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The effects of bovine trabecular bone matrix particulates on cortical bone repair.

This paper reports the effects of a synthetic bone substitute and bone allograft on cortical bone repair in an experimental model. To test the hypothesis that bovine trabecular bone matrix, BBM, can enhance the repair rate of cortical bone, osteotomies were created in the rabbit fibula and filled with either allograft or BBM particulates or left empty as controls. At five weeks post-surgery, mechanical tests and histological evaluations were performed. No significant differences were observed in the mechanical properties of the healing bone in the three animal groups (n=6). Histologically, the medullary cavity was obstructed and the cross-sectional area ratio of the osteotomies to intact bone was approximately 3 : 1. Highly significant area differences were observed between the intact bone group and both the BBM and the allograft groups (p< 0.001). At the junction between the original bone and the newly formed bone, both woven and lamellar bone microstructures were prevalent. However, in the BBM filled defects, the woven bone microstructure was not ostentatious. It is concluded that failure to demonstrate significantly differences between the treatments were due to the small sample sizes and or the efficacy of the tensile analysis.

Journal Article↗

The effects of long-term immobilization on the histomorphology of human cortical bone.

The cortical bone histomorphometrics, total visible osteon density, and mean osteonal cross-sectional area were determined for the major long bones and sixth ribs of two individuals with neurological deficit. One was a multiple sclerosis patient who had been in a wheelchair for 15 years. The other was a quadriplegic as a result of poliomyelitis. Statistically significant differences in osteon densities occurred only in the case of the quadriplegic. Nevertheless, in that subject, the total visible osteon densities for bones of the right arm were not statistically different from these of their age-matched (control) radii. Medical history records revealed that there had been partial use of this limb. These results support the belief that mechanical stress is an important factor in the maintenance of normal cortical bone remodeling. In addition, since there were subnormal osteon densities and normal mean osteonal cross-sectional areas, immobilization appears to be characterized by reduced activation frequency with a normal amount of bone turnover per BMU.

Adult↗

Interfacial behaviour of strontium-containing hydroxyapatite cement with cancellous and cortical bone.

The bone-bonding behaviors of various biomaterials have been extensively investigated. However, the precise mechanisms of bone bonding have not yet been clarified, and the differences in interfacial behaviors of biomaterial bonding with cancellous bone and cortical bone have not yet been understood. In this study, strontium-containing hydroxyapatite (Sr-HA) cement, in which 10% calcium ions were substituted by strontium, was performed in a rabbit hip replacement model. Six months later, the morphology and chemical composition of interfaces between Sr-HA cement with cancellous bone and cortical bone were evaluated by field emission scanning electron microscopy (FESEM) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). Remarkable differences between these two interfaces were suggested both in morphology and chemical compositions. An apatite layer was found between Sr-HA cement and cancellous bone with a thickness of about 70 microm. However, only a very thin interface (about 1 microm) was formed with cortical bone. As for the cancellous bone/cement interface, high ions intensity of Ca, P, Sr, Na, and O were confirmed by FESEM-EDX and ToF-SIMS. Differences in morphology and chemical component between these two interfaces provided convincing evidences for the proposed dissolution-precipitation coupling mechanism in the formation of biological apatite.

Animals↗

MRI of primary lymphoma of bone: cortical disorder as a criterion for differential diagnosis.

To investigate the pattern and dimension of cortical bone abnormality on magnetic resonance imaging (MRI) as a feature to distinguish primary lymphoma of bone from osteosarcoma and Ewing sarcoma, 46 patients with primary malignant bone lesions with a soft tissue mass (16 osteosarcomas, 15 Ewing sarcomas, 15 lymphomas) were examined with MRI (T1-weighted pre-/postcontrast spin-echo sequences and T2-weighted spin-echo and fast spin-echo sequences; 1.5 T system). Qualitative image analysis revealed no differences for signal characteristics and enhancement. Lymphomas appeared significantly more often homogeneous (47%; Ewing sarcoma 20%; osteosarcoma 6%/o), and patients were significantly older (cutoff point 30 years). Lymphomas showed significantly less frequent cortical abnormality (60%; Ewing sarcoma 87%; osteosarcoma 100%), complete penetration (13%; Ewing sarcoma 67%; osteosarcoma 87%), focal destruction (13%; Ewing sarcoma 40%; osteosarcoma 81%), and complete destruction (0%; Ewing sarcoma 13%; osteosarcoma 19%). In conclusion, primary lymphoma of bone is characterized by minimal cortical changes despite an accompanying soft tissue mass in a patient over 30 years of age.

Adolescent↗

Receptor activator of NF-[kappa]B ligand arrests bone growth and promotes cortical bone resorption in growing rats.

Receptor activator of NF-kappaB ligand (RANKL), produced by osteoblastic lineage cells and activated T cells, is an essential factor for osteoclast differentiation, activation, and survival. Therefore, RANKL is a focal point of therapies targeting bone diseases where there is an imbalance of bone metabolism in favor of bone resorption. The present study assesses the effects of exogenous RANKL on growing bone. RANKL (100 microg x kg-1x day-1 for 7 days) administered to Sprague-Dawley weanling rats caused major deficits in growth, appearance, and bone mineral densities (BMD). Urinary deoxypyridinoline crosslinks, a measure of bone turnover, were higher in the RANKL-treated rats (P = 0.031), and the bone mineral content was lower (P < 0.001). The final BMD in the RANKL-treated rats was lower (P = 0.039) than in the control rats (19 +/- 7 vs. 38 +/- 5 mg/cm3). Moreover, calculated cortical bone density in each bone slice (total BMD - trabecular BMD) indicated there was only 5% cortical bone remaining in RANKL-treated rats. We conclude that therapies targeting RANKL are likely to have effects on cortical as well as trabecular bone density.

Amino Acids↗

Stresses in mandibular cortical bone during mastication: biomechanical considerations using a three-dimensional finite element method.

This study investigated biomechanical aspects of the action of the biting force during mastication upon the mandibular bone in the lower first molar area. A three-dimensional (3D) finite element model (FEM) consisting of the tooth, periodontal ligament (PDL), alveolar bone, and cortical bone corresponding to the lower first molar area based on computed tomogram (CT) images was constructed. The model was then analyzed while applying a biting force during mastication, which was transmitted from the tooth to the cortical bone, through the PDL and cancellous bone. A compressive stress of 0.3-7.9 MPa acted on the cortical bone during mastication. In the model, the stress in the cortical bone was distributed from the linguo-superior margin to the basal area, and was also observed in the bucco-medial area. These areas completely agreed with the areas that were significantly thicker in the morphological study described by Masumoto et al. (10). It is suggested that there may be a relationship between masticatory force and cortical bone hypertrophy. Further study of the effects of various factors is required.

Alveolar Process↗

Bone regenerate formation in cortical bone during distraction lengthening. An experimental study.

The aim of this study was to delineate the pattern of bone regeneration from cortical bone segments during distraction lengthening. The lengthening procedure was applied for various periods through the Ilizarov system on the forearms of mature dogs. Bone was sectioned either by corticotomy, preserving the nutrient artery integrity, or by osteotomy. When an osteotomy was performed, the marrow cavity was in some cases plugged with either resorbable bone wax or nonresorbable material. Under distraction, both periosteal and medullary callus on either side of the gap gave rise to new bone trabeculae. The trabeculae on either side were oriented along the direction of distraction and progressively approached one another. This striated callus emerging from both sides was the most characteristic pattern of bone regeneration subsequent to distraction lengthening. Fusion was achieved approximately four weeks after the end of the lengthening period. Most of the new bone was formed by membranous ossification; some cartilaginous nodules developed. Corticalization of the bone trabeculae that had begun at three months was not fully achieved at five months after the lengthening period. There were no differences found in the pattern of bone healing and the amount of newly formed bone after corticotomy or osteotomy with or without resorbable bone wax plugging.

Animals↗

Nerves in cortical bone.

Modified electron-microscopic techniques permit the sectioning of fully mineralized compact bone. Cortical canals in human femur are extensively innervated. Most nerves are unmyelinated and range from 0.5 to 10 micrometers in diameter. I have found a few mixed nerves (myelinated and unmyelinated fibers), one of which was 130 micrometers in diameter.

Bone and Bones↗

Comparison of microcomputed tomographic and microradiographic measurements of cortical bone porosity.

Cortical bone is perforated by a network of canals that have a significant impact upon its material properties. Microcomputed tomography offers the possibility of noninvasively visualizing and quantifying cortical pores in both two and three dimensions. Establishing how two-dimensional (2D) microcomputed tomographic (microCT) analysis compares with conventional methods for analyzing cortical porosity is an important prerequisite for the wider adoption of this technique and the development of three-dimensional (3D) analysis. Therefore, we compared porosity-related parameters from 2D microcomputed tomographic images with those from matching microradiographic sections. Samples from five human femora were scanned at a 10-microm resolution and then sequentially sectioned and microradiographed. An average of eight image pairs were produced from each femur (total, n = 41). The repeatability and comparability of the two techniques was assessed for three parameters; cortical porosity (%), mean pore area (microm(2)), and pore density (pores/mm(2)). For repeatability, no significant difference ( P > 0.05) was found between the two methods for cortical porosity and mean pore area; however, pore density differed significantly ( P < 0.001). For comparability, the bias (+/- error) between the methods was found to be 0.51% (+/-0.31%) for cortical porosity and -155 microm(2) (+/-293 microm(2)) for mean pore area. The bias for pore density was dependent upon measurement size with microcomputed tomographic images having 14% (+/-9.3%) fewer pores per millimeter squared. The qualitative and quantitative similarities between the two techniques demonstrated the utility of 2D microcomputed tomographic for cortical porosity analysis. However, the relatively poor results for pore density revealed that a higher resolution (<10 microm) is needed to consistently visualize all cortical pores in human bone.

Femur↗

Mechanical strain, induced noninvasively in the high-frequency domain, is anabolic to cancellous bone, but not cortical bone.

Departing from the premise that it is the large-amplitude signals inherent to intense functional activity that define bone morphology, we propose that it is the far lower magnitude, high-frequency mechanical signals that continually barrage the skeleton during longer term activities such as standing, which regulate skeletal architecture. To examine this hypothesis, we proposed that brief exposure to slight elevations in these endogenous mechanical signals would suffice to increase bone mass in those bones subject to the stimulus. This was tested by exposing the hind limbs of adult female sheep (n = 9) to 20 min/day of low-level (0.3g), high-frequency (30 Hz) mechanical signals, sufficient to induce a peak of approximately 5 microstrain (micro epsilon) in the tibia. Following euthanasia, peripheral quantitative computed tomography (pQCT) was used to segregate the cortical shell from the trabecular envelope of the proximal femur, revealing a 34.2% increase in bone density in the experimental animals as compared with controls (p = 0.01). Histomorphometric examination of the femur supported these density measurements, with bone volume per total volume increasing by 32% (p = 0.04). This density increase was achieved by two separate strategies: trabecular spacing decreased by 36.1% (p = 0.02), whereas trabecular number increased by 45.6% (p = 0.01), indicating the formation of cancellous bone de novo. There were no significant differences in the radii of animals subject to the stimulus, indicating that the adaptive response was local rather than systemic. The anabolic potential of the signal was evident only in trabecular bone, and there were no differences, as measured by any assay, in the cortical bone. These data suggest that subtle mechanical signals generated during predominant activities such as posture may be potent determinants of skeletal morphology. Given that these strain levels are three orders of magnitude below strains that can damage bone tissue, we believe that a noninvasive stimulus based on this sensitivity has potential for treating skeletal complications such as osteoporosis.

Animals↗

Total body bone mineral content and tibial cortical bone measures in preschool children.

This study was undertaken to identify factors that influence total body bone area (TBBA), total body bone mineral content (TBBMC), and tibial cortical bone measures in 239 children aged 3-5 years. We obtained information on demographic and anthropometric characteristics and measurements of diet, physical activity, and strength. In multiple regression analysis, TBBA correlated with height (p < 0.001), weight (p < 0.001), percent body fat (p < 0.001), and calcium intake (p = 0.02). TBBMC correlated with TBBA (p < 0.001), age (p = 0.001), and weight (p = 0.02) and inversely correlated with height (p < 0.001) and percent body fat (p < 0.001). Children born preterm had lower TBBMC compared with children born at term (p = 0.02). Both periosteal and endosteal circumferences were correlated with weight (both,p < 0.001) and inversely correlated with age (p = 0.006 and p = 0.003, respectively) and percent body fat (p = 0.002 and p = 0.005 respectively). Endosteal circumference was greater and cortical bone area was lower in children born preterm compared with those born at term (both, p = 0.04). Findings of higher TBBA and lower TBBMC in children with high percent body fat indicate undermineralization of bone and suggest that obesity in preschool children may have detrimental effects on total body bone mass accretion. A smaller tibial periosteal circumference and thus cross-sectional area in children with the same weight but higher percent body fat also would lead to a biomechanical disadvantage in these children. Findings of low TBBMC and cortical bone area among children born preterm need to be confirmed in other populations. We speculate that differences in these measurements between children born preterm and at term may be caused by differences in activity.

Age Factors↗

The use of power tools in the insertion of cortical bone screws.

Cortical bone screws are commonly used in fracture surgery, most patterns are non-self-tapping and require a thread to be pre-cut. This is traditionally performed using hand tools rather than their powered counterparts. Reasons given usually imply that power tools are more dangerous and cut a less precise thread, but there is no evidence to support this supposition. A series of experiments has been performed which show that the thread pattern cut with either method is identical and that over-penetration with the powered tap is easy to control. The conclusion reached is that both methods produce consistently reliable results but use of power tools is much faster.

Bone Screws↗

Effects of age on cell size and ion uptake in canine cortical bone.

In cortical bone from dogs of various ages, the uptakes of two bone-seeking isotopes, 85Sr and 99mTc-methylene diphosphonate (MDP), were compared with that of the intracellular cation 42K by using the volume of distribution (VD) technique. The rate of bone remodeling and the osteocyte volume were estimated by morphometric techniques. The percentage cell volume was related to the VD of 42K (r = 0.83; P less than 0.001) and decreased with increasing age. The decline in the VD of 85Sr and 99mTc-MDP with aging was related to the decrease in bone formation (r = 0.90; P less than 0.001). On a logarithmic plot, the cell volume and the VD of 42K had a linear relationship with the rate of new bone formation, the VD of 85Sr, and the VD of 99mTc-MDP. Our results demonstrate that, with increasing age in dogs, the bone formation rate and cell size decrease, as does the uptake of 42K, 99mTc-MDP, and 85Sr.

Aging↗

Qualitative alterations of cortical bone in female rats after long-term administration of growth hormone and glucocorticoid.

A serious side effect of glucocorticoid treatment is the development of osteoporosis. We have earlier shown that long-term glucocorticoid administration results in a decrease in longitudinal bone growth, cortical bone mass, and biomechanical strength, while growth hormone administration increases these parameters. The result of biomechanical testing also indicates that glucocorticoid administration reduces the quality of bone. The glucocorticoid-induced osteopenia could not be inhibited by concomitant administration of large doses of growth hormone. The aim of the present study was to evaluate why glucocorticoid administration decreases the quality of cortical bone and why growth hormone administration had no beneficial effect on glucocorticoid-induced osteopenia. Five groups of female rats (3 1/2 months old) were treated for 80 days as follows: (1) glucocorticoid (prednisolone: Delcortol 5 mg/kg/day); (2) glucocorticoid and growth hormone; (3) saline; (4) growth hormone (recombinant human growth hormone 5 mg/kg/day); (5) Food restriction (consisting of restricted access to food to reduce their weight gain to match with that of the glucocorticoid injected rats). The animals were injected with tetracycline (15 mg/kg), 18 and 3 days before sacrifice, respectively. Furthermore, a baseline group (3 1/2-month-old female rats) was examined in order to enable us to differentiate between age-related changes and changes due to the hormone administration. Cortical mid-diaphysial cross sections of the femora were prepared and used for histological examination including determination of bone porosity, bone formation rate, and determination of the area of endosteal cavities as an indication of bone resorption. Furthermore, a cortical bone cylinder was cut from the mid-diaphysis and used for examinations of wet weight, dry weight, ash weight, volume, collagen content, and apparent density. Glucocorticoid administration resulted in an almost complete arrest of bone formation as shown by a decreased bone formation rate and a decreased periosteal mineralizing surface. Glucocorticoid administration also increased the porosity of bone indicating increased osteoclast activity. The increased porosity was due to a glucocorticoid-induced increase in the number of endosteal cavities in the mid-diaphysial cross section of the femora. The decreased bone formation and the increased bone resorption can explain the decrease in bone mass (volume and ash weight) found after glucocorticoid administration. Growth hormone administration, on the other hand, resulted in a marked increase in bone formation as shown by a marked increase in bone formation rate and periosteal mineralizing surface. In agreement with this, we found an increase in cortical bone mass (volume and ash weight). When the two hormones were given concomitantly, growth hormone administration did not increase bone formation. Our findings indicate the reason why growth hormone has no beneficial effect on cortical osteopenia induced by a high dose of glucocorticoid with protracted effect.

Administration, Oral↗

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.

Animals↗

Hypothalamic regulation of cortical bone mass: opposing activity of Y2 receptor and leptin pathways.

UNLABELLED: NeuropeptideY-, Y2 receptor (Y2)-, and leptin-deficient mice show similar anabolic action in cancellous bone but have not been assessed in cortical bone. Cortical bone mass is elevated in Y2(-/-) mice through greater osteoblast activity. In contrast, leptin deficiency results in reduced bone mass. We show opposing central regulation of cortical bone. INTRODUCTION: Treatment of osteoporosis is confounded by a lack of agents capable of stimulating the formation of bone by osteoblasts. Recently, the brain has been identified as a potent anabolic regulator of bone formation. Hypothalamic leptin or Y2 receptor signaling are known to regulate osteoblast activity in cancellous bone. However, assessment of these pathways in the structural cortical bone is critical to understanding their role in skeletal health and their potential clinical relevance to osteoporosis and its treatment. MATERIALS AND METHODS: Long bones of 16-week male ob/ob and germline and hypothalamic Y2(-/-) mice were assessed by QCT. Cortical osteoblast activity was assessed histologically. RESULTS: The femora of skeletally mature Y2(-/-) mice and of leptin-deficient ob/ob and Y2(-/-)ob/ob mice were assessed for changes in cortical osteoblast activity and bone mass. Ablation of Y2 receptors increased osteoblast activity on both endosteal and periosteal surfaces, independent of leptin, resulting in increased cortical bone mass and density in Y2(-/-) mice along the entire femur. Importantly, these changes were evident after deletion of hypothalamic Y2 receptors in adult mice, with a 5-fold elevation in periosteal bone formation. This is in marked contrast to leptin-deficient models that displayed reduced cortical mass and density. These changes were associated with substantial differences in calculated strength between the Y2(-/-) and leptin-deficient mice. CONCLUSIONS: These results indicate that the Y2-mediated anabolic pathway stimulates cortical and cancellous bone formation, whereas the leptin-mediated pathway has opposing effects in cortical and cancellous bone, diminishing the production of cortical bone. The findings from conditional hypothalamic Y2 knockout show a novel, inducible control mechanism for cortical bone formation and a potential new pathway for anabolic treatment of osteoporosis.

Animals↗

Preventive treatment of cortical bone loss with salmon nasal calcitonin in early postmenopausal women.

Thirty early postmenopausal women having risk factors for osteoporosis entered and 23 completed a six months double-blind placebo controlled study of the effect of nasal salmon calcitonin (SCT) (100 IU daily) plus oral calcium on bone turnover, cortical bone mass and sex-steroids. After the double-blind study SCT treatment was continued for six months in 20 women in both groups. A six months nasal SCT treatment was found to be effective in significantly increasing cortical bone mass and the gain was maintained following a 12 months treatment. The nasal SCT treatment was effective in significantly reducing parameters of bone turnover, as indicated by osteocalcin pBGP and urinary hydroxyproline levels, while during placebo administration an increasing trend of pBGP suggested a state of increasing bone remodeling. During the study, a small decrease in plasma testosterone not related to cortical bone mass and bone turnover was observed.

Absorptiometry, Photon↗

Promotion of bone repair in the cortical bone of the tibia in rats by low energy laser (He-Ne) irradiation.

The effect of low energy laser (He-Ne) irradiation on bone repair in the cortical part of the tibia of the rat was investigated using biochemical and radioactive labeling methods. A fixed round hole was created in the lateral aspect of the tibia and the newly formed tissue was collected from the gap in the cortical bone. Alkaline phosphatase (ALP) and calcium progressively accumulated at the site of injury, peaking at 9 and 13 days postinjury, respectively. Direct irradiation of the hole injury with He-Ne laser on days 5 and 6 postinjury altered osteoblastic activity at the injured site as reflected by alkaline phosphatase activity. The laser irradiation also caused a significant increase ( approximately 2-fold) in calcium accumulation at the site of injury for 9-18 days postinjury. The rate of calcium deposition, measured by radioactive calcium, was significantly higher (approximately 2-fold) in the laser-irradiated rats as compared with controls. It is concluded that the process of bone repair in a hole created in the rat tibia is markedly enhanced by direct He-Ne laser irradiation of the injured site at the optimal energy level and time postinjury.

Animals↗