Bone Volume In Group Research Articles

Bone Morphogenetic Protein 2 Promotes Bone Formation in Bone Defects in Which Bone Remodeling Is Suppressed by Long-Term and High-Dose Zoledronic Acid.

The use of long-term and high-dose bisphosphate is associated with severely suppressed bone turnover and the delayed union of fractures. However, therapeutic methods to overcome the negative effects of bisphosphonate use are lacking. Bone morphogenetic proteins (BMPs) are powerful osteoinductive proteins. The development of the delivery system using BMP has been verified to have an excellent effect on fracture healing and the enhancement of osteointegration. We hypothesized that BMPs had similar effects as autografts in patients with decreased bone healing potential due to long-term bisphosphonate treatment. Forty rats were divided into the following four groups depending upon the materials implanted into the femoral defect after ten weeks of bisphosphonate (zoledronic acid) injections: Group I: absorbable collagen sponge (control); group II: demineralized freeze-dried bone graft; group III: autogenous bone graft; and group IV: rhBMP-2 with an absorbable collagen sponge. Radiographic union, micro-computed tomography (CT) analysis, manual palpation, and histologic analysis were evaluated. The radiographic union rate, manual union rate, and micro-CT bone volume in groups III and IV were significantly higher than those in groups I and II. Groups III and IV showed similar results to each other. Although the amount of immature bone in the BMP-treated group was large, the effect was similar to that of autografts in the bone defect model in which bone turnover was severely reduced by bisphosphonate treatment. BMP might be a good substitute for autografts in patients with decreased bone healing potential due to long-term bisphosphonate treatment.

A Retrospective Comparative Study of Sodium Fluoride Na18F-PET/CT and 68Ga-PSMA-11 PET/CT in the Bone Metastases of Prostate Cancer Using a Volumetric 3-D Radiomic Analysis.

Bone is the most common metastatic site in prostate cancer (PCa). 68Ga-PSMA-11 (or gozetotide) and sodium fluoride-18 (Na18F) are rather new radiopharmaceuticals for assessing PCa-associated bone metastases. Gozetotide uptake reflects cell membrane enzyme activity and the sodium fluoride uptake measures bone mineralization in advanced PCa. Here, we aim to characterize this difference and possibly provide a new method for patient selection in targeted therapies. Methods: The study consisted of 14 patients with advanced PCa (M group > 5 lesions), who had had routine PET/CT both with PSMA and NaF over consecutive days, and 12 PCa patients with no skeletal metastases (N). The bone regions in CT were used to coregister the two PET/CT scans. The whole skeleton volume(s) of interest (VOIs) were defined using the CT component of PET (HU > 150); similarly, the sclerotic/dense bone was defined as HU > 600. Additional VOIs were defined for PET, with pathological threshold values for PSMA (SUV > 3.0) and NaF (SUV > 10). Besides the pathological bone volumes measured with each technique (CT, NaF, and PSMA-PET) and their contemporaneous combinations, overlapping VOIs with the CT-based skeletal and sclerotic volumes were also recorded. Additionally, thresholds of 4.0, 6.0, and 10.0 were tested for SUVPSMA. Results: In group M, the skeletal VOI volumes were 8.77 ± 1.80 L, and the sclerotic bone volumes were 1.32 ± 0.50 L; in contrast, in group N, they were 8.73 ± 1.43 L (skeletal) and 1.23 ± 0.28 L (sclerosis). The total enzyme activity for PSMA was 2.21 ± 5.15 in the M group and 0.078 ± 0.053 in the N group (p < 0.0002). The total bone demineralization activity for NaF varied from 4.31 ± 6.17 in the M group and 0.24 ± 0.56 in group N (p < 0.0002). The pathological PSMA volume represented 0.44−132% of the sclerotic bone volume in group M and 0.55−2.3% in group N. The pathological NaF volume in those patients with multiple metastases represented 0.27−68% of the sclerotic bone volume, and in the control group, only 0.00−6.5% of the sclerotic bone volume (p < 0.0003). Conclusions: These results confirm our earlier findings that CT alone does not suit the evaluation of the extent of active skeletal metastases in PCa. PSMA and NaF images give complementary information about the extent of the active skeletal disease, which has a clinical impact and may change its management. The PSMA and NaF absolute volumes could be used for planning targeted therapies. A cut-off value 3.0 for SUVPSMA given here is the best correlation in the presentation of active metastatic skeletal disease.

The Effect of Sericin on Bone Regeneration in a Streptozotocin-Induced Type I Diabetes Animal Model

There is an association between diabetes and impaired bone healing. The purpose of this study was to determine whether sericin had a positive effect on bone regeneration with streptozotocin-induced diabetes in a rat model. Sprague Dawley rats (n = 21) were assigned to one of three groups. A critical-sized bone defect was created on the calvaria. In the sericin group (S group, n = 7), the bone defect was filled with a sericin–gelatin combination, whereas in the gelatin group (G group, n = 7), only gelatin sponge was used. The control group (N group, n = 7) did not receive any graft. New bone formation was evaluated by micro-computerized tomogram and histological analysis. The regenerated bone volume in group S was the highest among the three groups (3.87 ± 2.51 mm3), followed by group N (1.71 ± 1.65 mm3) and group G (1.24 ± 1.05 mm3). The application of sericin in combination with a gelatin sponge enhanced the process of bone regeneration in streptozotocin-induced type I diabetes animal model.

Radiological evaluation of dextran sulfate/recombinant human bone morphogenetic protein 2/chitosan composite microspheres combined with coral hydroxyapatite artificial bone in repairing large segmental bone defects

To evaluate the osteogenic effect of dextran sulfate/recombinant human bone morphogenetic protein 2/chitosan (DS/rhBMP-2/CS) combined with coralline hydroxyapatite (CHA) in repairing large segmental bone defects by radiographic feature. Fifty-seven 24-week-old male New Zealand rabbits were prepared for establishing right radius bone defect model of 20 mm in length. In which 54 rabbits were randomly divided into 3 groups ( n=18), and the CHA, DS/rhBMP-2/CS/CHA, and rhBMP-2/CHA artificial bone grafts were implanted into the bone defect in groups A, B, and C respectively; the remaining 3 rabbits were implanted nothing as blank control group. After operation, the gross condition of the animals was observed; at 4, 8, and 12 weeks after operation, X-ray film observation, Micro-CT scanning, and three-dimensional reconstruction were performed to obtain the volume of the new bone. The experimental animals recovered well and were in normal condition. X-ray observation showed that the bone healing in group B was better than that in groups A and C at each time point. At each time point after operation, the X-ray scores of group B were significantly higher than that of group A and group C ( P<0.05); the scores of group C at 8 and 12 weeks after operation were significantly higher than that of group B ( P<0.05). Micro-CT scanning and three-dimensional reconstruction observation showed that at each time point after operation in group A, the bone defect area had less bone formation and poor osteogenesis; in group B, there were many new bone tissues in bone defect area, and the bone remodeling was well, and gradually closed to normal bone morphology at 12 weeks; in group C, there were many new bone tissues in bone defect area, but the bone formation was general. The new bone volume of group B was significantly higher than that of group A and group C ( P<0.05) at each time point after operation, and the score of group C was higher than that of group A at 8 weeks after operation ( P<0.05). The osteogenic effect of DS/rhBMP-2/CS/CHA sustained-release artificial bone is much better than that of single CHA and rhBMP-2/CHA, which can provide a new idea for treating bone defect by using bone tissue engineering in the future.

Low-Intensity Pulsed Ultrasound Enhances Posterior Spinal Fusion Implanted with Mesenchymal Stem Cells-Calcium Phosphate Composite Without Bone Grafting

Experimental study on the effect of low-intensity pulsed ultrasound (LIPUS) on rabbit spinal fusion with mesenchymal stem cell (MSC)-derived osteogenic cells and bioceramic composite. To investigate the efficacy of LIPUS in enhancing fusion rate and bone formation with porous tricalcium phosphate (TCP) bioceramic scaffold impregnated with MSCs without any bone grafts. The goal of spinal fusion in the corrective spinal surgery for spinal deformities is to achieve solid bony fusion between selected vertebral segments. Previous studies with bone morphogenetic proteins and genetically manipulated materials revealed significant difficulties in actual clinical application. Alternative such as LIPUS has been shown to be effective in enhancing healing of fracture and nonunion clinically. Its potential for enhancing spinal fusion warrants further in-depth study. Posterolateral intertransverse processes spinal fusion at the L5 and L6 levels were evaluated in New Zealand white rabbit model. The animals were divided into three groups with (A) TCP alone, (B) TCP with differentiated MSCs, and (C) TCP with differentiated MSCs and LIPUS treatment. At week 7 postoperation, manual palpation, peripheral quantitative computed tomography, and histomorphometric assessments were performed. At week 7 postoperation, a statistically significant increase in clinical fusion by manual palpation was observed in group C animals treated with LIPUS (86%) in comparing with groups A (0%) and B (14%) without LIPUS. With peripheral quantitative computed tomographic analysis, the bone volume of group C fusion mass was significantly larger than the other two groups. Group C fusion also had better osteointegration length between host bone and implanted composite and more new bone formed in the TCP implants. Importantly, all the group C animals had osteochondral bridging--early stage of bony fusion histologically. Endochondral ossification was observed at the junction between the cartilaginous and osseous tissues at the intertransverse processes area. Quantitative analysis showed that the fusion mass in group C had significantly smaller gap and larger area of cartilaginous tissue between the transverse processes. The present study showed that the combination of synthetic biomaterials, autologous differentiated MSCs, and LIPUS could promote clinical fusion in rabbit posterior spinal fusion model. The mechanism was likely to be mediated through better osteointegration between the host bone and implanted materials and enhanced endochondral ossification at the fusion site.

The effect of clomiphene citrate on osteoporosis in ovariectomized rats

The aim of this study was to investigate whether clomiphene citrate (CC) administration could be a new therapeutic agent in case of contraindication of estrogen therapy for hormone-dependent osteoporosis and to show the changes in bone structure by histomorphometric analysis in ovariectomized rats administered CC. This study was carried out in the Experimental Surgery Laboratory of the Brain Research Centre of the Medical Faculty of Ege University. Four-month-old Sprague-Dawley rats were used for the experiment. The study was carried out on six groups of animals each consisted of eight rats. Four groups of rats were ovariectomized and 2 groups of rats were used as control group. For 6 weeks every day, rats were injected physiological saline solution (1 ml/kg), clomiphene citrate (1 or 10 mg/1 ml/kg, Organon), 17beta-estradiol (50 microg/1 ml/kg, within susame oil, Sigma) or susame oil (1 ml/kg, Sigma). Drug administrations were carried out according to the weekly weight measurements. Group 1(PSS), n = 8, non-ovariectomized, were injected with physiological saline solution. Group 2(CC-1), n = 7, non-ovariectomized, were injected with CC (1 mg/1 ml/kg). Group 3(OVX + CC-1), n = 7, ovariectomized, were injected with CC (1 mg/1 ml/kg). Group 4(OVX + CC-10), n = 6, ovariectomized, were injected with CC (10 mg/1 ml/kg). Group 5(OVX + E), n = 8, ovariectomized, were injected with 17beta-estradiol (50 microg/1 ml/kg). Group 6(OVX), n = 8, ovariectomized, were injected with susame oil (1 ml/kg) Bone-specific serum alkaline phosphatase (ALP) levels were measured and statistical analyses were made by Kruskal Wallis test. Left femur bone histomorphometric studies were done. The uteri were dissected out to measure their weight and ANOVA was used to show the intergroup differences. The level of ALP in group 3 was significantly higher than the other five groups. Bone histomorphometric examination showed that total bone volume in group 3, 4, and 5 was higher than group 6, and group 4 had the highest level of bone volume compared to the rest of the groups. Uterus weights in group 1 were significantly higher than group 3 and 6 (P = 0.02, P = 0.01) and uterus weights in group 5 were significantly higher than group 3 and 4 (P = 0.00, P = 0.01) In ovariectomized rats, treatment with CC is seen as effective as estrogen treatment in preventing osteoporosis, without causing uterin hyperstimulation. Nevertheless, further investigations on more rats are needed to assess whether it is an alternative treatment method to estrogen.

Significance of minimodeling in dialysis patients with adynamic bone disease

We previously concluded from histomorphometric analysis that minimodeling contributes to bone formation in adynamic bone disease in patients with primary hypoparathyroidism. Presently we investigated whether this mechanism might be peculiar to adynamic bone disease. We histomorphometrically analyzed bone specimens obtained at biopsy or autopsy from 26 maintenance hemodialysis patients with hyperparathyroidism necessitating parathyroidectomy (group A) and from 27 dialysis patients with hypoparathyroidism (group B); respective mean ages were 60 +/- 7 years vs. 64 +/- 8 years; dialysis duration 14 +/- 6 years vs. 11 +/- 9 years; and serum intact parathyroid hormone (PTH) 1205 +/- 439 pg/mL vs. 41 +/- 27 pg/mL. Group B was divided further into outpatient and inpatient subgroups. By histomorphometry, group A patients were diagnosed with osteitis fibrosa, and those in group B with adynamic bone disease. Minimodeling bone volume and minimodeling bone number were significantly greater in group B than group A (P= 0.0028 and P= 0.0008, respectively). Minimodeling bone volume correlated significantly and positively correlated with total bone volume in group B (P= 0.0016), but not in group A. In group B, minimodeling bone volume and total bone voluem were greater in outpatients than inpatients (P < 0.0001 and P= 0. 025, respectively). Minimodeling bone volume and total bone volume showed significant negative correlation with age in group B (P < 0.001 and P= 0.005, respectively). Minimodeling might contribute to bone formation in dialysis patients with adynamic bone disease, in the absence of remodeling stimulated by parathyroid hormone (PTH), especially in relatively young patients with good activities of daily living.

Effects of 1,25(OH) 2D 3 on turnover, mineralization, and strength of bone in growing rats with liver cirrhosis induced by administration of carbon tetrachloride

To clarify the effects of 1 alpha,25-dihydroxyvitamin D 3 (1,25(OH) 2D 3) on bone growth, strength, and turnover in growing rats with liver cirrhosis induced by carbon tetrachloride (CCl 4) injection, groups of 4-week-old male Wistar rats ( n = 10, each) were injected intraperitoneally with CCl 4 twice weekly for 7 weeks. One group was treated with the vehicle alone (Group 1). Three CCl 4-injected groups were orally administered 1,25(OH) 2D 3 at doses of 0, 0.05, and 0.1 μg/kg, respectively (Groups 2, 3, and 4). At the end, serum levels of 1,25(OH) 2D 3, IGF-I, and osteocalcin were reduced in Group 2 compared to Group 1, and the corresponding values in Group 4 were larger than those in Group 2. Urinary deoxypyridinoline levels increased in Group 2 compared to Group 1, and did not significantly differ in Groups 2–4. The values for bone sizes, mineral content (BMC) in the lumbar vertebra and femur, and ultimate bending load in the femur were reduced in Group 2 compared to Group 1, and lumbar BMC in Group 3 and bone sizes in Group 4 were larger than those in Group 2. The values for lumbar trabecular bone volume in Group 2 were reduced compared to Group 1, and the corresponding values in Group 4 were larger than those in Group 2. Bone formation rates, reduced in Group 2 compared to Group 1, did not differ in Groups 2–4. Parameters for trabecular osteoclasts did not differ among all groups. In the proximal tibia, the value of activation frequency (Ac.f) in Group 2 significantly decreased compared to Group 1. Ac.f values in Groups 3 and 4 were larger than that in Group 2. These data demonstrated that retardation of bone growth in CCl 4-injected rats was associated with reduced serum 1,25(OH) 2D 3 and IGF-I levels. The trabecular bone in the rats exhibited low turnover osteopenia. 1,25(OH) 2D 3 administration partially prevented the growth disturbance, but did not substantially affect bone turnover. Factors other than 1,25(OH) 2D 3 and IGF-I appeared to be critical in the low turnover osteopenia evident in liver cirrhosis.