Risk factors for misdiagnosis in children with developmental dysplasia of the hip: a retrospective single centre study.

OBJECTIVE: To investigate risk factors of misdiagnosis at the first visit of children with developmental dysplasia of the hip (DDH) who did not participate in hip ultrasound screening. METHODS: A retrospective review was conducted on children with DDH admitted to a tertiary hospital in northwestern China between January 2010 and June 2021. We divided the patients into the diagnosis and misdiagnosis groups according to whether they were diagnosed at the first visit. The basic information, treatment process and medical information of the children were investigated. We made a line chart of the annual misdiagnosis rate to observe the trend in the annual misdiagnosis rate. Univariate and multivariate logistic regression analyses were used to identify significant risk factors for missed diagnosis. RESULTS: A total of 351 patients met the inclusion criteria, including 256 (72.9%) patients in the diagnosis group and 95 (27.1%) patients in the misdiagnosis group. The line chart of the annual rate of misdiagnoses among children with DDH from 2010 to 2020 showed no significant change trend. Multiple logistic regression analysis showed that the paediatrics department (v the paediatric orthopaedics department: OR 0.21, p<0.001), the general orthopaedics department (v the paediatric orthopaedics department: OR 0.39, p=0.006) and the senior physician (v the junior physician: OR 2.47, p=0.006) on the misdiagnosis at the first visit of children were statistically significant. CONCLUSION: Children with DDH without hip ultrasound screening are prone to be misdiagnosed at their first visit. The annual misdiagnosis rate has not been significantly reduced in recent years. The department and title of the physician are independent risk factors for misdiagnosis.

Quantification of femoral position on radiographic acetabular coverage in children.

An accurate assessment of the radiographic acetabular coverage is essential for clinical diagnosis or surgical decision-making in hip disorders. This study aimed to evaluate the effect of femoral position on acetabular coverage and to predict the actual acetabular coverage from nonstandard radiographs. A total of 21 children (34 hips) with normative acetabular coverage were screened in this retrospective study. The Mimics-based local-rotation fluoroscopy simulation method was used to tilt, incline, and rotate the femur in 4° increments within the range of femoral motion. The acetabular coverage, namely acetabular-head index (AHI) and center-edge angle (CEA), increased with femoral abduction but decreased with other motions. Compared to the femoral neutral position, no significant differences were identified in AHI with the rotation (range: 0°-16°) and in CEA with the tilt (range: -20°-4°), inclination (range: 0°-4°), or rotation (range: -8°-40°). The linear regression analysis showed that the CEA increased by about 0.20° for each 1° increase in femoral inclination and decreased by about 0.01°, 0.07°, 0.06°, or 0.07° for each 1° increase in internal rotation, external rotation, flexion, or extension, respectively. And a more significant change in AHI was observed. All femoral malpositions, especially the inclination, affected radiographic acetabular coverage in children. Therefore, each pelvic radiograph should assess potential femoral malpositioning before diagnosing hip disorders. This study will assist surgeons in predicting the acetabular coverage on nonstandard radiographs.

Closing-opening wedge osteotomy for the treatment of congenital kyphosis in children.

BACKGROUND: To evaluate the safety and effectiveness of posterior closed-open wedge osteotomy for treatment of congenital kyphosis in children. METHODS: Imaging and clinical data from January 2010 to December 2019 of posterior closed-open wedge osteotomy of congenital kyphosis with at least 2-year follow up was analyzed retrospectively. Perioperative indicators such as operation time, osteotomy site, osteotomy method and occurrence of complications, and imaging indicators were observed. The 3D printed models were used to measure the expanded distance of anterior edge vertebra and closed length of spinal canal line. The clinical effect was evaluated through SRS-22 questionnaires. RESULTS: There were 15 CK patients in this study. The osteotomy segments and details are as follows: 1 case each for T6-9 and L2, 2 cases at T11, 3 cases at T12, and 6 cases at L1. The average operation time was 314 min, the average blood loss was 970 mL, the average fusion range was 6.3 segments, and the average time of follow up was 70.5 months. The Cobb angle of local kyphosis was corrected from 65.6 ± 18.8° to 11.3 ± 7.1°(p < .001). The range of kyphosis correction was 40-90°, and average correction rate was 83.2% (67.7-95.7%). The correction was stable in follow-up, and the kyphotic angle was 11.0 ± 7.6 (p = .68). The preoperative SVA was 31.5 ± 21.8 mm, and the postoperative recovery was 18.0 ± 15.5, while the last follow-up was 9.1 ± 7.9. The p values were 0.02 and 0.07 respectively. By using 3D printed models, the expanded distance of anterior edge vertebra and closed length of spinal canal line were 14.5 ± 7.5 mm and 24.5 ± 8.0 mm respectively. Self-image and satisfaction in SRS-22 improved significantly. There was no recurrence of deformity and junctional kyphosis. CONCLUSIONS: The posterior closing-opening wedge osteotom for treatment of congenital kyphosis in children is satisfactory, if selected appropriately. During the longitudinal follow-up, the patients could achieve solid fusion and the correction could be well maintained.Evidence of Confidence: IVa.

Impairment of type H vessels by NOX2-mediated endothelial oxidative stress: critical mechanisms and therapeutic targets for bone fragility in streptozotocin-induced type 1 diabetic mice.

Rationale: Mechanisms underlying the compromised bone formation in type 1 diabetes mellitus (T1DM), which causes bone fragility and frequent fractures, remain poorly understood. Recent advances in organ-specific vascular endothelial cells (ECs) identify type H blood vessel injury in the bone, which actively direct osteogenesis, as a possible player. Methods: T1DM was induced in mice by streptozotocin (STZ) injection in two severity degrees. Bony endothelium, the coupling of angiogenesis and osteogenesis, and bone mass quality were evaluated. Insulin, antioxidants, and NADPH oxidase (NOX) inhibitors were administered to diabetic animals to investigate possible mechanisms and design therapeutic strategies. Results: T1DM in mice led to the holistic abnormality of the vascular system in the bone, especially type H vessels, resulting in the uncoupling of angiogenesis and osteogenesis and inhibition of bone formation. The severity of osteopathy was positively related to glycemic levels. These pathological changes were attenuated by early-started, but not late-started, insulin therapy. ECs in diabetic bones showed significantly higher levels of reactive oxygen species (ROS) and NOX 1 and 2. Impairments of bone vessels and bone mass were effectively ameliorated by treatment with anti-oxidants or NOX2 inhibitors, but not by a NOX1/4 inhibitor. GSK2795039 (GSK), a NOX2 inhibitor, significantly supplemented the insulin effect on the diabetic bone. Conclusions: Diabetic osteopathy could be a chronic microvascular complication of T1DM. The impairment of type H vessels by NOX2-mediated endothelial oxidative stress might be an important contributor that can serve as a therapeutic target for T1DM-induced osteopathy.

Implant Preservation versus Implant Replacement in Revision Surgery for Adjacent Segment Disease After Thoracolumbar Instrumentation: A Retrospective Study of 43 Patients.

OBJECTIVE: To evaluate the mechanical properties of a new connector rod aiming to preserve implants in revision surgery (RS) for adjacent segment disease, a problematic complication of instrumented spinal fusion, and to assess its clinical applicability. METHODS: The mechanical properties of the connector-rod construct (implant preservation) and traditional rod construct (implant replacement) were evaluated and compared. Forty-three patients underwent RS for adjacent segment disease in the thoracolumbar spine with implant preservation or replacement, and radiological and clinical outcomes were assessed. RESULTS: Mechanical properties in group A were comparable to those in group B. Total mean time from prior surgery to RS was 6.86 ± 1.08 years. Surgical time and blood loss values of group A were 40.14% and 29.29% statistically significantly smaller than values of group B. In group B, 12% (3/25) of patients developed surgical site infections. In both groups, the visual analog scale leg score decreased significantly after RS. Early postoperative (at 1-month and 3-month follow-up) Oswestry Disability Index and visual analog scale back scores of group A were significantly lower than those of group B; the difference in the visual analog scale back score between groups was significant until the 6-month follow-up. No implant failures occurred, and spinal fusion was achieved in all cases. CONCLUSIONS: The connector rod is considered safe and can reduce the surgical time, blood loss, risk of complications, and medical costs. Better early postoperative clinical outcomes can be achieved with the rod owing to less surgical trauma.

Plantar Pressure Distribution of Right and Left Foot in Bilateral Clubfoot Treated by Ponseti Method: A Correlation Analysis.

BACKGROUND Congenital clubfoot is a common pediatric orthopedic deformity that can be corrected by Ponseti method, and pedobarographic analysis has been used to assess the outcomes. However, the relationship between the plantar pressure distribution of the right and left foot in children with bilateral clubfoot has not been studied. In this study, the pedobarographic data of patients with bilateral clubfoot who were treated by the Ponseti method were reviewed, and a correlation analysis was conducted to clarify the relationship between the right and left foot. MATERIAL AND METHODS A retrospective cross-sectional study of children with bilateral clubfoot who were treated by the Ponseti method in infancy was performed, in which all the patients were available for clinical evaluation, and pedobarographic analysis was conducted on each patient after treatment. The Pearson's correlation coefficient (r) were calculated for all the measurements of the left and right foot. RESULTS A total of 20 children (mean age 6.9±1.07 years, range 4-8 years) with bilateral clubfoot who were treated by the Ponseti method were included. The Dimeglio and Pirani scores before and after treatment between the right and left foot were significantly correlated. All the pedobarographic measurements between the left and right foot were correlated, indicating different degrees of positive correlation. CONCLUSIONS The plantar pressure measurements between the 2 feet in patients with bilateral clubfoot were highly correlated before treatment, and a correlation was also observed after those patients were treated by the Ponseti method. We should take these correlations into consideration during study design and analysis of clubfoot cases.

One-stage Surgical Treatment of Simultaneous Osteotomy and Asymmetric Lengthening on Short Femur with Severe Deformity of Genu Valgus.

This study aimed to discuss the effects of one stage surgical treatment by simultaneous osteotomy and asymmetric lengthening by Ilizarov external fixator on short femur with severe deformity of genu valgus. A total of 12 cases with unilateral deformities treated by simultaneous osteotomy and Ilizarov asymmetric lengthening on short femur with severe deformity of genu valgus were retrospectively analyzed from January 2006 to April 2015. The affected limbs were 2.5-11 cm (5.2 cm on average) short, the femorotibial angle was 135°-158° (146.3° on average), and the ankle interval was 15-43 cm (24.7 cm on average). The Paley method was used to determine the osteotomy plane (distal femur) of genu valgus. According to this standard, the bone union results were as follows: 11 had excellent and 1 had good, where 7 patients had excellent and 5 had good functional outcomes. One stage surgical treatment by simultaneous osteotomy and asymmetric lengthening on short femur with severe deformity of genu valgus was considered to be an effective and reliable method with better osteotomy union, less trauma and fewer complications.

Pedobarographic Analysis following Ponseti Treatment for Unilateral Neglected Congenital Clubfoot.

Recent trends have led to an interest in Ponseti treatment for correcting neglected congenital clubfoot. Although good clinical and functional outcomes have been reported, the plantar pressure distribution after the treatment of neglected clubfoot has not been explored yet. The present study aimed to investigate whether plantar pressures normalized following Ponseti treatment in patients with neglected congenital clubfoot. Pedobarographic, clinical, and functional examinations were performed in 22 children (aged, 91.0 ± 40.3 months) with unilateral neglected congenital clubfeet, treated using Ponseti method at 27.8 ± 12.1 months of age. Plantar pressure parameters were recorded using a Footscan pressure plate. The contact time, contact area, peak pressure, and pressure-time integral were determined. The data of the affected feet were compared with those of the unaffected feet and healthy controls. Although clinical and functional examinations showed satisfactory results according to the Dimeglio and Pirani scores, considerable differences in plantar pressure parameters were identified among the affected feet, unaffected feet, and healthy controls. Internal foot progression angle and a load transfer from the medial forefoot and hindfoot to the lateral forefoot and midfoot were observed in the affected feet. Future studies should attempt to investigate the factors accounting for plantar pressure deviations and the possible effect of these deviations on the lower limb musculoskeletal development of children.

Reliability of the Footscan® Platform System in Healthy Subjects: A Comparison of without Top-Layer and with Top-Layer Protocols.

The Footscan platform is a useful tool for plantar pressure measurement. However, there is still controversy over whether or not the platform should be covered by top-layer during the test. This study was designed to compare the reliability of the Footscan platform and identify the differences of the foot loading parameters between without top-layer (WOT) and with top-layer (WT) protocols. Measurements were taken from thirty-two healthy subjects. Participants were tested with a Footscan platform using the WOT and WT protocols. Three trials were performed during two separate testing sessions with a 7-day interval. Peak pressure, contact time, contact area, and pressure-time integral at ten foot zones were recorded and calculated for intra- and intersession reliability using intraclass correlation coefficients (ICCs) and coefficients of variation (CVs). The reliability and values of the analyzed parameters for the two protocols were compared. Both protocols produced a moderate to good level of intra- and intersession reliability. Compared with the WT protocol, the WOT protocol showed higher ICCs, lower CVs, and higher values in most of the parameters analyzed. The results suggest that the WOT protocol showed better reliability than the WT protocol. We recommend not using the top-layer when performing the plantar pressure test.

Influence of the shape of the micro-finite element model on the mechanical properties calculated from micro-finite element analysis.

Assessing the biomechanical properties of trabecular bone is of major biological and clinical significance for the research of bone diseases, fractures and their treatments. Micro-finite element (µFE) models are becoming increasingly popular for investigating the biomechanical properties of trabecular bone. The shapes of µFE models typically include cube and cylinder. Whether there are differences between cubic and cylindrical µFE models has not yet been studied. In the present study, cubic and cylindrical µFE models of human vertebral trabecular bone were constructed. A 1% strain was prescribed to the model along the superior-inferior direction. E values were calculated from these models, and paired t-tests were performed to determine whether these were any differences between E values obtained from cubic and cylindrical models. The results demonstrated that there were no statistically significant differences in the E values between cubic and cylindrical models, and there were no significant differences in Von Mises stress distributions between the two models. These findings indicated that, to construct µFE models of vertebral trabecular bone, cubic or cylindrical models were both feasible. Choosing between the cubic or cylindrical µFE model is dependent upon the specific study design.

Normal foot loading parameters and repeatability of the Footscan® platform system.

BACKGROUND: The Footscan® platform system is one of the most commonly used clinical tools for the measurement of the foot pressure. The present study was designed to assess the repeatability of the system and identify the range of loading parameters observed in the normal foot. METHODS: Measurements were collected from 32 healthy participants, 15 females and 17 males, twice at an interval of 1 week. Peak pressure (PP), contact time (CT), contact area (CA), pressure-time integral (PTI), and maximum force (MaF) were recorded; these parameters were investigated in 10 areas of the foot: medial heel, lateral heel, midfoot, first to fifth metatarsals, hallux, and toes 2-5. The intra-session repeatability was evaluated by calculating the intraclass correlation coefficients (ICCs) and coefficients of variation (CVs) across the three repeated trials within the same session. The inter-session repeatability was assessed using the average of the three trials in each session to determine the ICCs and CVs. RESULTS: The ICCs showed moderate to good repeatability for every variable of interest, and the CVs were all <28%. The highest zones of PP were found under the second and third metatarsals, followed by the medial heel. The CT was 68.5-82.8% of the total stance time under the metatarsal heads. CA was highest under the midfoot, PTI was highest under the second metatarsal, and MaF was highest under the medial heel. CONCLUSIONS: Footscan® platform system was found to be repeatable. Thus, it can be used as a valuable tool in the assessment of plantar pressure distribution, and the normal values of the foot loading parameters identified in this study can be employed to provide a reference range for the gait analysis performed by the Footscan® system.

Adiponectin improves the osteointegration of titanium implant under diabetic conditions by reversing mitochondrial dysfunction via the AMPK pathway in vivo and in vitro.

Diabetes-induced reactive oxygen species (ROS) overproduction would result in compromised osteointegration of titanium implant (TI) and high rate of implant failure, yet the underlying mechanisms remain elusive. Adiponectin (APN) is a fat-derived adipocytokine with strong antioxidant, mitochondrial-protective and anti-diabetic efficacies. We hypothesized that mitochondrial dysfunction under diabetes may account for the oxidative stress in osteoblasts and titanium-bone interface (TBI) instability, which could be ameliorated by APN. To test this hypothesis, we incubated primary rat osteoblasts on TI and tested the cellular behaviors when subjected to normal milieu (NM), diabetic milieu (DM), DM+APN, DM+AICAR (AMPK activator) and DM+APN+Compound C (AMPK inhibitor). In vivo, APN or APN+Compound C were administered to diabetic db/db mice with TI implanted in their femurs. Results showed that diabetes induced structural damage, dysfunction and content decrease of mitochondria in osteoblasts, which led to ROS overproduction, dysfunction and apoptosis of osteoblasts accompanied by the inhibition of AMPK signaling. APN alleviated the mitochondrial damage by activating AMPK, thus reversing osteoblast impairment and improving the osteointegration of TI evidenced by Micro-CT and histological analysis. Furthermore, AICAR showed beneficial effects similar to APN treatment, while the protective effects of APN were abolished when AMPK activation was blocked by Compound C. This study clarifies mitochondrial dysfunction as a crucial mechanism in the impaired bone healing and implant loosening in diabetes, and provides APN as a novel promising active component for biomaterial-engineering to improve clinical performance of TI in diabetic patients. STATEMENT OF SIGNIFICANCE: The loosening rate of titanium implants in diabetic patients is high. The underlying mechanisms remain elusive and, with the rapid increase of diabetic morbility, efficacious strategies to mitigate this problem have become increasingly important. Our study showed that the mitochondrial impairment and the consequent oxidative stress in osteoblasts at the titanium-bone interface (TBI) play a critical role in the diabetes-induced poor bone repair and implant destabilization, which could become therapeutic targets. Furthermore, adiponectin, a cytokine, promotes the bio-functional recovery of osteoblasts and bone regeneration at the TBI in diabetes. This provides APN as a novel bioactive component used in material-engineering to promote the osteointegration of implants, which could reduce implant failure, especially for diabetic patients.

Effects of arthroscopic-assisted surgery on irreducible developmental dislocation of hip by mid-term follow-up: An observational study.

The purpose of this study was to investigate the indications, surgical technique, and the clinical effects of arthroscopic-assisted treatment of irreducible developmental dislocation of the hip by mid-term follow-up. Arthroscopic-assisted surgeries were performed on 40 children (52 hips) between January 2005 and December 2009. Anterior and antero-superior greater trochanter portals were used in these treatments. Spica cast and abduction splint were applied for 3 months postoperatively. The follow-up was conducted on every 3 months postoperatively. During 12-month follow-up, a secondary treatment such as acetabuloplasty and/or femoral osteotomy (shortening, varus, and derotation) was applied if the acetabular angle was greater than 25°. The pelvic acetabular angle, Mckay and Severin score were evaluated every 6 months in all children. With 36 to 96 months (average 71 months) follow-up, 35 children (44 hips) were successfully followed up with complete case data while 5 children unsuccessfully. According to Tönnis classification, there were 5 grade 1 hips, 14 grade 2 hips, 14 grade 3 hips, 11 grade 4 hips, in which 3 children (4 hips) were failed in arthroscopic reduction and femoral head avascular necrosis occurred in 2 children (4 hips). According to Mckay standard, the good rate is 100%. According to Severin standard, the good rate is 84.1%. Arthroscopic assisted treatment is an effective way of reduction of the irreducible hip. Compared with the open reduction, arthroscopic treatment combined with acetabuloplasty and/or femoral osteotomy has advantages of less trauma and better function preservation.

Relationship between sample volumes and modulus of human vertebral trabecular bone in micro-finite element analysis.

Micro-finite element (µFE) models have been widely used to assess the biomechanical properties of trabecular bone. How to choose a proper sample volume of trabecular bone, which could predict the real bone biomechanical properties and reduce the calculation time, was an interesting problem. Therefore, the purpose of this study was to investigate the relationship between different sample volumes and apparent elastic modulus (E) calculated from µFE model. 5 Human lumbar vertebral bodies (L1-L5) were scanned by micro-CT. Cubic concentric samples of different lengths were constructed as the experimental groups and the largest possible volumes of interest (VOI) were constructed as the control group. A direct voxel-to-element approach was used to generate µFE models and steel layers were added to the superior and inferior surface to mimic axial compression tests. A 1% axial strain was prescribed to the top surface of the model to obtain the E values. ANOVA tests were performed to compare the E values from the different VOIs against that of the control group. Nonlinear function curve fitting was performed to study the relationship between volumes and E values. The larger cubic VOI included more nodes and elements, and more CPU times were needed for calculations. E values showed a descending tendency as the length of cubic VOI decreased. When the volume of VOI was smaller than (7.34mm(3)), E values were significantly different from the control group. The fit function showed that E values approached an asymptotic values with increasing length of VOI. Our study demonstrated that apparent elastic modulus calculated from µFE models were affected by the sample volumes. There was a descending tendency of E values as the length of cubic VOI decreased. Sample volume which was not smaller than (7.34mm(3)) was efficient enough and timesaving for the calculation of E.

Pedobarographic Analysis Following Pemberton's Pericapsular Osteotomy for Unilateral Developmental Dysplasia of the Hip: An Observational Study.

Successful clinical and radiographic outcomes have been reported in patients with unilateral developmental dysplasia of the hip (DDH) following Pemberton pericapsular osteotomy (PPO). However, residual gait deviations are seen in both the affected and unaffected limbs. To date it is not known whether these deviations result in abnormal plantar pressure in such patients. This study investigated this possibility by performing pedobarographic, clinical, and radiographic examinations after PPO in 20 patients (age: 102.5 ±â€Š19.0 months) with unilateral DDH who underwent PPO at 34.2 ±â€Š9.8 months of age. Plantar pressure was evaluated using the Footscan pressure plate (RsScan International, Olen, Belgium). Each foot was subdivided into 10 zones and peak pressure, force-time integral as a percentage of total FTI, and contact time as a percentage of total stance time was estimated. The minimum duration of follow-up was 24 months (mean: 68.3 ±â€Š20.3 months). The data were compared with 20 age- and weight-matched healthy controls. Despite clinical and radiographic examinations showing satisfactory results according to modified McKay and Severin criteria, significant differences in plantar pressure parameters were identified between the affected limbs, the unaffected limbs, and normal controls. No significant differences were found between patients classified as "excellent or good" and those rated as "fair" according to the modified Severin criteria. Pedobarographic results showed the existence of the residual plantar pressure deviations during walking in patients treated with PPO for unilateral DDH. Longer follow-up will be needed to more fully evaluate the effect of these deviations on gait.

Time Related Changes of Mineral and Collagen and Their Roles in Cortical Bone Mechanics of Ovariectomized Rabbits.

As cortical bone has a hierarchical structure, the macroscopic bone strength may be affected by the alterations of mineral crystal and collagen, which are main components of cortical bone. Limited studies focused on the time related alterations of these two components in osteoporosis, and their contributions to bone mechanics at tissue level and whole-bone level. Therefore, the purpose of this study was to elucidate the time related changes of mineral and collagen in cortical bone of ovariectomized (OVX) rabbits, and to relate these changes to cortical bone nanomechanics and macromechanics. 40 Rabbits (7-month-old) were randomly allocated into two groups (OVX and sham). OVX group received bilateral ovariectomy operation. Sham group received sham-OVX operation. Cortical bone quality of five rabbits in each group were assessed by DXA, µCT, nanoindentation, Fourier transform infrared (FTIR) spectroscopy and biomechanical tests (3-point bending of femoral midshaft) at pre-OVX, 4, 6, and 8 weeks after OVX. As time increased from pre-OVX to 8 weeks, the mineral to matrix ratio decreased with time, while both collagen crosslink ratio and crystallinity increased with time in OVX group. Elastic modulus and hardness measured by nanoindentation, whole-bone strength measured by biomechanical tests all decreased in OVX group with time. Bone material properties measured by FTIR correlated well with nano or whole-bone level mechanics. However, bone mineral density (BMD), structure, tissue-level and whole-bone mechanical properties did not change with age in sham group. Our study demonstrated that OVX could affect the tissue-level mechanics and bone strength of cortical bone. And this influence was attributed to the time related alterations of mineral and collagen properties, which may help us to design earlier interventions and more effective treatment strategies on osteoporosis.

Temporal changes of microarchitectural and mechanical parameters of cancellous bone in the osteoporotic rabbit.

This study was aimed at elucidating the temporal changes of microarchitectural and mechanical parameters of cancellous bone in the osteoporotic rabbit model induced by ovariectomy (OVX) combined with glucocorticoid (GC) administration. Osteoporotic (OP) group received bilateral OVX combined with injections of GC, while sham group only received sham operation. Cancellous bone quality in vertebrae and femoral condyles in each group was assessed by DXA, µCT, nanoindentation, and biomechanical tests at pre-OVX and 4, 6, and 8 weeks after injection. With regard to femoral condyles, nanoindentation test could detect significant decline in tissue modulus and hardness at 4 weeks. However, BMD and microarchitecture of femoral condylar cancellous bone changed significantly at 6 weeks. In vertebrae, BMD, microarchitecture, nanoindentation, and biomechanical tests changed significantly at 4 weeks. Our data demonstrated that temporal changes of microarchitectural and mechanical parameters of cancellous bone in the osteoporotic rabbit were significant. The temporal changes of cancellous bone in different anatomical sites might be different. The nanoindentation method could detect the changes of bone quality at an earlier stage at both femoral condyle and vertebra in the osteoporotic rabbit model than other methods (µCT, BMD).

Insulin improves osteogenesis of titanium implants under diabetic conditions by inhibiting reactive oxygen species overproduction via the PI3K-Akt pathway.

Clinical evidence indicates that insulin therapy improves implant survival rates in diabetic patients; however, the mechanisms responsible for this effect are unknown. Here, we test if insulin exerts anti-oxidative effects, thereby improving diabetes-associated impaired osteoblast behavior on titanium implants. To test this hypothesis, we cultured primary rabbit osteoblasts in the presence of titanium implants and studied the impact of treatment with normal serum (NS), diabetic serum (DS), DS + insulin, DS + tempol (a superoxide dismutase mimetic), DS + insulin + tempol, and DS + insulin + wortmannin. We analyzed cell function, apoptosis, and reactive oxygen species (ROS) production in osteoblasts following the various treatments. Treatment with DS induced osteoblast dysfunction, evidenced by impaired cell attachment and morphology, decreased cell proliferation and ALP activity, and decreased expression of osteogenesis-related genes. We also observed a significant increase in apoptosis. Importantly, treatment with DS resulted in increased production of ROS in osteoblasts. In contrast, treatment with insulin inhibited ROS production, alleviated cell dysfunction, and decreased apoptosis of osteoblasts on the implants. Scavenging ROS with tempol also attenuated cell dysfunction. Compared to insulin treatment alone, the combination of insulin and tempol failed to further improve osteoblast functional recovery. Moreover, the anti-oxidative and pro-osteogenic effects afforded by insulin were almost completely abolished by the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin. These results demonstrate, for the first time, that insulin treatment alleviates the impaired osteogenesis of titanium implants under diabetic conditions by inhibiting ROS overproduction via a PI3K/Akt-dependent mechanism. Both the anti-oxidative and metabolic properties of insulin should make it a viable therapeutic option to combat diabetic implant failure.

A novel total cervical prosthesis for single-level cervical subtotal corpectomy: radiologic and histomorphometric analysis in a caprine model.

STUDY DESIGN: A novel total cervical prosthesis (TCP) for single-level cervical subtotal corpectomy was assessed in a caprine animal model. OBJECTIVES: To investigate the radiologic and histomorphometric characteristics of a novel TCP for single-level cervical subtotal corpectomy. SUMMARY OF BACKGROUND: Cervical disk replacement has emerged as a promising alternative to arthrodesis in the management of cervical disk herniation. However, they are designed for anterior cervical discectomy, and not suitable for cervical subtotal corpectomy. To solve this problem, our group has developed a novel TCP for single-level cervical subtotal corpectomy. MATERIALS AND METHODS: There were 12 adult Shannxi goats (2 y old) used in this study. The goats were divided into 2 groups based on postoperative survival periods of 3 (n=6) and 6 (n=6) months after surgery. Using an anterior surgical approach, a standard anterior C3 vertebra subtotal corpectomy and decompression of the spinal canal were performed, followed by implantation of the TCP device. Then all the goats were killed and underwent radiographic and histologic observations. RESULTS: The TCP implant procedures were successfully completed in all 12 goats without incidence of vascular or infectious complications. The range of motion of C2-C3 and C3-C4 segments were preserved in both of the groups. Three-dimensional images of specimens interface indicated confluent interdigitization of trabeculae at the prosthetic endplate-bone interface, without evidence of significant radiolucent lines or gaps. Histomorphometric analysis showed that there were a large number of fibrous tissue and a small amount of cartilage cells between the prostheses and bone in the 3 months' group. In the 6 months' group, part of fibrous tissue has changed into the cartilage tissue. CONCLUSIONS: Our data show that this prosthesis can maintain the stability of the cervical spine and retain the activity of the cervical spine in vivo. The findings in this study provide a foundation for ongoing clinical investigations using the TCP.

Optimal sample volumes of human trabecular bone in µCT analysis within vertebral body and femoral head.

Trabecular bones of different skeletal sites have different bone morphologies. How to select an appropriate volume of region of interest (ROI) to reflect the microarchitecture of trabecular bone in different skeletal sites was an interesting problem. Therefore, in this study, the optimal volumes of ROI within vertebral body and femoral head, and if the relationships between volumes of ROI and microarchitectural parameters were affected by trabecular bone morphology were studied. Within vertebral body and femoral head, different cubic volumes of ROI (from (1 mm)(3) to (20 mm)(3)) were set to compare with control groups(whole volume of trabecular bone). Five microarchitectural parameters (BV/TV, Tb.N, Tb.Th, Tb.Sp, and BS/BV) were obtained. Nonlinear curve fitting functions were used to explore the relationships between the microarchitectural parameters and the volumes of ROI. The volumes of ROI could affect the microarchitectural parameters when the volume was smaller than (8 mm)(3) within the vertebral body and smaller than (13 mm)(3) within the femoral head. As the volume increased, the variable tendencies of BV/TV, Tb.N, and Tb.Sp were different between these two skeletal sites. The curve fitting functions between these two sites were also different. The relationships between volumes of ROI and microarchitectural parameters were affected by the different trabecular bone morphologies within lumbar vertebral body and femoral head. When depicting the microarchitecture of human trabecular bone within lumbar vertebral body and femoral head, the volume of ROI would be larger than (8 mm)(3) and (13 mm)(3).