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Biologic remodeling after anterior cruciate ligament reconstruction using a collagen matrix derived from demineralized bone. An experimental study in the goat model.

A matrix of demineralized cortical bone was used to reconstruct the anterior cruciate ligament in the goat model. This graft underwent considerable site-specific remodeling and transformation from a Haversian system at time zero into a ligament-like structure at 1 year. This transformation included new bone formation filling the osseous tunnels and replacing the demineralized matrix, development of a ligament-like transition zone within the graft, and ligamentous collagen orientation with crimp in the intraarticular portion of the graft. One year after surgery, the mean anterior-posterior translation in the reconstructed stifle joints at 30 N of tibial loading was 2.1 +/- 0.4 (+/- SEM). The mean ultimate force to failure for the reconstructed ligament at 1 year was 474 +/- 146 N compared with the time-zero (initial) strength of the matrix of 73 +/- 9 N. The cellular repopulation of the graft had no associated inflammatory cells. The potential clinical significance of these findings includes 1) replacement of a collagen matrix with bone within the osseous tunnels, 2) establishment of a more physiologic fibrocartilage transition at the graft insertion site, 3) the time-zero structural properties of a collagen matrix increasing to more desired values with biologic remodeling, and 4) a sterile biologic allograft with essentially no long-term inflammatory response.

Animals↗

Bone in-growth induced by biphasic calcium phosphate ceramic in femoral defect of dogs.

Biphasic calcium phosphate (BCP) ceramics consisting of hydroxyapatite (HA) and tricalcium phosphate (TCP) has been used as a bone graft material during the last decade. In this paper, we report the bone in-growth induced by BCP ceramic in the experimentally created circular defects in the femur of dogs. This BCP ceramic consists of 55% hydroxyapatite (HA) and 45% b-tricalcium phosphate (TCP) prepared in situ by the microwave method. The defects were created as 4-mm holes on the lateral aspect of the femur of dogs and the holes were packed with the implant material. The defective sites were radiographed at a period of 4, 8, and 12 weeks postoperatively. The radiographical results showed that the process of ossification started after 4 weeks and the defect was completely filled with new woven bone after 12 weeks. Histological examination of the tissue showed the formation of osteoblast inducing the osteogenesis in the defect. The collageneous fibrous matrix and the complete Haversian system were observed after 12 weeks. The blood serum was collected postoperatively and biochemical assays for alkaline phosphatase activity were carried out. The measurement of alkaline phosphatase activity levels also correlated with the formation of osteoblast-like cells. This microwave-prepared BCP ceramic has proved to be a good biocompatible implant as well as osteoconductive and osteoinductive materials to fill bone defects.

Animals↗

Detection of vitronectin in mineralized bone matrix.

Adhesive glycoproteins in the bone matrix are of critical importance for cell anchorage, proliferation, migration, differentiation, and regulation of bone metabolism. The localization of the adhesive glycoprotein vitronectin (Vn) in murine bone tissue was evaluated by immunohistochemical staining. Vitronectin was present throughout the mineralized bone matrix of cancellous and cortical bone, whereas cartilage was devoid of Vn staining. To exclude the possibility that the positive Vn staining resulted from plasma Vn in blood vessels within the bone sections, adjacent tissue sections were stained with antibodies to fibrinogen, and abundant plasma protein. Fibrinogen immunoreactivity was confined to blood vessels in the bone marrow and Haversian system, whereas the mineralized bone matrix was devoid of staining. The presence of Vn in murine bones was confirmed by sequential extraction, followed by fractionation of the resulting polypeptides by gel electrophoresis and immunoblotting analysis. Hydroxyapatite affinity chromatography raises the possibility that mineral interactions, at least in part, mediate the incorporation of Vn into the bone matrix. These results indicate that Vn is a specific component of bone tissue and raise the possibility that Vn is involved in regulation of bone metabolism.

Animals↗

Cortical remodeling following suppression of endogenous estrogen with analogs of gonadotrophin releasing hormone.

The effects of estrogen suppression on osteonal remodeling in young women was investigated using transiliac biopsies (eight paired biopsies + four single pre; three single post biopsies) taken before and after treatment for endometriosis (6 months) with analogs of gonadotrophin releasing hormone (GnRH). Estrogen withdrawal increased the proportion of Haversian canals with an eroded surface (106%, p = 0.047), a double label (238%, p = 0.004), osteoid (71%, p = 0.002), and alkaline phosphatase (ALP) 116%, p = 0.043) but not those showing tartrate-resistant acid phosphatase (TRAP) activity (p = 0.25) or a single label (p = 0.30). Estrogen withdrawal increased TRAP activity in individual osteoclasts in canals with diameters greater than 50 microns (p = 0.0089) and also the number of osteons with diameters over 250 microns (p = 0.049). ALP activity in individual osteoblasts was increased but not significantly following treatment (p = 0.051). Wall thickness was significantly correlated with osteon diameter (p < 0.001). In a separate group of patients (four pairs + one post biopsy) on concurrent treatment with tibolone, there was no significant increase in the osteon density, cortical porosity, median canal diameter, or the markers of bone formation and resorption. Enzyme activities and numbers of active canals were also not increased with the concurrent treatment, but there was still an increase in the osteon diameter. As previously shown for cancellous bone, estrogen withdrawal increased cortical bone turnover. We have now shown that resorption depth within Haversian systems was also increased with treatment. The enhanced TRAP activity in individual osteoclasts supports the concept that osteoclasts are more active following estrogen withdrawal in agreement with theoretical arguments advanced previously. Understanding the cellular and biochemical mechanisms responsible for increased depth of osteoclast resorption when estrogen is withdrawn may allow the development of new strategies for preventing postmenopausal bone loss.

Acid Phosphatase↗

Bone growth, modeling and remodeling in a supernumerary metatarsal bone associated with segmental gigantism in cutis marmorata telangiectatica congenita.

Skeletal structure and processes of bone growth, modeling and remodeling were studied in a supernumerary metatarsal surgically removed from a 3-year-old boy affected by Cutis Marmorata Telangiectatica Congenita (CMTC), associated with hypertrophy of the right upper and lower limbs and postaxial hexadactylism of the homolateral hand and foot. No other anomalies were observed. The excess of periosteal growth, due to congenital anomaly, induced an abnormal development of both modeling and remodeling processes. In bone modeling, osteoblast activity on the periosteal surface was not paralleled by osteoclast resorption along the wall of the medullary canal, and this enormously increased the cortical thickness. In bone remodeling, osteoclastic resorption cavities were not refilled by secondary Haversian systems, thus inducing a severe bone loss. While the alteration of bone growth and modeling can be ascribed to the congenital disease, the unbalanced bone remodeling appears mainly to depend on mechanical disuse of the supernumerary metatarsal.

Bone Development↗

Bone remodeling in periodontal lesions.

This study was designed to investigate sites of major alveolar bone formation as a result of resorption of the interdental crest in periodontal lesions. Bone samples were taken from twelve patients requiring surgery as part of their periodontal treatment. Tetracycline was used in all cases to label bone recently formed. The selected areas were periodontal pockets ranging in depth from 6 to 8 mm. The bone deformities were of crater-form configuration. The buccal and lingual plates were removed. Later, the dehydrated speciemns were embedded in bioplastic and cut to sections 70 mu thick. Controls were healthy pieces of bone taken from the same patient in unaffected areas. Yellow fluorescent tetracycline labeling was observed in both periosteal and trabecular bone. In the trabecular bone, labeling was exhibited in the lamella of some Haversian systems, away form the bone resorption. There was a direct relationship between bone resorption and bone apposition as seen by the presence of tetracycline in the buccal and lingual alveolar plates. Controls showed only minimal labeling. The results of this study have posed the question as to whether inflammation could be the stimulus in the reactivation of osteocytes or bone formation, in the buccal and lingual walls of the periodontal lesions.

Alveolar Process↗

Bilateral subpontic osseous hyperplasia. A case report.

A case of osseous hyperplasia under the pontics of fixed partial dentures in right and left mandibular first molar regions is presented. Radiographs showed hemispherical radio-opacities on the alveolar ridges. Histologic examination revealed the lesions were composed of a dense mass of mature bone with well-developed lamellae and haversian systems, viable osteocytes in lacunae and a few marrow spaces filled with loose fibrous connective tissue. The review of the literature showed osseous hyperplasia under the pontic of a fixed partial denture has been seen only in the mandibular molar or premolar regions, but no conclusion about its etiology was made.

Adult↗

Biomechanical and histological evaluation of a calcium phosphate cement.

It is often difficult to achieve stable fixation of a comminuted fracture associated with a metaphyseal defect. The injection of a resorbable cement into an osseous defect may help to stabilize the fracture and to maintain osseous integrity as the cement is resorbed and replaced by bone. The purpose of the present study was to evaluate the repair of a metaphyseal defect after treatment with an injectable calcium-phosphate cement. The injectable cement undergoes isothermic curing in vivo to form a carbonated apatite (dahllite) with a compressive strength of twenty-five megapascals. Either the cement or allograft bone was placed in proximal tibial metaphyseal and distal femoral metaphyseal defects in seventy-two dogs and was evaluated from twenty-four hours to seventy-eight weeks postoperatively. Histological examination showed that the cement was osteoconductive; nearly the entire surface area was covered with bone two weeks after the injection. The resulting bone-cement composite underwent gradual remodeling over time in a pattern that was qualitatively similar to the remodeling of normal cortical and cancellous bone. Osteoclasts were found to resorb the cement and were usually associated with adjacent new-bone formation. With increasing time in vivo, the cement was penetrated by small blood vessels that became surrounded by circumferential lamellae of bone and that closely resembled evolving haversian systems. This process occurred more rapidly in the cortex than in the medulla. Mechanical testing showed that, by eight weeks, the tibiae that had been treated with cement had reached nearly 100 per cent of the torsional strength of the contralateral, control (intact) tibiae; this finding paralleled the histological observations of bone apposition to the cement and rapid restoration of the cortex. At no time was fibrous tissue present between the cement and the bone, and there was no evidence of acute inflammation. Small particles of cement were present within occasional macrophages during the process of cement resorption, but the macrophages disappeared over time and were not associated with fibrosis or unexpected resorption of bone. Resorption of the cement was incomplete in the medullary area at seventy-eight weeks, but the pattern of cement resorption and bone-remodeling suggested gradual restoration of a physiological proportion of bone and marrow in both the cortical and the medullary region with maintenance of mechanical function.

Animals↗

Surface osteomas of the appendicular skeleton.

OBJECTIVE: This study describes the radiographic, CT, and MR imaging features of surface osteomas of the appendicular skeleton in four patients without Gardner's syndrome or tuberous sclerosis and reviews the incidence and management options of this uncommon tumor. CONCLUSION: On imaging (best seen on CT), the osteomas were homogeneously dense-as dense at the periphery as the base-and without an accompanying soft-tissue mass, cortical destruction, or intramedullary invasion. The margins of each osteoma were smooth or smoothly lobulated. When the correct diagnosis was considered in two patients, close clinical follow-up or marginal excision were the management options chosen. Histologic examination of the tumors revealed dense sclerotic lamellar bone with haversian systems that showed features similar to those of normal cortical bone. During a follow-up period of 6 months to 5 years, patients have had no local recurrences or metastases.

Adult↗

Behaviour of cancellous bone graft with and without periosteal isolation in striated muscle. An experimental study.

The capacity of the periosteum to inhibit resorption of cancellous bone grafts into muscle was investigated in 34 four- to six-week-old rabbits. In 17 experiments the periosteum was wrapped around the grafts with the cambium layer facing the bone, and in seven experiments with the cambium layer facing the muscle. In the control group of 10 experiments there was no periosteal wrapping around the bone grafts. In Series 1 with the cambium layer of the periosteum facing the bone, after 20 weeks a tubular bone with Haversian system and bone marrow was seen. The transplants were surrounded by normal-looking periosteum. Bone formation from the periosteum occurred through enchondral ossification. Inductive bone growth was observed from the cancellous graft. In Series 2 with the cambium layer facing the surrounding muscle tissue, after 20 weeks two laminar bone blocks with periosteum in between and surrounding each block was observed. In the control series without periosteal covering, after 20 weeks only fibrous tissue remained in the transplantation site. It is obvious that periosteal isolation of cancellous bone grafts inhibits their resorption when transplanted into muscle in young animals.

Animals↗

On the origin of hematopoietic stem cells after local marrow extirpation.

The early hematopoietic regeneration in a depopulated segment of femur shaft is compared in +/+ and W/Wv mice and in W/Wv mice previously treated with +/+ marrow. Since the W/Wv mouse has an intrinsic CFU deficiency on spleen colony assay and since immigrant cells play a negligible role in the onset of regeneration after marrow extirpation, the W/Wv(+/+) chimera provides a model for evaluation of the contribution of residual cells to the regenerative program. There was little difference in the relative recovery of CFU in +/+, W/Wv, and W/Wv-(+/+), Moreover, +/+ derived CFU were responsible for nearly all of the CFU repopulation in chimeric mice. Thus, recovery of hemic cellularity must be due to residual stem cells rather than to stem cells derived by transformation of more primitive mesenchymal elements. The residual CFU are probably intimately associated with bone, most likely within the endosteum and haversian system.

Animals↗

Evaluating bone mass and bone quality in patients with breast cancer.

Bone remodeling is a process by which bone renews itself focally in distinct areas on cancellous (ie, trabecular) bone and/or in the Haversian systems of cortical (or compact) bone. Normal bone turnover involves the ordered metabolism of bone-resorbing cells (osteoclasts) and bone-forming cells (osteoblasts). Estrogen exerts a multitude of actions on bone tissues and is integral to bone health, and estrogen deprivation leads to accelerated bone loss. Bone strength reflects the integration of bone density and bone quality. Methods to assess bone strength fall into 3 categories: radiologic (ie, bone mineral density [BMD]), biochemical (ie, markers of bone turnover), and histologic (ie, bone biopsies for histomorphometry). The beneficial effect of aromatase inhibitors (AIs) and inactivators on breast cancer depends on reducing levels of circulating estrogens in the peripheral blood. There appears to be variability in the effects of AIs on bone in experimental animals, and this variability may not be the same in humans. In general, bone loss is an expected side effect of the AIs. For postmenopausal women receiving adjuvant anastrozole or other AIs, a BMD measurement using dual-energy x-ray absorptiometry is recommended, to be repeated every 1-2 years. Regular physical exercise is advised together with added calcium 1500 mg and vitamin D 800 U daily. If the T-score reaches a level of >2.5, or if it is between -1.5 and -2.5 in the presence of a fragility fracture or vertebral compression fracture, or if height loss > 2 cm occurs or BMD decreases > 3% in 1 year at the lumbar spine or > 5% at the femoral neck, bisphosphonate therapy should be considered.

Absorptiometry, Photon↗

Bone marrow regeneration after local injury: a review.

This paper is focused on a mechanically depleted medullary cavity as an experimental model for analysis of marrow regenerative programs. The reconstitution of marrow in an evacuated cavity is basically a local phenomenon in respect to the stimulus for regeneration and the origin of the responsible cells. The nature of the triggering stimulus is unknown, but it is probably related to disruption of the continuity of the marrow stroma and endosteum. The initiating cells appear to be independent lines of mesenchymal and hematopoietic stem cells bound to bone, most likely within the endosteum and haversian system. The mesenchymal cells form the characteristic marrow stroma. Hemic cell regeneration can occur without immigrant hematopoietic stem cells, although such cells are known to contribute to later stages of repopulation. The formation and resorption of trabecular bone appears to be intimately related to the development of a sinusoidal matrix, perhaps by serving as a callus or supporting lattice and perhaps by providing a mechanism for distribution of stromal progenitors. Hematopoiesis is initiated in sites of active bone resorptive. The interplay of events consequent to marrow removal is strikingly similar to that seen with heterotopic marrow implants. Because stromal stem cells, unlike hematopoietic stem cells, do not migrate from distant sites, marrow stroma is the limiting factor in recovery from localized injury. Stromal stem cells are fairly radiosensitive but are not as sensitive as hematopoietic stem cells. The apparent radioresistance of stromal elements in an intact marrow seems to be due to their very low turnover rate. Latent radiation damage can be readily unmasked by conditions that promote their proliferation. This no doubt accounts for the radiosensitivity of stroma in an evacuated femur or heterotopic implant in contrast to its continued functional integrity with similar irradiation of in situ marrow. Even in an intact marrow, however, exposures in the 1000 rad range can lead to slowly evolving hypocellularity associated with diminished blood flow. With higher doses, aplasia of the irradiated site becomes progressively more generalized. It remains to be seen whether this limiting condition is due to the loss of specific regulatory functions or stromal components or merely reflects sinusoidal damage.

Bone Marrow↗

Lingual osteoma: case report.

Lingual osteoma, a rare clinical entity, has been found mainly in the posterior region of tongue. It mostly affects women in their third and fourth decades of life and occurs less frequently in men. We report an unusual case of a 42-year-old male patient who developed a lingual osteoma near the foramen cecum. The patient underwent excision of the tumor mass under local anesthesia and had an uneventful postoperative course. Symptoms of the mass effect were noted to resolve after surgical intervention. Histologically, mature lamellar bone with haversian systems was seen. The pathogenesis of this rare tumor is a controversial problem and its nomenclature also remains an issue of debate. Discussion of the controversial pathogenesis of lingual osteoma and a review of the literature on its clinical characteristics are included in this report.

Adult↗

Ultrastructural evidence for vulnerability of hip region to fracture in the aged.

OBJECTIVE: To probe ultrastructurally into the mechanism why hip region is the predilected site of fracture in aged people, yet with femoral head exempted. METHODS: Proximal femoral ends were collected from 14 aged people, who had undergone endoprosthetic replacement for intra-capsular fracture of the femoral neck, and from 7 young men died of brain injury. These specimens were processed and subjected to scanning electron microscopic and transmission electron microscopic observation for bone resorption. RESULTS: As compared with the specimens from young men, there were three types of bone resorption in the proximal femoral ends of aged people, i.e. osteoclastic resorption and osteocytic resorption of the trabeculae of cancellous bone, and osteoclastic resorption of Haversian systems of the cortical bone. In the proximal femoral ends of the young men, the arch structures composed of trabeculae in the femoral head showed a round or roundish configuration, while those at the femoral head-neck junction revealed an oval profile and those in the femoral neck exhibited a narrow oval contour. In the proximal femoral ends of the aged people, the morphological characteristics of the trabecular arch remained unchanged despite overt bone resorption. CONCLUSIONS: Vulnerability of hip region to fracture in aged people is due to a decline in the structural strength of bone tissues of the proximal femoral ends resulting from osteoclastic and osteocytic resorption. The round and roundish trabecular arch of the femoral head can bear external forces from different directions, so that no fracture occurs here, while the oval and narrow oval arches at the head-neck junction and in the neck region fail to stand the horizontal external forces (abduction and adduction injuries), thereby fracture easily happens.

Adult↗

[Histological study of otological homografts (incus, cartilage and fascia) (author's transl)].

To summarise our morphological findings of this study the following conclusions are drawn: In bone grafts growth of vital cells originating from the Haversian canals is clearly demonstrated. The growth of connective tissue in the Haversian system is understandable on general principles of pathology. The morphology of the change of osteocytes from fibrocytes through osteoblasts is photographically clearly shown and is in keeping with the findings of Steinbach and of Kerr and Smyth. New bone formation was detected at earliest nine months after implantation. Our investigations do not confirm whether this new bone formation occurs persistently in all cases or to what extent the original homograft material, preserves in cialit solution, takes part in this process. A similar mechanism of tissue regrowth should be accepted in homograft cartilage. We have studied two cases, one after 6 months and the other after 5 years following implant. The three fascial grafts examined compare with earlier publications, with oedema, slight inflammation and little shrinkage occurring. The suitability for grafting of homograft incus, cartilage and fascia we believe to have been demonstrated.

Adult↗

[Effects of Qiang Gu Kang Wei prescription on morphology of bone in rats under simulated weightlessness].

OBJECTIVE: To investigate effects of Qiang Gu Kang Wei prescription on bone morphology in tail-suspended rats. METHOD: Rats were tail-suspended (-30 degrees) for 21 d to simulate weightlessness. The effects of this prescription on thickness of periost and cortex at epiphyseal plate of tibial shaft and 3 mm under it were examined. The effects of this prescription on histology and ultrastructure of tibia were also observed. RESULT: Compared with the normal control, cortex at both epiphyseal plate of tibial shaft and 3 mm under it in suspended rats thinned significantly (P<0.01 or P<0.05). Histological observation showed that in bone of suspended rats, uncalcific matrix was more, bone cells' number was lower and their appearance was more infantile, osteoblasts were less and smaller, while osteoclasts were more and larger, haversian system of transection also showed more irregular than in bone of normal control. Ultrastructure observation showed that the function of osteoblasts was inhabited and that of osteoclasts was active. All the three doses groups of the prescription could increase cortex at either epiphyseal plate of tibial shaft or 3 mm under it (P<0.01 or P<0.05) compared with the tail-suspended group. The appearance of bone in the three groups was improved as well under optical or electron microscope. CONCLUSION: This prescription could improve abnormal change in bone morphology resulted from being tail-suspended in rats and make it normal.

Animals↗

[An experimental study on the repair of the necrotic tubular bone with pedicled vascular periosteum grafting in rabbits].

OBJECTIVE: To investigate the mechanism of the repair of the necrotic tubular bone with pedicled vascular periosteum grafting in rabbits. METHODS: Twenty mature New Zealand rabbits aged 8 months were randomly divided into test and control groups by placebo-controlled protocol. A segment of radius measuring 1.2 cm in length with pedicled vascular periosteum of the rabbits in the test group was obtained from the middle distal part of the bone, and boiled for 30 minutes. The cooled bone was then re-grafted and wrapped with vascularized periosteum and immobilized, while those in the control group, no periosteal grafting was done. X-ray examinations of the bones were carried out at 2, 4, 6, 8 approximately 10 post operation weeks (POWs). Meanwhile 4-5 rabbits were sacrificed for the harvesting of the radius on both sides for histological examination. RESULTS: It was revealed by X-ray and histological study that the periosteal hyperplasia could be observed 2-4 weeks after operation in the test group. The sign of union of the fracture and the formation and reconstitution of the trabeculae could be observed 6-8 weeks after operation. The reconstitution of reticulated bone, the formation of the lamellar bone and new haversian system could be observed during 8-10 POW. The structure of the new formed bones became more mature and the fracture healed at 12 POW. In contrast, there was no changes in the necrotic bones in the control group at 2 POW and no signs of fracture healing at 4-6 POW, and the defect of the bones could be observed at 8 POW. The necrotic bones were totally dissolved and absorbed, and the bone defects could be observed clearly filled with fibrotic tissues at 12 POW. CONCLUSION: The necrotic bones could be replaced by regeneration of new bone originated from the pedicled vascular periosteum, so that the necrotic tubular bones could be repaired. But the necrotic bones in the control group were eventually absorbed, resulting in bone defects.

Animals↗