Following anterior cruciate ligament reconstruction (ACLR) using a semitendinosus (ST) autograft measures such as length, cross-sectional area, and volume may not fully describe the effects of tendon harvest on muscle morphology as these discrete measures cannot characterize three-dimensional muscle shape. This study aimed to determine between-limb ST shape similarity and regional morphology in individuals with a unilateral history of ACLR using a ST graft, and healthy controls. A secondary analysis of magnetic resonance imaging was undertaken from 18 individuals with unilateral history of ST ACLR and 18 healthy controls. ST muscles were manually segmented, and shape similarity were assessed between limbs and groups using Jaccard index (0-1) and Hausdorff distance (mm). ST length (cm), peak cross-sectional area (CSA) (cm2), and volume (cm3) was compared between surgically reconstructed and uninjured contralateral limbs, and between the left and right limbs of control participants with no history of injury. Cohen's d was reported as a measure of effect size. Compared to healthy controls, the ACLR group had significantly (p<0.001, d= −2.33) lower bilateral ST shape similarity. Furthermore, the deviation in muscle shape was significantly (p<0.001, d= 2.12) greater in the ACLR group. Within the ACLR group, maximum Hausdorff distance indicated ST from the ACLR limb deviated (23.1±8.68 mm) from the shape of the healthy contralateral ST, this was observed particularly within the distal region of the muscle. Compared to the uninjured contralateral limb and healthy controls, deficits in peak cross-sectional area and volume in ACLR group were largest in proximal (p<0.001, d= −2.52 to −1.28) and middle (p<0.001, d= −1.81 to −1.04) regions. Findings highlight morphological features in distal ST not identified by traditional discrete morphology measures. ST shape was most different in the distal region of the muscle, despite deficits in CSA and volume being most pronounced in proximal and middle regions. ST shape following ACLR may affect force transmission and distribution within the hamstrings and contribute to persistent deficits in knee flexor and internal rotator strength.
The study compared thigh-shank and shank-foot coordination during gait before and after total knee arthroplasty (TKA) with controls (CTRL). Twenty-seven patients (male=15/female=12; age=63.2±6.9 years) were evaluated one month prior to and twelve months after surgery, and compared to 27 controls (male=14/female=13; age=62.2±4.3). The participants were outfitted with a full-body marker set. Gait speed (normalized by leg length) was calculated. The time series of the thigh, shank, and foot orientation in relation to the laboratory coordinate system were extracted. The coordination between the thigh-shank and shank-foot in the sagittal plane were calculated using a vector coding technique. The coupling angles were categorized into four coordination patterns. The stance phase was divided into thirds: early, mid, and late stance. The frequency of each pattern and gait speed were compared using a one-way ANOVA with a post-hoc Bonferroni correction. Walking speed and shank-foot coordination showed no differences between the groups. The thigh-shank showed differences. The pre-TKA group showed a more in-phase pattern compared to the CTRL group during early-stance. During mid-stance, the pre- and post-TKA presented a more in-phase pattern compared to the CTRL group. Regarding shank-foot coordination, the groups presented an in-phase and shank pattern, with more shank phase during mid-stance and more in-phase during late-stance. The pre-TKA group showed greater differences than the post-TKA compared to the controls. The more in-phase pattern in the pre- and post-TKA groups could relate to a reduced capacity for the thigh that leads the movement. During mid-stance in normal gait, the knee is extending, where the thigh and shank movements are in opposite directions. The in-phase results in the TKA groups indicate knee stiffness during the stance phase, which may relate to a muscular deficit or a gait strategy to reduce joint stress.
With an aging population and increase in total knee arthroplasty, periprosthetic distal femur fractures (PDFFs) have increased. The differences between these fractures and native distal femur fractures (NDFF) have not been comprehensively investigated. The purpose of this study was to compare the demographic, fracture, and treatment details of PDFFs compared to NDFFs. A retrospective study of patients ≥ 18 years old who underwent surgical treatment for either a NDFF or a PDFF from 2010 to 2020 at a level 1 trauma center was performed. Demographics, AO/OTA fracture classification, quality of reduction, fixation constructs, and unplanned revision reoperation were compared between PDFF patients and NDFF patients using t-test and Fisher's exact test.
209 patients were identified with 70 patients having a PDFF and 139 patients having a NDFF. Of note, 48% of NDFF had a concomitant fracture of the ipsilateral knee (14%) or tibial plateau (15%). The most common AO/OTA classification for PDFFs was 33A3.3 (71%). NDFFs had two main AO/OTA classifications of 33C2.2 (28%) or 33A3.2. (25%). When controlling for patient age, bone quality, fracture classification, and fixation, the PDFF group had increased revision reoperation rate compared to NDFF (P < 0.05). PDFFs tend to occur in elderly patients with low bone quality, have complete metaphyseal comminution, and be isolated; whereas, NDFF tend to occur in younger patients, have less metaphyseal comminution, and be associated with other fractures. When controlling for variables, PDFF are at increased risk of unplanned revision reoperation. Surgeons should be aware of these increased risks in PDFFs and future research should focus on these unique fracture characteristics to improve outcomes.
Revision knee arthroplasty is a complex procedure with the number and cost of knee revision procedures performed per year expected to rise. Few studies have examined adverse events following revision arthroplasty. The objective of this study was to determine rates of serious adverse events in patients undergoing revision knee arthroplasty with consideration of the indication for revision (urgent versus elective indications) and to compare these with primary arthroplasty and re-revision arthroplasty. Patients undergoing primary knee arthroplasty were identified in the UK Hospital Episode Statistics. Subsequent revision and re-revision arthroplasty procedures in the same patients and same knee were identified. The primary outcome was 90-day mortality and a logistic regression model was used to investigate factors associated with 90-day mortality and secondary adverse outcomes including infection (undergoing surgery), pulmonary embolism, myocardial infarction, stroke. Urgent indications for revision arthroplasty were defined as infection or fracture, and all other indications were included in the elective indications cohort. 939,021 primary knee arthroplasty cases were included of which 40,854 underwent subsequent revision arthroplasty, and 9,100 underwent re-revision arthroplasty. Revision surgery for elective indications was associated with a 90-day rate of mortality of 0.44% (135/30,826; 95% CI 0.37-0.52) which was comparable to primary knee arthroplasty (0.46%; 4,292/939,021; 95% CI 0.44-0.47). Revision arthroplasty for infection, however, was associated with a much higher mortality of 2.04% (184/9037; 95% CI 1.75-2.35; odds ratio [OR] 3.54; 95% CI 2.81-4.46), as was revision for periprosthetic fracture at 5.25% (52/991; 95% CI 3.94-6.82; OR 6.23; 95% CI 4.39-8.85). Higher rates of pulmonary embolism, myocardial infarction, and stroke were also observed in the infection and fracture cohort. These findings highlight the burden of complications associated with revision knee arthroplasty. They will inform shared decision-making for patients considering revision knee arthroplasty for elective indications. Patients presenting with infection of a knee arthroplasty or a periprosthetic fracture are at very high risk of adverse events. It is important that acute hospital services and tertiary referral centres caring for these patients are appropriately supported to ensure appropriate urgency and an anticipation for increased care requirements.
The need for gender specific knee arthroplasty is debated. This research aimed to establish whether gender differences in patellar tendon moment arm (PTMA), a composite measure that characterises function of both the patellofemoral and tibiofemoral joints, are a consequence of knee size or other variation. PTMA about the instantaneous helical axis was calculated from positional data acquired using optical tracking. First, data post-processing was optimised, comparing four smoothing techniques (raw, Butterworth filtered, generalised cross-validation cubic spline interpolated and combined filtered/interpolated) using a fabricated knee. Then PTMA was measured during open-chain extension for N=24 (11 female) fresh-frozen cadaveric knees, with physiologically based loading and extension rates (420°/s) applied. Gender differences in PTMA were assessed before and after accounting for knee size with epicondylar width.Abstract
Objectives
Methods
To investigate differences in the drop vertical jump height in female adolescents with an ACL injury and healthy controls and the contribution of each limb in this task.
Forty female adolescents with an ACL injury (ACLi, 15.2 ± 1.4 yrs, 164.6 ± 6.0 cm, 63.1 ± 10.0 kg) and thirty-nine uninjured (CON, 13.2 ± 1.7 yrs, 161.7 ± 8.0 cm, 50.6 ± 11.0 kg) were included in this study. A 10-camera infrared motion analysis system (Vicon, Nexus, Oxford, UK) tracked pelvis, thigh, shank, and foot kinematics at 200Hz, while the participants performed 3 trials of double-legged drop vertical jumps (DVJ) on two force plates (Bertec Corp., Columbus, USA) sampled at 2000Hz.The maximum jump height normalised by dominant leg length was compared between groups using independent samples t-test. The maximum vertical ground reaction force (GRFz) and sagittal ankle, knee and hip velocities before take-off were compared between limbs in both groups, using paired samples t-test.
The normalised jump height was 11% lower in the ACLi than in the CON (MD=0.04 cm, p=0.020). In the ACLi, the maximum GRFz (MD=46.17N) and the maximum velocities of ankle plantar flexion (MD=79.83°/s), knee extension (MD=85.80°/s), and hip extension (MD=36.08°/s) were greater in the non-injured limb, compared to the injured limb. No differences between limbs were found in the CON. ACL injured female adolescents jump lower than the healthy controls and have greater contribution of their non-injured limb, compared to their injured limb, in the DVJ task. Clinicians should investigate differences in the contribution between limbs during double-legged drop vertical jump when assessing patients with an ACL injury, as this could help identify asymmetries, and potentially improve treatment, criteria used to clear athletes to sport, and re-injury prevention.
Mice are increasingly used for fracture healing research because of the possibility to use transgenic animals to conduct research on the molecular level. Mice from both sexes can be used, however, there is no consensus in the literature if fracture healing differs between female and male mice. Therefore, the aim of the present study was to analyze the similarities and differences in endochondral fracture healing between female and male C57BL/6J mice, since this mouse strain is mainly used in bone research. For that purpose, 12-weeks-old female and male mice received a standardized femur midshaft osteotomy stabilized by an external fixator. Mice were euthanized 10 and 21 days after fracture and bone regeneration was analyzed by biomechanical testing, µCT analysis, histology, immunohistochemistry and gene expression analysis. At day 21, male mice displayed a significantly larger fracture callus than female mice accompanied by higher number of osteoclasts, higher tissue mineral density and absolute values of bone volume, whereas relative bone volume to tissue volume ratio did not differ between the groups. Biomechanical testing revealed significantly increased bending stiffness in both fractured and intact femurs from male vs. female mice, whereas relative bending stiffness of fractured femurs related to the intact femurs did not differ. 10 days after fracture, male mice display significantly more cartilage and less fibrous tissue area in the fracture callus than female mice, whereas bone area did not differ. On the molecular level, male mice displayed increased active β-catenin expression in the fracture callus, whereas estrogen receptor α (ERα) expression was reduced. In conclusion, male mice showed more prominent cartilaginous callus formation, increased mineralization and whole callus tissue formation, whereas functional outcome after fracture did not differ from female mice. This might be due either to the heavier weight of male mice or because of differences in molecular signaling pathways.
The scapholunate interosseous ligament (SLIL) has a unique C-shape following the arc of the scaphoid and lunate surfaces from distal dorsal around to distal volar. This ligament comprises of three subregions: dorsal, proximal and volar. The SLIL enthesis, a specialized region where this ligament attaches to the scaphoid and lunate, has not previously been studied despite its important mechanical function in the biomechanics of the wrist joint. This study therefore aims to compare the histomorphological differences between the SLIL subregions, including at their entheses. This study will examine the qualitative and quantitative differences between the three subregions, as well as between the scaphoid and lunate attachments. Twelve fresh-frozen human cadaveric wrists were dissected and the gross dimensions of each SLIL subregion measured. Subregions were then histologically processed for qualitative and quantitative morphological and compositional analyses, including quantification of enthesis calcified fibrocartilage (CF) area.Abstract
Objectives
Methods
The meniscus is a fibrocartilaginous tissue that plays an important role in controlling the complex biomechanics of the knee. Many histological and mechanical studies about meniscal attachment have been carried out, and medial meniscus (MM) root repair is recommended to prevent subsequent cartilage degeneration following MM posterior root tear. However, there are only few studies about the differences between meniscus root and horn cells. The goal of this study was to clarify the differences between these two cells. Tissue samples were obtained from the medial knee compartments of 10 patients with osteoarthritis who underwent total knee arthroplasty. Morphology, distribution, and proliferation of MM root and horn cells, as well as gene and protein expression levels of Sry-type HMG box (SOX) 9 and type II collagen (COL2A1) were determined after cyclic tensile strain (CTS) treatment. Horn cells had a triangular morphology, whereas root cells were fibroblast-like. The number of horn cells positive for SOX9 and COL2A1 was considerably higher than that of root cells. Although root and horn cells showed similar levels of proliferation after 48, 72, or 96 h of culture, more horn cells than root cells were lost following 2-h CTS (5% and 10% strain). SOX9 and COL2A1 mRNA expression levels were significantly enhanced in horn cells compared with those in root cells after 2- and 4-h CTS (5%) treatment. This study demonstrates that MM root and horn cells have distinct characteristics and show different cellular phenotypes. Our results suggest that physiological tensile strain is important for activating extracellular matrix production in horn cells. Restoring physiological mechanical stress may be useful for promoting healing of the MM posterior horn.
Principal Component Analysis (PCA) is a useful method for analysing human motion data. The objective of this study was to use PCA to quantify the biggest variance in knee kinematics waveforms between a Non-Pathological (NP) group and individuals awaiting High Tibial Osteotomy (HTO) surgery. Thirty knees (29 participants) who were scheduled for HTO surgery were included in this study. Twenty-eight NP volunteers were recruited into the study. Human motion analysis was performed during level gait using a modified Cleveland marker set. Subjects walked at their self-selected speed for a minimum of 6 successful trials. Knee kinematics were calculated within Visual3D (C-Motion). The first three Principal Components (PCs) of each input variable were selected. Single-component reconstruction was performed alongside representative extremes of each PC to aid interpretation of the biomechanical feature reconstructed by each component.Abstract
Objectives
Methods
From a large 3D Caucasian bone data base, female population had significantly larger acetabular anatomical anteversion angle and combined acetabular-femoral anteversion angle than that of male population. There was no significant difference in femoral neck anteversion angles between the groups. Combined Anteversion (CA) angle of acetabular component and femoral neck is an important parameter for a successful Total Hip Arthroplasty (THA). The purpose of this study was to electronically measure the version angles of native acetabulum and femur in matured normal Caucasian population from large 3D CT data base. Our question was if there was any significant difference in CA between male and female population.Summary
Introduction
The aim of this study was to perform a comprehensive evaluation of the changes in function from pre- to post-surgery in total and unilateral knee arthroplasty (UKA/TKA) patients. Twenty healthy (age 62.4 ±5.9, 11 male), 14 UKA (age 60.9 ±10.1, 8 male) and 17 TKA (age 67.2 ±8.1, 9 male) patients were studied. KA patients were assessed four weeks pre- and six months post-operation. Measures of perceived pain and function were collected using Oxford Knee Score (OKS) questionnaire. Tests of objective function included joint range of motion (RoM), ultrasound imaging, and 3-D motion analysis/inverse modelling from gait and sit-stand. An optimal set of variables was used to classify KA function using the Cardiff DST method. Pre-KA and healthy individuals were accurately classified (96%). Post-operation questionnaire measures of function improved for both UKA and TKA groups. However, observed measures of RoM, muscle atrophy and gait had only limited gains. This resulted in 57% of UKA and only 27% of TKA patients being classified as healthy post-operation. The results of this study show that 6 months post-surgery UKA patients had higher function than TKA. Using statistical approaches to combine functional assessments has provided an accurate platform to classify function and estimate changes from pre- to post-surgery. The clinical application of this tool requires further investigation and comparison to commonly used clinical techniques.
The majority of studies assessing minimal clinical important difference in outcome do so for management of chronic low back pain. Those that identify MCID following spinal surgical intervention fail to differentiate between the different pathologies and treatments or use variable methods and anchors in the calculation. To identify the MCID in scores across the most common spinal surgical procedures using standardised methods of calculation.Background
Aim
Knee osteoarthritis (KOA) causes impairment through pain, stiffness and malalignment and knee joint replacement (KJR) may be necessary to alleviate such symptoms. There is disagreement whether patients with KJR increases their level of physical activity after surgery. The aim of this study is to investigate whether patients with KJR have a higher level of physical activity than patients with KOA, as measured by accelerometer-based method. Furthermore, to investigate whether patients achieve the same level of activity as healthy subjects five years post TJR. 54 patients with KOA (29 women, mean age 62±8.6, mean BMI 27±5), 53 patients who had KJR five years earlier (26 women, mean age 66±7.2, mean BMI 30±5) and 171 healthy subjects (76 women, mean age 64±9.7, mean BMI 26±5) were included in this cross sectional study. The level of physical activity was measured over a mean of 5.5 days with a tri-axial accelerometer mounted on the thigh. Number of daily short walking bouts ofIntroduction
Material and method
Anterior cruciate ligament deficiency (ACLD) affects the performance of walking in some patients (non-copers) while copers are able to minimize the effects via proper musculoskeletal compensations. Since many daily activities are more challenging than level walking, e.g., obstacle-crossing, it is not clear whether copers are able to cope with such a challenging task. A successful and safe obstacle-crossing requires not only sufficient foot clearance of the swing limb, but also the stability of the body provided mainly by the stance limb. Failure to meet these demands may lead to falls owing to loss of balance or tripping over obstacles. The purpose of the current study was to identify the motor deficits and/or biomechanical strategies in coper and non-coper ACLD patients when crossing obstacles of different heights for a better function assessment. Ten coper and ten non-coper ACLD patients were recruited in the current study. The non-coper ACLD subjects were those who had not been able to return to their pre-injury level activities, had at least once giving way during the last six months and their Lysholm knee scale was less than 70 [1]. Each subject walked and crossed obstacles of heights of 10%, 20% and 30% of their leg lengths at a self-selected pace. Kinematic and kinetic data were measured with a 7-camera motion analysis system (Vicon, Oxford Metrics, U.K.) and two force plates (AMTI, U.S.A.). The leading and trailing toe clearances were calculated as the vertical distances between the toe markers and the obstacle when the toe was directly above the obstacle. Joint angles of both limbs, and joint moments of the stance limb, were calculated. Peak extensor moments at the knee during stance phase and the corresponding joint angles were extracted for statistical analysis. A 3 by 2, 2-way mixed-model analysis of variance with one between-subject factor (group) and one within-subject factor (obstacle height) was performed (α=0.05). SAS version 9.2 was used for all statistical analysis. Compared with the copers, significantly reduced leading and trailing toe clearances were found in the non-coper group (P<0.05). The non-copers showed significantly decreased peak extensor moments (P<0.05) and flexion angle at the affected knee during the stance phase before leading limb crossing (P<0.05). Distinctive gait patterns were identified in coper and non-coper patients with unilateral anterior cruciate ligament deficiency during obstacle crossing. During the stance phase before the un-affected leading limb crossing, the non-copers showed significantly reduced flexion and peak extensor moments at the affected knee (i.e., quadriceps avoidance), primarily owing to the impaired stability at the affected knee. The significantly reduced leading and trailing toe clearances in the non-coper group indicate that the non-coper ACLD patients are at a higher risk of tripping over the obstacle, and may have difficulty in regaining balance owing to the unstable ACLD knee. Advanced rehabilitation program or reconstruction of the ACL is suggested for the non-coper group.
Meniscal tears commonly occur after a traumatic twisting injury to the knee (acute) or can form over time (degenerate). Symptoms include pain, swelling, and ‘locking’ of the knee. These symptoms are also commonly associated with osteoarthritis (OA). In some cases of OA, degenerative meniscal tears can also be present making it difficult to determine the cause of symptoms. Furthermore, acute meniscal lesions may be associated with early stage OA but often no radiological signs are evident. Many metabolites associated with joint disorders are released into the synovial fluid providing a real-time snap shot of joint pathology. The ability to examine concentrations of specific metabolites within synovial fluid could provide invaluable clinical information about the cause and stage of joint pathology. We have tested the hypothesis that ‘high resolution 1H-NMR can discriminate between osteoarthritic and meniscal tear-related metabolites within human synovial fluids and aid in clinical diagnosis.’ Synovial fluid samples have been obtained during arthroscopy or knee replacement from patients with varying degrees of joint pathology (cartilage graded 0-4; meniscal tears classified as acute or degenerative). Samples were also taken from patients undergoing Anterior Cruciate Ligament (ACL) reconstruction with no additional pathology. Samples were analysed using 500 MHz 1H NMR spectroscopy. Chemical shifts were referenced to known concentration NMR internal standard (TSP), peaks identified by reference to published synovial fluid NMR spectra (1) and peak integrals measured using the Bruker software Topspin 2.0. Spectroscopy revealed a number of differences in metabolites between OA, meniscal tear and ACL pathologies. These included significantly increased concentrations of glutamate, n-acetyl glycoprotein and β-hydroxybutyrate in OA (n=10) and acute meniscal tears (n=6) compared to ACL samples (p<0.05, T-test, n=6). Specific metabolites were also able to discriminate between OA with no meniscal tear and OA with meniscal tear synovial fluids. For example, concentrations of n-acetyl glycoproteins, glutamate and CH3 lipids were significantly increased in OA without tears (n=10) compared to OA plus meniscal tears (n=12); conversely ceramide concentrations were significantly increased in OA plus tears compared to OA only samples (p<0.05, T-test).Method
Results
Bone has a number of different functions in the skeleton including the physical roles of support, protection and sound wave conduction. The mechanical properties, required for these different functions varies and can be achieved by compositional adaption of the bone material, in addition to changes in shape and architecture. A number of previous studies have demonstrated the relationship between mechanical function and mineral to collagen ratio in bones from different species. The aim of this study is to test the hypothesis that the mineral to collagen ratio is higher in bone with a mechanically harder matrix within a species. The red deer The results showed that the hardness (Indentation Distance Increase) was lowest in the metacarpal (8.5µm), followed by the bulla bone (9.4µm) and highest in the antler (14.5µm). Raman spectroscopy showed a mineral:collagen ratio of 1:0.10 (bulla), 1:0.13 (metacarpal) and 1:0.15 (antler) for the different bones. This does not follow the more linear trend previously shown between young's modulus and the mineral:collagen ratio. The location of the mineral appeared to differ between bone types with pQCT revealing locations of concentrated density and banding patterns in antler. Interestingly, Raman spectra showed differences in the amide peaks revealing differences in protein structure. The results reject the hypothesis but also suggest that the organisation of mineral and collagen has an impact on the hardness modulus. We demonstrate that the red deer provides a good model for studying bone specialisation. This work will provide the basis for further investigation into collagen as a controlling factor in mineral deposition.
The purpose of this anatomical study was to explore the morphological variations of the semitendinosus and gracilis tendons in length and cross-section and the statistical relationship between length, cross-section, and body height. We studied the legs of 93 humans in 136 cadavers. In 43 specimens (46.2%) it was possible to harvest the tendons from both legs. We found considerable differences in the length and cross-section of the semitendinosus and the gracilis tendons with a significant correlation between the two. A correlation between the length of the femur, reflecting height, and the length of the tendons was only observed in specimens harvested from women. The reason for this gender difference was unclear. Additionally, there was a correlation between the cross-sectional area of the tendons and the length of the femur. Surgeons should be aware of the possibility of encountering insufficient length of tendon when undertaking reconstructive surgery as a result of anatomical variations between patients.
Tendon cross-sectional area (CSA) and stiffness increase in men during chronic exercise. The increase in tendon CSA and stiffness is not evident in women. In men, exercise increases tendon production of MMPs, IGF-1, and IL-6, which presumably contribute to tendon remodeling during chronic exercise. The purpose of this study was to determine if exercise-induced production of MMPs, IGF-1, and IL-6 are limited in women when compared to men. Young men (n=9, 27±1 y) and women (n=8, 26±1 y) performed a single bout of calf press exercise (8 sets of 15 repetitions at 70% of 15-RM). A microdialysis fiber (3000 kDa cut-off) was inserted into the space anterior to the Achilles tendon immediately after exercise and during a control experiment. All proteins were evaluated with ELISA kits.Introduction
Materials and Methods
Metaphyseal fracture healing is important in joint-adjacent fractures and appears to differ from diaphyseal healing. We recently found that a biomaterial delivering bone morphogenic protein-2 (BMP-2) and zoledronic acid (ZA) healed the metaphyseal bone in a tibial defect but failed closing the cortical defect. In this study we added a BMP-2 soaked collagen membrane to study cortical healing from the muscle tissue surrounding the bone. We used SD rats and a 4.5 mm metaphyseal circular tibial defect. In group 1 (G1), a porous gelatin-calcium sulphate-hydroxyapatite (GCH) biomaterial containing rhBMP-2 and ZA was used to fill the defect (GCH+5 μg BMP-2+10 μg ZA). In group 2 (G2), we used a collagen membrane (2 μg BMP-2) to cover the GCH filled defect (GCH+3μg BMP+10 μg ZA). Group 3 (G3) was an empty control. Animals were sacrificed after 8-weeks and bone regeneration was evaluated with micro-CT and histology. In both G1 (P<0.001) and G2 (p<0.001) a significantly higher mineralized volume was found in the defect compared to empty G3. In G2 higher mineralized volume was found in the cortical region compared to both G1 (p<0.01) and G3 (p<0.001) as seen via micro-CT. Histologically, G1 and G2 showed islands of trabecular bone in the defect peripherally but only G2 showed cortical healing. G3 was empty in the middle but showed healed cortex. In conclusion, GCH can be used to deliver BMP-2 and ZA to promote metaphyseal bone growth. A membrane (CM) doped with low dose BMP-2 improved cortical regeneration.