Aims. The association of auraptene (AUR), a 7-geranyloxycoumarin, on osteoporosis and its potential pathway was predicted by network pharmacology and confirmed in experimental osteoporotic mice. Methods. The network of AUR was constructed and a potential pathway predicted by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) terms enrichment. Female ovariectomized (OVX) Institute of Cancer Research mice were intraperitoneally injected with 0.01, 0.1, and 1 mM AUR for four weeks. The bone mineral density (BMD) level was measured by dual-energy X-ray absorptiometry. The bone microstructure was determined by histomorphological changes in the femora. In addition, biochemical analysis of the serum and assessment of the messenger RNA (mRNA) levels of osteoclastic markers were performed. Results. In total, 65.93% of the genes of the AUR network matched with osteoporosis-related genes. Osteoclast differentiation was predicted to be a potential pathway of AUR in osteoporosis. Based on the network pharmacology, the BMD and bone mineral content levels were significantly (p < 0.05) increased in the whole body, femur, tibia, and lumbar spine by AUR. AUR normalized the bone microstructure and the serum alkaline phosphatase (ALP), bone-specific alkaline phosphatase (bALP), osteocalcin, and calcium in comparison with the OVX group. In addition, AUR treatment reduced TRAP-positive osteoclasts and receptor activator of nuclear factor kappa-B ligand (RANKL). +. nuclear factor of activated T cells 1 (NFATc1). +. expression in the femoral body. Moreover, the expressions of initiators for osteoclastic resorption and bone matrix degradation were significantly (p < 0.05) regulated by AUR in the lumbar spine of the osteoporotic mice. Conclusion. AUR ameliorated bone loss by downregulating the RANKL/NFATc1 pathway, resulting in improvement of osteoporosis. In conclusion, AUR might be an ameliorative cure that alleviates bone loss in osteoporosis via inhibition of osteoclastic activity. Cite this article: Bone Joint Res 2022;11(5):304–316

Bone marrow cells are well known for improving healing. Recent studies report that stromal cell-derived factor-1 (SDF-1) and its receptor CXC chemokine receptor 4 (CXCR4) play roles in stem cell homing and are related to short-term and long-term engraftment. SDF-1 secreted from an injured organ can pass the endothelium barrier in a CXCR4-dependent manner into the bone marrow and recruit hematopoietic progenitors to the circulation. There is evidence to show that SDF-1 also has chemoat-tractive effects and is able to recruit mesenchymal stem cells and osteoprogenitors. Our previous study also showed that SDF-1 has an enhanced effect on osteoblas-tic differentiation of human mesenchymal stem cells. The purpose of this study is to investigate the effects of genetically modified bone marrow cells that overexpress SDF-1 on bone fracture healing in rat model. The hypothesis is that genetically modified rat bone marrow cells (rBMCs) that over expresses SDF-1 will enhance the fracture healing process compared to non-treated groups or to groups treated with only rBMCs. rBMCs were harvested from femora of young male Wistar rats. rBMCs were expanded ex vivo, and cells of passage 3 were used in the experiment. SDF-1 over-expressing rBMCs (rBMC-SDF-1) were engineered by infection of adenovirus carrying human SDF-1 gene at the multiplicity of infection (MOI) 500. Eighteen adult female Wistar rats were divided into three groups with 6 rats in each group:. rBMC-SDF-1,. rBMC and. control. A 3mm gap in the middle of femur was created during surgery and stabilized by an external fixator. In two groups three hundred thousand rBMCs or rBMCs-SDF-1 were seeded into a collagen sponge and transplanted into the gap. For the control group, sponges without cells were used. Rats were sacrificed 3 weeks after operation and the femora were harvested. Bone mineral content within the gap was measured immediately after operation and compared with the bone mineral content within the same gap at the third week by dual energy X-ray absorptiometry (DEXA) scanning. The area of new bone formation was measured using histomorphometery on H& E stained sections and quantified by imaging analysis system. In the present study, the rBMC-SDF-1 group showed the most dominant influence in both new bone formation and bone mineral increase. rBMC-SDF-1 not only increases new bone formation but also has higher bone mineral content after 3 weeks compare with the rBMC only. This bone healing progress may due to the enhanced local SDF-1/CXCR4 interaction that recruited more host’s stem cells into the fracture site. The control group showed an increased new bone formation in the histological analysis but a reduced bone mineral content after 3 weeks whereas in comparison the rBMC group showed a similar new bone area to the control group but a significantly higher bone mineral content. This may indicate a faster bone repairing ability with the BMCs. Both rBMC and rBMC-SDF-1 groups have a higher bone mineral content and a more compact new bone structure that may indicate an accelerate effect of rBMC in the bone mineralization. In this study, we show that SDF-1 induces improved bone formation in early fracture healing

Dual plate constructs have become an increasingly common fixation technique for midshaft clavicle fractures and typically involve the use of mini-fragment plates. The goal of this technique is to reduce plate prominence and implant irritation, as these are common reasons for revision surgery. However, limited biomechanical data exist for these lower-profile constructs. The study aim was to compare dual mini-fragment orthogonal plating to traditional small-fragment clavicle plates for biomechanical non-inferiority and to determine if an optimal plate configuration could be identified, using a cadaveric model. Twenty-four cadaveric clavicles were randomized to one of six groups (n=4 per group), stratified by CT-based bone mineral content (BMC). The six different plating configurations compared were: pre-contoured superior or anterior fixation using a single 3.5-mm LC-DC plate, and four different dual-plating constructs utilizing 2.4-mm and 2.7-mm reconstruction or LC-DC plates. The clavicles were plated and then osteotomized to create an inferior butterfly fracture, which was then fixed with a single interfragmentary screw (OTA 15.2B). Axial, torsional, and bending (anterior and superior surface loading) stiffness were determined for each construct through non-destructive cyclic testing, using an MTS 858 Bionix materials testing system. This was followed by a load-to-failure test in three-point superior-surface bending. Kruskal-Wallace H and Mann-Whitney U were used to test for statistical significance. There were no significant differences in BMC (median 7.9 g, range 4.2-13.8 g) for the six groups (p=1.000). For axial stiffness, the two dual-plate constructs with a superior 2.4-mm and anterior 2.7-mm plate (either reconstruction or LC-DC) were significantly stiffer than the other four constructs (p=0.021). For both superior and anterior bending, the superior 2.4-mm and anterior 2.7-mm plate constructs were significantly stiffer when compared to the 3.5-mm superior plate (p=0.043). In addition, a 3.5-mm plate placed anterior was a stiffer construct than a superior 3.5-mm plate (p=0.043). No significant differences were found in torsional stiffness or load-to-failure between the different constructs. Dual plating using mini-fragment plates is biomechanically superior for fixation of midshaft clavicle fractures when compared to a single superior 3.5-mm plate and has similar biomechanical properties to a 3.5-mm plate placed anteriorly. With the exception of axial stiffness, no significant differences were found when different dual plating constructs were compared to each other. However, placing a 2.4-mm plate superiorly in combination with a 2.7-mm plate anteriorly might be the optimal construct, given the biomechanical superiority over the 3.5-mm plate placed superior

Objectives. Osteoporosis is a systemic bone metabolic disease, which often occurs among the elderly. Angelica polysaccharide (AP) is the main component of angelica sinensis, and is widely used for treating various diseases. However, the effects of AP on osteoporosis have not been investigated. This study aimed to uncover the functions of AP in mesenchymal stem cell (MSC) proliferation and osteoblast differentiation. Methods. MSCs were treated with different concentrations of AP, and then cell viability, Cyclin D1 protein level, and the osteogenic markers of runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), alkaline phosphatase (ALP), bone morphogenetic protein 2 (BMP-2) were examined by Cell Counting Kit-8 (CCK-8) and western blot assays, respectively. The effect of AP on the main signalling pathways of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Wnt/β-catenin was determined by western blot. Following this, si-H19#1 and si-H19#2 were transfected into MSCs, and the effects of H19 on cell proliferation and osteoblast differentiation in MSCs were studied. Finally, in vivo experimentation explored bone mineral density, bone mineral content, and the ash weight and dry weight of femoral bone. Results. The results revealed that AP significantly promoted cell viability, upregulated cyclin D1 and increased RUNX2, OCN, ALP, and BMP-2 protein levels in MSCs. Moreover, we found that AP notably activated PI3K/AKT and Wnt/β-catenin signalling pathways in MSCs. Additionally, the relative expression level of H19 was upregulated by AP in a dose-dependent manner. The promoting effects of AP on cell proliferation and osteoblast differentiation were reversed by H19 knockdown. Moreover, in vivo experimentation further confirmed the promoting effect of AP on bone formation. Conclusion. These data indicate that AP could promote MSC proliferation and osteoblast differentiation by regulating H19. Cite this article: X. Xie, M. Liu, Q. Meng. Angelica polysaccharide promotes proliferation and osteoblast differentiation of mesenchymal stem cells by regulation of long non-coding RNA H19: An animal study. Bone Joint Res 2019;8:323–332. DOI: 10.1302/2046-3758.87.BJR-2018-0223.R2

Objectives. The aim of the current study was to assess whether calcaneal broadband ultrasound attenuation (BUA) can predict whole body and regional dual-energy x-ray absorptiometry (DXA)-derived bone mass in healthy, Australian children and adolescents at different stages of maturity. Methods. A total of 389 boys and girls across a wide age range (four to 18 years) volunteered to participate. The estimated age of peak height velocity (APHV) was used to classify children into pre-, peri-, and post-APHV groups. BUA was measured at the non-dominant heel with quantitative ultrasonometry (QUS) (Lunar Achilles Insight, GE), while bone mineral density (BMD) and bone mineral content (BMC) were examined at the femoral neck, lumbar spine and whole body (DXA, XR-800, Norland). Associations between BUA and DXA-derived measures were examined with Pearson correlations and linear regression. Participants were additionally ranked in quartiles for QUS and DXA measures in order to determine agreement in rankings. Results. For the whole sample, BUA predicted 29% of the study population variance in whole body BMC and BMD, 23% to 24% of the study population variance in lumbar spine BMC and BMD, and 21% to 24% of the variance in femoral neck BMC and BMD (p < 0.001). BUA predictions were strongest for the most mature participants (pre-APHV R. 2. = 0.03 to 0.19; peri-APHV R. 2. = 0.05 to 0.17; post-APHV R. 2. = 0.18 to 0.28) and marginally stronger for girls (R. 2. = 0.25-0.32, p < 0.001) than for boys (R. 2. = 0.21-0.27, p < 0.001). Agreement in quartile rankings between QUS and DXA measures of bone mass was generally poor (27.3% to 38.2%). Conclusion. Calcaneal BUA has a weak to moderate relationship with DXA measurements of bone mass in children, and has a tendency to misclassify children on the basis of quartile rankings. Cite this article: B. K. Weeks, R. Hirsch, R. C. Nogueira, B. R. Beck. Is calcaneal broadband ultrasound attenuation a valid index of dual-energy x-ray absorptiometry-derived bone mass in children? Bone Joint Res 2016;5:538–543. DOI: 10.1302/2046-3758.511.BJR-2016-0116.R1

Purpose of the study: The process of bone lengthening involves three phases: a latence period, distraction, then healing. The healing phase required stability maintained by an external fixator (EF) for 1.16 months/cm lengthening. This time exposes the patient to serious complications. The objective is to accelerate the healing phase in order to shorten the time the patient has to wear the EF. The effect of BMP on osteogenesis in distraction remains a controversial issue. This work was conducted to evaluate the benefit provided by rhBMP-2 for healing the regenerate bone after distraction. Material and methods: Thirty-nine subadult male rabbits were selected at random. On day 0, a tibial osteotomy was performed followed by installation of a M101 EF. After the latency period of seven days, the distraction began at the rate of 0.5mm/12 h for 21 days. At day 28, at the end of distraction, a new operation was performed and three groups of 13 individuals were created at random. The first group received no material, the second a collagen type 1 sponge, and the third group a collagen type 1 sponge soaked in 100 μg/kg rhBMP-2. The animals were monitored with x-rays, absorptiometry and ultrasound for the qualitative and quantitative analysis. Histological and biomechanical analyses were performed at two months. Results: Our complication rate was 41%. Qualitative analysis of the x-rays showed, in group 3, the development of more or less voluminous and dense, sometimes hypertrophic calluses. The progression curves of the bone mineral content showed higher values in group 3. The bone mineral content curves remained nevertheless parallel for the three groups. The calluses were thus denser in group 3 but with an early peak density. Groups 1 and 2 had equivalent radiographic and absorptiometric results. The statistical analysis of the imaging findings is ongoing. The histology and biomechanical exams are being performed. Discussion: The preliminary results show that rhBMP-2 used early in the healing phase enables formation of more dense and hypertrophic calluses. rhBMP-2 does not acceleration the rate of callus formation but stimulates its mineralization. Use of a collagen sponge alone had no effect on healing. Analysis of the histological and mechanic properties observed in the three groups will provide a more precise description of the hypertrophic and strongly mineralized calluses. Conclusion: Our early results show superior bone mineralization in the treated group

Segmental bone transport (SBT) using an external fixator is currently a standard treatment for large-diameter bone defects at the donor site with low morbidity. However, long-term application of the device is needed for bone healing. In addition, patients who received SBT treatment sometimes fail to show bone repair and union at the docking site, and require secondary surgery. The objective of this study was to investigate whether a single injection of recombinant human bone morphogenetic protein 2 (rhBMP-2)-loaded artificial collagen-like peptide gel (rhBMP-2/ACG) accelerates consolidation and bone union at the docking site in a mouse SBT model. Six-month-old C57BL/6J mice were reconstructed by SBT with external fixator that has transport unit, and a 2.0-mm bone defect was created in the right femur. Mice were divided randomly into four treatment groups with eight mice in each group, Group CONT (immobile control), Group 0.2mm/d, Group 1.0mm/d, and Group BMP-2. Mice in Group 0.2mm/d and 1.0mm/d, bone segment was moved 0.2 mm per day for 10 days and 1.0 mm per day for 2 days, respectively. Mice in Group BMP-2 received an injection of 2.0 μg of rhBMP-2 dissolved in ACG into the bone defect site immediately after the defect-creating surgery and the bone segment was moved 1.0 mm/day for 2 days. All animals were sacrificed at eight weeks after surgery. Consolidation at bone defect site and bone union at docking site were evaluated radiologically and histologically. At the bone defect site, seven of eight mice in Group 0.2mm/d and two of eight mice in Group 1.0mm/d showed bone union. In contrast, all mice in Group CONT showed non-union at the bone defect site. At the docking site, four of eight mice in Group 0.2 mm/d and three of eight mice in Group 1.0 mm/d showed non-union. Meanwhile, all mice in Group BMP-2 showed bone union at the bone defect and docking sites. Bone volume and bone mineral content were significantly higher in Group 0.2mm/d and Group BMP-2 than in Group CONT. HE staining of tissue from Group 0.2mm/d and Group BMP-2 showed large amounts of longitudinal trabecular bone and regenerative new bone at eight weeks after surgery at the bone defect site. Meanwhile, in Group CONT and Group 1.0mm/d, maturation of regenerative bone at the bone defect site was poor. Differences between groups were analyzed using one-way ANOVA and a subsequent Bonferroni's post-hoc comparisons test. P < 0.05 was considered significant. rhBMP-2/ACG combined with SBT may be effective for enhancing bone healing in large bone defects without the need for secondary procedures

For amputated patients, direct attachment of upper leg prosthesis to the skeletal system by a percutaneous implant is an alternative solution to the traditional socket fixation. Currently available implants, the OPRA system (Integrum AB, Göteborg, Sweden) and the ISP Endo/Exo prosthesis (ESKA Implants AG, Lübeck, Germany) [1-2] allow overcoming common soft tissue problems of conventional socket fixation and provide better control of the prosthetic limb [3], higher mobility and comfort [2, 4]. However, restraining issues such as soft-tissue infections, peri-prosthetic bone fractures [3, 5–8] and considerable bone loss around the stem [9], which might lead to implant's loosening, are present. Finally, a long a residual limb is required for implant fitting. In order to overcome the limiting biomechanical issues of the current designs, a new concept of the direct intramedullary fixation was developed. The aim was to restore the natural load transfer in the femur and allow implantations in short femur remnants (Figure 1). We hypothesize that the new design will reduce the peri-prosthetic bone failure risk and adverse bone remodeling. Generic CT-based finite element models of an intact femoral bone and amputated bones implanted with 3 analyzed implants were created for the study. Models were loaded with two loading cases from a normal walking obtained from the experimental measurements with the OPRA device [10-11]. Periprosthetic bone failure risk was evaluated by considering the von Mises stress criterion [12-14]. Subsequently the strain adaptive bone remodeling theory was used to predict long-term changes in bone mineral density (BMD) around the implants. The bone mineral content (BMC) change was measured around implants and the results were visualized in the form of DXA scans. The OPRA and the ISP implants induced the high stress concentration in the proximal region decreasing in the distal direction to values below physiological levels as compared with the intact bone. The stresses around the new design were more uniformly distributed along the cortex and resembled better the intact case. Consequently, the bone failure risk was reduced as compared to the OPRA and the ISP implants. The adaptive bone remodeling simulations showed high bone resorption around distal parts of the OPRA and the ISP implants in the distal end of the femur (on average −75% ISP to −78% OPRA after 60 months). The bone remodeling simulation did not reveal any bone loss around the new design, but more bone densification was seen (Figure 2). In terms of total bone mineral content (BMC) the OPRA and the ISP implants induced only a short-term bone densification in contrast to the new design, which provoked a steady increase in the BMC over the whole analyzed period (Figure 3). In conclusion, we have seen that the new design offers much better bone maintenance and lower failure probability than the current osseointegrated trans-femoral prostheses. This positive outcome should encourage further developments of the presented concept, which in our opinion has a potential to considerably improve safety of the rehabilitation with the direct fixation implants and allow treatment of patients with short stumps

PEMF is currently approved by the FDA for adjunctive treatment of lumbar/cervical spine fusion and for treatment of long-bone non-unions. Soft tissues are a potential new therapeutic application for PEMF due to pre-clinical studies showing a reduction of inflammatory markers following PEMF exposure. The aim was therefore to investigate the structural/functional effects of PEMFs on tendon-to-bone and tendon-to-tendon healing in a rotator-cuff (RC) and Achilles tendon (AT) repair model, respectively. RC study: Adult male rats (n=280), underwent bi-lateral supraspinatus tendon transections with immediate repair followed by cage activity until sacrifice (4, 8, and 16 weeks). Non-controls received PEMF for 1, 3, or 6 hours daily. AT study: Male rats underwent acute, complete transection and repair of the Achilles tendon (FULL, n=144) or full thickness, partial width injury (PART, n=160) followed by immobilization for 1 week. Sacrifice was at 1, 3, and 6 weeks. Outcome measures included passive joint mechanics, gait analysis, biomechanical assessments, histological analysis of the repair site and mCT (humerus) assessment (FULL only). RC study: Significant increases in modulus, stiffness, bone mineral content and improved collagen organization was observed for the PEMF groups. No differences in joint mechanics and ambulation were observed. AT study: A decrease in stiffness and limb-loading rate was observed for the PEMF groups for the FULL groups, whereas an increase in stiffness with no change in range-of-motion was seen for the PART groups. The combined studies show that PEMF can be effective for soft tissue repair but is dependent on the location of application

Stress shielding has been a well-recognised problem with uncemented femoral components resulting in proximal bone loss and dysfunction, but less attention has been paid to the preservation of acetabular bone stock. Uncemented acetabular components often demonstrate reduced bone density on plain radiographs in the mid-portion of the cup (zone 2), which may be due to the rigidity of the outer shell. This study compares the change in bone density around three different cups with varying moduli of elasticity at a minimum of 2 years. Our hypothesis was that less rigid cups would be associated with improved bone density and less stress shielding. This prospective randomised controlled trial compared the bone mineral content (BMC) adjacent to three different cups with marked differences in stiffness. Cup A was an all titanium shell, cup B was a titanium coated all polyethylene implant and cup C was a tantalum backed shell. All articulations used a 32mm ceramic femoral head. Cup B used polyethylene modified by treatment with vitamin E whereas cups A and C used a liner made of irradiated cross linked polyethylene. Five regions of interest (ROI) were established adjacent to the cup, regions 2, 3 and 4 where similar to the DeLee and Charnley regions 1, 2 and 3. Bone density was measured using IDXA preoperatively, postoperatively, 6 months, 1 and 2 years and compared for each ROI and implant. Precision measurements showed significant reliability. All areas showed a reduction in BMC following insertion of the acetabular cup. Bone loss was less in ROI 1 and 4 in the area of rim fit for all cups and the maximal bone loss was seen in ROI 2 and 3 at the dome of the cup. The more elastic cup (Cup B) produced the least bone loss in this area (p<0.05). Cup C produced the largest bone loss at ROI 2 (40%) which continued increasing at 2 years. Cup stiffness is related to bone loss adjacent to the acetabulum, presumably due to a similar process of stress shielding as seen in the femur. All cups produced similar changes at the periphery of the cup but the more elastic cup retained bone density beneath the cup which continued past 2 years. This improvement in bone quality is likely to be associated with better acetabular bone stock into the future and more reliable long term cup fixation

We studied the bone density and bone mineral content of 14 men and 10 women over the age of 60 years who had sustained a femoral neck fracture as a result of minor trauma. They were matched for age and gender with controls from a peri-urban black population. Among the men, the femoral T and Z scores were significantly lower in the patients than in the controls. There were no significant differences among the female patient and control groups. In the controls, the mean bone densities were lower than in hologic white controls. The differences were not age-related. The black female controls also had lower bone densities than hologic white controls. These densities fell rapidly after the age of 50 years and this was age-related. As measured by their T scores, most of the patients were at risk for fractures

Purpose and Background. Low birth weight is related to decreased lumbar spine vertebral canal size and bone mineral content later in life, suggesting that antenatal factors affect spine development. The purpose of this study was to explore associations between antenatal factors and lumbar spine morphology in childhood. Methods. Antenatal data and supine MR images of the lumbar spine were available for 161 children. Shape modelling, using principle components analysis, was performed on mid-sagittal images to quantify different modes of variation in lumbar spine shape. Previously collected measures of spine canal dimensions were analysed. Results. Almost 75 % of all of the variation in lumbar spine shape was explained by just three modes. Modes 1 and 3 described the total amount and the distribution of curvature along the spine, respectively. Mode 2 (M2) captured variation in vertebral shape and size; increasing mode scores represented flatter vertebral bodies with increasing anterior-posterior dimensions. We saw no significant associations between mode scores and birth weight z-scores, placental weight, gestation length and no effect of maternal smoking (P>0.05). Controlling for gestation length revealed a positive correlation between birth weight and M2 (P=0.02). Males, longer babies and those from heavier mothers had higher M2 scores (P<0.05). This sex difference remained even when controlling for the other factors (P<0.001). Modes 1 and 2 correlated with spine canal dimensions (P<0.05). Conclusions. Our results suggest that antenatal factors have some effect on vertebral body morphology but not overall lumbar spinal shape. Perhaps environmental factors during growth and genetics play a larger role in determining the overall spine shape. This abstract has not been previously published in whole or substantial part nor has it been presented previously at a national meeting. Conflicts of interest: No conflicts of interest. Sources of funding: This work was supported by a studentship granted to the University and awarded to AVP

We investigated the effect of adjuvant and neoadjuvant chemotherapy regimens on the tibial regenerate after removal of the external fixator in a rabbit model of distraction osteogenesis using New Zealand white rabbits. Forty rabbits were randomly distributed into two groups. In the neoadjuvant group, half of the rabbits received 1mg/kg cisplatinum & 2mg/kg adriamycin at eight weeks of age followed by 1mg/kg cisplatinum & 4mg/kg adriamycin at ten weeks of age. The remaining ten received an identical volume of normal saline using the same regimen. The adjuvant group differed only in the timing of the chemotherapy infusion. Half received the initial infusion ten days prior to the osteotomy, with the second infusion four days following the osteotomy. Again, the remaining ten rabbits received an identical volume of normal saline using the same regimen. This produced an identical interval between infusions and identical age at osteotomy in both groups. All rabbits underwent a tibial osteotomy at 12 weeks of age. Distraction started 24hours after osteotomy at a rate of 0.75mm a day for 10 days, followed by 18 days without correction to allow for consolidation of the regenerate. At week 16 there was no difference in Bone Mineral Density (BMD), Bone Mineral Content (BMC) or volumetric Bone Mineral Density (vBMD) in the adjuvant group. Neoadjuvant chemotherapy appears to have a significant detrimental effect on BMD, vBMD and BMC. Despite this there were no significant alterations in the mechanical properties of the regenerate. Histologically there was a trend for increased cortical thickness in the control groups compared to intervention however this did not prove statistically significant. In conclusion, adjuvant chemotherapy may be more beneficial for cases where distraction osteogenesis is being considered to replace segmental bone loss after tumour excision

Introduction. Dual energy X-ray absorptiometry (DEXA) is the gold standard for assessing bone mineral density (BMD) and fracture risk in vivo. However, it has limitations in the spine because vertebrae show marked regional variations in BMD that are difficult to detect clinically. This study investigated whether micro-CT can provide improved estimates of BMD that better predict vertebral strength. Methods. Ten cadaveric vertebral bodies (mean age: 83.7 +/− 10.8 yrs) were scanned using lateral-projection DEXA and Micro-CT. Standardised protocols were used to determine BMD of the whole vertebral body and of anterior/posterior and superior/inferior regions. Vertebral body volume was assessed by water displacement after which specimens were compressed to failure to determine their compressive strength. Specimens were then ashed to determine their bone mineral content (BMC). Parameters were compared using ANOVA and linear regression. Results. Measures of volumetric BMD obtained from Micro-CT were significantly higher than those obtained by DEXA (P<0.001), and estimates using the two techniques were not significantly correlated. DEXA measurements were strongly predictive of compressive strength, with areal BMD of the anterior vertebral body being the best predictor (R. 2. = 0.722, P = 0.002). Micro-CT measurements did not predict strength. Vertebral body BMD (derived from ash weight) correlated more highly with volumetric BMD values obtained from DEXA (R = 0.88) than those obtained from micro-CT (R = 0.72). Conclusion. BMD assessed by lateral DEXA predicted strength and BMC of osteoporotic vertebrae more accurately than micro-CT measures. Poor correlation between BMD measurements from DEXA and micro-CT suggests that ‘phantoms’ used in Micro-CT may require fine-tuning in order to better represent osteoporotic vertebrae

Bone mineral density (BMD) and bone mineral content (BMC) have not been previously assessed in unicompartmental knee replacement (UKR). We studied the early bone changes beneath the uncemented Oxford medial UKR. Our hypothesis was that this implant should decrease the shear stresses across the bone-implant interface and result in improved BMD and BMC beneath the tibial component. Using the Lunar iDXA and knee specific software we developed 7 regions of interest (ROI) in the proximal tibia and assessed 38 patients with an uncemented Oxford UKR at 2 years. We measured the replaced knee and contralateral unreplaced knee using the same ROI and compared the BMD and BMC. The initial precision study in 20 patients demonstrated high precision in all areas. There were 12 males and 16 females with an average age of 65.8 years (46–84 years). ROI 1 and 2 were beneath the tibial tray and had significantly less BMC (p=0.023 and 0.001) and BMD (p=0.012 and 0.002). ROI 3 was the lateral tibial plateau and this area also had significantly less BMC (p=0.007) and BMD (p=0.0001). ROI 4 and 5 immediately below the tibial keel had no significant change. These changes were independent of gender and age. These results were surprising in that the universal loss of BMC and BMD suggested that bone loading of the proximal tibia was not improved even after a UKR. The better BMD and BMC adjacent to the keel confirms other studies that show improved bone in-growth around keels and pegs in the uncemented tibial component. A prospective longitudinal study has been developed to compare BMD and BMC changes over time to see whether these changes are dynamic

Introduction: Conflicting opinions exist as to whether bone healing is affected by the administration of bisphosphonates for osteoporosis. In an animal model, we assessed the effect of bisphosphonates on osteoporotic fracture healing and whether the timing of administration made a difference. Methods: 36 female Wistar rats underwent a mid-diaphyseal femoral osteotomy six weeks after ovariectomy. They were then divided into 3 groups:. no treatment (control);. administration of alendronate (ALN) from 14 days after osteotomy;. ALN from the time of osteotomy. Fracture repair was assessed weekly with the use of standardised radiography, DEXA scan and in vitro peripheral quantative computed tomography (pQCT). The rats were sacrificed 42 days post-osteotomy and the femora underwent mechanical testing. Results: Of the 36 rats, 8 were unable to complete the study. Group 3 differed from control in three respects: higher bone mineral content (BMC) and density (BMD); larger callus; lower torsional stiffness. Group 2 did not differ significantly from control. There was a significant positive correlation between stiffness and change in BMC in group 1 (r=0.85, p< 0.001) but not so for group 2 (r=0.2, p> 0.05) and group 3 (r=0.04, p> 0.05). A similar trend existed for all radiographic parameters in the three groups. Conclusion: The results suggest that, with early bisphosphonate treatment, although there is an increase in the size of the callus, that callus is biomechanically inferior. Furthermore, administration of bisphosphonates at either stage destroys the relationship between radiographic and mechanical parameters used to assess fracture healing

Low intensity pulsed ultrasound (SAFHS, Exogen Inc.) was used to treat 15 immature New Zealand white rabbits following a mid diaphyseal tibial osteotomy and 1cm bone lengthening using an Orthofix M-100 device. Fifteen matched controls underwent an identical procedure but the ultrasound transducer was not switched on. At 4 and 6 weeks postoperatively the tibiae were analysed using DXA, QCT and 4 point bend mechanical testing. There were no differences identified between the active and control groups at 4 or 6 weeks with respect to bone mineral content or cross-sectional area of the regenerate, nor the bone proximal and distal to it. No improvement in strength of the regenerate was identified in either group. We cannot, therefore, support the use of the SAFHS to accelerate bone healing in patients undergoing limb lengthening. Low intensity pulsed ultrasound has been shown to accelerate fracture healing in animals and humans. The mechanisms of action are discussed and we propose that the intensity of the ultrasound may need to be increased mechanically to stimulate a bone that is rigidly fixed using the M-100 fixator

Objectives. Osteoporosis and osteomalacia lead to increased fracture risk. Previous studies documented dysregulated osteoblast and osteoclast activity, leading to a high-turnover phenotype, reduced bone mass and low bone mineral content. Osteocytes, the most abundant bone cell type, are involved in bone metabolism by enabling cell to cell interaction. Osteocytes presence and viability are crucial for bone tissue homeostasis and mechanical integrity. Osseo-integration and implant degradation are the main problems in developing biomaterials for systemically diseased bone. This study examines osteocyte localisation, morphology and on the implant surface and at the implant bone interface. Furthermore, the study investigates ECM proteins regulation correlated to osteocytes and mechanical competence in an ovariectomised rat model with a critical size metaphyseal defect. Methodology. After induction of osteoporosis, 60 female Sprague-Dawley rats were randomised into five groups: SrCPC (n=15), CPC (n=15), ScB30 (n=15), ScB30Sr20 (n=15) and empty defect (n=15). The left femur of all animals underwent a 4mm wedge-shaped metaphyseal osteotomy that was internally fixed with a T-shaped plate. The defect was then either filled with the above mentioned implants or left empty. After six weeks, histomorphometric analysis showed a statistically significant increase in bone formation at the tissue-implant interface in the SrCPC group compared to the other groups (p<0.01). Osteocyte morphology and networks were detected using silver and staining. ECM proteins were investigated through immunohistochemistry. Cellular populations were tested using enzyme histochemistry. Mineralisation was assessed using time of flight secondary ion mass spectrometry (TOF-SIMS). Statistical analysis was performed using Mann Whitney U test with Bonferroni correction. Results. In the SrCPC and compared to other test groups, osteocytes presence and morphology was enhanced. An increased osteocytic activity was also seen in ScB30Sr20 when compared to SCB30 alone. Local osteomalatic lesions characterised by the presence of excessive unmineralised osteoid as revealed by the VKVG staining in the intact bone was also seen. A regular pattern of osteocytes distribution reflecting a better bone maturation was also seen in case of the Sr substituted cements. Whereas in case of the ScB30 degenerated osteocytes with a comparatively irregular arrangement were seen. Nonetheless, ECM proteins indicating discrepant bone turnover (RANKL, OPG, BMP2, OCN; ASMA) were noticed to increase within these regions and were accompanied by the presence of apoptotic osteocytes. Interestingly, osteocytes were also localised near the blood vessels within the newly formed woven bone. On the other hand, osteocytes allocation at implant bone interface and on the implant surface were qualitatively better in the Sr substituted groups when compared to the other test groups. Furthermore, this correlates with healing enhancement and implant retention results obtained from the histomorphometry (BV/TV and Osteoclasts count). The first qualitative results of the sclerostin visualisation showed a lower expression in the Sr supplemented biomaterials compared to the Sr free ones. Conclusion. Osteoblasts, osteoclast and osteocytes are the key players to bone metabolism through production and mineralisation of ECM or resorption. The current study indicates the importance in therapeutically targeting osteocytes to regulate bone metabolism in osteoporotic/osteomalatic bone. Sr inhibits osteoclast activity which is important for implant degradation. However, in osteoporotic bone osteoclasts inhibition is crucial to enhance the healing. Our data suggest that osteocytes allocation at the bone implant interface and on the implant surface is aiding in implant degradation through osteocytes dependent resorption. Currently, discrepancies in mechanosensitivity, proliferation and fibrotic tissue formation are being investigated together with several anchorage proteins to quench further effects of osteocyte presence at the implant bone interface

Objective: The purpose of the present study was to assess whether clinicians are actually able to evaluate the mechanical status of lengthening callus from plain radiographs. Materials and Methods: 36 rats were employed in this study. Their left femurs were lengthened by 6 mm as a bone lengthening model. Rats were euthanized at 4 8 12 and 16 weeks after lengthening. Both femora were X-rayed and then bone density parameters (bone mineral content, bone mineral density and bone area) of lengthening callus were measured using pQCT. Three-point bending test was performed to determine the mechanical strength of the both bones. We defined the ratio of the strength of lengthening side to control side as estimated strength recovery rate (%). Then 20 orthopaedic surgeons evaluated only the X-ray photographs and tried to estimate the relative mechanical strength (%) of the affected side compared to the control side. Results: Between the recovery percentage of mechanical strength and bone mineral content, a positive simple correlation (R2=0.11, p< 0.05) was seen. No significant correlation was seen between the recovery percentage of mechanical strength estimated by orthopaedists and the mechanical strength measured by three-point bending test (qualified doctors: R2=0.0793 p=0.291 unqualified doctors: R2=0.0523 p=0.394). Discussion and conclusion: It became obvious that to estimate the strength of lengthening callus from plain radiographs alone is quite difficult as compared with the studies of the simple fracture model that have been reported until now

Introduction: Influence of beta-blockers against fracture is controversial. Role of beta-blockers in fracture treatment not explored. Objective: to analyze influence of propranolol, a beta-blocker, on fracture healing in a mouse model. Materials and Methods: Fracture and intramedullary nailing on right femur of 8 week, male C57BL/6 mice. Daily propranolol in drinking water: 0 (control), 4 (low dose) and 20 (high dose) mg/kg 3 week: microcomputed tomography (microCT), histological analyses 6 week: microCT, mechanical testing N = 5 üC 9/group Statistics: two-way ANOVA. Á = 0.05. Results: From 3 to 6 weeks, callus volume and bone mineral content (BMC) decreased, and tissue mineral density increased significantly in control groups. Callus volume and BMC decreased significantly in low dose groups. No significance in high dose groups. No significance with treatment. At 3 weeks, callus area and woven bone percentage not different with treatment. At 6 weeks, ultimate torque not different with treatment or fracture. Within the control groups, twist at ultimate torque significantly lower in fractured bones. Torsional rigidity increased significantly in fractured bones, but not different with treatment. Discussion: Most studies based on population observation or manipulation of sympathetic signaling using intact animal bones. The current fracture model may have created neural damage, thereby interrupting the sympathetic pathway and negating its regulation of bone metabolism. Whether neural signaling is compromised by fracture treatment requires further study and may be critical to the action of beta-blockers in bone