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PubMed2001

During aging, men lose less bone than women because they gain more periosteal bone, not because they resorb less endosteal bone.

Bone size is greater in young men than in women but the load imposed is also greater. Therefore, the load per unit area (stress) on the vertebral body is the same in men and women. Fractures are uncommon in young adulthood because volumetric bone mineral density (vBMD) is normal so that the stress imposed on the bone is well below its strength in both sexes. The gender difference in bone fragility emerges during aging because the biomechanical relationship between the stress on bone and its strength changes in men and women. Periosteal apposition occurs in both genders during aging but more in men than in women so that vertebral cross-sectional area (CSA) increases more in men than women. Consequently, the stress on bone decreases more in men than women. In addition, periosteal apposition offsets endosteal bone loss more in men than in women so that net bone loss is less in men than women. Thus, the stress on the bone decreases more and the strength of the bone decreases less in men than in women. The ratio of the stress on bone to its strength can be quantitated and is below unity in young men and women. During aging this ratio increases to approach or exceed unity, the value at which fracture risk is high because the stress on bone is similar to its strength. As the stress decreases more and strength decreases less in men, the ratio increases less in men than in women so that in old age only 2-3% of men but 20% of women have this stress to strength ratio exceeding unity. Men and women with spine fractures have the same vBMD and same stress to strength ratio which is no different from unity. Fewer men than women are at risk for fracture because fewer men than women have these structural determinants of bone strength below a level at which the loads exceed the bone's ability to tolerate them.

Aging↗

PubMed2004

Extracellular bone acidic glycoprotein-75 defines condensed mesenchyme regions to be mineralized and localizes with bone sialoprotein during intramembranous bone formation.

Bone acidic glycoprotein-75 is expressed very early during in vivo models of intramembranous bone formation, highly enriched in condensing osteogenic mesenchyme after marrow ablation and the osteoprogenitor layer of tibial periosteum. Bone sialoprotein accumulates within bone acidic glycoprotein-75-enriched matrix areas at a later stage in both models. Decalcification of initial sites of mineralization consistently revealed focal immunostaining for bone acidic glycoprotein-75 underneath these sites suggesting that mineralization occurs within bone acidic glycoprotein-75-enriched matrix areas. Ultrastructural immunolocalization of bone acidic glycoprotein-75 does not support a direct association with banded collagen fibrils, but rather suggests it is a component of a separate, amorphous scaffold occupying interfibrillar spaces. Double immunogold labeling demonstrated that a sizeable proportion of bone sialoprotein particles were located within a 50-nm radius of bone acidic glycoprotein-75. These results define bone acidic glycoprotein-75 as the earliest bone-restricted, extracellular marker of osteogenic mesenchyme. Based on this early bone-restricted expression pattern and a previously documented propensity of bone acidic glycoprotein-75 to form supramolecular complexes through self-association, bone acidic glycoprotein-75 may serve a key structural role in setting boundary limits of condensing osteogenic mesenchyme.

Animals↗

PubMed2000

Promoted bone healing at a rabbit skull gap between autologous bone fragment and the surrounding intact bone with biodegradable microspheres containing transforming growth factor-beta1.

This study is a trial to promote repairing of the rabbit skull bone gap between an autologous bone flap and the intact bone with biodegradable gelatin microspheres containing transforming growth factor-beta1 (TGF-beta1). A 10-mm diameter bone defect was prepared in rabbit skulls by drilling out a bone flap of 6 mm in diameter. After a surrounding gap defect of 2 mm was created and treated with 0.5 microg of free TGF-beta1 and gelatin microspheres containing 0.5 microg of free TGF-beta1, the circular autologous bone flap was placed in the center. Significant bone healing at the gap defect was observed 3 weeks after implantation of the TGF-beta1-containing gelatin microspheres. The bone mineral density (BMD) was significantly higher than that of other experimental groups. On the contrary, when applied with free TGF-beta1, a fibrous tissue initially infiltrated into the gap defect, resulting in impairing bone healing. The tissue response was similar to that at the defect implanted with empty gelatin microspheres and TGF-beta1-free phosphate-buffered saline solution alone. There was more space in the gap-filling bone in the 16-week view than the 3-week view. It is possible that this was an intermediate step along the way toward normal healing and formation of cancellous bone. We conclude that gelatin microspheres containing TGF-beta1 show promise as an agent to promote bone regeneration of subcritical size defects between surgically positioned autologous bone flaps and surrounding host bone.

Animals↗

PubMed1999

Bone lesions with soft-tissue mass: magnetic resonance imaging diagnosis of lymphomatous involvement of the bone marrow versus multiple myeloma and bone metastases.

Bone metastases from solid primary tumors, as well as multiple myeloma and secondary lymphoma may all present with bone lesions and associated soft-tissue masses on magnetic resonance images of the spine. In bone metastases and myeloma, the cortex of the affected bone is usually destroyed and a bulging contour is observed at the site of extraosseous spread. In cases of lymphomatous involvement of the bone marrow, however, we have observed that spread to the extraosseous soft-tissues occurs without alteration of the shape or contour of the affected bone. In order to assess whether this pattern of spread is indeed suggestive or even diagnostic of lymphoma of the bone marrow, we reviewed spinal bone marrow MR images of 66 patients, with bone metastases from solid primary tumors (33 patients), multiple myeloma (20 patients) and stage IV lymphoma with bone marrow involvement (13 patients), who had bone lesions and contiguous soft-tissue masses. If tumor was present on either side of the bony cortex but the contour of the affected bone was preserved, a "wrap-around" sign was diagnosed. A "wrap-around" sign was found in 12 of the 13 patients with lymphoma but in none of the patients with metastases or myeloma. On MR images of the bone marrow, the demonstration of tumor spread beyond the bony cortex without disruption of the outline of the diseased bone may favor the diagnosis of lymphoma more than that of metastases or multiple myeloma.

Adolescent↗

PubMed2002

Histomorphometrical analysis of bone formed after maxillary sinus floor augmentation by grafting with a combination of autogenous bone and demineralized freeze-dried bone allograft or hydroxyapatite.

BACKGROUND: Maxillary sinus floor augmentation procedures are currently the treatment of choice when the alveolar crest of the posterior maxilla is insufficient for dental implant anchorage. This procedure aims to obtain enough bone with biomaterial association with the autogenous bone graft to create volume and allow osteoconduction. The objective of this study was to histologically and histometrically evaluate the bone formed after maxillary sinus floor augmentation by grafting with a combination of autogenous bone, from the symphyseal area mixed with DFDBA or hydroxyapatite. METHODS: Ten biopsies were taken from 10 patients 10 months after sinus floor augmentation using a combination of 50% autogenous bone plus 50% demineralized freeze-dried bone allograft (DFDBA group) or 50% autogenous bone plus 50% hydroxyapatite (HA group). Routine histological processing and staining with hematoxylin and eosin and Masson's trichrome were performed. RESULTS: The histomorphometrical analysis indicated good regenerative results in both groups for the bone tissue mean in the grafted area (50.46+/-16.29% for the DFDBA group and 46.79+/-8.56% for the HA group). Histological evaluation revealed the presence of mature bone with compact and cancellous areas in both groups. The inflammatory infiltrate was on average nonsignificant and of mononuclear prevalence. Some biopsies showed blocks of the biomaterial in the medullary spaces close to the bone wall, with absence of osteogenic activity. CONCLUSIONS: The results indicated that both DFDBA and HA associated with an autogenous bone graft were biocompatible and promoted osteoconduction, acting as a matrix for bone formation. However, both materials were still present after 10 months.

Adult↗

PubMed1992

Growth and morphogenetic factors in bone induction: role of osteogenin and related bone morphogenetic proteins in craniofacial and periodontal bone repair.

Bone has considerable potential for repair as illustrated by the phenomenon of fracture healing. Repair and regeneration of bone recapitulate the sequential stages of development. It is well known that demineralized bone matrix has the potential to induce new bone formation locally at a heterotopic site of implantation. The sequential development of bone is reminiscent of endochondral bone differentiation during bone development. The collagenous matrix-induced bone formation is a prototype model for matrix-cell interactions in vivo. The developmental cascade includes migration of progenitor cells by chemotaxis, attachment of cells through fibronectin, proliferation of mesenchymal cells, and differentiation of bone. The bone inductive protein, osteogenin, was isolated by heparin affinity chromatography. Osteogenin initiates new bone formation and is promoted by other growth factors. Recently, the genes for osteogenin and related bone morphogenetic proteins were cloned and expressed. Recombinant osteogenin is osteogenic in vivo. The future prospects for bone induction are bright, and this is an exciting frontier with applications in oral and orthopaedic surgery.

Alveolar Process↗

PubMed2004

Impaired marrow osteogenesis is associated with reduced endocortical bone formation but does not impair periosteal bone formation in long bones of SAMP6 mice.

UNLABELLED: We used the SAMP6 osteoporotic mouse to examine the link between marrow osteogenic potential and in vivo cortical bone formation. SAMP6 marrow supported less in vitro osteogenesis than marrow from SAMR1 controls; SAMP6 mice had a corresponding deficit in endocortical mineralizing surface. This marrow/endocortical defect did not affect the periosteum, where SAMP6 mice had normal to enhanced bone formation. INTRODUCTION: With aging, there may be a reduction in the number or proliferative capacity of bone marrow osteoprogenitors that may contribute to age-related decreases in bone formation. To examine the link between the ability of the marrow to support osteogenesis and age-related changes in bone formation, we measured in vitro and in vivo indices of osteogenesis in a model of osteoporosis, the senescence-accelerated mouse SAMP6. MATERIALS AND METHODS: Femora and tibias from SAMP6 and SAMR1 (control) mice were harvested at 2, 4, 6, and 12 months of age (168 bones total). Bone marrow cells were cultured under osteogenic conditions and stained for alkaline phosphatase (ALP) and alizarin red. Dynamic indices of bone formation were assessed histologically from calcein labels. RESULTS: ALP+ and alizarin red-positive areas were significantly less in cultures from SAMP6 bones versus SAMR1 (p < 0.05), indicating less osteogenic potential. For example, SAMP6 tibial cultures had 21% less ALP+ area and 36% less alizarin red-positive area than SAMR1. Marrow from tibias had 2-fold greater osteogenesis than femoral marrow (p < 0.001). SAMP6 mice had a deficit in endocortical mineralizing surface across all age groups (p < 0.05), but no deficit in mineral apposition rate. Last, despite the marrow and endocortical deficits, SAMP6 mice had normal or slightly increased periosteal bone formation, consistent with their larger bone size. CONCLUSION: SAMP6 bone marrow supports less in vitro osteogenesis than SAMR1, consistent with a lower concentration of marrow osteoprogenitors in SAMP6. SAMP6 mice have less endocortical mineralizing surface than SAMR1 at all ages but no detectable deficit in mineral apposition rate, which suggests a reduction in osteoblast number but normal function. Periosteal bone formation is unimpaired in SAMP6 mice, indicating that the marrow/endocortical defect does not affect the periosteal surface.

Animals↗

PubMed2005

[Bone defect repair with a new tissue-engineered bone carrying bone morphogenetic protein in rabbits].

OBJECTIVE: To construct a new tissue-engineered bone with poly (D, L-lactide-co-glycolide) (PLGA), bone morphogenetic protein (BMP) and bone marrow-derived stem cells (BMSCs) and observe its effect in repairing segmental bone defects. METHODS: A 15-mm bone defect in the right radius was induced in New Zealand white rabbits, and the models were randomized into three groups to receive implantation of the tissue-engineered bone grafts constructed with PLGA carrying 5 mg BMP and about 1 x 10(6) BMSCs (experimental group), grafts of PLGA with about 1 x 10(6) BMSCs (control group), or grafts of exclusive PLGA (blank control group), respectively. The osteogenesis in the bone defect after the implantation on was evaluated X-ray films, and the histological changes of the tissues sampled from the bone defect 4, 8, and 12 weeks after operation were observed and new bone formation was measured by image analysis. RESULTS: The bone defect was completely repaired in the experimental group 12 weeks after the implantation, showing the best results among the 3 groups. The bone defects in the blank control group was filled with only fibrous and connective tissues at 12 weeks. CONCLUSION: This tissue-engineered bone constructed with PLGA, BMP and BMSCs possesses good ability in repairing segmental bone defect.

Animals↗

PubMed1996

Vitamin D receptor gene polymorphisms are not related to bone turnover, rate of bone loss, and bone mass in postmenopausal women: the OFELY Study.

Vitamin D receptor (VDR) gene polymorphisms have been reported to account for most of the well established genetic influence on bone mineral density (BMD). However, discordant studies have been published and it is still not clear whether VDR genotypes influence bone mass accretion and/or postmenopausal bone loss. In this study, we analyzed VDR gene polymorphisms, i.e., that of BsmI, ApaI, and TaqI restriction enzymes in 268 untreated postmenopausal women 1-26 years postmenopausal. There were 37 BBAA homozygote (absence of BsmI and ApaI restriction sites on both alleles), 55 bbaa homozygote (presence of restriction sites on both alleles), and 176 heterozygotes. At baseline, women between the three genotypes did not differ significantly in age, years since menopause, body mass index (BMI), nor dietary calcium intake. We found no relationship between VDR genotypes and bone turnover assessed by three serum markers of bone formation and three urinary bone resorption markers, nor with BMD measured at the spine, hip, forearm, and whole body by dual-energy X-ray absorptiometry (DXA). Rates of bone loss assessed by repeated DXA measurements over 2 years were highly significant (p = 0.02-0.0001) at all skeletal sites except for the lumbar spine but did not differ between genotypes at any sites either before or after adjustment for potential confounding factors such as years since menopause, BMI, calcium intake, serum 25 hydroxyvitamin D levels, and baseline BMD. When we restricted the analysis to early postmenopausal women, within 10 years of menopause (n = 128), lumbar spine bone loss became significant, but no significant difference between VDR genotypes in the rate of bone loss measured at any site was found. We conclude that VDR genotypes are not predictive of bone turnover, rate of postmenopausal bone loss, and bone mass in either early or late postmenopausal women. In a subgroup of women with a low calcium intake (below 600 mg/day), we also found no significant differences between genotypes in BMD and the rate of bone loss measured at any site, although the sample size (n = 64) may be too small to detect small differences. In conclusion, these data, along with the absence of relationships between VDR gene polymorphisms and peak bone mass that we recently reported, suggest that the determination of VDR genotypes is probably not a useful clinical test for the risk assessment of osteoporosis.

Absorptiometry, Photon↗

PubMed2004

Attainment of peak bone mass at the lumbar spine, femoral neck and radius in men and women: relative contributions of bone size and volumetric bone mineral density.

The age at which peak bone mineral content (peak BMC) is reached remains controversial and the mechanism underlying bone mass "consolidation" is still undefined. The aims of this study were to investigate; (1) the timing of peak BMC by studying bone size and volumetric BMD (vBMD) as separate entities and (2) to determine the relative contributions of bone size and vBMD to bone mass "consolidation". A total of 132 healthy Caucasian children (63 boys and 69 girls, ages 11-19 years) and 134 healthy Caucasian adults (66 men and 68 women, ages 20-50 years) were studied. BMC was measured by DXA at the AP and lateral lumbar spine (LS) femoral neck (FN) and ultradistal radius (UDR). vBMD and bone volume (size) were estimated. Bone mass "consolidation" was examined between age 16 years to the age peak bone values were attained. During growth, BMC and bone size increased steeply with age and approximately 80-90% of peak values were achieved by late adolescence. vBMD at the spine and UDR (in women) increased gradually, but vBMD at the FN and UDR in men remained almost constant. During "consolidation", bone size continued to increase with little change in vBMD. Peak vBMD at the lumbar spine was reached at 22 and 29 years in men and women, respectively, but earlier at the FN at 12 years. At the UDR peak vBMD was achieved at age 19 years in women, with little change in men. In conclusion, peak vBMD and bone size are almost fully attained during late adolescence. Although speculative, the lack of change in vBMD during consolidation implies that the continued increase in bone mass may primarily be due to increases in bone size rather than increases in either trabecular volume, cortical thickness or the degree of mineralisation of existing bone matrix (vBMD). Skeletal growth and maturation is heterogeneous, but crucial in understanding how the origins of osteoporosis may begin during childhood and young adulthood.

Adolescent↗

PubMed1990

Relationships between tooth eruption, occlusion and alveolar bone resorption: histochemical and cytological studies of bone remodeling on rat incisor alveolar bone facing the enamel after root resection.

The labial side of rat incisor alveolar bone facing the enamel is continuously resorbed as the result of compressive force produced by the occlusion and eruption of incisors. In order to clarify the relationship between this mechanical compressive force and the bone cells involved in bone remodeling, we examined morphological changes occurring in the alveolar bone once the compressive force was eliminated by the removal of the proliferative odontogenic base (root resection according to Berkovitz and Thomas, 1969). After root resection, the incisor migrated halfway along the socket. On the crestal part where incisor still existed, active osteoclasts were prominent on the bone surface, and flattened mononuclear cells lay close upon active osteoclasts. Sinusoidal blood vessels or capillaries were observed at short distances from the bone surface. On the basal part where socket was vacant, osteoblasts lined up on the newly formed bone, and the osteogenic cell layer lay on the osteoblasts. Between the two parts, which correspond to the reversal phase proposed by Baron (1977), osteoblastic cells with developed cell organelles increased in number and the distance between blood vessels and bone surface increased. Osteoclasts reduced their activities, and osteoblastic cells often wedged themselves between the osteoclasts and bone surface. These findings indicate that the elimination of compressive force mediated by incisors leads to the activation of osteoblastic cells and inactivation of osteoclasts, which results in a conversion from bone resorption to bone formation. Thus, osteoblastic cells may play an important role in controlling osteoclastic activity in conversion from bone resorption to bone formation, partly by a direct effect and partly by controlling the access of blood vessels to the bone surface.

Acid Phosphatase↗

PubMed1995

Expression of bone sialoprotein mRNA during bone formation and resorption induced by colchicine in rat tibial bone marrow cavity.

In the rat tibial bone marrow cavity, following colchicine injection, there is a phase of osteogenesis in which bone trabeculae replace the necrotic bone marrow tissues and fill the marrow cavity. The newly formed bone is subsequently resorbed by osteoclasts and normal bone marrow is restored. In this study, we correlated these morphologic events with the pattern of gene expression of bone sialoprotein (BSP), an extracellular matrix protein in mineralized tissues, to elucidate the possible functions of BSP in bone formation and resorption in vivo. The expressions of osteopontin (OPN) and type I collagen were also examined. Northern hybridization of the tibia demonstrated that OPN mRNA was gradually increased and expressed at a maximal level 10 days after colchicine injection (during the bone resorption process), while BSP mRNA expression already reached a maximal level at day 6 (during the initial process of bone formation). Its expression was, thus, quite temporary at the beginning of bone formation and different from that of type I collagen, which was continually elevated from days 6 to 10. In situ hybridization of the newly formed bone induced in the tibia revealed that BSP mRNA was evenly expressed in most osteoblasts and osteocytes, moreover in interconnecting colonies of spindle-shaped cells, possibly preosteoblasts, at day 6. At day 10, however, its expression became restricted to some cells on the bone surfaces, some osteoblasts, and most osteoclasts. These observations suggest that BSP may play an important role mainly in the initiation of bone formation and is also associated with the functions of osteoclast in vivo.

Amino Acid Sequence↗

PubMed1983

Effects of ethane-1-hydroxy-1,1-diphosphonate (EHDP) upon the kinetics of bone resorption and bone formation at the whole bone level in prelabelled chicks.

Chicks chronically prelabelled with 45Ca, 3H-tetracycline, and 3H-proline were used to measure the weekly effect of EHDP (5 mg P/kg for 28 days) on bone turnover at the whole bone level in vivo. Direct measurements were made of cortical bone resorption (loss of 3H-tetracycline and 3H-collagen from whole femur, blood-bone ratio of 45Ca), skeletal collagen formation and bone mineralization (collagen and calcium mass per whole femur, respectively). Chicks were sacrificed after 5, 14, 21 and 28 days of EHDP administration. By five days of treatment, EHDP caused a greater inhibition of bone mineralization (86%) than bone resorption (30-39%) without affecting skeletal collagen mass. The blood-bone ratio of 45Ca decreased 34%, which was similar in degree to the inhibition of 3H-tetracycline loss (30%) and 3H-collagen loss (39%). Almost complete inhibition of bone resorption and bone mineralization occurred by 14 days of treatment without effects on skeletal collagen mass. No additional effect was seen at 21 and 28 days of EHDP treatment. In chicks, EHDP inhibits almost completely bone mineralization (bone formation) and cortical bone resorption without affecting skeletal collagen mass.

Animals↗

PubMed2003

Serum levels of bone turnover markers parallel the results of bone scintigraphy in monitoring bone activity of prostate cancer.

OBJECTIVES: To investigate the usefulness of bone turnover markers as a modality for monitoring bone metastasis in patients with prostate cancer with bone metastasis. METHODS: Serial measurements of pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), carboxyterminal pro-peptide of type I procollagen (PICP), prostate-specific antigen (PSA), and the percentage of the positive area on the bone scan were prospectively performed before and after hormonal therapy in 84 patients with prostate cancer with bone metastasis for median follow-up of 29 months. RESULTS: Serial ICTP and PICP levels in 48 patients without progression of bone metastasis demonstrated a downward trend during treatment and were almost within the normal range by the end of follow-up. The remaining 36 patients, who had PSA failure with progression of bone metastasis, showed an upward trend for serial ICTP and PICP levels before the progression of bone metastasis. The rates of detecting bone progression using bone turnover markers were higher than those using PSA levels on the basis of the percentage of clinical effectiveness and receiver operating characteristic curves. CONCLUSIONS: Serial measurement of bone turnover markers is useful for monitoring the bone activity of prostate cancer and might detect early progression of bone metastasis in patients with PSA failure.

Aged↗

PubMed2000

Evidence for migration of donor bone marrow stromal cells into recipient thymus after bone marrow transplantation plus bone grafts: A role of stromal cells in positive selection.

Intrathymic T-cell differentiation is characterized by two selection events: positive and negative selection. It has been shown that thymic epithelial cells in the cortex are involved in the positive selection, while macrophages and dendritic cells, derived from hemopoietic stem cells, are involved in the negative selection. Here we investigate whether donor-derived bone marrow stromal cells can migrate into the thymus and participate there in positive selection after bone marrow transplantation plus bone grafts (to recruit bone marrow stromal cells). Allogeneic bone marrow transplantation with or without bone grafts was carried out in the [C57BL/6-->C3H] combination. Fluorescence-activated cell sorter analyses of recipient thymic adherent cells showed that donor-type bone marrow stromal cells exist in the thymus of mice that received bone marrow plus bone grafts but not in the mice that received bone marrow cells alone. Histological examination using confocal microscopy also confirmed the existence of donor-type stromal cells in the thymus of mice that received bone marrow cells plus bones. Both T-cell proliferation and plaque-forming cell assays indicated that the T cells of such mice show donor-type major histocompatibility complex-restriction. These findings strongly suggest that stromal cells can migrate from the bone marrow to the thymus, where they participate in the positive selection of thymocytes.

Animals↗

PubMed2006

Bone-composition imaging using coherent-scatter computed tomography: assessing bone health beyond bone mineral density.

Quantitative analysis of bone composition is necessary for the accurate diagnosis and monitoring of metabolic bone diseases. Accurate assessment of the bone mineralization state is the first requirement for a comprehensive analysis. In diagnostic imaging, x-ray coherent scatter depends upon the molecular structure of tissues. Coherent-scatter computed tomography (CSCT) exploits this feature to identify tissue types in composite biological specimens. We have used CSCT to map the distributions of tissues relevant to bone disease (fat, soft tissue, collagen, and mineral) within bone-tissue phantoms and an excised cadaveric bone sample. Using a purpose-built scanner, we have measured hydroxyapatite (bone mineral) concentrations based on coherent-scatter patterns from a series of samples with varying hydroxyapatite content. The measured scatter intensity is proportional to mineral density in true g/cm3. Repeated measurements of the hydroxyapatite concentration in each sample were within, at most, 2% of each other, revealing an excellent precision in determining hydroxyapatite concentration. All measurements were also found to be accurate to within 3% of the known values. Phantoms simulating normal, over-, and under-mineralized bone were created by mixing known masses of pure collagen and hydroxyapatite. An analysis of the composite scatter patterns gave the density of each material. For each composite, the densities were within 2% of the known values. Collagen and hydroxyapatite concentrations were also examined in a bone-mimicking phantom, incorporating other bone constituents (fat, soft tissue). Tomographic maps of the coherent-scatter properties of each specimen were reconstructed, from which material-specific images were generated. Each tissue was clearly distinguished and the collagen-mineral ratio determined from this phantom was also within 2% of the known value. Existing bone analysis techniques cannot determine the collagen-mineral ratio in intact specimens. Finally, to demonstrate the in situ potential of this technique, the mineralization state of an excised normal cadaveric radius was examined. The average collagen-mineral ratio of the cortical bone derived from material-specific images of the radius was 0.53+/-0.04, which is in agreement with the expected value of 0.55 for healthy bones.

Algorithms↗

PubMed1996

Monitoring of bone metabolism after bone marrow transplantation by measuring two different markers of bone turnover.

Bone marrow transplant recipients may be at increased risk of osteoporosis. In a cross-sectional study we therefore measured two biochemical markers of bone turnover, bone alkaline phosphatase and the C-terminal propeptide of type I procollagen, in 22 serum samples from 9 patients before allogeneic bone marrow transplantation and 85 serum samples from 14 patients after allogeneic bone marrow transplantation. Following allogeneic bone marrow transplantation, female (but not male) patients showed elevated serum bone alkaline phosphatase values (p < 0.05). After bone marrow transplantation both female and male patients were characterized by elevated serum concentrations of the C-terminal propeptide (p < 0.01). Both the duration of cyclosporin A therapy (p < 0.05) and the time since transplantation (p < 0.01) were independent predictors of serum bone alkaline phosphatase values, whereas the duration of cyclosporin A therapy was the only independent predictor of C-terminal propeptide serum concentrations (p < 0.01). There was a correlation between bone alkaline phosphatase serum concentrations and C-terminal propeptide values in serum (p < 0.0001). These findings indicate an accelerated bone turnover in patients following bone marrow transplantation due to the stimulation of osteoblasts by cyclosporin A. In addition, oestrogen deficiency after total body irradiation may accelerate bone mass loss in female patients.

Adult↗

PubMed2000

Peptidomimetic antagonists of alphavbeta3 inhibit bone resorption by inhibiting osteoclast bone resorptive activity, not osteoclast adhesion to bone.

Osteoclasts are actively motile on bone surfaces and undergo alternating cycles of migration and resorption. Osteoclast interaction with the extracellular matrix plays a key role in the osteoclast resorptive process and a substantial body of evidence suggests that integrin receptors are important in osteoclast function. These integrin receptors bind to the Arg-Gly-Asp (RGD) sequence found in a variety of extracellular matrix proteins and it is well established that the interaction of osteoclast alpha v beta 3 integrin with the RGD motif within bone matrix proteins is important in osteoclast-mediated bone resorption. In this study, we characterized the effects of two synthetic peptidomimetic antagonists of alpha v beta 3, SC-56631 and SC-65811, on rabbit osteoclast adhesion to purified matrix proteins and bone, and on bone resorption in vitro. SC-56631 and SC-65811 are potent inhibitors of vitronectin binding to purified alpha v beta 3. Both SC-56631 and SC-65811 inhibited osteoclast adhesion to osteopontin- and vitronectin-coated surfaces and time-lapse video microscopy showed that osteoclasts rapidly retract from osteopontin-coated surfaces when exposed to SC-56631 and SC-65811. SC-56631 and SC-65811 blocked osteoclast-mediated bone resorption in a dose-responsive manner. Further analysis showed that SC-65811 and SC-56631 reduced the number of resorption pits produced per osteoclast and the average pit size. SC-65811 was a more potent inhibitor of bone resorption and the combination of reduced pit number and size led to a 90% inhibition of bone resorption. Surprisingly, however, osteoclasts treated with SC-65811, SC-56631 or the disintegrin echistatin, at concentrations that inhibit bone resorption did not inhibit osteoclast adhesion to bone. These results suggest that alphavbeta3 antagonists inhibited bone resorption by decreasing osteoclast bone resorptive activity or efficiency but not by inhibiting osteoclast adhesion to bone per se.

Aniline Compounds↗