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Paleopathological study on a case of osteosarcoma.

This report concerns a probable case of osteosarcoma found in a precontact Hawaiian skeleton from the east coast of Oahu Island, Hawaii. A young adult female showed a tumorous bone proliferation with a coarse, corallike appearance at the distal metaphyseal area of the left femur. In gross observation, a profusion of coalescing bone was extended to the surrounding space and also invaded the marrow space. X-ray films revealed spotted and ringed shadows in the shaft and a "sunburst appearance" in the lesion. Histological examination of the tumor bone fragment showed a great deal of primitive bone tissue formation without any systemic Haversian structure. The diagnosis of osteogenic osteosarcoma is much more compatible than other primary malignant bone tumors such as Ewing's sarcoma, fibrosarcoma, and chondrosarcoma or osteoplastic metastatic carcinoma of the bone when the location and morphology of the tumor are considered along with the age of the decedent.

Female↗

Bioactivity and osseointegration study of calcium phosphate ceramic of different chemical composition.

Synthetic hydroxyapatite (HA) and tricalcium phosphate (TCP) are promising bone-substitute materials in the orthopaedic and dental fields, as their chemical composition is similar to that of bone. This study investigated the osseointegration performance of carbonated biphasic calcium phosphate (CBCP) ceramics containing carbonated hydroxyapatite and tricalcium phosphate prepared by microwave irradiation, in femoral defects of dogs. The defects were created as 3-mm holes on the lateral aspect of femur and filled with the implant material. The serum was collected postoperatively and biochemical assays for alkaline phosphatase activity levels were carried out. The animals' defective sites were radiographed at 4, 8, and 12 weeks. The radiographic results showed that the process of ossification started after 4 weeks and the defect was completely filled with new bone after 8 weeks. Histological examination of the tissue showed the osteoblastic activity inducing the osteogenesis in the defect. The complete haversian system with osteoblastic and osteoclastic activity and bone remodelling process were observed after 12 weeks. The alkaline phosphatase activity levels also correlated with the formation of osteoblast cells. This calcium phosphate ceramic has proved to work well as a biocompatible implant and as an osteoconductive and osteoinductive material for the filling of bone defects.

Animals↗

Behavior of dense and porous hydroxyapatite implants and tissue response in rat femoral defects.

Porous and dense hydroxyapatite cylinders (PHA and DHA) were implanted into cavities produced in rat femora and the sites of implantation were examined at different times over a period of 24 weeks by microradiologic and histological techniques. Microradiographs showed the presence of a layer of trabecular bone around the implants, which became more radiopaque and thinner along the experimental time. The microradiologic methodology used was suitable for the evaluation of the interface between hydroxyapatite and newly formed bone in nondecalcified materials. Microscopic observations showed that young bone grew over the surface of both types of implants after 1 and 2 weeks of surgery and that bone also grew inside PHA implants. Progressive bone absorption was observed in both types of implants after the fourth week. A layer of fibrous tissue was formed in the interface between new bone and DHA. Mature bone with haversian systems surrounded DHA implants and filled the pores of PHA implants throughout the experimental period. The pores of PHA implants were smaller than those commonly reported, which should have been a disadvantage, although it was observed that the extra cellular fluid induced disintegration of the ceramic granules, allowing the gradual growth of bone tissue into the spaces among them, without the interposition of fibrous tissue.

Animals↗

Characterization of the mechanical properties of demineralized bone.

Demineralized bone has had limited use as a medical implant, although, recently Jackson et al. (Am J Sports Med 1996;24(4):405-414) examined using demineralized bone as an anterior cruciate ligament (ACL) replacement and found that within 1 year the demineralized bone had remodeled from a haversian system (bone-like) into a ligament-like structure. Little research has been done to characterize the mechanical properties of demineralized bone and examine its potential as a ligament replacement. This research examined the mechanical properties of demineralized bone as a function of acid saturation time and methods of processing and sterilization using specimens from various anatomic locations. Bone specimens were manufactured from the tibia, metatarsus, femur, radius, and humerus of bovine bone. Tensile strength, strain, and modulus of elasticity were examined for various acid saturation times and sterilization treatments. Additionally, viscoelastic properties, creep and stress relaxation, and fatigue properties were examined. The findings indicate that completely demineralized bone has mechanical properties similar to the ACL and, therefore, has increased likelihood for success in ACL reconstruction surgery.

Age Factors↗

The role of sex hormones in the growth of antler bone tissue. I: Endocrine and metabolic effects of antiandrogen therapy.

Cyproterone acetate (CA), an antiandrogenic compound, was used in order to investigate the role of testosterone in bone growth processes. The formation of Haversian systems in the growing antlers of white-tailed deer (Odocoileus virginianus) were substantially affected by only 3.5 mg of CA kg/wk. The mineralization processes of the bone matrix were almost completely blocked and the antlers persisted in growing throughout the whole year. Plasma levels of thyroxine, alkaline phosphatase and GH were higher while cortisol and testosterone levels were lower than in controls. No differences were registered in plasma levels of Ca, P or urea nitrogen. Despite hypertrophy of interstitial tissue, spermatogenesis was almost completely blocked. The sexual behaviour and the body appearance of experimental animals was typical for castrates.

Alkaline Phosphatase↗

A comparative analysis of streaming potentials in vivo and in vitro.

Streaming potentials (SPs) measured in vivo at a specific site on intact cortical bone (canine tibia) have been compared with measurements from the same site in vitro, tested as an excised bone strip soaked in Hank's balanced salt solution. The amplitude of SPs per periosteal strain in vitro was larger in 13 tibias than in vivo (by an average x6.5 at 1 Hz), but values per transcortical strain difference were similar. In vitro, SP magnitudes rose more sharply to an asymptotic value as a function of bending frequency than did in vivo signals, possibly because of a difference in the internal state of canaliculi and/or Haversian systems. Similarly, SP response to step-loading decreased to zero more slowly with time in vitro than in vivo. Difficulties encountered in preliminary measurements due to electrical shunting through electrolyte and soft tissues suggest the need for caution in using both in vivo and in vitro SP measurements to extrapolate to electric field strengths on the cellular level.

Animals↗

Cytokines and local factors which affect osteoclast function.

Bone remodeling is a local phenomenon which occurs in discrete packets throughout the skeleton. The cellular events which comprise the remodeling sequence are controlled by cytokines which are generated in the microenvironment of the bone resorbing pockets. These cytokines are derived from marrow mononuclear cells or from bone cells themselves, or they are incorporated into the bone matrix and released in biologically active form as bone resorbs. Evidence is accumulating that some of these cytokines play an important role not just in physiological bone remodeling, but also in common diseases of bone remodeling such as osteoporosis, osteopetrosis, Paget's disease, and malignant diseases which involve bone and chronic inflammatory diseases such as rheumatoid arthritis and periodontal disease. Normal bone remodeling is clearly under local control. It occurs in discrete packets throughout the skeleton, each of which is geographically distinct. Local packets of bone remodeling are also asynchronous with respect to each other. The cellular events which comprise the remodeling sequence are thus regulated primarily by factors which are enriched in that microenvironment. The remodeling sequence, which is continuous, is the same on cancellous bone surfaces as it is within the Haversian systems of cortical bone. Since it is now known that powerful osteoclastotropic factors are produced in the microenvironment of these bone remodelling packets, these local factors or cytokines are the most likely major regulators of osteoclast function.

Animals↗

The mandibular body of the human fetus. Histologic analysis of the basilar part.

Histologic and microradiographic analyses of 47 human mandibles from 42 fetuses and 5 neonates have been carried out to study the development of the mandibular body. This not only entails woven bone formation along Meckel's cartilage but also endochondral ossification in the condylar cartilage, the pillars of which are included in the posterior part of the mandibular body. Progressively, woven bone is replaced by lamellar bone, and typical Haversian systems are already present at the fifth month of fetal life. This early occurrence of bone remodelling is related to the fact that the mandible is subjected to intense activity from sucking and swallowing.

Fetus↗

Tensile properties of antler bone.

The tensile deformation characteristics of compact bone from deer antler were measured in both the "dry" and "wet" states and compared with published values for bovine compact bone. The tensile strength in the wet state (108 +/- 5.1 MN/m2) was comparable to the value for bovine compact bone tested at the same strain rate. The modulus values was very low: 7.5 +/- 0.9 GN/m2. The work to fracture was comparatively high, about 3 times that for bovine compact bone. Fractographic examination revealed fibrillar and osteonal shear for samples fractured in the dry state. In the samples tested in the wet state, some regions exhibited pullout of lamellar segments from within a Haversian system. The results are explained in terms of the higher collagen content and lesser degree of mineralization in the antler.

Animals↗

Distribution of the perilacunar hypomineralized areas in cortical bone from patients with familial hypophosphatemic (vitamin D-resistant) rickets.

The perilacunar areas of low mineral density in microradiographs from cortical bone of patients with hypophosphatemic (vitamin D-resistant) rickets are not evenly distributed throughout the bone tissue. Their frequency and distribution were determined in bone from 9 patients with this disease. It was found that the lesion was more frequent in haversian bone than in interstitial bone, and along the inner circumference of growing haversian systems as compared with outer circumference. These findings indicate that the lesion is the result of retarded mineralization, and that mineralization slowly proceeds in these areas as the bone becomes older. A relatively high frequency of the lesion was also found in osteons with an elliptical cross section along the long axis of the ellipse. The cause of the abundance of the lesion at these sites is not clear, but it is possible to explain the uneven distribution in elliptical osteons by assuming an unequal rate of bone formation in these structures.

Adult↗

Fluoride ingestion during multiple pregnancies and lactations: microscopic observations on bone of the rat.

Female rats were given 150 ppm fluoride in the drinking water during three successive pregnancy and lactation periods; the femoral diaphyses were then examined for morphological alterations by light and scanning electron microscopy to determine the influence of fluoride ingestion during multiple pregnancies and lactations. The periosteal surface was dominated by areas of woven bone formation with some prolonged resting areas around osteocyte lacunae. The endosteal surface consisted mainly of areas of active bone resorption with some areas of bone formation. The interior of the cortex was characterized by numerous resorption cavities and remodeling in secondary Haversian systems. Fluoride, by the nature of its incorporation into bone crystals and by its direct cytotoxic effect on bone resorbing cells, reduces the availability of calcium from bone. It appears that fluoride ingestion during lactation created a heightened state of calcium homeostatic stress. As a result, bone mineral was mobilized by resorption of the endosteal surface and by cavitation of the interior of the cortex. Secondary hyperparathyroidism is thought to play an integral part in an attempt to maintain calcium homeostasis.

Animals↗

Triple bone labeling of canine mandibles.

Fluorescence microscopy was used for evaluation of new bone formation in 16 canine mandibles augmented with hydroxylapatite (HA) granules. Three fluorochromes were injected at different time intervals during therapeutic radiation treatment. Oxytetracycline, DCAF, and alizarin-complexone were given intravenously to mark the bone level at these times, respectively. Oxytetracycline, which defined the baseline of bone at implantation of HA, was detectable in 42% of animals that were irradiated and in no animal of the nonirradiated control group. The marker DCAF, designating levels of bone at the start of radiation, was demonstrated in 92% of irradiated animals, and in 75% of animals in the control group. The uptake of alizarin-complexone determined the level of bone found at the end of irradiation. This marker was demonstrated in 50% of the dogs irradiated and in 75% of the control dogs. Bony trabeculae were found between and at the surface of the HA granules. New generation of bone directly on the HA granule and in the surrounding haversian systems as part of normal bone turnover was demonstrated to take place more than 5 months after implantation of HA.

Alveolar Bone Loss↗

Microprobe analysis of lead in human femur by proton induced X-ray emission (PIXE).

A method is described for the measurement of the distribution of lead in bone tissue. Two cases of human femur have been analyzed; one worker was exposed to lead in heavy metal industry, the other case presents a reference worker from the same environment not excessively exposed to lead. Lead was determined through proton induced X-ray emission using microprobe technique. The mean lead concentration in the poisoned and the reference case was 70 and 30 ppm, respectively. The reference case showed an even lead distribution in the femur, while the poisoned case exhibited peaks in the distribution indicating that exposure to lead was not evenly distributed. The described technique has potential for microanalysis within the Haversian system for recording the history of exposure.

Bone and Bones↗

Biochemical signal transduction of mechanical strain in osteoblast-like cells.

The responses to mechanical loading of two types of osteoblast-like cells and skin fibroblasts were investigated using two new devices for applying defined and homogeneous strains to cells. The results indicate that only periostal (bone surface) osteoblasts are sensitive to strains within the physiological range and that a specific strain mechanism is responsible. Osteoblasts derived from the haversian system and skin fibroblasts do not respond except at higher, unphysiological strains. The mechanism is located in the cytoskeleton and activates the membrane phospholipase C within milliseconds and may react to distension of a strain sensitive protein. Activation of phospholipase C can account for only some of the observed responses of bone to mechanical loading such as stimulation of cell division, increase in collagen and collagenase production. Application of over 10,000 mu strains results in a de-differentiation of the osteoblasts and a change in cell morphology to become fibroblast-like.

Animals↗

Response of canine bone to a synthetic bone graft material.

A model simulating a spiral diaphyseal fracture with butterfly fragments and bone loss was utilized to evaluate an hydroxyapatite/tricalcium phosphate, and collagen composite bone graft substitute in twelve dogs. The resultant grafted and contralateral control femora were tested in torsion at one year. This study examines the histological response to the graft material as well as crack propagation and fracture surface morphology using light microscopy and SEM. SEM and gross evaluation of the grafted bones revealed that 8/12 had fractured through bone outside the osteotomy site and all fractures included bone outside the graft site. No graft material was demonstrated at the points of initiation or termination of fracture for any of the bones. It was apparent that recorticalization had begun to occur at the graft site but the canal had not yet fully formed. The HA/TCP was seen to be tightly bound in tissue which had the appearance of new bone. Bone was found to be in direct apposition to the surface of the ceramic and within pores with no intervening soft tissue. Much of the new bone had remodeled into well organized Haversian systems with some patchy areas of woven bone and osteoid seen with polarized light illumination.

Animals↗

Stereologic estimators of cortical bone remodeling including a kinetic model.

The purpose of this study was to describe cortical bone remodeling by means of a new stereologic model, which is based on isotropic uniform (IUR) histological sections and two fluorochrome tissue time markers (tetracycline and calcein) given with a 15-day interval. From each of five pigs two samples of cortical bone were sawed out from the middle part of the diaphysis of the left femoral bone and fixed in absolute methanol. Specimens were embedded undecalcified in methylmethacrylate, and the plane of sectioning was sampled by a new procedure, which produce IUR-sections. The extent of remodeling was estimated by length densities, that is, length of Haversian system undergoing resorption or formation per unit volume of bone. These estimates made it possible to express the activation rate and the remodeling rate at tissue level in absolute three-dimensional terms. Such estimates have not previously been published. The shortest diameter of osteon cross-sections was used for obtaining three-dimensional measures of osteons dimensions. The estimated true variance between animals as percentage of the observed variance was above 68% for all morphometric parameters except the length density of resorptive osteons (35%). It was concluded that the proposed stereologic methods enable a detailed description in three-dimensional terms of the remodeling process in cortical bone, and further information may be obtained by combining measurements with observations of cell morphology.

Analysis of Variance↗

Osteopetrosis: a scanning electron microscopic study.

Scanning electron microscopic investigation was conducted with bone in a case of osteopetrosis by comparing it with normal cortical bone. The fractured surface of the osteopetrotic bone was devoid of the orderly constructed lamellar haversian system seen in normal bone. It was occupied by a massive smooth cartilaginous matrix containing scattered rough areas of abnormal ossification. Tortuous channels were randomly distributed and corresponded to the abortive marrow spaces. The presence of many irregular fracture lines reflected the fragility of the bone. The findings support the concept of defective remodeling in the pathogenesis of osteopetrosis and provide a further explanation for the abnormal fragility of bone in osteopetrosis.

Adult↗