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PubMed1994

Longitudinal evaluation of perimenopausal vertebral bone loss: effects of a low-dose oral contraceptive preparation on bone mineral density and metabolism.

OBJECTIVE: To characterize the pattern of biochemical markers of bone metabolism and vertebral bone mineral density in eumenorrheic and oligomenorrheic perimenopausal women and to assess the effects of a combined oral contraceptive (OC) preparation on bone mass and metabolism. METHODS: Bone biochemical markers and vertebral bone density were evaluated in a longitudinal 2-year follow-up study conducted in healthy, normally menstruating perimenopausal women, perimenopausal oligomenorrheic women, and age-matched oligomenorrheic OC-treated women (20 micrograms ethinyl estradiol [E2] plus 0.15 mg desogestrel) (n = 27 in each group). The results were analyzed by factorial or repeated-measures analysis of variance, as appropriate. RESULTS: During our observation period, there were no significant modifications in menstrual cycle, plasma FSH and E2 levels, biochemical markers of bone turnover, and vertebral bone density in normal women. Conversely, oligomenorrheic women showed an increase in the cycle length with a concomitant decrease of plasma E2 and a corresponding rise in circulating plasma FSH levels (P < .05). In this group, an increase in both urinary excretion of hydroxyproline and plasma osteocalcin levels paralleled a significant decrease in vertebral bone density (P < .0001). In OC-treated women, the pattern of osteocalcin showed no modification, whereas urinary excretion of hydroxyproline showed a decrease, which paralleled a significant (P < .001) increase in vertebral bone density. CONCLUSION: Perimenopausal OC administration can prevent the increase in bone turnover and the decrease in bone density that follow the perimenopausal impairment of ovarian function.

Adult↗
PubMed1998

A new parameter for measuring metastatic bone involvement by prostate cancer: the Bone Scan Index.

In this report, we describe a method for quantitative bone scan interpretation (the Bone Scan Index or BSI) in advanced prostate cancer. The BSI estimates the fraction of the skeleton that is involved by tumor, as well as the regional distribution of the metastases in the bones. The purpose of this report is to describe the development and validation of this method in terms of reproducibility and the application of BSI for determining extent of disease and monitoring disease progression. We analyzed 263 bone scans from 90 patients being studied under four protocols at Memorial Sloan-Kettering Cancer Center for progressive, androgen-independent prostate cancer (AIPC), who had bone scans as a part of their work-up. We determined: (a) the intraobserver and interobserver variability of the BSI; (b) the comparison between a change in BSI and prostate-specific antigen (PSA); (c) the regional distribution of bony metastases in early stage D prostate cancer (<3% skeletal involvement); and (d) the rate of growth of bony metastases from prostate cancer. A cube root transformation of the percentage of involvement of the entire skeleton was used to stabilize the variance over the entire span of values (0-60% tumor involvement). The range of interobserver variability between readers was 0.2-0.5 times the cube root of the BSI (69 scans, 18 patients). Intraobserver variability was minimal when the same reader read the same scans after a 2-year interval, showing a correlation coefficient of 0.97 (reader 1) and 0.99 (reader 2), P < 0.001. There was a parallel rise in the BSI and the PSA in 24 patients (105 scans) treated for AIPC with hydrocortisone followed by suramin at PSA relapse (Pearson's moment correlation, 0.71). In a group of 27 patients with limited bone involvement by AIPC (i.e., <3% BSI), the distribution of early metastases was not random within the skeleton but was distributed in the central skeleton in a manner that matched the distribution of the normal adult bone marrow. Also, in a group of 21 patients (62 scans), the change in BSI as a function of time after diagnosis was explored graphically. The progression of bone scan changes in AIPC, from early involvement (<3%) to late involvement, was fitted to a Gompertzian equation. It showed a rapid exponential growth phase, with an estimated tumor doubling time of 43 days when the BSI was 3.3%. The change in BSI rapidly approached a more gradual slope as the percentage of skeletal involvement increased. The BSI provides a reproducible new parameter for quantitative assessment of bone involvement by AIPC. These results suggest that the BSI will be useful for stratifying patients entering treatment protocols for extent of tumor involvement of bone. Although further study is necessary, serial bone scan BSI appears capable of quantifying both the progression of bony involvement by tumor as well as the response to treatment.

Aged↗
PubMed2004

BMP-2 exerts differential effects on differentiation of rabbit bone marrow stromal cells grown in two-dimensional and three-dimensional systems and is required for in vitro bone formation in a PLGA scaffold.

Osteogenic differentiation of bone marrow stromal cells (BMSC) in a three-dimensional (3-D) scaffold has not been well studied. In this work, we studied expression of bone-related genes during differentiation of rabbit BMSCs in response to bone morphogenetic protein (BMP)-2 in both 2-D and 3-D culture systems. When BMSCs were cultured on films (2-D) of biodegradable poly(lactide-co-glycolide) (PLGA), increases in mRNA expression of type I collagen (Col I) and vascular endothelial growth factor (VEGF) became evident after 1 week. However, expression of both genes was only mildly stimulated by BMP-2. Expression of the osteopontin gene was highly stimulated by BMP-2 treatment. Expression of chordin, a BMP antagonist, increased significantly after 7 days. The increase was abrogated by BMP-2 treatment. BMP-2 was also able to stimulate mineralization of cultured BMSCs. After cells were switched to 3-D PLGA scaffolds for 24 h, expression of osteopontin and VEGF were markedly increased while expression of type I collagen and chordin remained unchanged. Expression of Col I did not increase with time in a 3-D culture as it did when cells were cultured on a 2-D film. We further explored the possibility of engineering bone tissue in vitro by seeding BMSCs into PLGA scaffolds. Cellular differentiation and bone formation in the scaffolds were analyzed histologically at 2 weeks and 2 months. Secretion of ECM by cells was evident at both 2-week and 2-month scaffolds, and was enhanced by rhBMP-2. Striking differences in 2-month scaffolds were observed between BMP-treated and untreated cells. A woven bone-like structure appeared in the scaffolds treated with BMP-2. The structure was verified to be bone-related by: (1) the presence of organized collagen fibrils; (2) the presence of mineral; and (3) morphological features of trabecular bone. Although collagen was abundant in the untreated 2-month scaffolds, it was disorganized. The untreated scaffolds also lacked mineral deposits, which were present in 2-D cultured cells even in the absence of BMP-2. Our results indicate that the requirement of osteo-inductive agents, such as BMP-2, is essential for bone tissue engineering.

Animals↗
PubMed2004

Bone metabolism in patients more than five years after bone marrow transplantation.

We investigated the bone metabolism of 22 patients (median age 38 years) over 6 years after allogeneic bone marrow transplantation (BMT). Biplanar roentgenograms of the thoracic and lumbar spine were used to diagnose vertebral deformities caused by fractures. The actual bone mineral density (BMD) of the lumbar spine and the femoral neck were measured. Laboratory tests included calcium, phosphate, parathyroid hormone, a marker of bone resorption (beta-crosslaps, CTX), markers of bone formation (osteocalcin, bone-specific alkaline phosphatase), osteoprotegerin (OPG)--antagonist of the osteoclast differentiation factor RANKL, and sex hormone status. One patient had a vertebral fracture. Seven patients (28%) had osteopenia in the lumbar spine while 12 patients (48%) had osteopenia in the femoral neck. Bone resorption was increased in nine patients (43%) and bone formation was increased in four patients (20%). BMT recipients had significantly increased serum levels of OPG (P=0.029). Three women (75%) and four men (25%) were hypogonadal. The data showed that BMD is reduced and bone metabolism is still disturbed more than 6 years after BMT. The RANKL/osteoprotegerin system appears to play an important role in the pathophysiology of late post transplantation osteoporosis.

Adult↗
PubMed2003

Ex vivo gene therapy in autologous bone marrow stromal stem cells for tissue-engineered maxillofacial bone regeneration.

This study examines the clinical relevance of tissue engineering integrating gene therapy and polymer science to bone regeneration. Bilateral maxillary defects (3 x 1.2 cm(2)) in 20 miniature swine were bridged with a bioresorbable internal splint. Constructs were created using ex vivo adenovirus bone morphogenetic protein (BMP)-2-mediated gene transfer to the expanded bone marrow mesenchymal stem cells (MSCs) 7 days before implantation. Controls were performed using adenovirus beta-galactosidase. The BMP-2 cell/construct displayed white solid bone formation after 3 months. Meanwhile, the hematoxylin and eosin and Von Kossa stains demonstrated exhibited mature woven bone with good mineralization. Additionally, three-dimensional computer tomography imaging revealed a nearly complete infraorbital rim repair. Quantitative analysis demonstrated a significant difference (P<0.001) in bone formation. Finally, biomechanical testing revealed no statistically significant difference in the maximal compressive strength of new bone formed by BMP-2 cell constructs and the normal maxilla. The data evidenced de novo bone formation capable of sustaining axial compressive loads. The measurement results showed that ex vivo replication defective adenovirus-mediated human BMP-2 gene transfer to MSCs enhances autologous bone formation in the repair of maxillary defects.

Adenoviridae↗
PubMed2003

Reduced bone mineralization in adolescent survivors of malignant bone tumors: comparison of quantitative ultrasound and dual-energy x-ray absorptiometry.

PURPOSE: To assess bone mineralization in adolescents with bone tumors at remission using quantitative digital ultrasound (QUS) and dual-energy x-ray absorptiometry (DEXA), and to compare the bone mineralization values obtained by both methods. METHODS: Patients studied were 36 adolescents (21 boys, 15 girls) who had completed treatment of a bone tumor at the University Hospital of the University of Navarra (Pamplona, Spain). QUS was performed at the distal metaphysis of the proximal phalanxes of the last four fingers of the nondominant hand. A DBM Sonic 1200 Ultrasound densitometer was used. DEXA measurements were made at the lumbar spine (vertebrae L1-L4) using the Hologic QDR 4500 W device. Calcium and vitamin D daily intake and grade of physical activity were recorded. RESULTS: Mean age at bone mineralization determination was 19.11 years. Disease-free survival was 4.97 years. Decreased bone mineralization was observed by both methods. Bone mineralization absolute values measured by QUS and DEXA were significantly correlated. The sensitivity, specificity, diagnostic accuracy, and positive and negative predictive values of QUS for predicting osteopenia were 36.4%, 80.0%, 66.7%, 44.4%, and 74.1%, respectively. Daily vitamin D intake was below the recommended dietary allowances. CONCLUSIONS: Adolescents in remission from bone tumors have low bone mineralization determined by DEXA or QUS.

Absorptiometry, Photon↗
PubMed2000

The use of water-jetting technology in prostheses revision surgery-first results of parameter studies on bone and bone cement.

Water-jet cutting techniques have been used in industrial applications for many different materials. Recently these techniques have been developed into a revolutionary cutting tool for soft tissues in visceral surgery. The present study investigates the usage of this cutting technology for the revision surgery of endoprostheses. In the first part of the study, samples of bovine bone and acrylic bone cement (PMMA) were cut using an industrial jet cutting device with pure water. Below 400 bar, only PMMA was cut; above 400 bar, bone was also cut, but only pressures above 800 bar resulted in clinically useful rates of material removal (cut depth 2. 4 mm at 10 mm/min traverse speed). In the second part of the study, the effect of adding biocompatible abrasives to the water in order to reduce the required pressure was investigated, resulting in a significantly higher removal of material. At 600 bar, PMMA was cut 5. 2 mm deep with plain water and 15.2 mm deep with added abrasives. The quality of the cuts was increased by the abrasive. Though there was no clear selectivity between bone and PMMA any more, the rate of material removal at similar pressures was significantly higher for PMMA than for bone (600 bar: 1.6 mm cut depth for bone samples, 15.2 mm for PMMA). The measured cut depths with either method were not influenced by a change of the cutting direction with respect to the main direction of the osteons in the bone. However, a reduction of the jet surface angle (90 degrees to 23 degrees ) resulted for bone in a significantly lower cut depth at 600 bar (plain water: 0.62 mm vs. 0.06 mm; abrasive: 1.61 mm vs. 0.60 mm). The laboratory experiments indicate that abrasive water jets may be suitable for cutting biomaterials like bone and bone cement.

Analysis of Variance↗
PubMed1993

Formation of mineralized nodules by bone derived cells in vitro: a model of bone formation?

The identification of the factors which regulate the proliferation and differentiation of cells of the osteoblast lineage remains one of the major challenges in the field of bone cell biology. Although considerable progress has been made in the isolation and culture of cells of the osteoblast lineage from both animal and, more recently, human bone, uncertainties have persisted as to the extent to which these cell populations retain the ability to differentiate into functional osteoblasts in vitro. The formation in vitro of mineralized nodules that exhibit the morphological, ultrastructural and biochemical characteristics of embryonic/woven bone formed in vivo, represents the first evidence that the differentiation of functional osteoblasts can occur in cultures of isolated animal bone-derived cell populations. It is clear, however, that the culture conditions employed at present only permit a small number of cells to differentiate to the extent of being capable of organising their extracellular matrix into a structure that resembles that of bone. Moreover, it has generally been found that the reproducible mineralization of this extracellular matrix requires supplementation of the culture medium with mM concentrations of beta-GP, which raises doubts as to the physiological relevance of this process. The formation of nodules has also been observed in cultures of human bone-derived cells. As found in cultures of animal bone-derived cells, reproducible mineralization of these nodules will occur in the presence of beta-GP. We have shown, however, that in the presence of the long acting ascorbate analogue Asc-2-P, the formation and mineralization of nodules can occur in the absence of beta-GP. The nodules formed in human bone-derived cell cultures have yet to be characterized as rigorously as those formed in cultures of animal bone-derived cells and thus it remains to be shown that they resemble bone formed in vivo.

Animals↗
PubMed2004

Chemical, structural properties, and osteoconductive effectiveness of bone block derived from porcine cancellous bone.

The purpose of this study is to determine the efficacy of bioactive calcium phosphate obtained from porcine cancellous bone for the treatment of bone defects and nonunion. Porcine cancellous bone blocks were heat treated at 1300 degrees C for 2 h. The chemical composition, calcium-to-phosphate ratio, and microstructure of the porcine bone blocks were examined. For in vivo implantation, bone defects were created on the anteromedial aspect of the proximal tibia in seven beagle dogs and the xenograft bone blocks were placed into these defects. Plain radiographs were taken at 2-week intervals for roentgenographic evaluation. At 12 weeks, the specimens were stained with hematoxylin and eosin (H&E). The composition and morphology of heat-treated porcine cancellous bone were found to be similar to heat-treated human cancellous bone. Radiographs showed union between the host bone/bone-block interfaces. At 12 weeks, uniform and substantial new bone formation was observed. It is concluded that heat-treated porcine cancellous bone demonstrated effective osteoconductivity. This high-temperature heat-treatment technique has several advantages, including decreased risk of disease transmission and immunoreactivity, while also offering excellent biocompatibility.

Animals↗
PubMed1996

Porous ceramics as bone graft substitutes in long bone defects: a biomechanical, histological, and radiographic analysis.

Three porous ceramic bone graft materials were compared with regard to their ability to heal a 2.5 cm defect created surgically in a bilateral canine radius model. The ceramic materials were analyzed at 12 and 24 weeks after surgery and included tricalcium phosphate, hydroxyapatite, and collagen hydroxyapatite, which contained a mixture of 35% tricalcium phosphate and 65% hydroxyapatite with added collagen. Each material was evaluated alone and with added bone marrow aspirate. All the implants were compared with a graft of autogenous cancellous bone in the contralateral radius. Biomechanical testing and radiographic evaluation revealed that the addition of bone marrow aspirate was essential for tricalcium phosphate and hydroxyapatite to achieve results comparable with those of cancellous bone. Collagen hydroxyapatite performed well without the addition of bone marrow, although the addition of marrow did have a positive effect. Further qualitative radiographic and histological analysis demonstrated that tricalcium phosphate was the only ceramic that showed any sign of degradation at 24 weeks. This observed degradation proved to be an important factor in evaluating radiographs because the radiodensity of collagen hydroxyapatite and hydroxyapatite interfered with the determination of radiographic union. At 24 weeks, tricalcium phosphate with bone marrow was the material that performed most like cancellous bone. In this study, the biomechanical and radiographic parameters of tricalcium phosphate with bone marrow were roughly comparable with those of cancellous bone at 12 and 24 weeks. Tricalcium phosphate was the only implant that showed significant evidence of degradation at 24 weeks by both histological and radiographic evaluations, and this degradation took place only after a degree of mechanical competence necessary for weight-bearing was achieved.

Animals↗
PubMed1996

Bone formation and bone resorption in failed total joint arthroplasties: histomorphometric analysis with histochemical and immunohistochemical technique.

To elucidate the reactions of bone around aseptically loosened total joint arthroplasties, 24 interface tissues with adjacent bone were obtained in 17 revision operations (11 hips and six knees). The morphology of the bone surface next to the interface membrane was investigated with histochemical and immunohistochemical techniques and then histomorphometrically analysed. One-third of the total bone surface. 32.69 +/- 5.16% (mean +/- SE) (n = 24), showed positive alkaline phosphatase activity. The bone surface in contact with the cells positive for CD11b (a macrophage marker) amounted to 19.33 +/- 5.16% (n = 24). The proportion of the osteoclastic bone resorption estimated by vitronectin receptor expression was 7.67 +/- 1.82% (n = 21). Tissues retrieved from the sites where radiographic evidence of osteolysis was present (n = 12) had a significantly larger extent of the bone surface in contact with CD11b-positive cells than did the tissues from areas without osteolysis (n = 12, p = 0.0067, Mann-Whitney U test), whereas no significant difference was observed in the extent of osteoclastic bone resorption. These data demonstrate that active bone formation, regarded as a repair process, is the most common feature even in revised cases. They also highlight the role played by macrophages, not as cells producing inflammatory mediators that could activate osteoclasts, but as cells primarily responsible for the bone loss in osteolytic lesions.

Adult↗
PubMed1998

In vitro differentiation of chick embryo bone marrow stromal cells into cartilaginous and bone-like tissues.

Bone marrow stromal cells, progenitor cells involved in repair of bone and cartilage, can potentially provide a source for autologous skeletal tissue engineering. We investigated which factors were required to induce in vitro differentiation of avian bone marrow stromal cells into three-dimensional cartilaginous and bone-like tissues. Bone marrow stromal cells from embryonic chicks were expanded in monolayers, seeded onto biodegradable polyglycolic acid scaffolds, and cultured for 4 weeks in orbitally mixed Petri dishes. Cell-polymer constructs developed an organized extracellular matrix containing glycosaminoglycans and collagen, whereas control bone marrow stromal cell pellet cultures were smaller and consisted predominantly of fibrous tissue. Bone marrow stromal cells expanded with fibroblast growth factor-2 and seeded onto polymer scaffolds formed highly homogeneous three-dimensional tissues that contained cartilage-specific molecular markers and had biochemical compositions comparable with avian epiphyseal cartilage. When cell-polymer constructs were cultured in the presence of beta-glycerophosphate and dexamethasone, the extracellular matrix mineralized and bone-specific proteins were expressed. Our work shows that cell expansion in the presence of fibroblast growth factor-2 and cultivation on a three-dimensional polymer scaffold allows differentiation of chick bone marrow stromal cells into three-dimensional cartilaginous tissues. In the in vitro system studied, the same population could be selectively induced to regenerate either cartilaginous or bone-like tissue.

Animals↗
PubMed1999

Gene therapy: adenovirus-mediated human bone morphogenetic protein-2 gene transfer induces mesenchymal progenitor cell proliferation and differentiation in vitro and bone formation in vivo.

This study reports that recombinant adenovirus-mediated human bone morphogenetic protein-2 gene transfer can induce mesenchymal progenitor cell differentiation and bone formation. The recombinant adenovirus with the human bone morphogenetic protein-2 gene was constructed, and mature human bone morphogenetic protein-2 expression mediated by adenovirus gene transfer was detected by specific antibody. Under adenovirus-mediated bone morphogenetic-protein gene transfer, mesenchymal progenitor cell line C3H/10T 1/2 showed cell proliferation dependent on adenovirus bone morphogenetic-protein dose. The C3H/10T 1/2 cells transduced by adenovirus bone morphogenetic protein also exhibited differentiation to osteoblast phenotype, which indicates alkaline phosphatase activity. Injection of the C3H/10T 1/2 cells into the thigh muscles of nude mice led to ossicle development detectable on radiographs. Histological analysis indicated that the new ossicles that developed in the thigh muscles of the mice had different osseous components including bone trabeculae, bone marrow, and chondrified tissue. The results of this study demonstrate the potential for gene therapy by adenovirus-mediated bone morphogenetic-protein gene transfer.

Adenoviridae↗
PubMed1991

Quantitation of the susceptibility difference between trabecular bone and bone marrow: experimental studies.

In this study we quantify the effects of different relaxation mechanisms on the signal intensity in gradient-echo images of tissue such as bone marrow in the presence of trabecular bone. The susceptibility difference between trabecular bone and soft tissue produces distortions in the magnetic lines of force which induce strong inhomogeneities in the static magnetic field. Diffusion of tissue protons in such magnetic field gradients produce a shortening of the transverse relaxation time T2, while the dephasing of the transverse magnetization due to susceptibility differences produces a shortening of the apparent relaxation time T2* as demonstrated in gradient-echo images. We have used specimens of dried human vertebrae with different bone densities immersed in either saline to simulate tissue water or an emulsion of oil and water to simulate bone marrow to quantify these relaxation mechanisms in vitro. We have measured the MR relaxation times T1, T2, and T2* of protons within the trabecular spaces and correlated their variations with trabecular bone density. We have found that in vitro, at 1.5 T, the relaxation times T1 and T2 do not show significant variations with bone density and there are no significant contributions to the transverse relaxation rate due to the diffusion of tissue water in the magnetic field gradients. However, the relaxation rate, 1/T2*, of saline in the presence of trabecular bone increases at a rate of 0.2 s-1/mg/cc due to the dephasing of the transverse magnetization in the magnetic field inhomogeneities. Similar bone density-related T2* variations were observed for fat protons within the trabeculae where the chemical-shift-induced modulations of signal intensity in an oil-water emulsion have been separated from the susceptibility-induced relaxation effects. In addition, we have verified these effects in vivo and quantified in vivo variations in fat and water relaxation rates of bone marrow in the epiphysis and diaphysis in the appendicular skeleton of normal volunteers and found that both fat and water T2* are shorter in the epiphysis compared to the diaphysis, which correlates well with previous observations.

Bone Marrow↗
PubMed1979

Bone modelling processes at the endosteal surface of human femora. Scanning electron microscopical studies in normal bone and in renal osteodystrophy.

In femoral bone of 10 adult patients without bone disease and of 15 patients with secondary hyperparathyroidism, thy after nonmineralised organic material had been removed from the endosteal surface by sodium hypochlorite. This technique permits one to analyse the effects of past osteoblastic and osteoclastic activities. Im normal bone, the endosteal envelope shows a highly ordered texture: The main part of the inner surface is represented by fully mineralised smooth surfaces without evidence of apposition or resorption (so called neutral surfaces). In apposition areas, collagen fibers are still incompletely mineralised. Ordered mineral deposits are observed, consisting of spindleshaped calcospherites of uniform size. The resorption areas are sharply delimited. The resorption layer shows a small difference of level with respect to the surrounding neutral surface. Resorption areas consist of numerous lacunae with a smooth bottom. Individual lacunae are encircled by shallow ridges which run almost perpendicularly to the main direction of collagen fibers that have been exposed by resorption. These findings suggest that in normal bone osteoclasts act as a corrdinated group of cells. The direction of advance of the resorption area is to some extent influenced by the collagen pattern of bone. In patients with secondary hyperparathyroidism, domain formation of the endosteal surface can no longer be recognized. The size and shape of caleospherites are extremely heterogeneous, a finding interpreted as evidence of formation of woven bone. Resorption areas are irregularly determined and often resemble worm-eaten wood. The planes of resorption vary in direction and depth and in general resorption cavities penetrate deeper than in normal bone. These findings point to loss of coordinated cell action under the influence of hyperparathyroidism. The observations suggest that in hyperparathyroidism endosteal cells do not respond to local factors which influence endosteal cell activities in modelling processes of normal bone. Such local factors consist of the pattern of collagen andlamellar organisation on one hand and mechanical forces presumably via pizo-electrical potentials, on the other. In hyperparathyroidism the interdependence between bone matrix texture and spatial orientation of bone surface lining cell activities is lost.

Adult↗
PubMed2004

Mechanotransduction of bone cells in vitro: mechanobiology of bone tissue.

Mechanical force plays an important role in the regulation of bone remodelling in intact bone and bone repair. In vitro, bone cells demonstrate a high responsiveness to mechanical stimuli. Much debate exists regarding the critical components in the load profile and whether different components, such as fluid shear, tension or compression, can influence cells in differing ways. During dynamic loading of intact bone, fluid is pressed through the osteocyte canaliculi, and it has been demonstrated that fluid shear stress stimulates osteocytes to produce signalling molecules. It is less clear how mechanical loads act on mature osteoblasts present on the surface of cancellous or trabecular bone. Although tissue strain and fluid shear stress both cause cell deformation, these stimuli could excite different signalling pathways. This is confirmed by our experimental findings, in human bone cells, that strain applied through the substrate and fluid flow stimulate the release of signalling molecules to varying extents. Nitric oxide and prostaglandin E2 values increased by between two- and nine-fold after treatment with pulsating fluid flow (0.6 +/- 0.3 Pa). Cyclic strain (1000 microstrain) stimulated the release of nitric oxide two-fold, but had no effect on prostaglandin E2. Furthermore, substrate strains enhanced the bone matrix protein collagen I two-fold, whereas fluid shear caused a 50% reduction in collagen I. The relevance of these variations is discussed in relation to bone growth and remodelling. In applications such as tissue engineering, both stimuli offer possibilities for enhancing bone cell growth in vitro.

Bone Remodeling↗
PubMed1979

Studies on the biology of fish bone. III. Ultrastructure of osteogenesis and resorption in osteocytic (cellular) and anosteocytic (acellular) bones.

The comparative ultrastructure of fish bone osteogenesis and resorption induced by scale removal was described in the osteocytic (cellular-boned) Carassius auratus and the anosteocytic (acellular-boned) Tilapia macrocephala. Osteocytes, present in osteocytic bone, were lacking in anosteocytic bone. In osteocytic bone the osteoblast secreted a collagenous preosseous matrix in which it became enmeshed and then was termed a preosteocyte. When the preosseous matrix mineralized, the preosteocyte was termed an osteocyte and was completely surrounded by bone. In anosteocytic bone the osteoblasts receded from the mineralizing front and never became trapped as osteocytes. During resorption, types A and B resorptive cells, present in both bone types, invaded the matrix and demineralized the osseous zone. These cells were characterized by large amounts of granular endoplasmic reticulum and intracellular inclusions containing crystal-like material. Although functionally similar to mammalian osteoclasts, these cells lacked a characteristic ruffled border and were not multinucleated. The osteocytes of cellular bone did not appear to be involved during demineralization.

Animals↗
PubMed1976

Comparison of whole calvarial bones and long bones during early growth in rats. II. Turnover of calcified and uncalcified collagen masses.

The increase of total collagen and its destruction were compared for whole calvaria and long bones from young growing rats prelabeled in utero with 3H-L-proline. Rats were compared from birth to 16 weeks of age. Long bones and calvaria were isolated as intact anatomical units for autoradiography or separated by collagenase into calified and uncalcified collagens. Autoradiography using 14C-L-proline demonstrated eccentric modeling of bone collagen. With growth the mass of calcified collagen (bone) increased rapidly in calvaria and long bones. A similar increase in the mass of uncalcified collagen (mainly cartilage) occured in the long bones; a very small increase occurred in the fibrous tissue of calvaria. Total and specific radioactivities of collagens at each age were compared to that present at birth. With growth remodeling an almost complete loss of pre-existing radioactive collagen occurred from uncalcified fibrous tissue of calvaria as compared to a smaller but substantial loss from the uncalcified cartilage of long bones. A marked loss of calcifed collagen occurred in long bones as compared to a smaller loss from calvarial bones. The istopic data indicate a large turnover of fibrous tissue (type I collagen) with growth remodeling as compared to a smaller turnover of bone (calcified, type I collagen) and cartilage (typc I collagen). The turnover rate of skeletal collagens depends upon whether the collagen is calcified or not, and not upon the type of collagen.

Animals↗