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Evaluation of bone turnover in type I osteoporosis using biochemical markers specific for both bone formation and bone resorption.

The aims of the study were to evaluate the use of bone-specific biochemical markers of turnover in type I osteoporosis, to test for evidence of heterogeneity of bone turnover in this condition, and to attempt to devise an 'uncoupling index' by using the relationship between bone-specific biochemical markers of bone formation and bone resorption. In women with type I osteoporosis (mean age 64 years, SD 5; n = 63) the mean level of serum osteocalcin, a specific biochemical marker of bone formation, was 9.9 ng/ml (SD 2.0), which was higher than the level in normal postmenopausal women (mean age 65 years, SD 6; n = 8.9 ng/ml (SD 2.0; p < 0.01). The variance of serum osteocalcin levels in the two groups was similar. Compared with this 11% increase in the biochemical marker for bone formation, the markers of bone resorption, total urinary deoxypyridinoline (bone-specific), pyridinoline and hydroxyproline were increased by 40% (p < 0.0001), 61% (p < 0.0001) and 25% (p < 0.01), respectively. Furthermore, these biochemical markers of bone resorption had greater variance in women in type I osteoporosis than in the normal postmenopausal women (p < 0.01). The urinary excretion of the free crosslinks deoxypyridinoline, pyridinoline and glycosylated pyridinoline were increased by 26% (p < 0.001), 17% (p < 0.01) and 13% (NS) respectively. An 'uncoupling index' was calculated for the difference between urinary deoxypyridinoline and serum osteocalcin using the results from the normal women and expressed as z-scores. We conclude that the pyridinium crosslinks of collagen enable better discrimination between normal and osteoporotic women than does hydroxyproline.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

pQCT bone strength index may serve as a better predictor than bone mineral density for long bone breaking strength.

Bone mineral density (BMD) is commonly used to predict osteoporotic fracture risk without considering the geometry of the bone. However, geometric parameters are also important in determination of bone strength. An index including both material and geometric properties may be therefore more relevant in prediction of fracture risk. We studied the correlation between parameters measured by noninvasive peripheral quantitative computed tomography (pQCT) and bone bending strength of the diaphysis of 45 fresh goat humeri and 27 femora. Multislice pQCT was used for measuring volumetric diaphyseal cortical BMD, total BMD, diaphyseal and cortical cross-sectional area (CSA), and cross-sectional moment of inertia (CSMI) and their derived bone strength indices (BSIs), including BSI(CSMI) (cortical BMD x CSMI) and BSI(CSA) (cortical BMD x cortical CSA). Conventional dual-energy absorptiometry (DXA) was also conducted to measure areal BMD of diaphysis for comparison. Ultimate fracture load was obtained via three-point bending test. Results showed that for femora, fracture load was correlated better with BSI(CSA) ( r = 0.697, P < 0.001) than cortical BMD ( r = 0.304, P > 0.05) and total BMD ( r = 0.387, P > 0.05) measured using pQCT and areal BMD ( r = 0.612, P < 0.001) measured using DXA. For humeri, fracture load was also correlated with BSI(CSA) ( r = 0.579, P < 0.001) but not with other pQCT parameters including cortical BMD and total BMD ( r = 0.282 and 0.305, respectively; P > 0.05, both). The best correlation was found with areal BMD measured by DXA ( r = 0.760, P < 0.001). In conclusion, pQCT noninvasive BSI(CSA) derived from cortical BMD (material) and its cortical CSA (bone geometry or distribution) may serve as an important noninvasive index for predicting long bone bending strength. The bending strength was also predicted by bone mass (areal BMD) measured by DXA, an integration of bone mineral and geometry. Further clinical studies are needed to validate the predictive value of BSI in long bone osteoporotic fracture.

Animals↗

The influence of screw torque, object radius of curvature, mode of bone plate application and bone plate design on bone-plate interface mechanics.

Using Fuji Prescale Pressure Sensitive Film we evaluated the influence of screw torque, object radius of curvature, mode of bone plate application (compression or neutral loading) and bone plate design on bone-plate interface mechanics. Testing was performed using 4.5 mm and 3.5 mm dynamic compression (DC) (stainless steel) and limited contact-dynamic compression (LC-DC) plates (titanium). Plexiglass tubing, having different radii of curvature, was used to simulate bone but having more uniform geometric and structural properties. With the film interposed between the bone plate and the plexiglass, bone plates were applied at predetermined levels of screw torque. The resultant image was digitized and then underwent computer-assisted analysis to yield the interface contact area (%) and the average force (in Newtons N) between the bone plate and the object to which it was applied. In any given object, screw torque had the most significant influence on both interface contact area (P = 0.0001) and average force (P = 0.0001) at the interface. The bone plates responded differently to dynamization. The DC plate, when applied in compression loading mode, was lifted off the object between the two central screws when compared to the same plate applied in neutral loading mode (P = 0.0001). Conversely, in the LC-DC plate, an increase in the overall interface contact area was observed when applied in compression loading mode (P = 0.0002). At a given level of applied screw torque, the object radius of curvature appeared to be a major determining factor for interface contact area and average force (P = 0.0001, P = 0.0001). We conclude that variables other than bone plate design also influence the interface contact area and average force between a bone plate and object to which it is applied.

Biomechanical Phenomena↗

Alveolar bone formation at dental implant dehiscence defects following guided bone regeneration and xenogeneic freeze-dried demineralized bone matrix.

The present study evaluated rate and extent of alveolar bone formation in dental implant dehiscence defects following guided bone regeneration (GBR) and implantation of xenogeneic freeze-dried demineralized bone matrix (xDBM). A total of 16 titanium plasma-sprayed (TPS) and 16 hydroxyapatite-coated (HA) titanium cylinder implants were inserted in 4 mongrel dogs following extraction of the mandibular premolar teeth. Four implant sites per jaw quadrant (2 TPS and 2 HA implant sites) were prepared into extraction sockets in each dog. Buccal alveolar bone was removed to create 3 x 5 mm dehiscence defects. Two jaw quadrants in separate animals received GBR, GBR + xDBM, xDBM (control), or gingival flap surgery alone (GFS; control). Thus, four conditions were available for each implant type (TPS or HA): GBR, GBR + xDBM; xDBM and GFS. The animals received fluorescent bone labels to allow observations of rate and extent of bone formation. Animals were sacrificed at 12 weeks postsurgery and block sections were harvested for histologic analysis. There were no apparent histologic differences between TPS and HA implant defects. GBR and GBR + xDBM resulted in almost complete bone closure of the dental implant dehiscence defect. Rate of bone formation appeared higher following GBR alone. Extent of bone formation appeared somewhat greater following GBR + xDBM; however, delayed. xDBM alone did not adequately resolve the bony defect. In conclusion, GBR results in rapid, clinically relevant bone closure of dental implant dehiscence defects. Adjunctive implantation of xDBM does not appear to significantly improve the healing response in the model used.

Alveolar Process↗

Influence of bone marrow on membrane-guided bone regeneration of segmental long-bone defects in rabbits.

Defects 10 mm long were created in long bone in the diaphysis of both radii of 18 rabbits (test and control side). On the test side, ingrowth of bone marrow into the defects was hindered or delayed by: plugging the opening of the cut bone ends with gutta-percha points (n = 7); plugging with Gelfoam (n = 6); or by removing the bone marrow by flushing with saline (n = 5). The defects on both test and control side were covered with an expanded polytetrafluoroethylene membrane, shaped as a tube. Healing was followed with radiographs for four to five months, after which the animals were killed and ground sections of the areas of the defects were prepared for histological examination. On the control side, nine of 18 animals had complete osseous bridging of the defect, and a small transverse non-mineralised zone remained in the centre of the healed defect in the other animals. This zone consisted of loose connective and cartilagenous tissue as well as connective tissue obviously derived from the outside of the membrane. By preventing or delaying the ingrowth of bone marrow we retarded the regeneration of mineralised bone, particularly in the gutta-percha and flushed bone marrow groups. The principle of guided tissue regeneration may be used to achieve regeneration of extensive long-bone defects. Any attempts to delay or prevent bone marrow ingrowth into the defects did retard regeneration of segmental long-bone defects.

Animals↗

Prognostic value of the serum levels of bone formation and bone resorption markers in prostate cancer patients with bone metastasis.

OBJECTIVE: The aim of the present study was to determine whether the serum levels of a bone formation marker, i.e., the carboxy-terminal propeptide of type I procollagen (PICP), and a bone resorption marker, i.e., the carboxy-terminal telopeptide of type I collagen (ICTP) have prognostic value in prostate cancer patients with bone metastasis, compared with alkaline phosphatase (ALP) and prostate-specific antigen (PSA). METHODS: The serum levels of PICP, ALP, ICTP and PSA were examined in 116 untreated prostate cancer patients (40 patients with bone metastasis, 76 patients without bone metastasis), and the prognoses of the patients with bone metastasis were evaluated using univariate and multivariate analyses. RESULTS: The bone metastasis patients with low PICP or ALP values had significantly better outcomes compared to the bone metastasis patients with high PICP or ALP values. A multivariate analysis of PICP, ICTP, ALP, PSA and the patients' age revealed that PICP and patients' age were important prognostic factors for survival. The pretreatment levels of ICTP and PSA did not show any substantial relation to the prognosis of these patients. CONCLUSIONS: The results suggest that the pretreatment serum bone formation marker is an important prognostic indicator for prostate cancer patients with bone metastasis.

Aged↗

[Repair of large bone defect due to excision of bone tumor with bone allograft].

OBJECTIVE: To study the reparative and reconstructive methods for the large bone defect due to the excision of bone tumor. METHODS: According to the size and shape of the bone defect, we selected the proper bone and joint or manipulated bone segment of the profound hypothermia freezing allograft and gave locked intramedullary nails or steel plate and screws for stable internal fixation. RESULTS: In the 22 cases, 20 survived without tumor and 2 died. One patient treated with the allograft of semi-knee joint was found rejection. Then the wound did not heal. After the skin flap grafting was performed, the wound still did not heal, so the patient accepted amputation(4.5%). In the other 21 cases, the X-ray and 99mTc SPECT showed some callus or concentration of nuclein which implied bone union. According to Markin bone graft criterion, the excellent rate of function recovery was 81.8%. CONCLUSION: Allografting of bone and joint is a good and workable method in repairing and reconstructing the bone defect due to the excision of bone tumor. It should be further studied and be applied.

Adolescent↗

Interactions between the bone matrix proteins osteopontin and bone sialoprotein and the osteoclast integrin alpha v beta 3 potentiate bone resorption.

We have investigated the mechanism by which osteoclasts adhere to and resorb bone. We show that these cells express beta 1 and beta 3 integrins which are involved in attachment to purified bone matrix proteins. Binding to osteopontin and bone sialoprotein is mediated by alpha v beta 3, while a beta 1 integrin is responsible for attachment to fibronectin. Both the rapid attachment by osteoclasts to intact bone particles and their subsequent resorption are blocked by a monoclonal antibody directed to the alpha v beta 3 complex but not by an antibody against beta 1 integrins. Attachment of osteoclasts to bone is also inhibited with soluble osteopontin, Arg-Gly-Asp-containing peptides derived from both osteopontin and bone sialoprotein, or a monospecific polyclonal antibody against osteopontin. We conclude that both osteoclast adherence to bone and subsequent resorption of its matrix are dependent on interactions between the bone matrix proteins osteopontin and/or bone sialoprotein and the integrin alpha v beta 3. Moreover, collagen, which constitutes 90% of its organic matrix, is minimally involved in binding of chicken osteoclasts to bone.

Amino Acid Sequence↗

Blood coagulation and bone metabolism: some characteristics of the bone resorptive effect of thrombin in mouse calvarial bones in vitro.

Chronic inflammatory processes are often associated with bone resorption. Stimulated by the current great interest in the role of coagulation factors in inflammation and immune injury, we have studied the effect of thrombin on mouse calvarial bones in vitro. Thrombin caused a dose-dependent (0.1-7 U/ml) stimulation of 45Ca release from neonatal mouse calvarial bones. Thrombin also stimulated the mobilization of stable calcium and inorganic phosphate, the release of 3H from [3H]proline-labelled calvaria, the production of lactate and the release of the lysosomal enzymes, beta-glucuronidase and beta-N-acetylglucosaminidase. Thrombin also enhanced 45Ca release from fetal rat long bones, although this bone resorption assay was less sensitive to thrombin than the mouse calvarial system. The bone resorption stimulatory activity of thrombin in mouse calvaria could be inhibited by calcitonin and an increased concentration of phosphate in the culture medium. Thrombin-induced 45Ca release in mouse calvaria was sensitive to inhibition by hydrocortisone and dexamethasone. By contrast, 45Ca release response to parathyroid hormone was insensitive to corticosteroids. The prostaglandin synthetase inhibitors indomethacin, meclofenamic acid and naproxen and 5,8,11,14-eicosatetraynoic acid reduced 45Ca release from thrombin-stimulated calvaria. However, significant stimulation by thrombin could be achieved also in bones treated with inhibitors of arachidonate metabolism. The results obtained suggest that thrombin can stimulate cell-mediated bone resorption by an osteoclast-dependent mechanism. The mechanism of action may involve both prostaglandin-dependent and prostaglandin-independent pathways. Our findings indicate that thrombin may contribute to the bone resorptive processes seen in periodontal disease and rheumatoid arthritis.

Adrenal Cortex Hormones↗

Dynamic scintigraphy of bone and bone marrow in multiple myeloma patients with bone-marrow transplants.

PURPOSE: To determine whether dynamic registration at bone and bone-marrow scintigraphy produces additional information compared to subsequent static registrations of bone-marrow transplants in multiple myeloma patients. MATERIAL AND METHODS: In a prospective study, 8 dynamic bone and 6 dynamic bone-marrow scintigraphies were performed in 10 patients. The dynamic scintigraphies were compared with conventional radiography, MR images, and static scintigraphies of bone and bone marrow. RESULTS: No additional information was revealed by the dynamic registration method; on the contrary, 4 of the 8 known lesions were not discerned at dynamic registration. An incidental observation was that the time-activity curves of both radiopharmaceuticals had a specific pattern. CONCLUSION: Dynamic registration at bone and bone-marrow scintigraphy was not useful for detecting disease in multiple myeloma lesions.

Adult↗

Treatment of aneurysmal bone cysts by introduction of demineralized bone and autogenous bone marrow.

BACKGROUND: On the assumption that an aneurysmal bone cyst has an intrinsic potential to heal by ossification, a new, minimally invasive protocol was developed. Demineralized bone powder mixed with bone-marrow aspirate was introduced into the cyst to halt the expansion phase and to allow the cyst to ossify. We hypothesized that, in order to induce bone-healing, cells from the cyst are needed to respond to the inductive material but that curettage or extensive surgery is not necessary. The goals of the present study were to assess cyst-healing and to determine the prevalence of recurrence associated with this new procedure. METHODS: Thirteen biopsy-proven primary aneurysmal bone cysts were entered through a small incision, and a paste of demineralized bone and autologous bone marrow was introduced with an applicator. The study group included three male and ten female patients with a mean age of 16.6 years. The cyst was located in a long bone in six patients, the pelvis in five patients, and the scapular glenoid and the calcaneus in one patient each. Five patients had not received treatment previously, whereas one had had a preoperative embolization and seven had recurrent lesions that had been treated previously. RESULTS: After a mean duration of follow-up of 3.9 years, healing was achieved in eleven patients. CONCLUSIONS: This minimally invasive method is able to promote the self-healing of a primary aneurysmal bone cyst. As no curettage is required, the proposed treatment avoids extensive surgery and blood loss and is convenient for the treatment of poorly accessible lesions such as those occurring in the pelvis. LEVEL OF EVIDENCE: Therapeutic Level IV.

Adolescent↗

[Role of recombinant human bone morphogenetic protein 2/collagen as an onlay bone graft on adult rat calvarial bone].

OBJECTIVE: To evaluate the bone regenerative potential of recombinant human bone morphogenetic protein 2(rhBMP-2)/collagen on adult rat calvarial bone. METHODS: A tight subperiosteal pocket was produced under both sides of the temporal muscle in rats. rhBMP-2/collagen was implanted in one side and collagen alone was implanted in the other side as control. The rats were sacrificed 2, 4 and 8 weeks after operation. The specimen was harvested and examined histologically. For morphometric analysis, the thickness of the temporal bone of both sides was measured and compared. RESULTS: The rhBMP-2/collagen onlay implant resulted in active bone formation and the augmented bone was connected directly with the original bone, whereas the collagen alone resulted in neither bone nor cartilage production. The ossification process in the rhBMP-2/collagen occurred directly through bone formation, similar to intramembranous ossification. CONCLUSION: rhBMP-2/collagen is an effective material as a biological onlay implant.

Animals↗

[Mineralogic research of bone union formation after transplantation of autogenic bone marrow and stromal cells into the bone defect from in vitro culture. Experimental studies. III].

In experimental studies on 3 groups of rabbits (1. with autogenic bone marrow transplantation, 2. with stromal cells from in vitro culture transplantation, 3. control group) the mineralogic changes within healing fracture have been observed. These changes were investigated with scanning microscope and chemically using Cameca electronic microprobe and X-ray diffractometer. In each group there were differences in the time of arising of trabecular structures and their mineralization. Bone trabeculae were visible first in a group of rabbits with performed transplantation of stromal cells. They were present in a great number and their structure was homogeneous. They contained prominent quantity of apatites similar to the one found in normal bone. In the final phase of observation, trabeculae of external part of union demonstrated a parallel orientation and a tendency to transformation into a compact bone. After some time trabeculae arose in rabbits after autogenic bone marrow transplantation. They were less numerous and their structure was disordered. They were characterized by a significant chemical heterogeneity. The content of Ca and P was similar to their content in a normal bone. At the very and trabeculae arose in the control group. Their structure however was heterogeneous. In the final phase of observation the content of Ca and P did not reach the level found in a normal bone. Within the whole bone union a spongy bone arose.

Animals↗

[Clinical studies using measurement of N-telopeptides of type 1 collagen (NTx) in patients with bone metastasis--comparison with bone scintigraphy and other metabolic bone markers].

Urinary metabolites of N-telopeptide of type 1 collagen cross-links (NTx) are known as a bone resorption marker. We performed a multi-center trial of NTx measurement in evaluation of bone metastasis. In total, 251 patients with or without bone metastasis from various malignancies were studied. Comparing with other bone markers such as urinary total deoxypyridinoline, osteocalcin, and bone specific alkaline phosphatase, NTx was the most sensitive one to detect bone metastasis and its levels correlated well with the extensiveness of bone metastasis. Measurement of NTx will be useful to determine to order bone scan in patients with malignancy and to monitor the clinical course in patients with bone metastasis.

Adult↗

Bone stiffness predicts strength similarly for human vertebral cancellous bone in compression and for cortical bone in tension.

The yield strength and ultimate strength of cortical and cancellous bone tissue are very highly correlated to bone stiffness. For samples of human vertebral cancellous bone in compression and for bovine cortical bone in tension, the coefficient of determination (r2) for regression between ultimate strength and stiffness was 0.89 and 0.92, and between yield strength and stiffness it was 0.94 and 0.93, respectively. The slope of the regression for human vertebral cancellous bone ultimate strength predicted by stiffness was not statistically different from similar regressions for cortical bone in tension in either a bovine sample or in published data from multiple species. We believe that the observed correlation results from the evolutionary need to build sufficiently strong bones using cells that are sensitive to deformation and that directly control bone stiffness, but not strength. The practical significance of this work is that an in vivo estimate of bone stiffness (e.g., from ultrasound measurement) may be a surrogate for bone strength.

Adaptation, Physiological↗

Indexes of bone mineral content on second metacarpal bone roentgenogram analyzed by digital image processing: a comparison with other bone mass quantifying methods.

A new photodensitometric technique (digital image processing, DIP) was performed to assess the bone mineral content of the metacarpal bone as a screening test for bone loss in 340 healthy or osteoporotic women as well as 35 steroid-dosed patients and 46 patients with chronic renal failure on hemodialysis. This procedure was compared with single photon absorptiometry and dual photon absorptiometry in terms of clinical value. Two bone mineral indexes, metacarpal index and sigma GS/D (the integrated bone mineral density of cortical and trabecular bone on a cross section in the middle of the second metacarpal bone), were equal to other methods in the quantification of decreases in bone mineral content due to aging in healthy or osteoporotic women. In addition, sigma GS/D was sensitive enough to detect decreases in bone mineral content in patients with vertebral fractures, on steroid therapy, and with chronic renal failure. Thus, sigma GS/D measured by DIP was shown to have clinical value as a tool in screening for decreased bone mineral content.

Absorptiometry, Photon↗

Effects of platelet-rich plasma on bone healing in combination with autogenous bone and bone substitutes in critical-size defects. An animal experiment.

OBJECTIVES: An animal study was carried out to investigate the influence of platelet-rich plasma (PRP) on the regeneration of bony defects. MATERIAL AND METHODS: Critical-size defects in the forehead region of a mini-pig were filled with randomly distributed combinations of autogenous bone, tricalcium-phosphate granules (CeraSorb), bovine spongious blocks (BioOss) and a bovine bone inducing collagenous sponge (Colloss) with and without PRP in two preparations (Cusasan, 3i). The animals were killed after 2, 4 and 12 weeks. The specimens were evaluated microradiographically and immunohistologically. RESULTS: Autologous bone (38 +/- 9.9%) and Colloss (52.6 +/- 4.0%) showed the highest remineralization rates at 2 weeks. The initial high expression of BMP-2 in the Colloss-group gives evidence of an early initiation of bony regeneration. At 2 weeks PRP ad modum 3i was able to enhance bone healing significantly (P=0.028) only when applied in combination with autogenous bone (62.8 +/- 1.6%). Four weeks after surgery, both PRP preparations did no longer increase bony regeneration in the autogenous groups. The osteoconductive effect of Bio-Oss (38.7 +/- 5.5%) and CeraSorb (41+/-4.9%) was remarkable as well 4 weeks after surgery. Nevertheless, the addition of PRP hardly influenced bony regeneration, ceramic degradation or cytokine expression when bone substitutes were applied. At 12 weeks, the level of reossification had adjusted similarly in all groups. CONCLUSION: PRP did not add additional benefit when xenogenic bone substitutes were used. However, a significant effect on bone regeneration was found in the autogenous group initially when PRP is added.

Animals↗