Characterization of extracellular vesicles in osteoporotic patients compared to osteopenic and healthy controls

Extracellular vesicles (EVs) are mediators of a range of pathological conditions. However, their role in bone loss disease has not been well understood. In this study we characterized plasma EVs of 54 osteoporotic (OP) postmenopausal women compared to 48 osteopenic (OPN) and 44 healthy controls (CN), and we investigated their effects on osteoclasts and osteoblasts. We found no differences between the three groups in terms of anthropometric measurements and biochemical evaluation of serum calcium, phosphate, creatinine, PTH, 25-hydroxy vitamin D and bone biomarkers, except for an increase of CTX level in OP group. FACS analysis revealed that OP patients presented a significantly increased number of EVs and RANKL(+) EVs compared with both CN and OPN subjects. Total EVs are negatively associated with the lumbar spine T-score and femoral neck T-score. Only in the OPN patients we observed a positive association between the total number of EVs and RANKL(+) EVs with the serum RANKL. In vitro studies revealed that OP EVs supported osteoclastogenesis of healthy donor peripheral blood mononuclear cells at the same level observed following RANKL and M-CSF treatment, reduced the ability of mesenchymal stem cells to differentiate into osteoblasts, while inducing an increase of OSTERIX and RANKL expression in mature osteoblasts. The analysis of miRNome revealed that miR-1246 and miR-1224-5p were the most upregulated and downregulated in OP EVs; the modulated EV-miRNAs in OP and OPN compared to CN are related to osteoclast differentiation, interleukin-13 production and regulation of canonical WNT pathway. A proteomic comparison between OPN and CN EVs evidenced a decrease in fibrinogen, vitronectin, and clusterin and an increase in coagulation factors and apolipoprotein, which was also upregulated in OP EVs. Interestingly, an increase in RANKL(+) EVs and exosomal miR-1246 was also observed in samples from patients affected by Gorham-Stout disease, suggesting that EVs could be good candidate as bone loss disease biomarkers. (c) 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)

Estudo de seguimento por dois anos de idosos residentes em São Paulo, Brasil: metodologia e resultados preliminares

INTRODUCTION: Previous cross-sectional studies have shown a high prevalence of chronic disease and disability among the elderly. Given Brazil s rapid aging process and the obvious consequences of the growing number of old people with chronic diseases and associated disabilities for the provision of health services, a need was felt for a study that would overcome the limitations of cross-sectional data and shed some light on the main factors determining whether a person will live longer and free of disabling diseases, the so-called successful aging. The methodology of the first follow-up study of elderly residents in Brazil is presented. METHOD: The profile of the initial cohort is compared with previous cross-sectional data and an in-depth analysis of nonresponse is carried out in order to assess the validity of future longitudinal analysis. The EPIDOSO ( Epidemiologia do Idoso ) Study conducted a two-year follow-up of 1,667 elderly people (65+), living in S. Paulo. The study consisted of two waves, each consisting of household, clinical, and biochemical surveys. RESULTS AND CONCLUSIONS: In general, the initial cohort showed a similar profile to previous cross-sectional samples in S. Paulo. There was a majority of women, mostly widows, living in multigenerational households, and a high prevalence of chronic illnesses, psychiatric disturbances, and physical disabilities. Despite all the difficulties inherent in follow-up studies, there was a fairly low rate of nonresponse to the household survey after two years, which did not actually affect the representation of the cohort at the final household assessment, making unbiased longitudinal analysis possible. Concerning the clinical and blood sampling surveys, the respondents tended to be younger and less disabled than the nonrespondents, limiting the use of the clinical and laboratory data to longitudinal analysis aimed at a healthier cohort. It is worth mentioning that gender, education, family support, and socioeconomic status were not important determinants of nonresponse, as is often the case.INTRODUÇÃO: Estudos transversais recentes mostraram alta prevalência de doenças crônicas e incapacidades físicas entre idosos. Considerando o rápido processo de envelhecimento do Brasil e as conseqüências que esse aumento de idosos com doenças crônicas e incapacidades associadas acarretará para o sistema de saúde, fazia-se necessário estudo que pudesse superar as limitações dos dados transversais, permitindo determinar quais os fatores determinantes de uma vida longa e livre de doenças incapacitantes, o chamado envelhecimento bem sucedido. É apresentada a metodologia do primeiro estudo epidemiológico longitudinal com idosos residentes na comunidade, no Brasil. MÉTODO: O perfil do cohorte inicial é comparado com dados de estudos anteriores a com o perfil dos não respondentes para avaliar a validade de análises longitudinais futuras.O projeto EPIDOSO (Epidemiologia do Idoso) seguiu por dois anos 1.667 idosos (65+), residentes em São Paulo. Consistiu de duas ondas, cada qual com três inquéritos: domiciliar, clínico e laboratorial. RESULTADOS E CONCLUSÕES: O perfil da população não diferiu de estudos anteriores, mostrando maioria de mulheres, viúvas, vivendo em domicílios multigeracionais, com uma alta prevalência de doenças crônicas, distúrbios psiquiátricos e incapacidades físicas. A despeito de todas as dificuldades inerentes a um estudo longitudinal, o grupo de não-respondentes ao segundo inquérito domiciliar não diferiu significativamente dos respondentes, assegurando análises longitudinais livres desse tipo de viés. Em relação aos inquéritos clínico e laboratorial, os não-respondentes mostraram-se mais velhos e mais incapacitados que os respondentes, limitando o uso dos dados clínicos e laboratoriais a análises pertinentes a uma cohorte mais jovem e saudável. Sexo, educação, apoio familiar e nível socioeconômico não influenciaram de forma significativa a taxa de não - resposta, ao contrário do que se costuma verificar.Universidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

Bone wax in the treatment of partial epiphysiodesis of distal femoral growth plate: Case report at 10-year follow-up

The growth plate is the weakest structure in the skeleton of a child and a frequent site of injury or fracture; physeal injuries represent 15%–30% of all fractures in children. Of all growth plate fractures, the incidence of growth arrest and disorders is around 15%. Here, we discuss a female patient who, at the age of 5 years, was treated for a polytrauma that involved a complex lesion of the growth plates of the knee. Four days after trauma, she underwent closed reduction surgery and internal fixation with cannulated screws for femoral and tibial fractures of the growth plate. A 20° valgus deviation of the left knee was found at 3-month postoperative clinical check-up likely as a result of a growth disorder of the femur. She was diagnosed with valgus knee secondary to epiphysiodesis of the lateral portion of the femoral physis and she was readmitted to the hospital. In the operating theater, an open femoral de-epiphysiodesis was performed with a burr; the drilled hole was then filled with bone wax. At 20-month post-trauma follow-up, the left knee was still valgus about 20° relative to the other side. During follow-up, a slow but progressive improvement in the axis of the lower limbs was noted. Clinical and radiographic control 10 years after the trauma showed a complete recovery of the axis of the lower limbs. In the initial stages, the presence of bone wax in the area of de-epiphysiodesis allowed for stabilization of the deformity on the 20° of preoperative valgus. The interpretation of the growth cartilage activity occurred in an asymmetrical way such as to realign the femoral load axis, it can be based on the different mechanical stimulus on the two knee areas due to the preexisting deformity. There is no unanimous evidence in the literature in terms of management of growth disorders resulting from this type of injury. Bone wax resulted in effectively filling the hole of de-epiphysiodesis in the distal femoral growth plate and allowed us to obtain the response of the growth plate and to improve the recovery time in young children

Molecular and crystal structure of a dehydroalanine dipeptide

The molecular and crystal structure of the synthetic, terminally blocked, model dipeptide t-Boc-L-Val-ΔAla-OMe (1) was determined by single-crystal X-ray diffraction. Crystal data for 1 are: C14H24N2O5, hexagonal, space group P65 (no.170), a = 10.8000(2) Å, c = 27.077(2) Å, and Z = 6. The crystal structure was solved by direct methods. The least-squares refinement led to R and Rw values of 0.077 and 0.075, respectively, for 1298 reflections F ≥ 5 σ(F). The conformation of the Val residue is partially extended, while that of ΔAla residue is trans, cis. The N-terminal protecting groups is in the trans, trans disposition

Initial In-Brace Correction: Can the Evaluation of Cobb Angle Be the Only Parameter Predictive of the Outcome of Brace Treatment in Patients with Adolescent Idiopathic Scoliosis?

Background: Patients with a better initial in-brace correction could show a higher probability of a successful outcome. However, no one has investigated whether parameters can affect the outcomes. The aim of this retrospective study was to evaluate if the initial correction rate (ICR) could be predictive of the bracing outcome and to determine the role of some mechanical and biological parameters in ICR. Methods: The study population comprised 449 patients who met the inclusion criteria. Curve correction > 10° Cobb defines brace treatment success. Success and failure groups were compared in terms of the Risser sign, initial Cobb angle, initial Perdriolle value and ICR. Results: ICR significantly correlates with initial Perdriolle. The success group had a significantly lower value of Pedriolle and initial Cobb angles, Risser sign and ICR than the failure group. The ICR and lower Risser were significantly associated with the brace treatment outcome. This seems particularly suitable for positivity prediction (Predicting value VP+: 87%). Conclusions: This study confirms that immediate in-brace correction can foretell the brace treatment outcome. Patients with a low Risser sign and a high rate of in-brace correction showed a bracing success of 87%. A correlation between rotation and in-brace correction confirms that rotation is among the parameters that influence the deformed spine reaction to corrective actions the most

Recommendations from the Italian Society of Pediatric Orthopaedics and Traumatology for the management of pediatric orthopaedic patients during the COVID19 pandemic and post-pandemic period in Italy

The rapid spread of the COVID-19 outbreak in Italy has dramatically impacted the National Healthcare System, causing the sudden congestion of hospitals, especially in Northern Italy, thus imposing drastic restriction of almost all routine medical care. This exceptional adaptation of the Italian National Healthcare System has also been felt by non-frontline settings such as Pediatric Orthopaedic Units, where the limitation or temporary suspension of most routine care activities met with a need to maintain continuity of care and avoid secondary issues due to the delay or suspension of the routine clinical practice. The Italian Society of Pediatric Orthopaedics and Traumatology formulated general and specific recommendations to face the COVID-19 outbreak, aiming to provide essential care for children needing orthopaedic treatments during the pandemic and early post-peak period, ensure safety of children, caregivers and healthcare providers and limit the spread of contagion