to each other and to the changes in the size of parameters. A good fit was observed when validated the model with existed experimental results in sagital plane. The comparison shows more reliable results out of this 2D model than cited 3D complex models in flexion and extension.

Simvastatin treatment partially prevents ovariectomy-induced bone loss while increasing cortical bone formation

Statins are commonly prescribed drugs that inhibit hepatic cholesterol synthesis and thereby reduce serum cholesterol concentrations. Some of the statins are thought to possess bone anabolic properties. Effects of statin on tibia, femur, and vertebral cortical and cancellous bone were studied in ovariectomized (OVX) rats. Sixty Wistar female rats, 4 months old, were allocated into four groups: baseline control, sham + placebo group, OVX + placebo, OVX + simvastatin. Simvastatin, 20 mg/kg, or placebo was given twice daily by a gastric tube for 3 months. The rats were labeled with tetracycline at day 11 and calcein at day 4 before sacrifice. Concerning cortical bone, the tibial diaphysis bending strength was increased by 8% and the periosteal bone formation rate (BFR) at the mid-diaphysis increased by twofold in the OVX + simvastatin group compared with the OVX + placebo group, in harmony with increased serum osteocalcin concentrations. Simvastatin did not affect the endocortical bone formation. Concerning cancellous bone, the cancellous bone volumes in the proximal tibia and vertebral body were reduced in both OVX groups, but the reduction was less in the OVX + simvastatin group compared with the OVX + placebo group. This reduction in cancellous bone loss is in agreement with the 36% decreased activity of serum tartrate-resistant-acid-phosphatase 5b (TRAP-5b), indicating decreased osteoclast activity in the OVX + simvastatin group compared with the OVX + placebo group. In conclusion, simvastatin induces a moderate increase in cortical bone formation at the periosteal bone surface. The new cortical bone exhibits a normal lamellar structure, and simvastatin seems to respect the regional pattern of bone formation, bone resorption, and drift; for example, no periosteal bone formation is observed in the vertebral canal. Furthermore, simvastatin reduces the loss of cancellous bone induced by ovariectomy.

Linked deficiencies in extracellular PP(i) and osteopontin mediate pathologic calcification associated with defective PC-1 and ANK expression.

Osteopontin and PP(i) both suppress hydroxyapatite deposition. Extracellular PP(i) deficiency causes spontaneous hypercalcification, yet unchallenged osteopontin knockout mice have only subtle mineralization abnormalities. We report that extracellular PP(i) deficiency promotes osteopontin deficiency and correction of osteopontin deficiency prevents hypercalcification, suggesting synergistic inhibition of hydroxyapatite deposition. Nucleotide pyrophosphatase phosphodiesterase (NPP) isozymes including PC-1 (NPP1) function partly to generate PP(i), a physiologic calcification inhibitor. PP(i) transport is modulated by the membrane channel protein ANK. Spontaneous articular cartilage calcification, increased vertebral cortical bone formation, and peripheral joint and intervertebral ossific ankylosis are associated with both PC-1 deficiency and expression of truncated ANK in ank/ank mice. To assess how PC-1, ANK, and PP(i) regulate both calcification and cell differentiation, we studied cultured PC-1 -/- and ank/ank mouse calvarial osteoblasts. PC-1 -/- osteoblasts demonstrated approximately 50% depressed NPP activity and markedly lowered extracellular PP(i) associated with hypercalcification. These abnormalities were rescued by transfection of PC-1 but not of the NPP isozyme B10/NPP3. PC-1 -/- and ank/ank cultured osteoblasts demonstrated not only comparable extracellular PP(i) depression and hypercalcification but also marked reduction in expression of osteopontin (OPN), another direct calcification inhibitor. Soluble PC-1 (which corrected extracellular PP(i) and OPN), and OPN itself (> or = 15 pg/ml), corrected hypercalcification by PC-1 -/- and ank/ank osteoblasts. Thus, linked regulatory effects on extracellular PP(i) and OPN expression mediate the ability of PC-1 and ANK to regulate calcification.

Calcitonin simultaneously regulates both periosteal hyperostosis and trabecular osteopenia in the spinal hyperostotic mouse (twy/twy) in vivo.

The twy (tiptoe-walking-Yoshimura) mouse, established in Japan in 1978 by brother-sister mating of ICR strain mice, is a valuable mutant as a model of ossification of the posterior longitudinal ligament (OPLL). OPLL causes severe myelopathy and has been thought to be very similar to ankylosing spinal hyperostosis (ASH) and diffuse idiopathic skeletal hyperostosis (DISH). In the twy mouse, both an increase in vertebral cortical membranous bone formation and a decrease in trabecular bone mass due to accelerated bone resorption occur simultaneously. This process is attributed to an inherited autosomal recessive single gene (twy). Calcitonin's suppression of bone resorption has been well established in the past, whereas the effects of this hormone on bone formation remain to be defined. Of particular interest is the simultaneous action of calcitonin on the abnormally accelerated bone formation and resorption. Thirty twy mice and 14 ICR mice were divided into seven groups, and changes induced by calcitonin on vertebral cortical appositional rate and on trabecular bone mass were investigated histomorphometrically. Results were (1) osteoclastic activity on trabecular surface was clearly suppressed by chicken calcitonin injected subcutaneously for 4 weeks; (2) no significant difference between the lumbar vertebral periosteal bone formation of calcitonin (CA) and vehicle-administrated twy mice groups. However, on the periosteal surface of the cervical vertebrae of the 6-week-old twy mice, the abnormally accelerated bone formation was suppressed by CA administration. This was also true for the elderly twy mice, although the effect was less pronounced. In conclusion, CA suppressed the abnormally hyperactivated periosteal bone formation. Results also suggested a possible therapeutic value of CA for OPLL.