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Bone metabolic markers in the evaluation of bone scan flare phenomenon in bone metastases of breast cancer.

Bone scan flare seriously complicates evaluations of the therapeutic response of bone metastases. The value of bone metabolic markers in monitoring the therapeutic response for bone metastases in breast cancer was assessed. Twenty-three breast cancer patients with bone metastases treated by combined chemotherapy of cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF) were monitored using bone scans; a bone resorption marker, pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP); a bone formation marker, bone-specific alkaline phosphatase (BAI-p); and a tumor-specific marker (CA15-3). Bone scans were performed before and 3 or 4 months after therapy. After CAF therapy, markers were measured monthly. As a control, the markers of nine patients without bone metastases who received adjuvant CAF therapy were also measured monthly. The therapeutic effect on bone metastases was assessed after the study. Five patients had progression of disease (PD), three had no change (NC), and 15 patients had partial responses (PR). Bone scan flare-up was seen in five PR patients. In patients who received adjuvant therapy, ICTP, BAI-p, and CA15-3 did not change. ICTP increased significantly in PD patients. ICTP did not increase in either NC or PR, including bone scan flare patients. BAI-p and CA15-3 did not show any discernible pattern among PD, PR, flare, and NC patients. Thus measuring ICTP could distinguish PD from NC or PR patients' responses to CAF therapy. This was true also for patients who showed bone scan flare-up. Measuring a bone resorption marker, ICTP, allows clinicians to monitor patients' responses to CAF therapy and may prevent prolonged ineffective therapy or unnecessary changes in therapy as a result of the flare phenomenon.

Adult↗

Current topics in pharmacological research on bone metabolism: regulation of bone mass by the function of endogenous modulators of bone morphogenetic protein in adult stage.

Bone formation in adults determines the basic mass of bone and hence it is crucial to understand the mechanisms of its regulation. As remodeling is proceeding, bone resorption is determined by the physical conditions. Especially in women, postmenopausal bone loss is characterized by rapid bone loss due to increase in bone resorption and relative negative balance between such bone resorption and accelerated bone formation. Bone formation is also critical in considering measures to treat patients with very low bone mass. In these subjects, simple suppression of bone resorption would not be enough to maintain bone mass. Thus, bone formation in the adult is of importance in terms of both pathological and therapeutic aspects. This review addresses the possible roles of bone formation modulators in the maintenance of bone mass in the light of understanding the determination of adult bone mass.

Age Factors↗

Bone induction using autogenous bone mixed with demineralised bone matrices.

The aim of the present study was to examine the healing of endochondral (EC) autogenous bone grafts in the presence of demineralised bone matrix prepared from intramembranous bone (DBMIM), or prepared from endochondral bone (DBMEC) using quantitative analysis. Thirty bone defects were created on the parietal bone of fifteen New Zealand White rabbits. In the experimental groups, five defects were grafted with EC bone, five defects were grafted with EC bone mixed with DBMIM (EC-DBMIM) and six defects were grafted with EC bone mixed with DBMEC (EC-DBMEC). In the control groups, ten defects were left empty (passive control) and four defects were grafted with rabbit skin collagen (positive control). They were all sacrificed at day fourteen post grafting, and the defects were prepared for histological analysis. Serial sections were cut across the whole defect. Quantitative analysis was performed on 152 sections of the experimental groups by image analysis. Four hundred and fourteen per cent more new bone was formed in defects grafted with composite EC-DBMIM than those grafted with EC bone alone (p < 0.001). Eighty-five per cent more new bone was formed in defects grafted with composite EC-DBMEC than those grafted with EC bone alone (p < 0.001). No bone was formed in either passive or positive controls. In conclusion, DBM, especially DBMIM, have extremely high osteoinductive properties and greatly enhance the integration of EC bone grafts with defects created in IM bone.

Analysis of Variance↗

The use of coralline hydroxyapatite with bone marrow, autogenous bone graft, or osteoinductive bone protein extract for posterolateral lumbar spine fusion.

STUDY DESIGN: A posterolateral lumbar arthrodesis animal model using coralline hydroxyapatite as a bone graft substitute. OBJECTIVE: To determine the effectiveness of coralline hydroxyapatite as a bone graft substitute for lumbar spine fusion when used with bone marrow, autogenous bone graft, or an osteoinductive bone protein extract. SUMMARY OF BACKGROUND DATA: Coralline hydroxyapatite is commonly used as a bone graft substitute in metaphysial defects but its use in a more challenging healing environment such as the posterolateral spine remains controversial. There are no published animal studies in which the use of coralline hydroxyapatite has been evaluated in a posterolateral lumbar arthrodesis model. METHODS: Single-level posterolateral lumbar arthrodesis was performed at L5-L6 in 48 adult New Zealand White rabbits. Rabbits were assigned to one of three groups based on the graft material they received: 3.0 mL coralline hydroxyapatite 1.5 mL plus bone marrow; 1.5 mL coralline hydroxyapatite plus 1.5 mL autogenous iliac crest bone; and, 3.0 mL coralline hydroxyapatite plus 500 micrograms bovine-derived osteoinductive bone protein extract on each side. Rabbits were killed after 2, 5, or 10 weeks, and the spines were excised and evaluated by manual palpation, radiographs, tensile biomechanical testing, and nondecalcified histology. RESULTS: Fusions were assessed by manual palpation at 5 weeks for comparisons among the three groups of graft materials. The coralline hydroxyapatite used with bone marrow produced no solid fusions (0/14). When combined with an equal amount of autogenous iliac crest bone, coralline hydroxyapatite resulted in solid fusion in 50% (7/14) of the rabbits (P < 0.05). When combined with the osteoinductive growth factor extract, the coralline hydroxyapatite resulted in solid fusion in 100% (11/11) of the rabbits (P < 0.05). The fusion masses in the growth factor group were significantly stronger (1.8 +/- 0.2 vs. 1.3 +/- 0.1; P = 0.02) and stiffer (1.5 +/- 0.2 vs. 1.2 +/- 0.1, P = 0.04) based on tensile testing to failure when normalized to the adjacent unfused level. CONCLUSION: These data indicate that coralline hydroxyapatite with bone marrow was not an acceptable bone graft substitute for posterolateral spine fusion. When combined with autogenous iliac crest bone graft-coralline hydroxyapatite served as a graft extender yielding results comparable to those obtained with autograft alone. Coralline hydroxyapatite served as an excellent carrier for the bovine osteoinductive bone protein extract yielding superior results to those obtained with autograft or bone marrow.

Animals↗

A histochemical investigation of the bone formation process by guided bone regeneration in rat jaws. Effect of PTFE membrane application periods on newly formed bone.

BACKGROUND: Guided bone regeneration (GBR) has been widely utilized for the promotion of bone augmentation in bone loss areas. However, little information has been available regarding chronological changes in newly formed bone and alterations in the nature of newly formed bone after removal of a barrier membrane. The present study attempted to establish a GBR model for rat maxillae. We also examined the effects of membrane application periods on newly formed bone and its remodeling process after removal of the membrane in this experimental model. METHODS: Thirty-five Wistar rats were divided into 2 groups: a membrane application group and a membrane removal group. The chronological changes of newly formed bone were evaluated histologically and statistically. RESULTS: At 2 weeks after the GBR procedure, bony cavities had completely filled the newly formed bone in the experimental side. In the control side, corticalization on the surface of the newly formed bone proceeded with a decrease in the bone marrow cavity, whereas the bone marrow space had enlarged by 12 weeks post-surgery in the experimental side. In the membrane removal group, the osteoblasts appeared on newly formed bone at 1 week after membrane removal. Comparatively thick compact bone had formed on the surface of the newly formed bone at 4 weeks after membrane removal, and corticalization proceeded later. CONCLUSIONS: The long-term application of a barrier membrane induces the enlargement of the bone marrow spaces. We suggest that PTFE membrane removal in adequate time promotes the corticalization and maturation of the newly formed bone by the GBR technique.

Acid Phosphatase↗

Impact of supplement withdrawal and wheat middling inclusion on bone metabolism, bone strength, and the incidence of bone fractures occurring at slaughter in pigs.

The objective of this study was to determine if supplement withdrawal (omission of dietary vitamin and trace mineral premixes and 2/3 of inorganic P) 28-d preslaughter and the feeding of wheat middlings (dietary concentrations of 5, 15, or 30% from weaning to 16 kg, 16 to 28 kg, and 28 kg to slaughter, respectively) affect bone metabolism, bone strength, bone density, and the incidence of bone fractures at slaughter in pigs. Crossbred barrows (n = 64) were assigned to a 2 x 2 factorial arrangement of treatments (with or without supplement withdrawal, and with or without wheat middlings). Serum was collected on d 0, 14, and 27 of the preslaughter withdrawal period to determine changes in the concentrations of osteocalcin, an indicator of bone formation, and pyridinoline, an indicator of bone resorption. The serum osteocalcin and pyridinoline concentrations on d 14 and 27 were analyzed as change from the d-0 concentration. At slaughter, radiographs of the lumbar vertebrae and of the right and left femurs were taken to determine the incidence of bone fractures. Third metacarpal bones were analyzed for bone mineral density, peak load, ultimate shear stress, and percent ash. Supplement withdrawal increased (P < 0.05) serum osteocalcin and pyridinoline concentrations, indicating an increase in osteoblast activity and bone resorption. Supplement withdrawal decreased (P < 0.01) bone mineral density, peak load, ultimate shear stress, and percent ash of the metacarpal bones. Dietary wheat middling inclusion did not alter bone quality. Neither supplement withdrawal nor wheat middling inclusion affected the incidence of bone fractures at slaughter. The results of this study indicate that removing inorganic P, vitamin premix, and trace mineral premix for 28 d preslaughter increases bone turnover and decreases bone quality.

Abattoirs↗

Long-term evaluation of bone formation by osteogenic protein 1 in the baboon and relative efficacy of bone-derived bone morphogenetic proteins delivered by irradiated xenogeneic collagenous matrices.

To investigate the long-term efficacy of irradiated recombinant human osteogenic protein 1 (hOP-1) in bone regeneration and morphogenesis, hOP-1 was combined with a bovine collagenous matrix carrier (0, 0.1, 0.5, and 2.5 mg hOP-1/g of matrix), sterilized with 2.5 Mrads of y-irradiation, and implanted in 80 calvarial defects in 20 adult baboons (Papio ursinus). The relative efficacy of partially purified bone-derived baboon bone morphogenetic proteins (BMPs), known to contain several osteogenic proteins, was compared with the recombinant hOP-1 device in an additional four baboons. Histology and histomorphometry on serial undecalcified sections prepared from the specimens harvested on day 90 and day 365 showed that gamma-irradiated hOP-1 devices induced regeneration of the calvarial defects by day 90, although with reduced bone area compared with a previous published series of calvarial defects treated with nonirradiated hOP-1 devices. One year after application of the irradiated hOP-1 devices, bone and osteoid volumes and generated bone tissue areas were comparable with nonirradiated hOP-1 specimens. Moreover, 365 days after healing regenerates induced by 0.5 mg and 2.5 mg of irradiated hOP-1 devices showed greater amounts of bone and osteoid volumes when compared with those induced by nonirradiated hOP-1 devices. On day 90, defects treated with 0.1 mg and 0.5 mg of bone-derived baboon BMPs, combined with irradiated matrix, showed significantly less bone compared with defects receiving irradiated devices containing 0.1 mg and 0.5 mg hOP-1; 2.5 mg of partially purified BMPs induced bone and osteoid volumes comparable with the 0.1-mg and 0.5-mg hOP-1 devices. Control specimens of y-irradiated collagenous matrix without hOP-1 displayed a nearly 2-fold reduction in osteoconductive bone repair when compared with nonirradiated controls. These findings suggest that the reduction in bone volume and bone tissue area on day 90 may be caused by a reduced performance of the irradiated collagenous matrix substratum rather than to a reduction in the biological activity of the irradiated recombinant osteogenic protein. This is supported by the results of in vitro and in vivo studies performed to determine the structural integrity of the recovered gamma-irradiated hOP-1 before application in the baboon. Recoveries by high-performance liquid chromatography (HPLC) and sodium dodecyl sulfate/ polyacrylamide gel electrophoresis (SDS/PAGE)/immunoblot analyses indicated that doses of 2.5-3 Mrads of gamma-irradiation did not significantly affect the structural integrity of the recovered hOP-1. Biological activity of the recovered hOP-1 was confirmed in vitro by showing induction of alkaline phosphatase activity in rat osteosarcoma cells (ROS) and in vivo by de novo endochondral bone formation in the subcutaneous space of the rat. These findings in the adult primate indicate that a single application of gamma-irradiated hOP-1 combined with the irradiated xenogeneic bovine collagenous matrix carrier is effective in regenerating and maintaining the architecture of the induced bone at doses of 0.5 mg/g and 2.5 mg/g of carrier matrix.

Alkaline Phosphatase↗

Bone marrow fat and bone mineral density on proton MR spectroscopy and dual-energy X-ray absorptiometry: their ratio as a new indicator of bone weakening.

OBJECTIVE: Bone weakening can be affected by agents other than bone mineral density (BMD). Increased bone marrow fat may have a direct link to bone loss. This pilot study analyzes the relationship between bone marrow fat and BMD in subjects with normal and structurally weakened vertebrae. SUBJECTS AND METHODS: Twenty-six subjects underwent both dual-energy X-ray absorptiometry and proton MR spectroscopy of 71 lumbar vertebrae. Fifteen subjects had normal-appearing vertebrae on MRI, and 11 had signs of bone weakening. RESULTS: We found that high bone marrow fat did not consistently equate with low BMD. Bone marrow fat can indicate bone weakening nearly as well as BMD, but neither parameter alone is suitable to be used independently as an indicator. The bone marrow fat/BMD ratio showed significant diagnostic power to detect bone weakening, even in this relatively small subject sample. CONCLUSION: An inverse relationship between bone marrow fat and BMD could not be confirmed. Bone marrow fat can be used to diagnose reduced bone strength nearly as well as BMD. The bone marrow fat/BMD ratio is a significant diagnostic indicator of bone weakening.

Absorptiometry, Photon↗

Bone quality at the implant site after reconstruction of a local defect of the maxillary anterior ridge with chin bone or deproteinised cancellous bovine bone.

The purpose of this study was to investigate the quality of bone at grafted implant sites in the anterior maxilla. Grafting of these sites was necessary because of insufficient bone volume in a buccopalatinal direction (width at the top of the crest 1-3mm). Reconstruction was performed with chin bone (N=5), chin bone and a resorbable Bio-Gide GBR membrane (N=5) or Bio-Oss spongiosa granules in combination with a Bio-Gide GBR membrane (N=5). Biopsies were taken prior to implantation, i.e. 3 months after grafting with chin bone, and 6 months after grafting with Bio-Oss. Evaluation was done by assessing the histological and histomorphometric characteristics of full-length biopsies taken from the actual implant site. Both areas with non-vital bone and areas with apposition of bone and remodelling phenomena were observed in the chin bone group at the time of placement of the implants. Similar results were observed at implant sites reconstructed with a chin bone graft covered by a membrane. In the chin bone group without and with a GBR membrane, the mean total bone volume (TBV) was 55.2+/-6.8% and 57.7+/-11.5%, respectively; the marrow connective tissue volume (MCTV) was 44.8+/-6.8% and 42.3+/-11.5%, respectively. Remnants of the resorbable GBR membrane were not detected. In the Bio-Oss((R)) group, at implant placement some newly formed bone was observed in the connective tissue surrounding the Bio-Oss((R)) particles (mean TBV (newly formed bone) 17.6+/-14.5%), but most particles were surrounded by connective tissue. No convincing signs of remodelling were observed (mean remaining Bio-Oss volume 40.5+/-9.3%; mean MCTV 41.9+/-13.1%). No implants were lost during follow up (12 months). At the time of placement of the implants the grafting material (either chin bone or Bio-Oss is still not fully replaced by new vital bone. In case of Bio-Oss, most of the grafting material is even still present. Despite these differences, the 1-year clinical results were very good and comparable between the various grafting techniques applied.

Adolescent↗

[Reconstruction of the anterior cruciate ligament: comparison of patellar bone-tendon-bone and hamstring tendon graft methods. Part 1. Evaluation of patients treated by the patellar bone-tendon-bone graft technique].

PURPOSE OF THE STUDY: Reconstruction of the anterior cruciate ligament (ACL) by means of a patellar bone-tendon-bone (B-T-B) graft is currently one of the most frequent arthroscopic procedures. Progress in alternative techniques, particularly the use of hamstring tendon grafts and different methods for graft anchorage, was the reason for evaluation of our group of patients. The results were assessed at 18 months of follow-up. MATERIAL: We evaluated 137 surgically treated knees in 136 patients, 20 female and 117 male, on the basis of the Lysholm score system completed with a clinical examination of knee joint stability by Lachman's test and the pivot shift test and the ability of assuming a squatting position. We completed the evaluation with the patient's report on their satisfaction with the outcome and willingness to undergo the surgery again in the case of the other knee instability. METHODS: We carried out surgery under general anesthesia with the extremity in flexion and application of a tourniquet. Arthroscopy is performed from the anterolateral portal and graft is harvested, though a longitudinal incision, from the middle third of the patellar ligament and with the bony blocks from the patella and tibial tubercle. The graft width is 9 to 10 mm. Tibial or femoral tunnels are drilled by means of a tibial of femoral reamer and the inserted graft is fixed with metal interference screws. Cefazolinum with low-molecular heparin is administered during surgery. Rehabilitation of the extremity on a continuous passive motion (CPM) device begins on the first day. Full weight-bearing is allowed from the sixth week. RESULTS: The average Lysholm score of the group was 86.9. Excellent, good and satisfactory outcomes were achieved in 46.38%, 23.91% and 14.49% of the knees, respectively; 14.49% showed poor outcomes. Satisfaction with the outcome of surgery was reported by 90.5% of the patients, 75.18% complained of problems with knee-bend and pain at the donor site and scar. DISCUSSION The results of our evaluation are similar to those reported in the relevant literature. There are no differences in Lysholm scores from literature data or from the results recorded in a group of patients operated on with the use of the Rigidfix system and hamstring tendon grafts, in whom the average score was 84.3. The patients treated by the B-T-B technique, however, experience more problems at the graft harvest site, with subsequent femoropatellar complaints. CONCLUSIONS: ACL reconstruction with a patellar B-T-B graft is a surgical technique which resolves the patient's existing complaints due to knee instability, but may also have a preventive effect. This technique is suitable for sportsmen and sportswomen. Because of frequent postoperative complaints of pain at the donor site, it is not indicated for persons with femoropatellar problems, elderly persons and those who have kneeling jobs.

Adolescent↗

[Bone and bone related biochemical examinations. Bone and collagen related metabolites. Urinary and serum NTX as bone resorption markers].

Serum (S-) or urinary (U-) type I collagen N-telopeptide (NTX) reflect bone resorption by cathepsin K or matrix metalloproteinase (MMP). In our analysis of 18 patients with serum creatinine (S-Cr) less than 2.0 mg/dL, there was a significant positive correlation between S-NTX and U-NTX (U-NTX = 3.7 x S-NTX-13 [r = 0.84, P<0.0001) ] . Because diurnal and day-to-day variations are large in U-NTX assay, it is recommended that U-NTX be measured in the first or second urine of the day. In contrast, physiological variation in S-NTX is relatively small. However, we should bear in mind that S-NTX is interfered with renal function. Before interpretation of S-NTX, we should estimate glomerular filtration rate by using Cockcroft-Gault formula, especially in elderly patients with low body mass index such as rheumatic patients, whose S-Cr-is in normal ranges Both markers are very useful for estimating the risk of bone fracture and for monitoring therapeutic effects of anti-resorptive agents such as bisphosphonate or selective estrogen receptor modulator.

Biomarkers↗

[Bone and bone related biochemical examinations. Bone and collagen related metabolites. Bone resorption marker; urinary and serum CTX].

The determination of C-terminal telopeptide of type I collagen degradation products (CTX) was made by using the monoclonal antibody recognizing the eight amino acids that are specific for alpha1 chain of type I collagen. CTX values show a diurnal variation, with a nadir from 1 to 11 o'clock in the afternoon, increase at midnight with peaks from 2 to 8 o'clock in the morning. The levels of CTX at peaks are approximately twice those at a nadir, which implies the sampling of serum and urine should be made at an identical time at each patient. There were significant correlations in patients on hormone replacement therapy (HRT) between lumbar spine bone density at 2-yr and percent changes of serum, or urinary CTX at 3-month and the percent change of CTX at 3-month alone could predict the percent change of lumbar spine bone density at 2-yr.

Adult↗

Estrogen maintains trabecular bone volume in rats not only by suppression of bone resorption but also by stimulation of bone formation.

Estrogen is generally considered to maintain bone mass through suppression of bone resorption. We have previously demonstrated that administration of pharmacologic doses of estrogen increases bone formation in ovary-intact rats. To assess the effects of physiological concentrations of estrogen on bone formation, estrogen was administered to ovariectomized rats in which bone resorption was suppressed by the bisphosphonate 3-amino-1-hydroxypropylidene-1-bisphosphonate (AHPrBP). Animals receiving exogenous 17 beta-estradiol (E2) (1, 10, and 100 micrograms/kg daily for 17 d) showed a dose-dependent increase in trabecular bone volume of 1.9, 25.8, and 43.6%, respectively, compared with those rats treated with AHPrBP alone. The increase in bone volume was associated with an increase in bone formation in E2-treated animals, in which bone resorption had been almost completely suppressed by AHPrBP. Neither ovariectomy, AHPrBP, nor E2 treatment had a significant effect on the volume or rate of formation of cortical bone. Thus, the increased bone resorption, which is a consequence of estrogen-deficiency, entrains increased bone formation, which masks a simultaneous reduction in estrogen-dependent bone formation. Therefore, in addition to the nonspecific effect of estrogen to depress formation via coupling, we have identified a specific effect of estrogen to increase formation independent of coupling. Thus it appears that estrogen maintains bone volume not only through inhibition of bone resorption, but also through stimulation of bone formation.

Animals↗

An uncoupling agent containing strontium prevents bone loss by depressing bone resorption and maintaining bone formation in estrogen-deficient rats.

Trabecular bone loss in estrogen deficiency is associated with enhanced bone resorption with a smaller increase in bone formation. We previously reported that low doses of strontium can increase trabecular bone volume in rodents by affecting bone resorption and formation. In this study we determined the effect of a new divalent strontium salt (S12911) on bone loss induced by E2 deficiency. Sprague-Dawley female rats (230 g, n = 15-25 per group) were sham operated or ovariectomized (OVX) and treated with 17 beta-estradiol (E2, 10 micrograms/kg/day, sc) or S12911 by gavage at the dose of 77, 154, or 308 mg/kg/day or the vehicle. Treatment for 60 days with S12911 resulted in a dose-dependent increase in plasma, urine, and bone strontium concentrations without any deleterious effect on total or skeletal growth. OVX rats were osteopenic compared to sham rats as shown by decreased femoral dry bone weight and mineral content measured on bone ash and by DXA. Treatment of OVX rats with S12911 prevented bone loss as bone ash and bone mineral content were restored to the values in sham rats. Trabecular bone volume measured by histomorphometry on the tibial metaphysis was decreased by 46% in OVX rats and was corrected by E2. Treatment of OVX rats with S12911 increased the trabecular bone volume by 30-36%. Histomorphometric indices of bone resorption (osteoclast surface and number) were increased in OVX rats and were reduced by S12911 to the levels in sham rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

The use of bone-marrow-derived fibroblastoid cells and fresh bone marrow in the treatment of bone defects: an experimental study.

Bone-marrow aspirate (containing bone progenitor cells), in vitro expanded autologous bone-marrow-derived stromal fibroblastoid cells, and a combination thereof were tested for the potential to fill bone defects. They were compared to grafts of fresh autologous bone or allogeneic devitalized bone. Mandibular defects in rabbits were chosen for this study. The best results were obtained with a combination of in vitro expanded bone-marrow-derived stromal fibroblastoid cells and fresh autologous bone marrow or fresh autologous marrow alone. The effects of these two grafts were similar to grafts of fresh autologous bone and significantly superior to grafts of devitalized allogeneic bone providing only a bone matrix. The in vitro expanded marrow stromal cells induced very significant bone ingrowth, and their effects were only slightly inferior to fresh autologous bone but were superior to devitalized allogeneic bone. These studies suggest that bone marrow is a good source of osteogenic cells both for immediate transplantation and for in vitro expansion and subsequent transplantation.

Animals↗

Xenogeneic osteogenin, a bone morphogenetic protein, and demineralized bone matrices, including human, induce bone differentiation in athymic rats and baboons.

Subcutaneous implantation of xenogeneic demineralized bone matrix does not initiate endochondral bone differentiation. Dissociative extraction in 4 M guanidine-HCl or 6 M urea has shown that the apparent species-specificity of intact bone matrix resides in its insoluble immunogenic component, since there is homology in solubilized osteogenic proteins amongst mammals. To further investigate the species-specificity and cross-species reactivity of bone matrix components, baboon and human demineralized bone matrix (DBM) and bovine osteogenin, purified greater than 50,000-fold and with an apparent molecular mass of 28-42 kilodaltons, were implanted in the subcutaneous space of athymic and euthymic rats and into the rectus abdominis of 16 baboons (Papio ursinus). Baboon DBM was also implanted in athymic and euthymic mice. Alkaline phosphatase activity and histology of implants harvested at day 11 and 30 showed that baboon and human DBM induced endochondral bone differentiation both in athymic rats and baboons. Bovine osteogenin in conjunction with baboon insoluble collagenous matrix induced extensive bone differentiation in athymic rats and baboons. Baboon and human DBM did not induce bone differentiation in euthymic rats and, in athymic mice, baboon DBM failed to induce bone differentiation, determining instead the recruitment of multinucleated giant cells. The results indicate that in rodents bone differentiation induced by intact bone matrix is species specific and that T-cell functions are not a requirement for bone induction, although immunologically competent rats block bone differentiation from xenogeneic matrix. Bone differentiation induced by human DBM in baboons suggests that intact bone matrices may not be species-specific amongst primates.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Benefits of growth hormone treatment on bone metabolism, bone density and bone strength in growth hormone deficiency and osteoporosis.

Bone mass is reduced in patients with GH deficiency (GHD) leading to an increased vertebral fracture rate and clinically significant osteoporosis. Patients with GHD of juvenile onset have reduced skeletal mineralization. When substituting GH in patients with GHD, bone turnover is increased and bone mineral density initially decreases during the first year due to the increase in remodelling space. From the experience in patients with acromegaly, cortical bone mass is increased and trabecular bone mass is normal in eugonadal or decreased in the hypogonadal patients. However, bone mineral content and bone area are increased leading to a higher biomechanical competence of bone as shown in rats. In patients with GHD of juvenile onset, mineralization and bone maturation are achieved during treatment with GH in adult life after having reached final body height leading to an increase in bone mass. The GH/ IGF-I system is dysregulated in patients with post-menopausal osteoporosis. This is shown by reduced systemic IGF and IGFBP-3-levels in osteoporosis suggesting a decrease of endogenous GH-secretion or a dysregulation of the GH receptor system which is beyond the normal ageing process of the GH/IGF system, the "somatopause". A premature somatopause may be responsible for the dysregulation in some patients with osteoporosis. However, 24-h GH profiles do not differ between patients suffering from osteoporosis or osteoarthritis. Treatment of osteoporosis with GH might be beneficial due to the increased bone metabolism and improved bone geometry which occurs with GH. The substantial increase of bone remodelling achieved with GH may be helpful during late post-menopause with decreased bone turnover and impaired osteoblastic function. Using GH to prevent physiological bone loss that occurs with age seems possible, but has to be discussed on an ethical and economic basis.

Acromegaly↗

Exercise-induced bone gain is due to enlargement in bone size without a change in volumetric bone density: a peripheral quantitative computed tomography study of the upper arms of male tennis players.

Bilateral bone characteristics of the humerus (proximal, shaft, and distal sites) and radius (shaft and distal sites) in 12 former Finnish national-level male tennis players (mean age 30 years) and their 12 age-, height-, and weight-matched controls were measured with peripheral quantitative computed tomography (pQCT). The pQCT variables analyzed were bone mineral content (BMC), total cross-sectional area of bone (Tot.Ar), cross-sectional area of the marrow cavity (M.Cav.Ar), cortical bone (Co.Ar) and trabecular bone (Tr.Ar), volumetric density of cortical (Co.Dn) and trabecular (Tr. Dn) bone, cortical wall thickness (Co.Wi.Th), bone strength index (BSI), and principal moments of inertia (I(min) and I(max)). In the players, significant side-to-side differences, in favor of the dominant (playing) arm, were found in BMC (ranging 14%-27%), Tot.Ar (16%-21%), Co.Ar (12%-32%), BSI (23%-37%), I(min) (33%-61%), and I(max) (27%-67%) at all measured bone sites, and in Co.Wi.Th. (5%-25%) at the humeral and radial shafts, and distal humerus. The side-to-side M.Cav.Ar difference was significant at the proximal humerus (19%) and radial shaft (29%). Concerning the players' Co.Dn and Tr.Dn, the only significant side-to-side difference was found in the Co.Dn of the distal humerus, with the playing arm showing a slightly smaller Co.Dn than the nonplaying arm (-2%). In controls, significant dominant-to-nondominant side differences were also found, but with the majority of the differences being rather small, and significantly lower than those of the players. In conclusion, despite the large side-to-side differences in BMC, the volumetric bone density (Co.Dn, Tr.Dn) was almost identical in the dominant and nondominant arms of the players and controls. Thus, the players' high playing-arm BMC was due to increases in the Tot.Ar, M.Cav.Ar, Co.Ar, and CW.Th. In other words, the playing arm's extra bone mineral, and thus increased bone strength, was mainly due to increased bone size and not due to a change in volumetric bone density. These upper arm results may not be generalized to the entire skeleton, but the finding may give new insight into conventional dual-energy X-ray absorptiometry (DXA)-based bone density measurements when interpreting the effects of exercise on bone.

Adult↗