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PubMed2004

Arthritis induces lymphocytic bone marrow inflammation and endosteal bone formation.

UNLABELLED: Arthritis can destroy the cortical bone barrier and expose bone marrow to synovial tissue. This study examines bone marrow changes in arthritis and its effects on cortical bone remodeling. Bone marrow next to arthritic lesions exhibits B-lymphocyte-rich infiltrates, which express BMPs and stimulate endosteal bone formation. Thus, bone marrow actively participates in the arthritic process. INTRODUCTION: Imaging studies have shown that bone marrow changes occur in patients with rheumatoid arthritis (RA). To examine whether bone marrow is affected during arthritis, human TNF transgenic (hTNFtg) mice, which constitute an established animal model of human RA, were examined for bone marrow changes. MATERIALS AND METHODS: The hind paws (tarsal area) of 22 untreated hTNFtg mice, 5 hTNFtg mice treated with anti-TNF (infliximab), and 5 wildtype (WT) mice were examined histologically, immunohistochemically, and by means of mRNA in situ hybridization. RESULTS AND CONCLUSIONS: All untreated hTNFtg mice with moderate (n = 10) and severe (n = 7) disease developed inflammatory bone marrow lesions during the course of disease, whereas no such lesions appeared in hTNFtg mice with mild disease (n = 5) and WT mice. Bone marrow infiltrates were almost exclusively composed of lymphocytes, and the overwhelming proportion (>80%) was B-cells. Presence and extent of bone marrow infiltrates were closely linked to severity of arthritis. In addition, blockade of TNF effectively reduced bone marrow inflammation. Interestingly, osteoblast numbers were increased at the endosteal surface in the vicinity of these lesions. Moreover, osteoid deposition; expression of bone matrix proteins, such as osteocalcin and osteopontin; and mineralization were enhanced, suggesting that inflammatory bone marrow infiltrates induce bone formation. Indeed, B-lymphocytes of these lesions expressed bone morphogenetic protein (BMP)-6 and -7, which are important stimulators of new bone formation. Thus, we conclude that bone marrow actively participates in destructive arthritis by generating B-lymphocyte-rich bone marrow lesions and inducing endosteal bone formation.

Animals↗
PubMed2004

Bone formation in the presence of platelet-rich plasma vs. bone morphogenetic protein-7.

Growth factors contained in platelet-rich plasma (PRP) have recently been proposed to enhance maturation of bone grafts and, in combination with anorganic bovine bone, to support repair in the treatment of small bone defects in maxillofacial surgery. Bone morphogenetic proteins (BMP) carried in a matrix may be able to replace the autologous bone graft in the treatment of critical size defects. However, no studies have compared the bone stimulating capacity of PRP and BMP. Likewise there is no data comparing the effects of PRP in either an autologous bone graft or in anorganic bovine bone. We augmented the mandible of Wistar rats (n = 28) on both sides with either anorganic bovine bone (Bio-Oss) or autologous rib bone. On the test side we applied either 20 microl of autologous PRP or 10 microl of rhBMP-7 (4 groups, n = 7). In addition, bone induction was evaluated in an extraskeletal site (n = 14). A polychrome sequential labeling was performed. The animals were sacrificed by intra-vital perfusion on day 50. Undecalcified ground sections were evaluated by microradiography, digitized histomorphometry and under fluorescent light. The qualitative analysis of fluorochrome labels suggested that PRP and rhBMP-7 accelerated bone growth. However, histomorphometric analysis revealed no significant differences in the area of newly mineralized bone under either the influence of PRP or rhBMP-7 on autologous bone graft. Likewise, the addition of PRP to anorganic bovine bone showed no statistical difference to the control group. The strongest bone stimulating effect was seen for the combination of rhBMP-7 with anorganic bovine bone (p = 0.028). In the extraskeletal model, newly formed bone was evident in the presence of rhBMP-7, but not of PRP. In conclusion, according to the histomorphometry, the addition of platelet-rich plasma failed to enhance bone formation on anorganic bovine bone and on autologous bone grafts.

Animals↗
PubMed2002

Bone metabolism markers and bone mass in healthy pubertal boys and girls.

OBJECTIVE: During puberty, bone growth and mineralization as well as bone turnover increase dramatically. The relation between height velocity and bone turnover is already known, but there are few studies in which both bone metabolism markers and bone mass throughout puberty have been measured. DESIGN: Semi-longitudinal study. In 155 healthy boys (12.0 +/- 1.5 years; range 8.8-15.7 years) and 151 healthy girls (11.2 +/- 1.6 years; range 8.2-14.0 years) markers of bone formation and bone resorption were measured as well as sex steroids, IGF-1 and IGF-BP3, together with bone mineral content (BMC) and bone mineral density (BMD) of the lumbar spine, femur and total body during puberty. All bone measurements were repeated after 1 year. RESULTS: BMC and BMD increased throughout puberty in both sexes. Bone turnover markers increased significantly until maximum values were reached at stage G4 in boys and stage B3 in girls. Height velocity (HV) had a similar changing pattern. Sex steroids and IGF-1 increased and reached adult values at pubertal stage 4. The correlations between bone metabolism markers and BMC were highly significant in boys, while correlations between bone metabolism markers and the increase in BMC over 1 year were significant in both sexes, as was observed for the correlations with HV. CONCLUSIONS: Our data suggest that bone metabolism markers are good predictors of bone mass in boys and of bone mass increase in both sexes. In early puberty, sex steroids stimulate the pubertal growth spurt in conjunction with GH and IGF-1. The fast increase in height gives rise to an increase in bone turnover and bone mineral apposition. It is known that at the end of puberty high levels of oestradiol inhibit chondrocyte proliferation. This leads to a decline in height velocity and bone turnover. Bone mass still increases under the influence of sex steroids and IGF-1. The data in our study confirm previous reports that markers of bone turnover relate positively to height velocity.

Adolescent↗
PubMedDate not supplied

[Biocompatibility testing of different sterilised or disinfected allogenous bone grafts in comparison to the gold standard of autologous bone grafts--an "in vitro" analysis of immunomodulation].

INTRODUCTION: Repair of large skeletal defects using bone allografts has become a routine procedure in orthopaedic and trauma surgery. Different procedures of sterilisation (82.5 degrees C disinfection; 121 degrees C autoclaving; PES; Tutoplast; 25 kGy gamma irradiation) are available to inactivate bacteria and fungi, including their spores, as well as viruses in human bone allografts. The efficiency of these procedures has been proven. However, the effects on the cellular response are rarely investigated. This present in vitro study investigates the immunological answer of human bone marrow cells to human allogenous and autologous bone platelets which were sterilised by different methods. MATERIALS AND METHODS: Human bone marrow cells and the bone platelets were harvested from patients undergoing a total hip replacement. All patients provided informed consent. Human bone platelets, 10 mm in diameter, 3 mm in height, were produced from femoral heads which were removed within the scope of total hip replacements. They were sterilised by different procedures or were disinfected (gamma radiotherapy, PES/ethanol treatment, Tutoplast procedure, 121 degrees C autoclaving, > 82.5 degrees C thermodisinfection). In addition, an autologous in vitro bone donation was simulated and compared with the allogenous bone grafts. Endobon was evaluated as a bovine hydroxyapatite ceramic. As control a human bone marrow cell culture without bone platelets was used. Over a period of four weeks the changes of the immunogenic cell populations were analysed in vitro (FACS analysis). Light and scanning microscopy were done to reveal morphological differences. As a vitality test the trypan-blue staining was performed. RESULTS: Light and scanning microscopy demonstrated large differences between the various sterilisation and disinfection methods. After 4 weeks the autologous bone platelets were completely covered with homogenously distributed human osteoblast like cells. The heat-sterilised/disinfected transplants demonstrated similar effects compared to the autologous bone grafts while the irradiated bone platelets demonstrated less cell coverage. 2/3 of the cells were vital on average after four weeks, with the exception of the irradiated bone platelets. The FACS analysis revealed in comparison to the control group provable differences in the immunological answer for the autologous bone donation as well as for the differently sterilised or disinfected allogenous bone grafts. The heat sterilisation or, respectively, disinfection methods compared to the autologous bone donation demonstrated almost similar in vitro effects. By far the worst results, characterised by an excessively increased portion of cytotoxic T-cells and a decreased amount of viable cells, were seen in the 25 kGy gamma irradiation samples. CONCLUSIONS: The results demonstrate the influence of the different sterilisation and disinfection procedures on the differentiation of human marrow cells (host). Similar in vitro effects were seen for the autologous and heat-treated bone platelets. The treatment of allogenous bone grafts with PES/ethanol and the Tutoplast procedures showed, just as Endobon, only low differences in comparison with the control cultures. The worse results in the case of the irradiated bone platelets may be explained by the production of free radicals which led to an excessive cell death.

Blood Platelets↗
PubMed1977

The degree of bone mineralization in different parts of human skeleton estimated from bone phosphorus/hydroxyproline.

To evaluation the uniformity of the degree of mineralization in the skeleton the bone phosphorus/hydroxyproline ratio (bone P/Hypro) was determined in different localizations of ten human skeletons. Marked differences in bone P/Hypro were found between cortical bone and spongy bone. No difference was found between cortical bone from humerus, femur and cranium. But the mean value of these cortical bones was significantly higher than the mean value of the studied spongy bones. No significant correlation was found between the two bone types. Differences in bone P/Hypro were also found between different spongy bones. In pelvis the value did not differ between four spongy bone localizations but the mean value was significantly lower than for the other spongy bones (thoracal column, lumbal column and clavicle). Between these other spongy bones no difference was found in mean bone P/Hypro, and the mean of the pelvic bone localizations correlated significantly to the other spongy bones. The study demonstrates differences in the chemical composition of the human skeleton. A value of bone P/Hypro in the iliac crest can be used to estimation of bone P/Hypro in other spongy bones but not in cortical bones.

Adult↗
PubMed2001

Analysis of the effects of growth hormone, exercise and food restriction on cancellous bone in different bone sites in middle-aged female rats.

The aim of this study is to determine the effects of growth hormone (GH), exercise (EX), GH+EX and food restriction on cancellous bone in middle-aged female rats. Female F344 rats aged 13 months were divided into (1) age-matched controls; (2) GH treated (2.5 mg/kg. 5 day/week); (3) EX (voluntary wheel running); (4) GH+EX; and (5) food restricted (FR) (fed 60% of the ad libitum food intake). The animals were treated for 18 weeks, at the end of which they were sacrificed. Cancellous bone and cortical bone in the fourth lumbar vertebra, proximal tibial metaphysis (PTM), distal femoral metaphysis (DFM) and femoral neck (NF) were analyzed using peripheral quantitative computerized tomography (pQCT) densitometry. Growth hormone increased cancellous bone area, cancellous bone mineral content, cortical bone area and cortical bone mineral content in the vertebra, PTM, DFM and NF. The tibial muscle wet weight was increased significantly after GH treatment. Exercise increased the cancellous bone area in the vertebra, PTM and DFM. Cortical bone area and cortical bone mineral content increased after EX in the vertebra, PTM, DFM and NF. No significant change was seen in the tibial muscle wet weight after EX. Growth hormone+EX increased cancellous bone area in the vertebra PTM and DFM but had no effect in neck of the femur. Cancellous bone mineral content, cortical bone area and cortical bone mineral content increased with GH+EX in the vertebra, PTM, DFM and NF. The tibial muscle wet weight was increased significantly with GH+EX. Food restriction decreased cancellous bone area and cancellous bone mineral content in all the bones studied. The decrease was statistically significant only at the distal femoral metaphysis. The tibial muscle wet weight decreased when compared with the age-matched control, but this decrease was not statistically significant. We conclude that the effect of the dose of GH used and the levels of voluntary wheel running EX used increased cancellous bone in intact rats; the effect of GH is much greater and different bones respond with varying intensities. The effects of combined treatment of GH and EX on cancellous bone are not always significantly higher than those of GH alone. FR at the level studied has a mostly negative effect on cancellous bone.

Animals↗
PubMed1995

In vivo evaluation of demineralized bone matrix as a bone graft substitute for posterior spinal fusion.

STUDY DESIGN: Posterior lumbar spinal fusion segments were evaluated in 9 adult mongrel dogs 6, 12, and 26 weeks after implantation. Four sites on each animal received implants consisting of demineralized bone matrix alone, demineralized bone matrix with allograft bone, allograft bone alone, and autograft bone. Each unilateral fusion spanned one motion segment with one intervening vertebral level left undisturbed using T13-L7. The fusions were evaluated radiographically, mechanically, and histologically. OBJECTIVE: The purpose of this study was to determine the efficacy of demineralized bone matrix as a bone graft substitute for stable posterior spinal fusion. SUMMARY OF BACKGROUND DATA: Posterior spinal fusion is a procedure commonly performed for spinal stabilization. Increasing the incidence and speed of stable spinal fusion is a primary goal in spinal surgery. Concerns have developed regarding the graft material used to induce bone healing at the fusion site. The advent of osteoinductive materials, such as demineralized bone matrix, may eliminate the need to harvest autograft bone and may circumvent the immunologic response and lower osteogenic potential associated with allograft bone. METHODS: The quality of fusion and new bone formation was evaluated radiographically using plain films, computed tomography, and magnetic resonance imaging. After the dogs were killed, each fusion segment was evaluated mechanically in torsion to determine stiffness and histologically to determine qualitative parameters of new bone formation and remodeling. RESULTS: Radiographic studies showed that autograft bone sites achieved stable fusion by 26 weeks after surgery. Conversely, the demineralized bone matrix alone and with allograft bone demonstrated some new bone formation at 6 and 12 weeks, but did not achieve fusion by 26 weeks. The fusion sites of allograft bone alone showed minimal new bone formation at all time periods. Mechanically, the autograft fusion sites demonstrated torsional stability that was significantly greater than that of all other fusion sites at all time periods. The remaining fusion sites showed equivalent torsional stiffness at all time periods. Histologic analysis confirmed the radiographic and mechanical findings. CONCLUSIONS: The results indicate that demineralized bone matrix alone or with allograft bone is ineffective in achieving stable posterior spinal fusions.

Animals↗
PubMed1999

Recombinant human bone morphogenetic protein-2 stimulation of bone formation around endosseous dental implants.

BACKGROUND: Successful endosseous implant placement requires that the implant be stable in alveolar bone. In certain cases, the implant can be stabilized in native bone but some part of the implant is not covered by bone tissue. This often occurs during placement of implants into extraction sites or in areas where bone resorption has occurred and the ridge width is not sufficient to completely surround the implant. In those cases, the clinician usually employs a procedure to encourage bone formation. These procedures typically include a bone graft and/or membrane therapy. Recent advances have led to the isolation, cloning, and production of recombinant human proteins that stimulate bone formation. One of these bone morphogenetic proteins (rhBMP-2) has been extensively studied in animal models and is currently being tested in human clinical trials. METHODS: In this study, rhBMP-2 was tested using a collagen sponge carrier to stimulate bone formation in defects in the canine mandible around endosseous dental implants. Six animals had a total of 48 implants placed. rhBMP-2 with the collagen carrier was implanted around 24 of these, the remainder having only the collagen carrier placed. Half the sites were covered with a nonresorbable expanded polytetrafluoroethylene membrane. Histologic analysis was performed after 4 and 12 weeks. The area of new bone formed, percentage of bone-to-implant contact in the defect area, and percentage fill of the defect was calculated. RESULTS: The addition of rhBMP-2 resulted in significantly greater amounts of new bone area and percentage of bone-to-implant contact and with more percentage fill after 4 and 12 weeks of healing. The area of new bone formed was reduced after 4 weeks when a membrane was present but after 12 weeks, there was no significant difference between membrane and non-membrane treated sites. In some specimens, new bone was found coronal to the membranes, with rhBMP-2-treated sites having greater amounts than non-rhBMP-2-treated sites. CONCLUSIONS: These data demonstrate that a bone differentiation factor significantly stimulates bone formation in peri-implant bone defects in the canine mandible. In addition, bone-to-implant contact was significantly enhanced along the rough implant surface. Membrane-treated sites had less new bone formation after 4 weeks of healing but were similar to non-membrane sites after 12 weeks. These results demonstrate that rhBMP-2 can be used to stimulate bone growth both around and onto the surface of endosseous dental implants placed in sites with extended peri-implant osseous defects.

Animals↗
PubMed2001

Histomorphometric and densitometric changes in bone volume and structure after avascular bone grafting in the extremely atrophic maxilla.

AIM: To evaluate changes in volume and structure of bone after autogenous iliac crest bone grafting to the maxilla. To discover the predictive value of computed tomographic (CT) measurements of bone density and study their correlation with the results of histomorphometric analyses of bone structure. PATIENTS AND METHODS: In 25 patients with atrophic maxillae (mean age 47 years, range 15-71), who had onlay bone grafting and sinus floor augmentation with autogenous iliac crest bone, a CT analysis was carried out immediately before and after grafting, and 5 months (range 4-6) later, at the time of endosseous implantation. On both occasions, bone biopsy specimens were taken. HISTOLOGY OF BONE: After preparing and digitizing semithin sections, histomorphometry (NH-Image) was done to establish the ratio of trabeculae to medullary cavity. CT ANALYSIS: The available transverse and vertical bone and the bone density of natural and augmented bone were analyzed using the Simplant Program and the CT data. As reference, the bone density of the first cervical vertebra was used. By regression analysis, the correlation of CT bone density and histological bone structure was investigated. RESULTS: After a median healing period of 4.5 months, no significant changes were found in bone volume compared with the measurements made immediately after grafting. The changes in density in the cancellous portion of the grafted bone showed no correlation (correlation coefficient: +0.16) with the results of histomorphometric analysis of bone structure. CONCLUSIONS: The predictive value of measurement of bone density to evaluate bone structure on the basis of the D1-D4 classification needs to be reconsidered. The most favourable time for secondary implantation is 4-6 months after iliac crest bone grafting.

Adolescent↗
PubMed2006

Osteoclastic bone degradation and the role of different cysteine proteinases and matrix metalloproteinases: differences between calvaria and long bone.

UNLABELLED: Osteoclastic bone degradation involves the activity of cathepsin K. We found that in addition to this enzyme other, yet unknown, cysteine proteinases participate in digestion. The results support the notion that osteoclasts from different bone sites use different enzymes to degrade the collagenous bone matrix. INTRODUCTION: The osteoclast resorbs bone by lowering the pH in the resorption lacuna, which is followed by secretion of proteolytic enzymes. One of the enzymes taken to be essential in resorption is the cysteine proteinase, cathepsin K. Some immunolabeling and enzyme inhibitor data, however, suggest that other cysteine proteinases and/or proteolytic enzymes belonging to the group of matrix metalloproteinases (MMPs) may participate in the degradation. In this study, we investigated whether, in addition to cathepsin K, other enzymes participate in osteoclastic bone degradation. MATERIALS AND METHODS: In bones obtained from mice deficient for cathepsin K, B, or L or a combination of K and L, the bone-resorbing activity of osteoclasts was analyzed at the electron microscopic level. In addition, bone explants were cultured in the presence of different selective cysteine proteinase inhibitors and an MMP inhibitor, and the effect on resorption was assessed. Because previous studies showed differences in resorption by calvarial osteoclasts compared with those present in long bones, in all experiments, the two types of bone were compared. Finally, bone extracts were analyzed for the level of activity of cysteine proteinases and the effect of inhibitors hereupon. RESULTS: The analyses of the cathepsin-deficient bone explants showed that, in addition to cathepsin K, calvarial osteoclasts use other cysteine proteinases to degrade bone matrix. It was also shown that, in the absence of cathepsin K, long bone osteoclasts use MMPs for resorption. Cathepsin L proved to be involved in the MMP-mediated resorption of bone by calvarial osteoclasts; in the absence of this cathepsin, calvarial osteoclasts do not use MMPs for resorption. Selective inhibitors of cathepsin K and other cysteine proteinases showed a stronger effect on calvarial resorption than on long bone resorption. CONCLUSIONS: Our findings suggest that (1) cathepsin K-deficient long bone osteoclasts compensate the lack of this enzyme by using MMPs in the resorption of bone matrix; (2) cathepsin L is involved in MMP-mediated resorption by calvarial osteoclasts; (3) in addition to cathepsin K, other, yet unknown, cysteine proteinases are likely to participate in skull bone degradation; and finally, (4) the data provide strong additional support for the existence of functionally different bone-site specific osteoclasts.

Animals↗
PubMed1998

Ability of commercial demineralized freeze-dried bone allograft to induce new bone formation is dependent on donor age but not gender.

Demineralized freeze-dried bone allografts (DFDBA) have been used extensively in periodontal therapy. DFDBA is used because it contains bone morphogenetic protein (BMP), which induces new bone formation during the healing process. Most commercial bone banks do not verify the presence or activity of BMP in DFDBA nor the ability of DFDBA to induce new bone. Recently, we showed that different bone bank preparations of DFDBA, even from the same bank, varied considerably in their ability to induce new bone, suggesting inherent differences in the quality of the material. Therefore, we examined whether donor age or gender contributed to the variability seen with these preparations. Twenty-seven batches of DFDBA from different donors were donated by one bone bank which had been shown previously to supply DFDBA that was consistently able to induce new bone formation. Each batch was implanted bilaterally in the thigh muscle of nude mice. After 56 days, the implants were excised and examined by light microscopy and histomorphometry. Seventy percent of the preparations tested induced new bone formation. Most of these preparations produced ossicles containing cortical bone surrounding bone marrow-like tissue. The ability to induce bone appears to be age-dependent, with DFDBA from older donors being less likely to have strong bone-inducing activity. By contrast, no difference in ability to induce new bone was noticed between male or female donors. The results of this study confirm that commercial preparations of DFDBA differ in their ability to induce new bone formation. In fact, some of the batches had no activity at all. The ability of DFDBA to induce new bone formation is suggested to be age-dependent, but not gender-dependent by our study. These results indicate that commercial bone banks need to verify the ability of DFDBA to induce new bone formation and should reconsider the advisability of using bone from older donors.

Adolescent↗
PubMedDate not supplied

Comparison and discrepancy of 18F-2-deoxyglucose positron emission tomography and Tc-99m MDP bone scan to detect bone metastases.

The purpose of this study was to evaluate the usefulness of positron emission tomography with 18F-2-deoxyglucose (FDG-PET) for the detection of malignant bone metastases, and to compare FDG-PET results with conventional technetium-99m methylene diophosphate (Tc-99m MDP) bone scan findings. Twenty-four patients (10 females, 14 males, ages: 39-71 years) with biopsy-proven malignancy and suspected bone metastases, underwent whole body FDG-PET and bone scan to detect bone metastases. Bone metastases were established in 39 discordant bone lesions by histopathological examination of biopsy samples, MRI/CT, and follow-up bone scan/FDG-PET findings showing progressively and extensively widespread bone lesions. A total of 98 bone lesions found on either FDG-PET or bone scan were evaluated For 39 bone lesions with discordant findings between FDG-PET and bone scan, histopathological examination, MRI/CT and follow-up bone scan/FDG-PET findings revealed 8 metastatic and 0 benign bone lesions with positive FDG-PET findings, not detected on bone scan. Eleven metastatic and 20 benign bone lesions with positive bone scan findings were not detected on FDG-PET. FDG-PET has a better specificity, but a lower sensitivity for detecting malignant bone metastases when compared with bone scan.

Adult↗
PubMed1986

Loss of bone resulting from accumulation of aluminum in bone of patients undergoing dialysis.

The effects of accumulation of aluminum on cancellous bone mass and histomorphometric parameters of bone formation and resorption are evaluated in three separate studies: a cross-sectional study in 120 patients receiving long-term maintenance dialysis, including patients with and without stainable bone aluminum; a longitudinal retrospective study in eight patients receiving hemodialysis, who had progressive accumulation of aluminum in bone. These patients had two bone biopsies 11 to 16 months apart; a longitudinal prospective study in 10 patients receiving long-term hemodialysis, who had histologically proved renal osteodystrophy and stainable bone aluminum. These patients were given deferoxamine for 9 to 12 months. Repeat bone biopsies were done thereafter, and decrease or disappearance of stainable bone aluminum was observed. The results of the independent studies demonstrate that aluminum accumulation in bone is associated not only with disturbed mineralization but also with loss of cancellous bone mass, and that removal of aluminum from bone results in gain in bone volume. The mechanisms of this phenomenon are related to a disproportionately greater effect of aluminum on bone formation than on bone resorption. The negative effect on bone formation is caused by decreased number and activity of osteoblasts, which is reversed by removal of aluminum from bone. In addition, the data show that aluminum induces suppression of bone turnover, with uncoupling between bone formation and resorption whereby the effects on bone formation exceed those on bone resorption. Thus, fractures in patients with renal failure and accumulation of aluminum may result not only from osteomalacia but also from osteopenia.

Adolescent↗
PubMed2000

Is the amount of trabecular bone-loss dependent on bone mineral Density? A study performed by three centres of osteoporosis using high resolution peripheral quantitative computed tomography.

For the risk getting osteoporosis as well as for diagnosis of osteoporosis 3 facts are highly important: bone-mass, the amount of bone-loss and bone-structures (microarchitecture of bone). All three parameters can be validated today with high precision but the amount of bone-loss seems to be the most important one, even for the decision of either antiresorptive or bone-stimulating therapy. But to calculate the amount of bone-loss until now at least two measurements of bone mineral density (BMD) are necessary which have to be performed within a certain period of time, depending on the reproducibility of the method to be used. If on the other hand the amount of bone-loss would be dependent on actual base-line bone-mass the right therapy could be started already after only one measurement of BMD. The aim of this study was therefore to investigate if there is any relation between the amount of bone-loss and base-line volumetric BMD. For this we separately measured trabecular and cortical bone densities of 135 women in three independent centres of osteoporosis in Zurich and Munich using the method of high resolution quantitative computed tomography - pQCT - with the Densiscan 1000, Scanco Medical, Zurich. We did this at least twice and then compared absolute volumetric BMD in the first step before we calculated trabecular and cortical bone loss per year for each woman. We could not only confirm again that bone loss in trabecular bone was significantly higher than in cortical bone and that the non-weight-bearing trabecular bone as could be found in the distal radius seems to be the skeletal site of maximum bone-loss, but moreover - and this is the more important finding - we could show that the amount of relative bone-loss was the higher the lower trabecular base-line volumetric BMD was. According to this the rate of fast-loser (more than 3.5% per year) increased the lower trabecular base-line volumetric BMD was. These results may lead to a new screening-test for the assessment of the individual risk of osteoporosis and for the individual risk of fast bone-loss which now can be evaluated with only one single measurement of BMD, to treat the so classified patients not only earlier but even more rational, dependent if either antiresorptive therapy or stimulation of bone-formation seems to be more important.

Adult↗
PubMed2005

[The fate of donor bone cells in different diameter bone grafts: an experiment study].

OBJECTIVE: To investigate the fate of donor bone cells in bone grafts of different diameters during repairing bone defects. METHODS: One hundred sixteen female syngeneic inbred DA rats were established as radial defect model of 3 kinds: structural bone grafting group (n = 56), morselized bone grafting group (n = 56), and blank group (without bone grafting, n = 4), to be used as receptors The ilia of 58 male inbred DA rats, as donors, were harvested and made into structural bone grafts 2 mm in diameter and morselized bone grafts 0.3 - 0.5 mm in diameter to be transplanted into the radial defects of the female receptors. One and four days, and 1, 2, 4, 6, and 8 weeks after transplantation DNA was extracted from the grafted bones and polymerase chain reaction (PCR) specific for the sex-determining region of Y-chromosome (Sry) was performed to observe the presence and relative amount of Y-chromosome originating from the bone grafts, expression of the sex-determining gene Sry in the receptors' bones and the histology of the receptors' bones. RESULTS: In structural bone grafting group, the amounts of Sry-specific bands decreased in the early time and disappeared 1 week after transplantation, and re-appeared 4 weeks after transplantation with the amount increasing with the lapse of time. In morselized bone grafting group, Sry-specific bands were detected all the time but their amounts decreased with the lapse of time. At each time point, morselized bone graft provided more living osteocytes with better effect of osteogenesis in comparison with the structural bone graft. CONCLUSION: Bone grafts of different diameters provide donor cells in repairing bone defects. Having more surviving osteocytes, morselized bone grafts may accelerate the healing pf bone defects, thus providing a new and effective method to repair bone defects and spinal fusion clinically.

Animals↗
PubMed2003

Over expression of bone morphogenetic protein-3b (BMP-3b) using an adenoviral vector promote the osteoblastic differentiation in C2C12 cells and augment the bone formation induced by bone morphogenetic protein-2 (BMP-2) in rats.

BMP-3b is a novel BMP-3-related protein and its biological functions are unknown. In order to investigate the biological actions of BMP-3b, we constructed a BMP-3b-expressing recombinant adenoviral vector (AxCAKBMP-3b). We show that over expression of BMP-3b stimulated the induction of differentiation and the osteoinduction activity of a human BMP-2-expressing recombinant adenoviral vector (AxCAOBMP-2). C2C12 cells were infected in vitro with AxCAKBMP-3b, AxCAOBMP-2 and a control vector containing no foreign genes (AxCAwt). Cells infected with AxCAOBMP-2 and AxCAKBMP-3b produced more alkaline phosphatase and secreted more osteocalcin into the culture medium than cells infected with AxCAOBMP-2 and AxCAwt. When AxCAOBMP-2, AxCAKBMP-3b, and AxCAwt were injected into the calf muscles of nude rats (F 344/N Jcl-rnu), the osteoinduction seen with AxCAOBMP-2 and AxCAKBMP-3b was greater than that seen with AxCAOBMP-2 and AxCAwt.

Adenoviridae↗