Bone adaptation impact of stemless shoulder implants: a computational analysis.

BACKGROUND: Despite stemless implants showing promising functional and radiologic clinical outcomes, concerning signs of complications, such as bone resorption, have been reported. The aim of this study was to investigate the influence of 5 stemless designs on the bone adaptation process of the humerus. METHODS: Three-dimensional finite element models of shoulder arthroplasties were developed considering stemless designs based on the Eclipse, Global Icon, SMR, Simpliciti, and Sidus stemless systems. For the designs not possessing a collar that covers the entire resected surface of the humerus, conditions of contact and no contact were simulated between the humeral head components and the bone surface. By use of a bone remodeling model, computational simulations were performed considering 6 load cases of standard shoulder movements. The bone adaptation process was evaluated by comparing differences in bone density between the implanted models and the intact model of the humerus. RESULTS: Overall, the design of the stemless implants had a relevant impact on the bone adaptation process of the humerus. The Eclipse-based design caused the largest bone mass loss, whereas the SMR-based design caused the least. When contact was simulated between the humeral head components of the SMR-, Simpliciti-, and Sidus-based designs and the resected bone surface, bone resorption increased. DISCUSSION: Considering only the bone adaptation process, the results suggest that the SMR-based implant presents the best performance and that contact between the humeral head component and the resected bone surface should be avoided. However, because other factors must be considered, further investigation is necessary to allow definite recommendations.

Pseudomalignant osteoblastoma of the odontoid process.

INTRODUCTION: The anterior elements of the spine, particularly the odontoid processes, are a rare location for osteoblastomas. Pseudomalignant osteoblastomas are themselves rare histologic types and are also extremely rare in this location. Most osteoblastomas are Enneking stage 2 lesions; less frequently, they can be more aggressive with extra-capsular extension (Enneking stage 3). En bloc resection is recommended for aggressive lesions, but the literature is less clear regarding the approach to stage 2 tumors, particularly those with pseudomalignant histologic features. CASE REPORT: A 6-year-old male child presented with a type III pathologic fracture of the odontoid. The fracture healed but upon 6-month follow-up CT scanning, an expansile lesion was detected. Surgical biopsy revealed an osteoblastoma which was treated with intralesional excision. Meanwhile, the excised specimen showed histological features of a pseudomalignant osteoblastoma. Despite this diagnosis, no further treatment was undertaken. At a 10-year follow-up, the patient was free from pain and had full range of motion of the cervical spine; no recurrence was detected. CONCLUSION: This unique case of odontoid osteoblastoma illustrates that malignant behavior may not be predicted only by the presence of pseudomalignant features on histology.

Arthroscopic versus open treatment of cam-type femoro-acetabular impingement: retrospective cohort clinical study.

PURPOSE: The purpose of this study was to determine if there were significant differences between patients submitted to hip arthroscopy (HA) and surgical hip dislocation (SHD) to treat femoro-acetabular impingement (FAI), which variables were significantly associated with hip function before surgery and those predictive of the applied functional outcome scale and its variation rate after surgery. METHODS: We selected 198 patients treated with HA or SHD with a mean follow-up of 59 months. Inclusion criteria were ages 18-50 years, isolated FAI cam morphology and complete clinical and radiologic documentation. The subjective outcome measure used was the nonarthritic hip score (NAHS). We compared pre-operative and post-operative NAHS, alpha angles and complication rates. Multiple linear regression analyses were performed to find which variables could influence NAHS values. RESULTS: The mean alpha-angle value improved from 71.5° to 40.8°, and mean NAHS improved from 50 to 83 points, with no difference between groups (HA/SHD). We found only a 16.9% influence rate on the pre-operative score, explained by variables of gender/pre-operative alpha angle and presence of degenerative changes/age. The influence rate on the NAHS variation ratio after surgery was 62.8%, explained by the variables of pre-operative score, type of surgery and type of surgery/alpha angle. The complication rate was 7%. CONCLUSIONS: FAI surgery can be considered effective in improving patient symptoms. There were no differences in clinical or radiographic results between techniques. We could more accurately predict the variation ratio of NAHS after surgery than its pre-operative value.

Effect of the strain rate on the twisting of trabecular bone from women with hip fracture.

As one of the major functions of bone is to provide structural support for the musculoskeletal system, it is important to evaluate its mechanical strength. Bones may be subjected to multiaxial stresses due to bone pathologies, accidental loads which may lead to hip, wrist fracture, or to a prosthetic joint replacement. Twist loading may lead to fractures, especially involving long bones from lower limbs. The aim of this work was to study the effect of the strain rate on the shear properties of trabecular bone samples from women with hip fracture (from 65 to 100 years). Cylindrical samples were core drilled from human femoral heads along the primary trabecular direction. The cylinder's ends were polished and embedded in blocks of polymeric material which fit the grips of the testing device. Deformation rates of 0.005, 0.01, 0.015, and 0.05 s⁻¹ were applied. Twisting tests were conducted with or without an applied axial load of 500 N. From the torque-angular displacement curves, the shear stress-strain curves were obtained. The maximum shear strength and the shear modulus (i.e. the slope of the linear region) were determined. A large scatter of the results of the shear strength and the shear modulus was found, which is probably related to the heterogeneity of nonhealthy human bone samples. There is no significant effect of the strain rate on the maximum shear stress and the shear modulus, either in tests undertaken with or without the application of an axial load. The effect of strain rate on nonhealthy bone trabecular twisting properties did not follow the trend observed on the effect of strain rate in healthy bone, where an increase is detected.

At the moment of occurrence of a fragility hip fracture, men have higher mechanical properties values in comparison with women.

BACKGROUND: It is well established that males have lower fracture risk in comparison with females, which suggests a higher bone resistance in men. The aim of our study was to find out if in older patients with hip fragility fractures, gender has also an impact on trabecular bone material behaviour, specifically to determine whether trabecular mechanical properties under compressive loading differ between men and women who suffered a fragility hip fracture. METHODS: Femoral epiphyses were consecutively collected during hip replacement surgery due to proximal femur fragility fracture. Trabecular bone cylinders were drilled and submitted to uniaxial compression tests and mechanical properties were assessed. RESULTS: Seventy-three patients, 55 women (mean age 81 years and standard deviation of 7 years) and 18 men (mean age 81 years and standard deviation of 8 years) were evaluated. The ultimate stress of trabecular bone was significantly higher in men than in women: the median values and the interquartile range (IQR) were respectively 8.04(5.35-10.90) MPa vs. 4.46(3.02-7.73) MPa, (p-value = 0.005). The same difference between male and female was observed in the Young's modulus: 293.68(166.67-538.18) MPa vs. 174.26(73.07-322.28) MPa, (p-value = 0.028), and also in the energy to failure: 0.25(0.07-0.42) MJ/m³ vs. 0.11(0.05-0.25) MJ/m³, (p-value = 0.058). These differences were also verified after adjusting the analysis for age in a multivariate model analysis. CONCLUSIONS: Our observations demonstrated that, even in a population who suffered a fragility hip fracture, men still have higher trabecular bone mechanical properties in comparison with women.

Smoking is a predictor of worse trabecular mechanical performance in hip fragility fracture patients.

Clinical risk factors (CRFs) are established predictors of fracture events. However, the influence of individual CRFs on trabecular mechanical fragility is still a subject of debate. In this study, we aimed to assess differences, adjusted for CRFs, between bone macrostructural parameters measured in ex-vivo specimens from hip fragility fracture patients and osteoarthritis patients, and to determine whether individual CRFs could predict trabecular bone mechanical behavior in hip fragility fractures. Additionally, we also looked for associations between the 10-year risk of major and hip fracture calculated by FRAX and trabecular bone mechanical performance. In this case-control study, a group of fragility fracture patients were compared with a group of osteoarthritis patients, both having undergone hip replacement surgery. A clinical protocol was applied in order to collect CRFs [body mass index (BMI), prior fragility fracture, parental history of hip fracture, long-term use of oral glucocorticoids, rheumatoid arthritis, current smoking, alcohol consumption, age and gender]. The 10-year probability of fracture was calculated. Serum bone turnover markers were determined and dual X-ray absorptiometry performed. Femoral head diameter was evaluated and trabecular bone cylinders were drilled for mechanical testing to determine bone strength, stiffness and toughness. We evaluated 40 hip fragility fracture and 52 osteoarthritis patients. Trabecular bone stiffness was significantly lower (p = 0.042) in hip fragility fracture patients when compared to osteoarthritic individuals, adjusted for age, gender and BMI. No other macrostructural parameter was statistically different between the groups. In hip fragility fracture patients, smoking habits (ß = -0.403; p = 0.018) and female gender (ß = -0.416; p = 0.008) were independently associated with lower stiffness. In addition, smoking was also independently associated with worse trabecular strength (ß = -0.323; p = 0.045), and toughness (ß = -0.403; p = 0.018). In these patients, the 10-year risk of major (r = -0.550; p = 0.012) and hip fracture (r = -0.513; p = 0.021) calculated using only CRFs was strongly correlated with femoral neck bone mineral density but not with mechanical performance. Our data showed that among fragility fracture patients active smoking is a predictor of worse intrinsic trabecular mechanical performance, and female gender is also independently associated with lower stiffness. In this population, the 10-year risk of fracture using CRFs with different weights only reflects bone mass loss but not trabecular mechanical properties.

The influence of the pelvic bone on the computational results of the acetabular component of a total hip prosthesis.

The computational models developed to evaluate the hip joint performance usually neglect the presence of the pelvic bone. However, deformation depends on the stiffness of the underlying bone, and thus, the inclusion of the pelvic bone in the model influences the computed contact pressure and wear. This work discusses the influence of the pelvic bone, and how it depends on the acetabular component stiffness. It was modeled as two different polyethylene acetabular cups, considering or not a metal-backing for both 28 mm and 32 mm diametric cups. Two finite element models are developed, considering either the acetabular component rigidly fixed or attached to the deformable bone. Results present 28% and 42% difference on the contact pressure for a polyethylene cup without metal-backing when the support conditions are changed, for the 28 mm and 32 mm cups, respectively. Linear wear results present 21% and 31% difference for the same type of cups of 28 mm and 32 mm, correspondingly. The numerical results obtained in the present work show that to model the pelvic bone of the patient with a metal-backed cup did not greatly affect contact pressures and linear wear. However, when a total hip replacement is performed with an all-polyethylene acetabular cup, the presence of the pelvic bone in the model has a major influence.

Blood Management and Risk Assessment for Transfusion in Pediatric Spinal Deformity Surgery.

OBJECTIVES: Evaluate the impact of a Quality and Safety Program (QSP) on the reduction of blood loss and transfusion needs in pediatric spinal deformity surgery, while defining risk factors for transfusion. BACKGROUND: Multimodal plan aiming to minimize transfusion needs has been shown to reduce transfusions and index rates in spinal deformity surgery. Anticipating blood loss and transfusion may help direct resources to patient needs or encourage reconsideration of the surgical plan. METHODS: This is a single-center retrospective study of prospectively collected data. Impact of this multimodal plan was studied on idiopathic deformities (Group A, 109 patients) and scoliosis associated with syndromic, neuromuscular, and muscular dystrophies (Group B, 100 patients), both before and after QSP. RESULTS: A decrease in total estimated blood loss was observed. In Group A, transfused patients decreased from 83.7% to 28% (p < 0.001, odds: 0.077), and, in Group B, from 98.7% to 66% (p < 0.01, odds: 0.038). Pearson's correlation identified patient body weight (r = 0.245, p=0.001) and Cobb angle (r = 0.175, p=0.017) as factors related to blood loss. A linear regression model to estimate hematic losses revealed that only body weight and transfusion showed predictive power, resulting in a low predictive model (R 2 = 0.156; F(3,167) = 15.483, p < 0.001). A mediated model to explain blood loss was built based on a set of variables influencing transfusion which is, in turn, related to blood loss. CONCLUSION: Transfusion needs in scoliosis surgery can be substantially reduced following a multimodal approach. The success of a program is strongly dependent on team effort, and the introduction of a risk assessment tool for transfusion needs indirectly assesses surgical risk, thus allowing relocation of resources to decrease blood loss.

Palm-up test and range of motion in flexion and external rotation provide best correlation with disability and perceived pain in patients with shoulder complaints.

The aim of this study was to find a reliable set of clinical tests to predict pain and disability in patients with shoulder pain. Shoulder pain is the second most frequent musculoskeletal complaint in the primary care setting and has a great impact in work and leisure activities. Patient reported outcomes measuring pain and disability are available, but they are time-consuming, often biased by psychological and sociological factors and depend on patient collaboration. This was an observational, cross-sectional study, including patients with shoulder pain aged 18 to 70 years. Patients filled in the questionnaires Disabilities of the Arm, Shoulder and Hand outcome measure (DASH) and Shoulder Pain and Disability Index (SPADI) pain scale. A Visual Analogue Scale (VAS) for current pain was applied and sociodemographic and clinical data were collected. Physical examination included the Jobe, Neer and palm-up signs, range of motion (ROM) of shoulder abduction, flexion and rotation (internal and external), both active and passive. An independent t-test to compare differences between groups and the Spearman's coefficient for evaluation of bivariate correlation were used. Linear regression analysis was applied to relevant predictors. Tests were two-tailed and p values < 0.05 were considered significant. A total of 127 patients were included. Female patients and those with a positive Jobe, Neer or palm-up tests, complaints on dominant side, no leisure activity involving shoulder effort, a history of previous shoulder tendinopathy or taking analgesics had significantly higher DASH scores. Age and all range of motion variables significantly correlated with DASH scores. A linear regression model with six dependent variables (Palm-up test, range of motion in active flexion and external rotation, age, gender and complaints on dominant side) produced the highest correlation (R = 0.665), explaining 44% of the variance of DASH score. A model based on few physical examination items and individual objective data like age, gender and dominancy, can help predict disability and perceived pain in shoulder disorders. Palm-up test and range of motion in active flexion, abduction and external rotation showed best correlation with the outcome, but abduction was found redundant for the obtained prediction model.

Short-term results (1 year) of vented versus solid polyetheretherketone anchors in treatment of rotator cuff tears.

BACKGROUND: Due to the rotator cuff retear after being surgically repaired, some strategies have been developed. The authors verified that the possibility of polyetheretherketone (PEEK) vented anchors promoted a better clinical and healing process than PEEK solid anchors. METHODS: A prospective and randomized study was designed with 38 patients treated with PEEK anchors, 18 of whom with vented anchors and 20 with solid ones. Demographic, clinical and radiologic data were collected before and during surgery (time 0) and at 12 months of follow-up. RESULTS: In the final follow-up (12 months), there was no difference in the visual analogic scale (VAS) scale between groups (1.7 points vs 1.9 points; p = 0.731), neither in the DASH score (34.2 points vs 23.9 points; p = 0.268), nor in absolute Constant score (76.9 points vs 77.3 points; p = 0.910). In MRI, 10 patients had their cuff tear healed in the vented group and 15 in the solid group (p = 0.173). CONCLUSION: The new designed vented anchors do not add any advantage when compared to solids ones, at least within the first year after surgery.

Impact of Surgery on the Quality of Life of Adolescent Idiopathic Scoliosis.

Background: The impact of surgery on the quality of life of adolescents with idiopathic scoliosis (AIS) remains to be clarified as most of the studies are retrospective and few include quality of life questionnaires completed in the pre- and postoperative periods. Methods: Operated patients with AIS who completed preoperative and postoperative SRS-22 questionnaires were selected for evaluation. The demographic data were collected and quality of life improvement was assessed by comparing deviation to the means with standard deviation at both moments. Using the Minimal Important Clinical Difference (MICD) concept, individual improvement was also assessed. Results: 28 patients (27 females) with an average age of 14.4 years (min: 12 - max: 18) and an average Cobb angle of 61.46º (min: 35º- max: 98º) were retrospectively reviewed. The correction rate was 68% with a final Cobb angle of 18.97º (min: 7.37º - max: 37.6º). The Global SRS22 score and all sub domains showed a significant variation (p<0,01). Self-image, followed by mental health, were the subdomains where the mean differences was more relevant, with the highest effect dimension given by d-Cohen analyses (Self-image d-Cohen 2.51; Mental health -d-Cohen 0.86). Both mean score differences as well as global SRS22 score reached the MICD but, while 96.4% of the patients did so for self-image ,the same only happened in 50% of the patients in Mental health and global score. No clinical relevant change occurred in pain or activity domains. Conclusion: Taking into consideration the AIS natural history and the fact that the most relevant change after surgery occurs in patients' self-esteem, the advantages of a surgical treatment should be thoroughly evaluated not only based on curve severity but also by looking at which quality of life subdomains are mostly affected and which are expected to improve in order to meet proper patient expectations.Level of evidence: III.

Late implant migration with neurologic compromise as a complication of scoliosis surgery.

Late neurological deficit following scoliosis surgery is a rare event and any change in the patient's neurological status deserves immediate attention. We report on two clinical cases (at 2 and 6 years of follow-up) where two different types of proximal instrumentation resulted in lateral drift into the spinal canal causing cord compression with neurological deficit. Late neurological compromise in a posterior spinal-fusion setting deserves a prompt and complete spine investigative search for non-union, infection, or implant migration into the spinal canal.

[ß-Tricalcium Phosphate in the Surgical Treatment of Proximal Humeral Fractures]. / Fosfato ß-Tricálcico Monobloco no Tratamento de Fraturas Proximais do Ãmero Cirúrgicas.

INTRODUCTION: The proximal humeral fractures are becoming more frequent, with a greater tendency for its surgical treatment by osteosynthesis with plate and locked screws. The mechanical and biological failure in these fractures and devices, despite the evolution of this type of implants, highlighted the synthetic bone grafts became an option. MATERIAL AND METHODS: Over a period of 96 months, patients considered were those with proximal humeral fractures treated surgically with a plate and locked screws, and in which ß-tricalcium phosphate bone graft had been used. Functional results were evaluated by the shoulder range of motion as the radiological results. RESULTS: In 19 patients, with a medial follow up of 53 months, we obtained an average shoulder range of motion of 140º in abduction, 142º in forward flexion, 37º in external rotation and L3 hand position in internal rotation for a cefalo-diaphyseal angle of 136º. DISCUSSION: The ß-tricalcium phosphate synthetic bone graft allows the maintenance of reduction after fixation of proximal humeral fractures stabilized with plate and locked screws. This reduction which means the maintenance of cefalo-diaphyseal angle is in close relationship with functional results as shown by shoulder range of motion in all planes. CONCLUSION: The ß-tricalcium phosphate synthetic bone graft should be seen as an adjuvant therapy in extramedullary fixation of proximal humeral fractures, especially those with greater comminution of the medial calcar.

Introdução: As fraturas proximais do úmero são cada vez mais frequentes, com maior tendência para o seu tratamento cirúrgico, predominado a utilização da osteossíntese com placa e parafusos bloqueados. Pela falência mecânica e biológica, apesar da evolução deste tipo de implantes, a utilização de enxertos ósseos sintéticos passaram a ser uma opção. Material e Métodos: Num período de 96 meses, avaliámos os doentes com fraturas proximais do úmero, tratados cirurgicamente com placa e parafusos bloqueados e nos quais foi usado enxerto ósseo sintético de fosfato ß-tricálcico. Avaliaram-se os resultados funcionais pelo arco de mobilidade e pelos exames radiográficos. Resultados: Nos 19 doentes avaliados, para um follow-up médio de 53 meses, obteve-se um arco de mobilidade com valores médio de abdução de 140º, flexão anterior de 142º, rotação externa de 37º e rotação interna com mão a L3, para um ângulo cefalo-diafisário de 136º. Discussão: A utilização de enxerto ósseo sintético de fosfato ß-tricálcico permite a estabilização da redução após fixação das fraturas proximais do úmero estabilizadas com placa e parafusos bloqueados. Esta redução que se traduz na manutenção do ângulo cefalodiafisário, permite a obtenção de bons resultados funcionais como o demonstra o arco de mobilidade nos vários planos. Conclusão: O enxerto ósseo sintético de fosfato ß-tricálcico deverá ser encarado como uma terapêutica auxiliar na osteossíntese extramedular das fraturas proximais do úmero, principalmente naquelas com maior dificuldade de manutenção da redução pela maior cominução do calcar medial.

Critical analysis of musculoskeletal modelling complexity in multibody biomechanical models of the upper limb.

The inverse dynamics technique applied to musculoskeletal models, and supported by optimisation techniques, is used extensively to estimate muscle and joint reaction forces. However, the solutions of the redundant muscle force sharing problem are sensitive to the detail and modelling assumptions of the models used. This study presents four alternative biomechanical models of the upper limb with different levels of discretisation of muscles by bundles and muscle paths, and their consequences on the estimation of the muscle and joint reaction forces. The muscle force sharing problem is solved for the motions of abduction and anterior flexion, acquired using video imaging, through the minimisation of an objective function describing muscle metabolic energy consumption. While looking for the optimal solution, not only the equations of motion are satisfied but also the stability of the glenohumeral and scapulothoracic joints is preserved. The results show that a lower level of muscle discretisation provides worse estimations regarding the muscle forces. Moreover, the poor discretisation of muscles relevant to the joint in analysis limits the applicability of the biomechanical model. In this study, the biomechanical model of the upper limb describing the infraspinatus by a single bundle could not solve the complete motion of anterior flexion. Despite the small differences in the magnitude of the forces predicted by the biomechanical models with more complex muscular systems, in general, there are no significant variations in the muscular activity of equivalent muscles.

Subject-specific bone remodelling of the scapula.

Finite element analyses, with increasing levels of detail and complexity, are becoming effective tools to evaluate the performance of joint replacement prostheses and to predict the behaviour of bone. As a first step towards the study of the complications of shoulder arthroplasty, the aim of this work was the development and validation of a 3D finite element model of an intact scapula for the prediction of the bone remodelling process based on a previously published model that attempts to follow Wolff's law. The boundary conditions applied include full muscle and joint loads taken from a multibody system of the upper limb based on the same subject whose scapula was here analysed. To validate the bone remodelling simulations, qualitative and quantitative comparisons between the predicted and the specimen's bone density distribution were performed. The results showed that the bone remodelling model was able to successfully reproduce the actual bone density distribution of the analysed scapula.

Rheumatoid arthritis bone fragility is associated with upregulation of IL17 and DKK1 gene expression.

Our aim was to compare bone gene expression in rheumatoid arthritis (RA) and primary osteoporosis (OP) patients. Secondary aims were to determine the association of gene expression of the Wnt/ß-catenin signaling pathway with inflammatory cytokines in the bone microenvironment and to assess the serum levels of Wnt/ß-catenin proteins in both groups. RA patients referred for hip replacement surgery were recruited. Primary OP patients were used as controls. Gene expression of Wnt pathway mediators, matrix proteins, and pro-inflammatory cytokines were analyzed in bone samples. Bone turnover markers, inflammatory cytokines, and Wnt mediators were measured in serum. Twenty-two patients were included: 10 with RA and 12 with primary OP. The expressions of Wnt10b (p = 0.034), its co-receptor LRP6 (p = 0.041), and its negative regulator DKK1 (p = 0.008) were upregulated in RA bone. IL17 gene expression in bone was upregulated in RA patients (p = 0.031) and correlated positively with Wnt10b (r = 0.810, p = 0.015), DKK2 (r = 0.800, p = 0.010), and RANKL/OPG ratio (r = 0.762, p = 0.028). DKK2 (p = 0.04) was significantly decreased in RA serum compared with primary OP. In conclusion, bone fragility in RA patients is induced by an unbalanced bone microenvironment and is associated with a specific gene expression pattern, namely, the upregulation of IL17 and DKK1, suggesting that the modulation of these two pathways might prevent RA systemic bone loss.

Bone remodelling analysis of the humerus after a shoulder arthroplasty.

The shoulder arthroplasty has become an efficient treatment for some pathologies. However there are complications that can compromise its success. Among them, the stress shielding effect on the humerus has been reported as a possible cause of failure. The objective of this work was to investigate the bone remodelling in the humerus after a shoulder arthroplasty. For this purpose, computational models were developed to analyse the stress shielding contribution to the humeral component failure of shoulder arthroplasties, with a cemented and an uncemented prosthesis. A computational remodelling model was used to characterize the bone apparent density at each site of the humerus. The density distribution was obtained by the solution of a problem that takes into account both structural stiffness and the metabolic cost of bone maintenance. Bone was subjected to 6 load cases that include the glenohumeral reaction force and the action of 10 muscles. In the implanted models, different interface conditions were tested for the bone-implant and the cement-implant interfaces. Moreover, a pathological case defined by a poorer quality of bone was considered. In the healthy situation, the models that better model in vivo conditions showed no significant changes in bone mass. However, the results for the pathological case showed some bone resorption which supports the importance given to the quality of bone in the success of the joint replacement. Bearing in mind the conditions addressed, the results lead to conclude that the stress shielding is not a key factor for the humeral component failure of shoulder arthroplasties in a healthy situation though several issues, including muscle function and bone quality, may heighten its effect.

Low osteocalcin/collagen type I bone gene expression ratio is associated with hip fragility fractures.

INTRODUCTION: Osteocalcin (OC) is the most abundant non-collagenous bone protein and is determinant for bone mineralization. We aimed to compare OC bone expression and serum factors related to its carboxylation in hip fragility fracture and osteoarthritis patients. We also aimed to identify which of these factors were associated with worse mechanical behavior and with the hip fracture event. METHODS: In this case-control study, fragility fracture patients submitted to hip replacement surgery were evaluated and compared to a group of osteoarthritis patients submitted to the same procedure. Fasting blood samples were collected to assess apolipoproteinE (apoE) levels, total OC and undercarboxylated osteocalcin (ucOC), vitamin K, LDL cholesterol, triglycerides and bone turnover markers. The frequency of the apoε4 isoform was determined. Femoral epiphyses were collected and trabecular bone cylinders drilled in order to perform compression mechanical tests. Gene expression of bone matrix components was assessed by quantitative RT-PCR analysis. RESULTS: 64 patients, 25 submitted to hip replacement surgery due to fragility fracture and 39 due to osteoarthritis, were evaluated. Bone OC/collagen expression (OC/COL1A1) ratio was significantly lower in hip fracture compared to osteoarthritis patients (p<0.017) adjusted for age, gender and body mass index. Moreover, OC/COL1A1 expression ratio was associated with the hip fracture event (OR ~0; p=0.003) independently of the group assigned, or the clinical characteristics. Apoε4 isoform was more frequent in the hip fracture group (p=0.029). ucOC levels were higher in the fracture group although not significantly (p=0.058). No differences were found regarding total OC (p=0.602), apoE (p=0.467) and Vitamin K (p=0.371). In hip fracture patients, multivariate analysis, adjusted for clinical characteristics, serum factors related to OC metabolism and gene expression of bone matrix proteins showed that low OC/COL1A1 expression ratio was significantly associated with worse trabecular strength (ß=0.607; p=0.013) and stiffness (ß=0.693; p=0.003). No association was found between ucOC and bone mechanics. Moreover, in osteoarthritis patients, the multivariate analysis revealed that serum total OC was negatively associated with strength (ß=-0.411; p=0.030) and stiffness (ß=-0.487; p=0.009). CONCLUSION: We demonstrated that low bone OC/COL1A1 expression ratio was an independent predictor of worse trabecular mechanical behavior and of the hip fracture event. These findings suggest that in hip fracture patients the imbalance of bone OC/COL1A1 expression ratio reflects disturbances in osteoblast activity leading to bone fragility.

Upregulation of inflammatory genes and downregulation of sclerostin gene expression are key elements in the early phase of fragility fracture healing.

BACKGROUND: Fracture healing is orchestrated by a specific set of events that culminates in the repair of bone and reachievement of its biomechanical properties. The aim of our work was to study the sequence of gene expression events involved in inflammation and bone remodeling occurring in the early phases of callus formation in osteoporotic patients. METHODOLOGY/PRINCIPAL FINDINGS: Fifty-six patients submitted to hip replacement surgery after a low-energy hip fracture were enrolled in this study. The patients were grouped according to the time interval between fracture and surgery: bone collected within 3 days after fracture (n = 13); between the 4(th) and 7(th) day (n = 33); and after one week from the fracture (n = 10). Inflammation- and bone metabolism-related genes were assessed at the fracture site. The expression of pro-inflammatory cytokines was increased in the first days after fracture. The genes responsible for bone formation and resorption were upregulated one week after fracture. The increase in RANKL expression occurred just before that, between the 4(th)-7(th) days after fracture. Sclerostin expression diminished during the first days after fracture. CONCLUSIONS: The expression of inflammation-related genes, especially IL-6, is highest at the very first days after fracture but from day 4 onwards there is a shift towards bone remodeling genes, suggesting that the inflammatory phase triggers bone healing. We propose that an initial inflammatory stimulus and a decrease in sclerostin-related effects are the key components in fracture healing. In osteoporotic patients, cellular machinery seems to adequately react to the inflammatory stimulus, therefore local promotion of these events might constitute a promising medical intervention to accelerate fracture healing.

[Epidemiology of hip fractures and its social and economic impact. A revision of severe osteoporosis current standard of care]. / A epidemiologia e o impacto sócio-económico das fracturas da extremidade proximal do fémur. Uma reflexão sobre o padrão actual de tratamento da osteoporose grave.

Hip fractures (HF) following low-impact trauma are the most visible and dramatic consequences of osteoporosis (OP). It is estimated that within one year after HF, 10 to 20% of the patients die, 50% become disabled and only 30% fully recover their previous functional levels. Therefore, its medical, societal and economic impact is huge and it is not fully delivered by the event itself, but rather by its consequences. This systematic review aims to collect available epidemiology data about HF and to revise the national data regarding the current OP treatment of patients after HF. In Portugal, over 9500 HF occur every year and have been growing along with due associated refracture and mortality rates. Despite the high vulnerability of patients and their continuous loss of bone mineral density, only 4.5 to 14.4% of them receive any OP medication. This lack of treatment represents a public health issue which is rising along with the ageing of populations and thus should not be disregarded. According to the clinical guidelines there are several pharmacological options available to stabilize bone mineral losses. This includes zoledronic acid which is associated with a significant reduction in the rate of new clinical fractures and improved survival after HF. Therefore, it is expected that by increasing the number of patients treated for OP after suffering a HF will translate in a significant benefit in terms of health outcomes and due public expenditure. This article illustrates how negative the current scenario is, not only from a clinical perspective, but also from an epidemiological one. This represents an unrestrained public health problem which should concern all health professionals and sectors related with OP fractures.