Osteoporosis accounts for a leading cause of degenerative skeletal disease in the elderly. Osteoblast dysfunction is a prominent feature of age-induced bone loss. While microRNAs regulate osteogenic cell behavior and bone mineral acquisition, however, their function to osteoblast senescence during age-mediated osteoporosis remains elusive. This study aims to utilize osteoblast-specific microRNA-29a (miR-29a) transgenic mice to characterize its role in bone cell aging and bone mass. Young (3 months old) and aged (9 months old) transgenic mice overexpressing miR-29a (miR-29aTg) driven by osteocalcin promoter and wild-type (WT) mice were bred for study. Bone mineral density, trabecular morphometry, and biomechanical properties were quantified using μCT imaging, material testing system and histomorphometry. Aged osteoblasts and senescence markers were probed using immunofluorescence, flow cytometry for apoptotic maker annexin V, and RT-PCR. Significantly decreased bone mineral density, sparse trabecular morphometry (trabecular volume, thickness, and number), and poor biomechanical properties (maximum force and breaking force) along with low miR-29a expression occurred in aged WT mice. Aging significantly upregulated the expression of senescence markers p16INK4a, p21Waf/Cip1, and p53 in osteoporotic bone in WT mice. Of note, the severity of bone mass and biomechanical strength loss, as well as bone cell senescence, was remarkably compromised in aged miR-29aTg mice. In vitro, knocking down miR-29a accelerated senescent (β-galactosidase activity and senescence markers) and apoptotic reactions (capsas3 activation and TUNEL staining), but reduced mineralized matrix accumulation in osteoblasts. Forced miR-29a expression attenuated inflammatory cytokine-induced aging process and retained osteogenic differentiation capacity. Mechanistically, miR-29a dragged osteoblast senescence through targeting 3′-untranslated region of anti-aging regulator FoxO3 to upregulate that of expression as evident from luciferase activity assessment. Low miR-29a signaling speeds up aging-induced osteoblast dysfunction and osteoporosis development. Gain of miR-29a function interrupts osteoblast senescence and shields bone tissue from age-induced osteoporosis. The robust analysis sheds light to the protective actions of miR-29a to skeletal metabolism and conveys a perspective of miR-29a signaling enhancement beneficial for aged skeletons

In osteoporosis treatment, current interventions, including pharmaceutical treatments and exercise protocols, suffer from challenges of guaranteed efficacy for patients and poor patient compliance. Moreover, bone loss continues to be a complicating factor for conditions such as spinal cord injury, prescribed bed-rest, and space flight. A low-cost treatment modality could improve patient compliance. Electrical stimulation has been shown to improve bone mass in animal models of disuse, but there have been no studies of the effects of electrical stimulation on bone in the context of bone loss under hormone deficiency such as in post-menopausal osteoporosis. The purpose of this study was to explore the effects of electrical stimulation on changes in bone mass in the ovariectomized rat model of post-menopausal osteoporosis. All animal protocols were approved by the institutional Animal Research Ethics Board. We developed a custom electrical stimulation device capable of delivering a constant current, 15 Hz sinusoidal signal. We used 30 female Sprague Dawley rats (12–13 weeks old). Half (n=15) were ovariectomized (OVX), and half (n=15) underwent sham OVX surgery (SHAM). Three of each OVX and SHAM animals were sacrificed at baseline. The remaining 24 rats were separated into four equal groups (n=6 per group): OVX electrical stimulation (OVX-stim), OVX no stimulation (OVX-no stim), SHAM electrical stimulation (SHAM-stim), and SHAM no stimulation (SHAM-no stim). While anaesthetized, stimulation groups received transdermal electrical stimulation to the right knee through bilateral skin-mounted electrodes (10 × 10 mm) with electrode gel. The left knee served as a non-stimulated contralateral control. The no-stimulation groups had electrodes placed on the right knee, but not connected. Rats underwent the stim/no-stim procedure for one hour per day for six weeks. Rats were sacrificed (CO2) after six weeks. Femurs and tibias were scanned by microCT focussed on the proximal tibia and distal femur. MicroCT data were analyzed for trabecular bone measures of bone volume fraction (BV/TV), thickness (Tb.Th), and anisotropy, and cortical bone cross-sectional area and second moment of area. Femurs and tibias from OVX rats had significantly less trabecular bone than SHAM (femur BV/TV = −74.1%, tibia BV/TV = −77.6%). In the distal femur of OVX-stim rats, BV/TV was significantly greater in the stimulated right (11.4%, p < 0 .05) than the non-stimulated contralateral (left). BV/TV in the OVX-stim right femur also tended to be greater than that in the OVX-no-stim right femur, but the difference was not significant (17.7%, p=0.22). There were no differences between stim and no-stim groups for tibial trabecular measures, or cortical bone measures in either the femur or the tibia. This study presents novel findings that electrical stimulation can partially mitigate bone loss in the OVX rat femur, a model of human post-menopausal bone loss. Further work is needed to explore why there was a differential response of the tibial and femoral bone, and to better understand how bone cells respond to electrical stimulation. The long-term goal of this work is to determine if electrical stimulation could be used as a complementary modality for preventing post-menopausal bone loss

Introduction. Stress shielding is one of the major concerns of load bearing implants (e.g. hip prostheses). Stiff implants cause stress shielding, which is thought to contribute to bone resorption1. On the contrary, low-stiffness implants generate high interfacial stresses that have been related to pain and interfacial micro-movements². Different attempts have been made to reduce these problems by optimizing either the stem design3 or using functionally graded implants (FGI) where the stem's mechanical properties are optimized4. In this way, new additive manufacturing technologies allow fabricating porous materials with well-controlled mesostructure, which allows tailoring their mechanical properties. In this work, Finite Element (FE) simulations are used to develop an optimization methodology for the shape and material properties of a FGI hip stem. The resorbed bone mass fraction and the stem head displacement are used as objective functions. Methodology. The 2D-geometry of a femur model (Sawbones®) with an implanted Profemur-TL stem (Wright Medical Technology Inc.) was used for FE simulations. The stem geometry was parameterized using a set of 8 variables (Figure 1-a). To optimize the stem's material properties, a grid was generated with equally spaced points for a total of 96 points (Figure 1-b). Purely elastic materials were used for the stem and the bone. Two bone qualities were considered: good (Ecortical=20 GPa, Etrabecular=1.5 GPa) and medium (Ecortical=15 GPa, Etrabecular=1 GPa). Poisson ratio was fixed to v=0.3. Loading corresponded to stair climbing. Hip contact force along with abductors, vastus lateralis and vastus medialis muscles were considered5 for a bodyweight of 847 N. The resorbed bone mass fraction was evaluated from the differences in strain energy densities between the intact bone and the implanted bone2. The displacement of the load point on the femoral head was computed. The optimization problem was formulated as the minimization of the resorbed bone mass fraction and the head displacement. It was solved using a genetic algorithm. Results. For the Profemur-TL design, bone resorption was around 36% and 56% for good and medium bone qualities, respectively (Fig. 2). The corresponding head displacements were 11.75 mm and 21.19 mm. Optimized solutions showed bone resorption from 15% to 26% and from 44% to 65% for good and medium bone qualities, respectively. Corresponding head displacements ranged from 11.85 mm to 12.25 mm and from 16.9 mm to 22.6 mm. Conclusion. The obtained set of solutions constitutes an improvement of the implant performance for this functionally graded implant (FGI) compared to the original implant for both bone qualities. From these simulations, the final solution for the FGI could be chosen based on manufacturing restrictions or another performance indicator

Rapidly progressive osteoarthritis of the hip (RPOH) is an unusual subset of osteoarthritis. It is characterized by rapid joint space loss, chondroly­sis, and sometimes marked femoral head and acetabular destruction as a late finding. The exact pathogenetic mechanism is unknown. Potential causes of RPOH include subchondral insufficiency fracture resulting from osteoporosis, increasing posterior pelvic tilt as a mechanical factor, and high serum levels of matrix metalloproteinase (MMP)-3 as biological factors. This study was aimed to identify some markers that associate with the destructive process of RPOH by analyzing the proposed pathological factors of the disease, MMP-3, pelvic tilt, and osteoporosis. Of female patients who visited our hospital with hip pain from 2012 through 2018, this study enrolled female patients with sufficient clinical records including the onset of hip pain, age and body mass index (BMI) at the onset, a series of radiographs during the period of >12 months from the onset of hip pain, and hematological data of MMP-3 and C-reactive protein (CRP). We found the hip joints of 31 patients meet the diagnostic criteria of RPOH, chondrolysis >two mm in one year, or 50% joint space narrowing in one year. Those patients were classified into two groups, 17 and 14 patients with and without subsequent femoral head destruction in one year shown by computed tomography, respectively. Serum MMP-3 and CRP were measured with blood samples within one year after the hip pain onset. The cortical thickness index (CTI) as an indicator of osteoporosis and pelvic tilt parameters were evaluated on the initial anteroposterior radiograph of the hip. These factors were statistically compared between the two groups. This study excluded male patients because RPOH occurs mainly in elderly females and the reference intervals of MMP-3 are different between males and females. There was no difference in age at onset or bone mass index between the RPOH patients with and without subsequent femoral head destruction. Serum levels of MMP-3 were significantly higher in the RPOH patients with the destruction (152.1 ± 108.9 ng/ml) than those without the destruction (66.8 ± 27.9 ng/ml) (P = 0.005 by Mann-Whitney test). We also found increased CRP in the patients with femoral head destruction (0.725 ± 1.44 mg/dl) compared with those without the destruction (0.178 ± 0.187 mg/dl) (P = 0.032 by Mann-Whitney test). No difference in the duration between the hip pain onset and the blood examination was found between the two groups. There was no significant difference in CTI or pelvic tilt between the two groups. The pathological condition that may increase serum MMP-3 and CRP could be involved in femoral head destruction after chondrolysis of the hip in patients with RPOH

Introduction. Osteoporosis is a common skeletal disorder characterised by a reduced bone mass and a progressive micro-architectural deterioration in bone tissue leading to bone fragility and susceptibility to fracture. With a progressively aging population, osteoporosis is becoming an increasingly important public health issue. The Wnt/β-catenin pathway is a major signalling cascade in bone biology, playing a key role in regulating bone development and remodelling, with aberrations in signalling resulting in disturbances in bone mass. Objectives. To assess the effects of silencing the expression of the Wnt antagonist Dickkopf-1 (Dkk1) on the bone profile of primary human osteoblasts exposed in vitro to 10-8M dexamethasone. Methods. Primary human osteoblasts (HOBs) were cultured in vitro and exposed to 10-8M dexamethasone over a time course of 4hr, 12hr and 24hr. Dkk1 expression was silenced using small interfering RNA (siRNA). Quantitative RT-PCR was performed to confirm gene knockdown. Control and Dex-treated phObs (silenced & non-silenced) were compared with respect to bone turnover. Markers of bone turnover analyzed included alkaline phosphatase activity, calcium deposition and osteocalcin expression as determined by pNPP assay, quantitative alizarine red staining and ELISA respectively. Results. Dkk1 expression in HOBs was increased in response to dexamethasone exposure with an associated reduction in alkaline phosphatase activity, calcium deposition and osteocalcin expression. Silencing of Dkk1 expression, as confirmed by quantitative RT-PCR, was associated with a rescue effect in dexamethasone-induced bone loss in vitro. Conclusions. Dkk1 is an antagonist of Wnt/β-catenin signalling and plays a key role in regulating bone development and remodelling. Silencing the expression of Dkk1 in primary human osteoblasts has been shown to rescue the effects of dexamethasone-induced bone loss in vitro. The pharmacological targeting of the Wnt/β-catenin signalling pathway offers an exciting opportunity for the development of novel anabolic bone agents to treat osteoporosis and disorders of bone mass

Aims

This study explored the shared genetic traits and molecular interactions between postmenopausal osteoporosis (POMP) and sarcopenia, both of which substantially degrade elderly health and quality of life. We hypothesized that these motor system diseases overlap in pathophysiology and regulatory mechanisms.

Purpose. Medial tibial condylar fractures (MTCFs) are rare but a serious complication after unicompartmental knee arthroplasty (UKA). The reasons for MTCFs was thought to be associated with the surgical procedures that are the halls for the guide pins, extended cut of the posterior tibial cortex, an incorrect positioning of the tibial keel groove, and an excessive force application when placing the tibial component. However, the relationship between MTCFs and the alignment of the tibial component has not been proven. The purpose of the study was to investigate the effect of the tibial component alignment to the MTCFs using the finite element method (FEM). Materials and Methods. We used three-dimensional (3D) image model of the tibia (Sawbones: Washington, US) on the FEM analysis software (ANSYS Design Space ver. 12, Tokyo, Japan). We measured the bone stresses in the 3D image model of the tibia at the site of the medial metaphyseal cortex and the anterior/posterior cortex. The tibial component was placed 0°, 3°varus, 3°valgus, 6°varus, and 6° valgus relative to the tibial anatomical axis in the coronal plane (Figure 1). In sagittal plane, tibial component was positioned 7° posterior inclination relative to the tibial anatomical axis. And, making an additional vertical groove at the posterior cortex by the extended sagittal saw cut of 2° and 10° posterior inclination, the impact of posterior cortical bone stress was evaluated (Figure 2). A load of 900 N was applied to the center of the tibial component parallel to the tibial axis, the maximum bone stress was subsequently calculated. Furthermore, to evaluate the stress distribution, we calculated the bone mass of the 3D bone model below the tibia component under the various alignment of the tibial component (Figure 3). Results. The bone stress at the medial metaphyseal cortex and the anterior cortex did not change depending on the alignment of the tibial component (Figure 4). When the tibial component was placed varus, the bone stress at the posteiror cortex decreased. By contrast, the valgus position of the tibial component increased the bone stress. An extended sagittal saw cut increased the bone stress depending on the depth of the groove. The bone mass of the tibia below the tibial component decreased as positioning the tibial component valgus. Conclusions. Surgeons should be aware of the potential pitfalls of valgus alignemnt of the tibial component and an extended sagittal saw cut, because this can lead to increased risk of the MTCFs

To test the hypothesis that: CERAMENT[™]|G (C-G) would improve new bone growth and decrease infection rate after debridement as compared with 1) CERAMENT|BONE VOID FILLER (CBVF) and 2) no void filler in a rat osteomyelitis model. 72 Sprague Dawley rats were injected with 1.5 × 10∧6 CFU of S. aureus into a drill hole in the right tibia. After 3 weeks, the osteomyelitic defect was debrided, and filled with either: 1) C-G (n=32), 2) CBVF (n=20), or 3) nothing (n=20). 6 weeks after the second surgery, 20 rats from each group were sacrificed and the right tibias were harvested. A long-term group (n=12) of C-G treated rats were also sacrificed at 6 months after the second surgery. The tissues were sonicated and the colony forming units in the sonicate were quantified by serial dilutions and culture. MicroCT was used to quantify the new bone growth (BV/TV) in the debrided osteomyelitic void. Histological samples were analyzed for the presence of a neutrophil response by a blinded pathologist. (*: p<0.05). Positive cultures in:. ○ 30% of animals treated with CBVF. ○ 25% of animals treated with no void filler. ○ 0% of animals treated with C-G (*). Neutrophil reaction in:. ○ 35% of animals treated with CBVF. ○ 50% of animals treated with no void filler. ○ 0% of animals treated with C-G (*). The BV/TV in:. ○ C-G treated rats was 24% greater than CBVF treated rats (*). ○ C-G treated rats was 94% greater than rats treated with no void filler (*). ○ CBVF treated rats was 56% greater than rats treated with no void filler (*). Animals sacrificed at 6 months which were treated with C-G did not have any evidence of infection by culture or histology. The bone mass of the implanted limb was higher than the contralateral (non-operated) side. CERAMENT|G decreased the rate of infection and increased new bone growth as compared with both CBVF and no void filler in a debrided osteomyelitic environment. Animals treated with C-G at 6 months showed no evidence of infection and retained a higher bone mass relative to the contralateral (non-operated) side. This study supports the use of CERAMENT|G as a readily available void filler which could be used in osteomyelitic environments after debridement

Aims. Spontaneous osteonecrosis of the knee (SONK) mainly affects the medial femoral condyle, would be a good indication for UKA. The primary aim of this study was to assess the clinical, functional and radiographic outcomes at middle to long-term follow-up, of a consecutive series of fifty UKA used for the treatment of SONK. The secondary aim was to assess the volume of necrotic bone and determine if this influenced the outcome. Patients and Methods. We reviewed 50 knees who were treated for SONK. Patients included ten males and 38 females. The mean age was 73 years (range, 57 to 83 years). The mean height and body weight were, respectively 153 cm (141 ∼171 cm) and 57 kg (35 ∼75kg). All had been operated on using the Oxford mobile-bearing UKA (Zimmer-Biomet, Swindon, United Kingdom) with cement fixation. The mean follow-up period was 8.4 years (range, 4 to 15years). We measured the size (width, length and depth) and the volume to be estimated (width x length x depth) of the necrotic bone mass using MRI in T1-weighted images. The clinical results were evaluated using the Knee Society Scoring System (KSS) and Oxford Knee Score (OKS). The flexion angle of the knee was evaluated using lateral X-ray images in maximum flexion. Results. There were no implant failures, but there were 4 deaths (from causes unrelated to UKA) mean 6.6 years after surgery(5∼8), 3 cases were lost mean 3.3 years after surgery(2∼5). The mean size of the necrotic lesion were 17.2mm (14.7∼25.3) in width, 28.2mm (6.2∼38.3) in length and 11.3mm (3.2∼14.3) in depth. The mean volume of it was calculated to be approximate 5.4 cm. 3. (0.7∼11.1). The mean flexion of the knee, KSS Knee Score, Function Score and OKS increased from a preoperative 128.7 degrees (110 ∼ 140 degrees) to 137.5 degrees (110 ∼ 153 degrees), 52.3 (30 ∼ 64) to 91.3 (87 ∼ 100), 39.7 (15∼ 55) to 90.2 (65 ∼ 100) and 21.6 (12∼ 28) to 40.2 (34∼ 48), respectively at the latest follow-up. At last follow-up all patients had good or excellent OKS. Conclusions. There was a 100% survival rate of the Oxford Phase 3 UKA for SONK in the middle to long-term (up to 15 years after surgery) in this independent study. All patients had good/excellent results at last follow-up and there were no reoperations or major complications. This suggests that Oxford mobile-bearing UKA is a good and definitive treatment for medial femoral SONK, whatever the size of the lesion

Advances in the performance and longevity of total joint arthroplasty (TJA) have been enabled by related progress in implant materials, device designs, and surgical techniques. Successful TJA also depends upon adequate bone quality to provide an enduring mechanical foundation. Bone quality can be defined as the ability to repetitively withstand physiologically-relevant loads without excess deformation or fracture. It is now recognized that bone quality encompasses more than just material quantity, i.e. densitometrically-measured bone mass. Bone quality is also determined by: material composition and arrangement, cortical and cancellous structure, and extent of microdamage. These properties, together with the appropriate mass, confer bone with the biomechanical competence needed to meet the repetitive load-bearing demands imposed by total joint implants. The need for TJA continues to increase in the aging global baby-boomer population. Unfortunately, this group is also experiencing increases in related comorbidities including: osteoporosis, kidney dysfunction, and diabetes, among others. Collectively these three comorbidities afflict more than 74 million Americans, and each is increasing at 2–8% annually. More importantly, each of these comorbidities negatively affects bone quality through alterations in bone turnover independent of bone mass changes commonly associated with these diseases. Specifically, alterations in bone turnover result in abnormal mineral-to-matrix ratios as measured by Fourier transform infra-red (FTIR) spectroscopy (Fig. 1) and altered Young's moduli (shape-independent resistance to deformation) as measured by nanoindentation (Fig. 2). These parameters are related to bones' fracture toughness and load-bearing capabilities, respectively. Also, low bone turnover is associated with mechanically important structural changes, i.e., decreased trabecular thickness (Fig. 3), cortical thickness and cancellous volume. Furthermore, low bone turnover may result in reducing the repair rate of physiologically – induced bone microdamage. This may lead to increases in the number or length of bone cracks, crack coalescence, and ultimately reduced energy needed for fracture. Therefore, patients needing TJA who also have comorbidities associated with abnormal bone quality are at risk for inferior arthroplasty results. Recognition and treatment of the TJA-relevant biomechanical implications of these comorbidities may help improve outcomes

Bone fracture healing is regulated by a series of complex physicochemical and biochemical processes. One of these processes is bone mineralisation, which is vital for normal bone development, its biomechanical competence and fracture healing. Phosphatase, orphan 1 (PHOSPHO1), a bone-specific phosphatase, has been shown to be involved in the mineralisation of the extracellular matrix in bone. It can hydrolyse phosphoethanolamine and phosphocholine to generate inorganic phosphate, which is crucial for bone mineralisation. Phospho1−/− mice show hypomineralised bone and spontaneous fractures. All these data led to the hypothesis that PHOSPHO1 is essential for bone mineralisation and its structural integrity. However, no study to our knowledge has shown the effects of PHOSPHO1 on bone fracture healing. In this study, we examined how PHOSPHO1-deficiency might affect the healing and quality of the fractured bones in Phospho1−/− mice. We performed rodded immobilised fracture surgery on the right tibia of control wild type (WT) and Phospho1−/− mice (n=16 for each group) at eight weeks of age. Bone was left to heal for four weeks and then the mice were euthanised and their tibias were analysed using Faxitron X-ray analyses, microCT, histology and histomorphometry and three-point bending test. Our microCT and X-ray analyses revealed that the appearance of the callus and several static parameters of bone remodeling at the fracture sites were markedly different in WT and Phospho1−/− mice. We observed a significant increase of BS/BV, BS/TV and trabecular number and decrease in trabecular thickness and separation in Phospho1−/− callus in comparison to the WT callus. These observations were further confirmed by histomorphometry. The increased bone mass at the fracture sites of Phospho1−/− mice appears to be caused by increased bone formation as there is a significant increase of osteoblast number, while osteoclast numbers remained unchanged. There was a marked increase of osteoid volume over bone volume (OV/BV) in the Phospho−/− callus. Interestingly, the amount of osteoid was markedly higher at the fracture sites than that of normal trabecular bones. The three-point bending test showed that Phospho 1 −/− fractured bone had more of an elastic characteristics than the WT bone as they underwent more of a plastic deformity before the breakage point compare to the WT. Our work suggests that PHOSPHO1 plays an integral role during bone fracture repair. PHOSPHO1 can be an interesting target to improve the fracture healing process

An understanding of forces that act on the shoulder joint is important for designing, testing, and evaluating shoulder arthroplasty products. Last year, we presented data describing upper arm motion during eight in-situ hours of occupational and recreational tasks. Using that data the associated humeral head joint forces were calculated with an upper extremity model in OpenSim. Five subjects from a nonrandom sampling of occupations wore the Inertial Measurment Units during a four hour period while at their work place performing their normal work duties and then during the four hour period of non-work activities immediately following. An unscented Kalman filter (UKF) was used to produce the 3D humeral – thoracic angles at 128 Hz from the IMU data. Because of the very large number of data points collected with the IMUs, ninety samples of twenty second duration were randomly selected from each four hour collection period. Using the sampled files, the time scales of the sampled files were scaled by a factor of five and then analyzed with the SUEM static optimization and joint reaction features. Not every sample file could be modeled resulting in an average number of sampled files of 66.7 per subject and condition (work/recreation). The humeral – thoracic angles were then used as input to the Stanford Upper Extremity Model (SUEM) in the OpenSim environment. The SUEM model allowed 2 rotation degree of freedom (rdof) for the forearm (flexion twist), 3 rdof at the humeral – scapular joint, and predicted scapular motion based on the humeral – thoracic elevation angle. All models were run for an assumed 80 kg body weight and included the bone mass of the scapula, clavical, humerus, radius, and ulna, but none of the soft tissue mass. Shoulder muscles were represented by 15 actuators: three heads for each of the deltoid, latissimus dorsi, and pectoralis, and 1 head each for the coracobrachialis, infraspinatous, subscapularis, supraspinatous, termes major, and teres minor. The 5. th. , 50. th. , and 95. th. percentile values of each force component acting on the humeral head from each sampled file for each subject and condition were calculated and the distribution of forces was plotted as a histogram. The overall mean and standard deviation for the 5. th. , 50. th. , and 95. th. percentile values were also determined. Of the A-P and S-I force components, anterior and inferior directed force components were larger than the posterior and superior directed force components. For the M-L force component, the forces were nearly exclusively directed in the medial direction. The 5. th. and 95. th. percentile forces during these subjects' ADL were generally lower than those described by Westerhoff 2009, suggesting that within the limitations of the modeling assumptions, loading experienced during in-situ ADL may be different than loading during laboratory simulation of representative motions

Introduction. The decreased bone mass or local osteoporosis at the proximal femur is often recognized in patients of rheumatoid arthritis (RA). In total hip arthroplasty (THA), the cancellous bone will be lost when rasping technique is applied for the preparation of stem insertion. In addition, cutting or elongation for contracted muscles around the hip joint can be required to insert the stem. To avoid these problems, the non-broaching, non-rasping impaction technique for the stems was applied in THA for the patients with RA. We report clinical and radiographic results of this method. Materials and Methods. In surgery, the femoral neck was cut and prepared without using a box chisel, reamer or broaches, instead, a series of trial stems were used with the method of impaction technique. After impaction of cancellous bone with the final size of the trial stem, the stem is fixed by bone cement without taking any cement mantle. Full weight bearing was allowed for all patients from the next day of the surgery. We investigated short-term clinical and radiographic results and the incidence of complication that was related to this technique. Post-operative radiological results with the minimum follow-up of 12 months after surgery were analyzed in 31 joints (25 cases) with this technique. The mean age at the time of surgery was 66.3 years (46∼82). The mean duration after surgery was 62 months (14∼108). Results. No case showed hypotension, decrease of saturation of oxygen concentration during this technique in surgery. Neither pulmonary embolism nor venous thrombosis of the leg was recognized in those cases. All cases showed good walking performance and did not show any hip and thigh pain at the time of follow up. The preoperative mean HHS score was 32.7 (±12.1) and improved to 79.4 (±11.7) at the time of follow up. Although two cases showed slight subsidence of the stem, no case showed the development of the loosening or any adverse effect such as radiolucent line, breakage of the bone cement, and any migration around the stem at the time of follow up. Conclusion. Although the number of our cases is small and also the follow up period is short, the non-broaching, non-rasping impaction method for stem in THA is thought to be better technique to preserve cancellous bone of the proximal femur, to avoid cutting or elongation of muscles around the hip joint, and to obtain good implant fixation for the patients with osteoporotic proximal femur

The success of a cementless Total Hip Arthroplasty (THA) depends not only on initial micromotion, but also on long-term failure mechanisms, e.g., implant-bone interface stresses and stress shielding. Any preclinical investigation aimed at designing femoral implant needs to account for temporal evolution of interfacial condition, while dealing with these failure mechanisms. The goal of the present multi-criteria optimization study was to search for optimum implant geometry by implementing a novel machine learning framework comprised of a neural network (NN), genetic algorithm (GA) and finite element (FE) analysis. The optimum implant model was subsequently evaluated based on evolutionary interface conditions. The optimization scheme of our earlier study [1] has been used here with an additional inclusion of an NN to predict the initial fixation of an implant model. The entire CAD based parameterization technique for the implant was described previously [1]. Three objective functions, the first two based on proximal resorbed Bone Mass Fraction (BMF) [1] and implant-bone interface failure index [1], respectively, and the other based on initial micromotion, were formulated to model the multi-criteria optimization problem. The first two objective functions, e.g., objectives f1 and f2, were calculated from the FE analysis (Ansys), whereas the third objective (f3) involved an NN developed for the purpose of predicting the post-operative micromotion based on the stem design parameters. Bonded interfacial condition was used to account for the effects of stress shielding and interface stresses, whereas a set of contact models were used to develop the NN for faster prediction of post-operative micromotion. A multi-criteria GA was executed up to a desired number of generations for optimization (Fig. 1). The final trade-off model was further evaluated using a combined remodelling and bone ingrowth simulation based on an evolutionary interface condition [2], and subsequently compared with a generic TriLock implant. The non-dominated solutions obtained from the GA execution were interpolated to determine the 3D nature of the Pareto-optimal surface (Fig. 2). The effects of all failure mechanisms were found to be minimized in these optimized solutions (Fig. 2). However, the most compromised solution, i.e., the trade-off stem geometry (TSG), was chosen for further assessment based on evolutionary interfacial condition. The simulation-based combined remodelling and bone ingrowth study predicted a faster ingrowth for TSG as compared to the generic design. The surface area with post-operative (i.e., iteration 1) ingrowth was found to be ∼50% for the TSG, while that for the TriLock model was ∼38% (Fig. 3). However, both designs predicted similar long-term ingrowth (∼89% surface area). The long-term proximal bone resorption (upto lesser trochanter) was found to be ∼30% for the TSG, as compared to ∼37% for the TriLock model. The TSG was found to be bone-preserving with prominent frontal wedge and rectangular proximal section for better rotational stability; features present in some recent designs. The optimization scheme, therefore, appears to be a quick and robust preclinical assessment tool for cementless femoral implant design. To view tables/figures, please contact authors directly

Published investigations with custom short stems have reported very encouraging results (Walker, et al, 1). However, off-the-shelf (OTS) versions of shorter length prostheses has not met with the same success. Several basic questions must be addressed. First, what is the purpose of a stem? Second, can stem length be reduced and if so by how much can this be safely done. Third, what are the effects of stem shortening and are there other design criteria which must take on greater importance in the absence of a stem to protect against implant aseptic failure. To examine these issues a testing rig was constructed which attempts to simulate the in vivo loading situation of a hip, Fig. 1 (Walker, et, al.). Fresh cadaveric femora were tested with the femora intact and then with femoral components of varying stem length implanted to examine the distribution of stresses within the femur under increasing loads as a function of stem length. This was correlated with observations of prospective DEXA measurement of proximal femoral bone mass and implant migration following THR (Leali, 3). We then initiated a prospective multi-center study of a specific short stem design which included three geometric features to ensure initial implant stability. This report documents that after 2 years, in the first 200 stems implanted, this design has been shown to provide stability against subsidence, flexion/extetnsion and rotational forces. This is consistent with the findings of the in-vitro studies and identical to the previously published clinical results of a similarly designed full length version of this same stem. Our studies indicated that a stem is not an absolute requirement in order to achieve a well functioning, stable implant. Initial stability can be achieved in the absence of a stem, by a “rest fit,” if adequate design features are incorporated. These studies also demonstrated that simply reducing the length of an existing implant to accommodate changes in surgical techniques may not be a reasonable or safe design change. Such shortened versions of existing stem designs must undergo rigorously in-vitro testing and clinical validation before being released for implantation

Sclerostin is a negative regulator of osteoblast differentiation and bone formation, probably through inhibition of the Wnt pathway. Distraction osteogenesis (DO) can be complicated by osteopenia and poor anabolic response, which may benefit from anabolic therapy. Sclerostin antibody (Scl-Ab) has been reported to stimulate bone formation and restore bone mass and strength in aged ovariectomised rats as well as to enhance fracture healing. We sought to examine the effects of Scl-Ab in a rat model of DO. A femoral osteotomy was stabilised with an EBI fixator in male Sprague Dawley rats, with distraction of 0.25mm twice daily to a total 7mm. Saline or Scl-Ab was administered twice weekly throughout distraction and/or up to 4 or 6 weeks post-commencement of distraction. Three groups were examined, Saline, Delayed Scl-Ab (D Scl-Ab, post distraction only) and Continuous Scl-Ab (Cont Scl-Ab). Radiographs demonstrated a trend for increased union rates with Scl-Ab at 6 weeks, with 50% of animals for D Scl-Ab or Cont Scl-Ab versus 20% of control animals. DEXA scans at 2 weeks revealed a 63% increase in regenerate BMD in the Cont Scl-Ab group (p< 0.01) and a 41% increase in the D Scl-Ab group (p< 0.05), compared to Saline. In addition, an increase of 116% in BMC was seen in the Cont Scl-Ab group (p< 0.01). At 6 weeks regenerate bone area was increased 18% in D Scl-Ab and 23% in Cont Scl-Ab. μCT scans of the regenerate revealed an 85%-89% increase in bone volume with Scl-Ab treatment at 6 weeks (p< 0.05). Bone volume ratio (BV/TV) was increased 77%-82% (p< 0.05). Scl-Ab treatment enhanced the amount of bone formed in this distraction model, when given throughout or post-distraction. Histological assessment of dynamic bone formation parameters will reveal the mechanism behind the enhanced repair, and its mechanical consequences will be examined

Purpose. Up to 70% of the differences in human bone mass have been attributed to genetic background. These differences are associated with alterations in the biomechanical properties, micro-architecture and remodeling of bone as well as its susceptibility to fracture and its capacity for repair. In previous work it was shown that C57Bl6 mice carrying one copy of the parathyroid hormone related protein (PTHrP+/−) gene developed osteopenia by four months of age. The current study was designed to determine if the haploinsufficient phenotype was maintained on a C3H background. Method. PTHrP+/+ and PTHrP+/− mice on C57Bl6 and C3H backgrounds were euthanised between 6 and 18 months of age. The femurs were harvested, fixed in 4% paraformaldehyde overnight and scanned on a Skyscan 1172 equipped with a 10kV X-ray source and a 10 megapixel camera at a resolution 5μm. The amount and quality of cortical and trabecular bone was quantified from 2D images and 3D reconstructions using CTAn, CTvol and CTVox software. The undecalcified specimens were embedded at low temperature in MMA, sectioned at 5 μm and stained with Von Kossa and Toluidine Blue to distinguish mineralized from unmineralized tissue. Results. A novel application of CTAn was developed to automatically and consistently separate cortical from trabecular bone for high throughput, independent quantification. At all ages, PTHrP+/− mice on the C57Bl6 background had less trabecular bone, which was of poorer quality, than their wild type counterparts. In contrast, no difference was seen between PTHrP+/− and PTHrP+/+ mice on the C3H background at any age. No difference in cortical thickness was seen between PTHrP+/− and PTHrP+/+ mice on either background at any age, although the femoral cortices of the C3H mice were consistently thicker than those of the C57Bl6 mice. Conclusion. The osteopenic phenotype of young adult PTHrP+/− mice on a C57Bl6 background is lost when the mutation is bred onto a C3H background. This suggests that some other osteogenic agent can compensate for the lack of PTHrP during bone development in the C3H mice

Background. Distraction Osteogenesis can be complicated by regenerate insufficiency resulting in prolonged implant usage or regenerate failure with malalignment or fracture. Experimental evidence has demonstrated that bisphosphonates may mediate improved local limb BMD and regenerate strength. Methods. A prospective series of 14 patients over 5 years. One cohort (Group A) of these cases presented with established regenerate insufficiency leading to consideration for surgical intervention. Patients received a therapeutic regime of intravenous bisphosphonate A further cohort (Group B) of 7 patients was commenced on bisphosphonate therapy at an earlier stage, prior to the regenerate maturation phase. Results. Mean age at primary surgery was 11.6 years (3-17 yrs) with a minimum follow-up of 12 months after fixator removal. The sites of regenerate insufficiency were tibia (12) and distal femur (3), with 1 patient undergoing both femoral and tibial lengthening. Mean fixator time was 108 days prior to treatment for a mean lengthening of 5.3 cm. At time of treatment measurements demonstrated a reduced BMD in the bone, mean 44% (39-58%) of the normal limb, the primary consolidation index was high at 40.5 (46-68) days/cm, reflecting observed regenerate insufficiency. Significant increase in regenerate bone mass and mineral density was observed after the first dose of intravenous bisphosphonate. No significant systemic complications were encountered. After a mean 130 days (range 103-231 days) of therapy the bone consolidated to unencumbered full weight bearing, final healing index of 82 days/cm (Range 67-108days/cm). Cases demonstrated a rapid and sustained improvement in local BMD (increasing to mean 78% of the normal side). Remodelling was seen radiologically from 12 months post-therapy. However, subsequently, one femoral regenerate fractured and required intramedullary nail stabilisation. Conclusion. This is early clinical evidence that Bisphosphonate therapy has potential therapeutic benefit in managing regenerate insufficiency and counteracting local osteopenia in distraction osteogenesis

Introduction. Anterior reconstruction has the advantage of conferring immediate stability to the cervico-thoracic junction. Aims and objectives. Assess clinical and radiological outcome in cervico-thoracic kyphosis treated with anterior reconstruction. Material and methods. 62 cases were treated with anterior reconstruction from 1996-2007. Minimum follow-up was 2years (2-6). Indications included tuberculosis (45), dysplastic(10), neoplastic (3) and traumatic (4). Average age was 28.6 years (13-72 years). Average pre-operative kyphosis was 26.4 degrees (5-84). Patients were grouped as long-neck (35) and short-neck (27) according to classification proposed by Bapat and Laheri. The caudal normal vertebra (CNV) matched on plain radiology and MRI in 40 (64.51%). In 22 level of fixation was extended due to poor bone mass in the adjacent vertebral body (caudal 17, cranial 5). Pre-operative neurological deficit was seen in 57 (91.3%) and average Nurick's grade was 3.8 (0-5). Results. 32 long-neck patients required strap-muscle tenotomy to expose the CNV. In 3(9.3%) manubriotomy was required (large neck girth 1, thyroid goitre 2). 26 short-neck patients required manubriotomy for plate placement. In 42 (67.8%) patients a standard anterior cervical plate was used. In 22 locking plate was used. Commonest cranial and caudal vertebrae instrumented were C7 (32) and T2 (20) respectively. Post-operative kyphosis averaged 14.68 degrees (0-78) and correction averaged 11.72 degrees. Average post-operative Nurick's grade was 2.8. One patient with fracture dislocation of T1-T2 and traumatic oesophageal rupture died. In 1 the implant loosened and was revised with posterior construct. In 1, screw loosening was observed but implant position remained unaltered. 2 patients had recurrent laryngeal palsy. Iatrogenic pleural rent occurred in 2 patients. Transient dysphagia was noticed in 12. The scar hypertrophy was seen in 30(48.38%). The loss of correction averaged 2.3mm (0-4mm) at the final follow-up. Conclusion. Anterior reconstruction allows excellent reconstruction of cervico-thoracic junction obviating need for a posterior construct

INTRODUCTION. Trabecular Titanium™ is an innovative material characterised by an high open porosity and composed by multi-planar regular hexagonal cells. It is not a traditional coating and its tri-dimensional structure has been studied to optimise osteointegration. Furthermore, it has excellent mechanical properties, as a very high tensile and fatigue resistance and an elastic module very similar to the that of the trabecular bone. The aim of this study is to evaluate the osteointegration and bone remodelling measuring the longitudinal pattern of change in BMD around a cementless acetabular cup made from Trabecular Titanium™ (Delta TT cup, Lima Corporate, Italy) in primary total hip arthroplasty (THA). METHODS. Dual-energy x-ray absorptiometry (DEXA) analysis, radiographic evaluation on standard AP and lateral views and clinical evaluation with Harris Hip Score (HHS) and SF-36 were performed at 1 week, 3, 6, 12 months after surgery. RESULTS. Between February 2009 and June 2010, 72 patients underwent primary THA with Delta TT cup at 4 centres. There were 36 (50%) female and 36 (50%) male with an average age of 63 (range 39-75). Preliminary results include 72 patients with 56 at 3 months, 42 at 6 months and 28 at 12 months. The mean HHS improved from 48 points (range 14-79) preoperatively to 88 (range 74-100) at 3 months, to 94 (range 71-100) at 6 months and to 97 (range 94-100) at 12 months. SF-36 reported a progressive improvement of all domains. An initial transient decrease of the bone mineral density (BMD) occurred between 1 week and 3 months after surgery, then bone mass returns to baseline values after 6 months and increased at 12 months. No radiolucent lines nor osteolysis have reported and no revision occurred. There were 2 complications not related to the implant on study: one dislocation solved with a close reduction and one dislocation solved with a revision of the neck and the head, but not compromising the cup. CONCLUSIONS. Delta TT acetabular cup allows to obtain a very good primary stability, thanks to the high friction coefficient of the Trabecular Titanium™, followed by a good and fast osteointegration, as reported by early DEXA outcomes. Preliminary results showed also a very good clinical and functional improvement. Long-term follow-up is ongoing in order to prove these promising results