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Effects of insulin on in vitro bone formation in fetal rat parietal bone.

We examined the effects of insulin on bone formation including the mineralizing process. Twenty-day fetal rat parietal bones were cultured for 96 h on grids in a serum-free medium. For the precise assessment of bone formation, histomorphometry, with an image analyzing system, was used to measure the areas of mineralized bone and bone matrix, and the numbers of osteoblasts and osteoclasts. In order to confirm the effects of insulin on bone mineralization, the calcium content of the bone and the release of previously incorporated 45Ca into the medium were measured. Insulin, at a concentration of 10(-6) M or higher, increased the areas of mineralized bone and bone matrix, and the number of osteoblasts. Osteoclasts were seldom observed in bones on day 0 or in bones treated with insulin. In bones treated with insulin at a concentration of 10(-6) M, the calcium content of bone increased. At an insulin concentration of 10(-7) M or higher, the dry weight of decalcified bone increased. Lactate production in the medium increased dose-dependently. The inhibited release of 45Ca in bones indicated that insulin acts by increasing calcium retention. We demonstrated that insulin has an effect on bone-forming and bone-resorbing cells to enhance the bone forming process from matrix formation to mineralization.

Animals↗

Highly precise peripheral quantitative computed tomography for the evaluation of bone density, loss of bone density and structures. Consequences for prophylaxis and treatment.

The importance of serial examinations over time with peripheral quantitative computed tomography (pQCT) is that they enable the detection of patients at high risk of osteoporosis, and the individualisation of prophylaxis and treatment. We have shown that postmenopausal patients with high bone turnover evaluated by biochemical markers are identical to fast bone losers as determined by pQCT. As a consequence, we use agents that inhibit bone resorption in patients who are fast bone losers and agents that stimulate bone formation in patients who are slow bone losers. To visualise bone microarchitecture, and to evaluate bone density and the rate of bone loss, we used a highly sensitive pQCT system (DENSISCAN 1000, reproducibility of 0.3% in a mixed population of normal individuals and patients with osteopenia or osteoporosis). This system enabled us to separately assess trabecular and cortical bone density in the radius and tibia, and to differentiate between fast and slow bone losers within a few months (threshold: 3% loss of trabecular bone density in the radius per year). We have shown that the lower the trabecular bone density in the distal radius, the higher the relative bone loss. To classify patients as slow and fast losers in the future, we may need only one measurement. With this highly precise measurement method, we have shown that calcitonin and etidronate are more effective in fast than in slow bone losers, and that vitamin D metabolites (calcitriol or 1 alpha-calcidol) and estrogens can halt fast bone loss. In conclusion, highly sensitive pQCT enables us to adapt the treatment to different forms of osteoporosis and bone turnover, resulting in an increase in the number of patients successfully treated and also in patient compliance. Because our treatment is based on precise, objective measurements, treatment modifications--especially in those who change from a slow to a fast bone-loser state--can be easily justified.

Adult↗

[Experimental study on repairing segmental bone defects with three bio-bone derived materials].

OBJECTIVE: To evaluate the osteogenesis of three bio-bone derived materials in repairing segmental bone defects. METHODS: Sixty Japanese rabbits were made 10 mm radius segmental defects and divided into 5 groups (groups A, B, C, D and E, n=12). Composite fully deproteinised bone (CFDB, group A), partially deproteinised bone (PDPB, group B), partially decalcified bone (PDCB, group C), autogenous iliac bone graft (group D) and no implant (group E) were implanted into the radius segmental bone defects of rabbits. The specimens were examined after 4, 8, 12 and 24 weeks; the osteogenesis was evaluated through X-ray radiograph and undecalcified solid tissue histological examination. RESULTS: The border between the material and host's bone was distinct after 4 weeks and blurred after 8 weeks; the density of partial edge of the material was similar to that of radii after 12 weeks. The medullary cavity of bone reopened in group B; the density of most defect area was similar to that of the host bone and there was a few high density shadow in group C; the density of most defect area was higher than that of host bone in group A after 24 weeks. There was no significant difference in radiograph scoring between groups A, B and C after 4 weeks and 8 weeks (P>0.05); the scores of group B and C were higher than that of group A after 12 weeks (P<0.05); and the scores were arranged as follow: group D > group B > group C > group A after 24 weeks (P<0.05). Bone callus grew toward defect area and new bone adhered to the material after 4 weeks and 8 weeks; more new bone formed, and the materials were absorbed and degraded with time. The quantity of bone formation was more in group D than in group B and in group B than in group C and in group C than in group A after 24 weeks (P<0.05). CONCLUSION: PDPB had good osteogenesis in repairing the segmental bone defect, PDCB was inferior to it, both PDPB and PDCB are fit to repair segmental bone defect. Both of them were inferior to autogenous bone.

Animals↗

Biochemical markers of bone turnover in patients with metastatic bone disease.

Several biochemical markers of bone formation and bone resorption have recently been developed. These markers have been evaluated for clinical utility in patients with metabolic bone disease, including Paget disease and osteoporosis, and for their potential use in cancer patients whose disease has metastasized to bone. We have evaluated seven markers of bone turnover in the plasma and urine of 94 patients with newly diagnosed or progressive malignancy with and without clinical evidence of bone metastases. As determined by a positive bone scan and (or) bone survey, 30 patients had metastases to bone; 51 patients had metastatic cancer without overt bony involvement; and 13 patients had local disease without bone metastases. To evaluate the predictive value of these markers in the metastatic population, we utilized a "Z-score" and logistic regression analysis to distinguish patients with documented bone metastatic disease from those patients without clinical evidence of bone metastases. The higher the Z-score, the better the marker predicts the presence of bone metastases. With this statistical approach, urine N-telopeptide measurements had the highest Z-score and the most significant association with the probability of bone metastases. Urine deoxypyridinoline was the second most predictive marker of bone metastases. Thus, biochemical markers of bone resorption might be of use to predict the presence of bone metastases in cancer patients and to monitor the efficacy of antiresorptive therapy in patients treated for metastatic bone disease.

Alkaline Phosphatase↗

Treatment of peri-implantitis using guided bone regeneration and bone grafts, alone or in combination, in beagle dogs. Part 2: Histologic findings.

The aim of this study was to histologically evaluate and compare the treatment of ligature-induced peri-implantitis using guided bone regeneration, two bone grafts alone, or guided bone regeneration combined with one of the two bone graft materials. Mandibular premolars and first molars in seven beagle dogs were extracted. After placement of Brånemark implants and connection of abutments, experimental peri-implantitis was induced. Flap surgery was performed, abutments were removed, and implant surfaces were treated with an air-powder abrasive unit. Bony defects were randomly treated with either (1) debridement only; (2) debridement plus resorbable hydroxyapatite; (3) debridement plus canine demineralized freeze-dried bone; (4) debridement plus guided bone regeneration; (5) debridement plus resorbable hydroxyapatite and guided bone regeneration; or (6) debridement plus canine demineralized freeze-dried bone and guided bone regeneration. Four months after surgery, a flap was elevated and the barriers were removed. One month later, the animals were sacrificed, and the implants with their supporting peri-implant tissues were processed for histologic evaluation. Guided bone regeneration procedures resulted in the greatest amount of new bone formation, followed by bone grafts alone, and flap debridement. There was no significant difference between guided bone regeneration and both guided bone regeneration/graft combinations in terms of bone regeneration; however, the guided bone regeneration/graft combinations resulted in a greater amount of "reosseointegration" than all of the other treatments. Therefore, the combination of guided bone regeneration with either demineralized freeze-dried bone or resorbable hydroxyapatite appears to be the treatment of choice for plaque-induced peri-implant defects.

Animals↗

PGE2 stimulates both resorption and formation of bone in vitro: differential responses of the periosteum and the endosteum in fetal rat long bone cultures.

The ability of PGE2 to stimulate bone resorption in vitro and in vivo is well established but the effects of this compound on bone formation are still controversial. Recent clinical reports have suggested that long-term infusion of PGE in infants with cyanotic heart diseases led to a stimulation of periosteal bone formation and to hyperostosis. In the present report, we describe the effects of PGE2 (10(-5) M) in bone organ cultures on bone resorption, measured by the release of 45Calcium and the number of osteoclasts in sections of cultured bones, and bone volume, by measuring separately medullary and cortical areas. PGE2 induced a marked increase in 45Ca release and in cortical and medullary osteoclast numbers over 4 days in vitro; despite this increase in bone resorption, cortical bone volume remained constant, indicating a parallel increase in bone resorption and formation at this site. Morphological and quantitative data demonstrated a higher extent of osteoblastic surface along the periosteum of PGE2-treated bones when compared with control cultures. Medullary bone volume, on the other hand, decreased sharply during the culture period, demonstrating a lack of parallel increase in bone formation at this site. It is concluded that, under these experimental conditions, prostaglandin E2 stimulated both resorption and formation along the periosteum and only bone resorption along the endosteum of the cultured bones. The overall effect of PGE2 on bone as a whole, however, was net bone loss.

Animals↗

In vitro studies on bone resorption in neonatal mouse calvariae using a modified dissection technique giving four samples of bone from each calvaria.

Bone resorption in a modified bone culture system, based on incubation of small fragments from neonatal mouse calvarial bones, has been studied. Four bone fragments were dissected out from each mouse calvaria and were thereafter cultured in CMRL 1066 medium in plastic multiwell dishes. Bone resorption was assessed by 45Ca release from prelabeled bones. The rate of bone resorption in response to parathyroid hormone (PTH) was less in the anterior part of the calvaria compared to the posterior part. After removing the anterior region, four parietal bone fragments that showed identical basal and PTH-stimulated release of 45Ca could be dissected out from each mouse. Excretion of lactate dehydrogenase and beta-glucuronidase was the same in bones cultured submerged or on grids. Uptake of [3H]thymidine in bones cultured submerged was 54% of [3H]thymidine uptake in bones cultured on grids. Dose-response curves, established by using parietal bone fragments, showed that the sensitivity and the magnitude of the increase in 45Ca release seen after stimulation with PTH, prostaglandin E2, and 1 alpha-hydroxyvitamin D3 were the same for bones cultured submerged or on grids. The 45Ca release in response to stimulation with PTH, prostaglandin E2, and 1 alpha-OHD3 was the same in calvarial fragments cultured submerged and those previously obtained with calvarial halves cultured on grids. Thus, even though the rate of DNA synthesis was slower in bones cultured submerged, the rate and the magnitude of resorption were the same in bones cultured on grids or submerged. These data show that it is possible to perform studies on bone resorption with small fragments of neonatal mouse parietal bones.

Animals↗

Bone induction using demineralized bone in the rabbit femur: a long-term study.

While traditional bone grafting is the standard for replacement of segmental bony defects, alternative options (avoiding morbidity of autologous grafts) are attractive and continue to be sought. This study attempted to determine whether demineralized bone powder could be used reliably to replace a significant bony deficit at a weight-bearing site. The long-term functional characteristics of this induced bone were analyzed to determine whether it maintained its strength and shape and reacted normally to physiologic stress over an extended period of time (12 months). In 55 New Zealand White rabbits, a 1-cm length of femur was removed (approximately 20 percent of the total length of the rabbit femur). The femur was then reconstructed with a titanium mandibular plate, leaving the gap intact. In 38 of the animals, this gap was filled with demineralized bone powder in an attempt to induce bone to form across the defect. In group 1 (n = 23), the mandibular plate remained in place for the duration of the study (12 months). In group 2 (n = 15), the plate was removed 8 weeks after placement of the demineralized bone powder, and the animals were followed for an additional 12 months. In group 3 (n = 10), nothing was placed within the bony gap. In group 4 (n = 7), the gap was repaired with autologous bone graft. All the animals that received demineralized bone powder completely filled the osteotomy gap with new bone within 6 to 8 weeks after implantation. None of control group 3 formed bone across the gap (p < 0.001). Eighty-six percent of control group 4 (autologous bone graft) successfully formed bone across the osteotomy gap. In addition, 90 percent of control group 3 had hardware failure within 8 weeks after surgery compared with 0 percent (0 of 38) of the group that received demineralized bone powder (p < 0.001). In group 1, analysis after 12 months revealed that the bone formed ultimately became thin and easily fractured, most likely because of shielding from stress loading by the mandibular plate. In contrast, in group 2 (in which the plate was removed after 8 weeks), the bone remodeled and hypertrophied in response to the physiologic stress of weight bearing and at the end of the 12-month period was essentially identical to normal femur. In certain circumstances, reconstruction of bony defects using bone-induction techniques may be as good as autologous bone grafting, with the advantage of limiting the donor-site morbidity for the patient.

Animals↗

Experimental spinal fusion using sintered bovine bone coated with type I collagen and recombinant human bone morphogenetic protein-2.

STUDY DESIGN: Posterolateral lumbar transverse process fusion using recombinant human bone morphogenetic protein (rhBMP)-2 carried by sintered bovine bone and Type I collagen complex was compared with fusion achieved using autogeneous bone graft or sintered bovine bone alone. OBJECTIVES: This study examined the efficacy of sintered bovine bone coated with Type I collagen as a carrier of rhBMP-2 for lumbar intertransverse process arthrodesis. SUMMARY OF BACKGROUND DATA: Posterolateral intertransverse process arthrodesis using osteoinductive growth factors is performed experimentally in the lumbar spine. The previous studies revealed the efficacy of osteoinductive factors applied to carriers having no bony structures, such as collagen sheet or polylactic acid polymer, for the spinal fusion. However, in their studies, a large amount of osteoinductive proteins have been applied for the spinal fusion. We used the sintered bovine bone "True Bone Ceramics" (TBC; Koken Co., Tokyo, Japan) coated with type I collagen as the carrier. True Bone Ceramics is the only biomaterial possessing a natural trabecular structure and an organized crystal of bone minerals. METHODS: Twenty-two adult rabbits underwent bilateral lumbar intertransverse process arthrodesis at L4-L5. The animals were divided into four groups and had materials implanted as follows: autologous bone group, grafted autologous corticocancellous bone harvested from the posterior iliac crest; implanted TBC group; TBC collagen group, implanted TBC coated with Type I collagen infiltrating into the porous space; and BMP group, implanted sintered bovine bone coated with Type I collagen infiltrated with 100 micrograms of rhBMP-2. Spinal fusion was evaluated by radiographic analysis, manual palpation, biomechanical testing, and histologic examination 6 weeks after surgery. RESULTS: Two rabbits were killed because of infection and lumbar plexus palsy. Radiographs of the BMP group showed a homogeneous fusion mass at the intertransverse area, and stability was confirmed by dynamic radiographs at 3 and 6 weeks after surgery. In the BMP group, a bony mass in the intertransverse area was more prominent than in the other groups. The BMP group had a higher fusion rate based on manual palpation than the-other groups, and BMP fusions showed significantly higher tensile strength and stiffer fusion. The histologic findings in the BMP group demonstrated membranous bone and endochondral bone formations between the transverse process and the fusion mass. In the other groups, continuous trabecular bone formation was observed in the area surrounding the transverse process, but gaps between grafted fragments and less mature bone formation were present in the intertransverse area. CONCLUSIONS: Sintered bovine bone coated with Type I collagen and rhBMP-2 resulted in a higher fusion rate than the autograft and can be used as a carrier for rhBMP-2 in spinal fusion.

Animals↗

[Effects of hindlimb unloading on bone histomorphometry and bone mass in rats].

OBJECTIVE: To study the effects of hindlimb unloading on bone histomorphometry, bone local growth factor, bone biomechanical properties and bone contents in rats. METHOD: Male SD rats were arranged into free active control group (CON) and tail-suspended group (TS) with 9 rats in each group. The experiment lasted for 3 weeks. Bone histomorphometry, bone local growth factor, biomechanical properties and bone contents were measured before and after tail suspension. RESULT: Structure of the trabecular bone was disorganized. Compared with CON, trabecular bone volume (% Tb. Ar), mean trabecular plate thickness (Tb. Th), osteoblast surface (Ob. S) were significantly reduced in TS. The eroded surface (Oc. N/BS) tended to be higher, though not significant at this stage of tail suspension; alkaline phosphatase (ALP) activity in the tibia were significantly reduced, but NO content in the femoral trunk was significantly decreased; bone biomechanical properties, bone mineral content (BMC), bone density (BD) and bone collagen density (BCD) in the femur were significantly reduced. CONCLUSION: Hindlimb unloading may lead to regression of bone microstructure, change of bone local growth factor content, reduction of bone biomechanical properties and bone content.

Alkaline Phosphatase↗

Effect of allogeneic, freeze-dried, demineralized bone matrix on guided bone regeneration in supra-alveolar peri-implant defects in dogs.

This randomized, split-mouth design study evaluated the adjunctive effect of allogeneic, freeze-dried, demineralized bone matrix on guided bone regeneration in a critical-size, supra-alveolar, peri-implant defect model. Contralateral supra-alveolar peri-implant defects, 5 mm in height, each including two titanium implants, were surgically created in five beagle dogs. Demineralized bone matrix in autologous blood was placed over the implants in one randomly selected mandibular jaw quadrant. A space-making expanded-polytetrafluoroethylene membrane was used to provide guided bone regeneration bilaterally. Following a 16-week healing interval, tissue blocks were harvested and prepared for histometric analysis. Differences between experimental conditions (guided bone regeneration sites with and without demineralized bone) were evaluated using paired t tests (n = 4). Demineralized bone particles were discernible, with limited signs of resorption. The bone matrix particles appeared to be solidified within a dense connective tissue matrix and in close contact with the implants. Limited matrix remineralization was apparent adjacent to the alveolar crest. No statistically significant differences were found between experimental conditions for any parameter examined. Peri-implant defect height averaged 5.0 +/- 0.2 mm and 4.9 +/- 0.4 mm, vertical bone regeneration 1.5 +/- 0.9 mm and 1.1 +/- 0.4 mm, osseointegration within the extent of the defect 10.0 +/- 3.9% and 15.3 +/- 5.3%, osseointegration within the extent of regenerated bone 30.4 +/- 13.7% and 52.1 +/- 17.9%, and osseointegration within the alveolar base 68.8 +/- 13.1% and 74.4 +/- 7.1% for guided bone sites with and without demineralized bone, respectively (P > .05). The results suggest that freeze-dried demineralized bone has no adjunctive effect on guided bone regeneration in supra-alveolar peri-implant defects, that guided bone regeneration has a limited potential to enhance alveolar regeneration in this defect model, and that a 16-week healing interval appears insufficient for turnover and maturation of demineralized bone under provisions for guided bone regeneration.

Alveolar Bone Loss↗

The effects of 1-year gluten withdrawal on bone mass, bone metabolism and nutritional status in newly-diagnosed adult coeliac disease patients.

OBJECTIVES: To evaluate the impact of a 1-year gluten-free diet on bone metabolism and nutritional status in coeliac disease. METHODS: Bone mineral density, serum indices of bone remodelling, clinical and biochemical nutritional assessment were evaluated in 86 consecutive newly-diagnosed, biopsy proven, coeliac disease patients (untreated). A complete reevaluation, including intestinal biopsy, was repeated within 1 year of dietary treatment (treated). RESULTS: Untreated: according to WHO criteria, 34% of patients had a normal bone mineral density, 40% had osteopenia and 26% osteoporosis. Between males and females there were no statistical differences in bone metabolism or in most of the nutritional indices, while, between fertile and postmenopausal women, bone mineral density and several bone metabolism markers were significantly different. Compared to subjects with a normal bone mineral density, osteopenics had higher bone specific alkaline phosphatase (BAP) and Bone-Gla-protein (BGP) values. In patients with a concomitant BAP increase and 25OH vitamin D serum level reduction, bone mineral density and several bone turnover markers were statistically different compared to patients without such a serological pattern. Treated: notwithstanding intestinal biopsy which showed a mucosal recovery in only 57%, gluten-free diet led, even in postmenopausal women, to a significant improvement in bone mineral density, bone metabolism and nutrition, except for folic acid, albumin and pre-albumin serum levels which persisted as abnormal in patients with obdurate mucosal impairment. CONCLUSIONS: Coeliac disease patients are at high risk for developing a low bone mineral density and bone turnover impairment. A gluten-free diet can improve this situation even in postmenopausal women and in patients with incomplete mucosal recovery.

Adult↗

[New-bone formation by osteogenic protein-1 and autogenic bone marrow in a critical tibial defect model in sheep].

AIM: Osteogenic Protein-1 (OP-1) is known to be a very potent osteoinductive growth factor. However, experimental studies using critical-size defect models in the weight-bearing lower extremity show non-uniform results. Therefore, we studied the osteoinductivity of OP-1 in a tibial worst-case defect model in sheep. Potential improvement of OP-1 induced new bone formation using a composite graft with autogenous bone marrow was to be investigated. METHOD: In 19 sheep a 5 cm segmental defect of the tibial diaphysis was treated by intramedullary nailing and filled with the following implants: 5 mg OP-1 + inactivated demineralized bone matrix (group 1; n = 6); 5 mg OP-1 + inactivated demineralized bone matrix + 5 ml autogenous bone marrow (group 2; n = 5); autogenous cancellous bone (group 3; n = 4), or inactivated demineralized bone matrix + 5 ml autogenous bone marrow (group 4; n = 4). RESULTS: In total, 3 out of 10 defect sites treated with OP-1 were completely bridged radiographically by 12 weeks. Initially, x-rays showed accelerated new bone formation by use of the composite grafts containing OP-1 and autogenous bone marrow. However, 12 weeks post surgery 3D-CT-volumetry could not detect significant differences of new bone formation within the defect sites treated by OP-1 with or without bone marrow, while new bone formation by autogenous cancellous bone was better than by OP-1. CONCLUSION: In our worst case defect model, the osteoinductive potential of OP-1 is initially accelerated but 12 weeks post surgery not increased when combined with autogenous bone marrow transplantation. So far, critical segmental bone defects of the weight-bearing lower extremity can not be bridged regularly in our model by use of OP-1. Therefore, for the treatment of such critical defects with rotational instability the examined application device of OP-1 can not yet be recommended.

Animals↗

Reduced bone stress as predicted by composite beam theory correlates with cortical bone loss following cemented total hip arthroplasty.

Clinical and experimental evidence suggest that periprosthetic bone loss following total hip arthroplasty is caused in part by stress-shielding. Changes in bone stress in the proximal femur following implantation can be estimated with use of composite beam theory. We hypothesized that the degree of stress-shielding predicted by beam theory correlates with the magnitude of bone loss following cemented total hip arthroplasty. We analyzed cross sections from the proximal femur of 13 patients who had undergone unilateral cemented total hip arthroplasty. A matching implant was inserted contralaterally, and the cross-sectional properties of the implant and bone and the bone density were determined. Bone loss was calculated on the basis of differences between contralateral (control) and ipsilateral (remodeled) sections and correlated to several beam-theory parameters calculated from the control sections: implant rigidity, bone rigidity, ratio of implant to bone rigidity, and predicted decrease in bone stress. All parameters except implant rigidity were significantly correlated with bone loss (p < 0.05). Parameters that included implant and bone properties were more strongly correlated with bone loss than were those based on bone properties alone. The predicted decrease in bone stress explained 50-60% of the variance in bone loss. The data also indicated that patients were not likely to lose substantial amounts of bone unless the reduction in bone stress exceeded a threshold value. Although limited by a small and heterogeneous sample, these results indicate that beam-theory predictions correlate with the degree of femoral resorption and should be investigated further as a means to identify patients at high risk for bone loss.

Arthroplasty, Replacement, Hip↗

Comparing whole body (18)F-2-deoxyglucose positron emission tomography and technetium-99m methylene diphosphonate bone scan to detect bone metastases in patients with breast cancer.

PURPOSE: At present, bone metastases are usually assessed using conventional technetium-99m methylene diphosphonate whole-body bone scan, which has a high sensitivity but a poor specificity. However, positron emission tomography with (18)F-2-deoxyglucose (FDG-PET) can offer superior spatial resolution and improved specificity. We attempted to evaluate the usefulness of FDG-PET for detecting bone metastases in breast cancer and to compare FDG-PET results with bone scan findings. PATIENTS: The study group comprised 48 patients with biopsy-proven breast cancer and suspected of having bone metastases who underwent bone scan and FDG-PET to detect the bone metastases. The final diagnosis of bone metastases was established by operative, histopathological findings or during a clinical follow-up longer than 1 year by additional radiographs or following FDG-PET/bone scan findings showing progressive widespread bone lesions. RESULTS: A total of 127 bone lesions including 105 metastatic and 22 benign bone lesions found by either FDG-PET or bone scan were evaluated. Using FDG-PET, 100 metastatic and 20 benign bone lesions were accurately diagnosed, and using bone scan 98 metastatic and 2 benign bone lesions were accurately diagnosed. The diagnostic sensitivity and accuracy of FDG-PET were 95.2% and 94.5%, and of bone scan were 93.3% and 78.7%, respectively. CONCLUSIONS: Our findings suggest that FDG-PET shows a similar sensitivity and a better accuracy than bone scan for detecting bone metastases in patients with breast cancer.

Adult↗

Age-related changes in cortical bone in men: metacarpal bone mass measurement study.

Metacarpal cortical bone mass was measured in 507 healthy Japanese men aged 40-95 years, using a microdensitometer to determine age-related changes in cortical bone in these middle-aged and elderly men. Total bone mass showed a significant negative correlation with age (r = -0.281; P < 0.0001). While bone width showed no significant correlation with age, bone marrow width showed a significant positive correlation (r = 0.210; P < 0.0001), and cortical bone width and cortical bone density showed a significant negative correlation with age (r = -0.265; P < 0.0001; r = -0.268; P < 0.0001, respectively). On the other hand, cortical bone width and cortical bone density showed a significant positive correlation with total bone mass (r = 0.814; P < 0.0001; r = 0.474, P < 0.0001, respectively). These findings suggest that cortical bone mass decreases significantly with aging in middle-aged and elderly men, perhaps as a result of two factors - decreased cortical bone width, ie, cortical bone thinning due to bone loss at the endosteal side of the cortex, and decreased cortical bone density due to progression of intracortical porosity. Cortical bone thinning may influence age-related cortical bone loss more than decreasing cortical bone density.

Adult↗

Effects of droloxifene on prevention of cancellous bone loss and bone turnover in the axial skeleton of aged, ovariectomized rats.

The purpose of this study was to determine the efficacy of droloxifene (DRO), an estrogen antagonist/agonist, in preventing ovariectomy (OVX)-induced lumbar vertebral cancellous bone loss and bone turnover in aged female rats. Fifty-three Sprague-Dawley female rats were OVX or sham-operated at 19 months of age, and divided into 6 groups: (I) sham-operated controls; (II) OVX vehicle controls; (III) OVX rats treated with E2 at 30 micrograms/kg/day; (IV)-(VI) OVX rats treated with DRO at either 2.5, 5, or 10 mg/kg p.o. daily. The treatment period was 8 weeks. Static and dynamic cancellous bone histomorphometric parameters were determined on 4 and 10 microns thick, undecalcified, double-fluorescent labeled sections of the fourth lumbar vertebral body. Changes in body weight, uterine weight, and total serum cholesterol were also determined. OVX for 8 weeks in 19-month-old female rats resulted in reduced trabecular bone volume (-18%) and trabecular width (-10%) and increased labeling perimeter (+52%), bone formation rate/bone surface referent (+60%), bone formation rate/bone volume referent (+77%), osteoclast number (+41%), and osteoclast perimeter (+41%). E2 treatment at 30 micrograms/kg/day for 8 weeks prevented OVX-induced cancellous bone loss and decreased bone resorption, bone formation, and bone turnover to the values of sham controls. DRO at 2.5-10 mg/kg/day completely prevented bone loss and bone turnover associated with estrogen deficiency. Osteoclast number and perimeter were significantly decreased in DRO-treated-OVX rats compared to both sham and OVX controls. Trabecular bone volume, trabecular width, labeling perimeter, bone formation rate/bone surface referent, and bone formation rate/bone volume referent showed no differences in DRO-treated OVX rats compared to those of E2-treated OVX rats and sham controls. These histomorphometric results indicated that DRO is an estrogen agonist on cancellous bone of lumbar vertebral bodies of aged, OVX rats. Further, E2 treatment prevented the OVX-induced increase in body weight gain and nonsignificantly reduced total serum cholesterol compared to OVX controls. Body weight gain and total serum cholesterol did not differ between OVX rats treated with E2 and sham controls. In OVX rats treated with DRO, body weight decreased significantly in a dose-response manner, and total serum cholesterol was significantly reduced by 65% to 70% compared to both sham and OVX controls. In addition, treatment with E2 increased uterine weight to the value of sham controls in OVX rats. However, DRO had no effect on uterine weight at either 2.5 or 10 mg/kg/day, while it only slightly but significantly increased uterine weight over OVX controls at 5 mg/kg/day. We conclude that DRO was efficacious in the prevention of lumbar vertebral cancellous bone loss and in the decline of total serum cholesterol but had no effect on uterine weight in the aged, OVX female rats. Our data suggest that DRO is a potentially useful agent for the prevention of vertebral bone loss leading to spinal fractures in postmenopausal women.

Administration, Oral↗

Relationships between static histomorphometry and bone strength measurements in human iliac crest bone biopsies.

It has been well established that trabecular bone strength has a power relationship to apparent bone density. It has been argued that the apparent bone density is not the sole factor determining cancellous bone strength, and that bone strength may also depend on the structure of the trabecular network. Various different measures of bone microstructure have been suggested: marrow space star volume; node-strut analysis; connectivity density; trabecular number; and trabecular separation. The aim of this study was to assess which of the histomorphometric measures, trabecular bone volume, marrow space star volume, node-strut analysis, connectivity density, trabecular number, and trabecular separation, give the best prediction of the bone strength. Moreover, a comparison of the suggested "structural" measures was carried out to establish whether they actually quantified the bone structure or something different. Finally, the influence of age and gender was investigated. The material comprised unilateral transiliac crest bone biopsies from 32 females (21-96 years, mean 59.1 years) and 32 males (24-94 years, mean 59.0 years). The bone biopsies were embedded in Technovit 9100, sectioned, and stained with aniline blue. Trabecular bone volume, marrow space star volume, node-terminus ratio, connectivity density, trabecular number, and trabecular separation were measured. A neighboring biopsy was compressed to obtain the compressive strength of the trabecular network. Trabecular bone volume was the measure that gave the strongest correlation with bone strength (r = 0.76 for females and r = 0.86 for males). High correlation was found between trabecular bone volume, marrow space star volume, node-terminus ratio, and trabecular separation--indicating that they carried the same information. A poor correlation was seen between these measures and connectivity density. Connectivity density was the only measure showing gender-dependent behavior. A multiple regression analysis showed that the trabecular bone volume is the best histomorphometric predictor of bone strength, and neither marrow space star volume, node-terminus ratio, connectivity density, trabecular number, nor trabecular separation could improve the predictive value of trabecular bone volume.

Adult↗