Función de las hormonas sexuales en la homeostasis del hueso y su papel en el desarrollo de la osteoporosis masculina: Una revisión narrativa / Role of sex hormones in bone homeostasis and their role in the development of male osteoporosis: A narrative review

El hueso es un tejido dinámico, que se encuentra en constante adaptación durante la vida de los vertebrados con el fin de alcanzar tamaño, forma, preservar la integridad estructural del esqueleto y regular la homeostasis mineral. Su desarrollo durante la infancia es determinante para alcanzar la estatura, así como la resistencia a fracturas en edad avanzada. Las hormonas sexuales juegan un papel importante en el remodelado óseo, tanto en hombres como en mujeres y las alteraciones en los perfiles hormonales pueden conducir al desarrollo de enfermedades asociadas con el metabolismo del hueso. En mujeres, la deficiencia de estrógenos durante la menopausia es una de las principales causas de osteoporosis, mientras que en hombres los andrógenos pueden influir en la salud ósea al unirse directamente a los receptores de andrógenos o indirectamente a receptores de estrógenos. En esta revisión se explora el papel y los efectos de las hormonas sexuales sobre el metabolismo óseo, las vías de señalización implicadas y los efectos que pueden conducir al desarrollo de enfermedades como la osteoporosis. (AU)

Bone is a dynamic tissue that undergoes constant adaptation throughout the life of vertebrates to achieve size, shape, preserve the structural integrity of the skeleton, and regulate mineral homeostasis. Bone growth during childhood is crucial to achieve height and resistance to fractures later in life. Sex hormones play a key role in bone remodeling in men and women alike, and changes to hormonal profiles can trigger bone metabolism-related diseases. In women, estrogen deficiency during menopause is one of the leading causes of osteoporosis, while in men, androgens can have an impact on bone health by binding directly to androgen receptors or indirectly to estrogen receptors. This review explores the role and effects of sex hormones on bone metabolism, the signaling pathways involved, and the effects that can trigger diseases such as osteoporosis. (AU)

Perfil asistencial del paciente con osteoporosis tributario de visita de telemedicina en la era post-COVID-19 / Care profile of susceptible patients with osteoporosis by telemedicine visits in the post-COVID-19 era

Definir el perfil del paciente con osteoporosis candidato y no candidato a la asistencia en la teleconsulta de osteoporosis, en la era post-COVID-19. Propuesta de un protocolo de manejo para su seguimiento ambulatorio. Métodos: Hemos realizado una revisión bibliográfica mediante una búsqueda sistemática en las bases de datos de Pubmed.gov de la evidencia disponible de artículos en inglés y español con fecha de inclusión hasta octubre del 2020 siguiendo las recomendaciones del sistema GRADE (Grading of Recommendations, Assessment, Development and Evaluation). Base de datos cuyo objetivo es la localización y recuperación de información relevante para esta revisión de forma actualizada. Resultados: El perfil del paciente candidato a teleconsulta sería aquel paciente con historia de osteoporosis, que conoce su enfermedad, con tratamiento y que precisa de seguimiento. La COVID-19 se ha dado en un contexto en el que las principales causas de mortalidad son las enfermedades crónicas y la necesidad de protegerse frente a la transmisión. Conclusiones: Proponemos un consenso del manejo de dicho paciente, con apartados diferenciados para las distintas etapas del proceso asistencial telemático, que ayude a la toma de decisiones clínicas y que sirva de ayuda en el proceso de seguimiento y adherencia terapéutica, y, por tanto, en la optimización de recursos asistenciales. (AU)

Objetive: Define the profile of the candidate and non-candidate osteoporosis patient for assistance in osteoporosis teleconsultation, in the post-COVID-19 era. Proposal of a management protocol for outpatient follow-up. Methods: We have carried out a bibliographic review through a systematic search in the Pubmed.gov databases of the available evidence of articles in English and Spanish with an inclusion date until October 2020, following the recommendations of the GRADE system (Grading of Recommendations, Assessment, Development and Evaluation). Database is aimed at locating and accessing relevant information for this review in an updated way. Results: The profile of the patient candidate for teleconsultation would be of those who present a history of osteoporosis, previously diagnosed, with treatment and requiring follow-up. COVID-19 has occurred in a context in which the main causes of mortality are chronic diseases and the need to protect against transmission. Conclusions: We propose a consensus for managing this patient, with differentiated sections for the different stages of the telematic care process. This will help in clinical decision-making and also in the process of follow-up and therapeutic adherence and, therefore, in optimal use of healthcare resources. (AU)

A comprehensive study on feature types for osteoporosis classification in dental panoramic radiographs.

BACKGROUND AND OBJECTIVE: Osteoporosis is a disease characterized by a decrease in bone density. It is often associated with fractures and severe pain. Previous studies have shown a high correlation between the density of the bone in the hip and in the mandibular bone in the jaw. This suggests that dental radiographs might be useful for detecting osteoporosis. Use of dental radiographs for this purpose would simplify early detection of osteoporosis. However, dental radiographs are not normally examined by radiologists. This paper explores the use of 13 different feature extractors for detection of reduced bone density in dental radiographs. METHODS: The computed feature vectors are then processed with a Self-Organizing Map and Learning Vector Quantization as well as Support Vector Machines to produce a set of 26 predictive models. RESULTS: The results show that the models based on Self-Organizing Map and Learning Vector Quantization using Gabor Filter, Edge Orientation Histogram, Haar Wavelet, and Steerable Filter feature extractors outperform the rest of the 22 models in detecting osteoporosis. The proposed Gabor-based algorithm achieved an accuracy of 92.6%, a sensitivity of 97.1%, and a specificity of 86.4%. CONCLUSIONS: The oriented edges and textures in the upper and lower jaw regions are useful for distinguishing normal patients from patients with osteoporosis.

Application of ICF conceptual framework in Osteoporosis.

Background: Osteoporosis (OP) is a metabolic bone disease defined by low bone strength and deterioration of bone tissue, which has wide clinical presentations. The World Health Organization's International Classification of Functioning Disability and Health (ICF) provides a common language, classification system, and conceptual framework to describe the consequences of health conditions in terms of body function and structure, activities and participation, environmental and personal factors. Objectives: The ICF conceptual framework was used, in this paper, to integrate OP research-based knowledge into clinical application using clinical vignettes. Results: Body functions and structures, activities and participation, environmental factors and personal factors are described, and the inter-connection among these factors is explored. The vignettes highlight the importance of different components of the ICF framework and to demonstrate how the ICF framework can capture individual differences in how disability can be experienced in OP. Conclusion: The ICF conceptual framework provides a holistic representation of disability by facilitating a critical appraisal of the health status of people with OP. The framework creates an awareness of the broad and multidimensional nature of OP on the health of individual patients, integrates dimensions of functioning, and highlights the complexity of the evaluation and management of OP.

A Contemporary View of the Definition and Diagnosis of Osteoporosis in Children and Adolescents.

The last 2 decades have seen growing recognition of the need to appropriately identify and treat children with osteoporotic fractures. This focus stems from important advances in our understanding of the genetic basis of bone fragility, the natural history and predictors of fractures in chronic conditions, the use of bone-active medications in children, and the inclusion of bone health screening into clinical guidelines for high-risk populations. Given the historic focus on bone densitometry in this setting, the International Society for Clinical Densitometry published revised criteria in 2013 to define osteoporosis in the young, oriented towards prevention of overdiagnosis given the high frequency of extremity fractures during the growing years. This definition has been successful in avoiding an inappropriate diagnosis of osteoporosis in healthy children who sustain long bone fractures during play. However, its emphasis on the number of long bone fractures plus a concomitant bone mineral density (BMD) threshold ≤ -2.0, without consideration for long bone fracture characteristics (eg, skeletal site, radiographic features) or the clinical context (eg, known fracture risk in serious illnesses or physical-radiographic stigmata of osteoporosis), inappropriately misses clinically relevant bone fragility in some children. In this perspective, we propose a new approach to the definition and diagnosis of osteoporosis in children, one that balances the role of BMD in the pediatric fracture assessment with other important clinical features, including fracture characteristics, the clinical context and, where appropriate, the need to define the underlying genetic etiology as far as possible.

Osteoporosis transitoria migratoria en miembros inferiores / Transient migratory osteoporosis in lower limbs

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The underlying pathophysiology and therapeutic approaches for osteoporosis.

With an increase in the ageing population worldwide, the prevalence of osteoporosis increases at an alarming rate in both male and female irrespective of their ethnicity. At present, the currently available therapeutic options are mostly limited to either bone resorptive or bone forming efficacies and both approaches are associated with serious side effects. Despite these options, there is still need for newer therapeutics to treat osteoporosis, which can offer beneficial effects for maintaining balanced dynamics between bone formation and bone resorption, devoid of any side effect. The proper understanding of pathophysiology of the disease is essential for designing or investigating an effective and safe anti-osteoporotic agent. This review represents a discussion around the molecular targets with their implications in disease progression, available therapeutic options, the emerging targets, and the importance of designing an effective anti-osteoporotic agent.

Clinical guidelines for the prevention and treatment of osteoporosis: summary statements and recommendations from the Italian Society for Orthopaedics and Traumatology.

BACKGROUND: The Italian Society for Orthopaedics and Traumatology conceived this guidance-which is primarily addressed to Italian orthopedic surgeons, but should also prove useful to other bone specialists and to general practitioners-in order to improve the diagnosis, prevention, and treatment of osteoporosis and its consequences. MATERIALS AND METHODS: Literature reviews by a multidisciplinary team. RESULTS: The following topics are covered: the role of instrumental, metabolic, and genetic evaluations in the diagnosis of osteoporosis; appraisal of the risk of fracture and thresholds for intervention; general strategies for the prevention and treatment of osteoporosis (primary and secondary prevention); the pharmacologic treatment of osteoporosis; the setting and implementation of fracture liaison services for tertiary prevention. Grade A, B, and C recommendations are provided based on the main levels of evidence (1-3). Toolboxes for everyday clinical practice are provided. CONCLUSIONS: The first up-to-date Italian guidelines for the primary, secondary, and tertiary prevention of osteoporosis and osteoporotic fractures are presented.

Primary osteoporosis in children.

Osteoporosis in childhood is uncommon, and it may be secondary to a spectrum of diverse conditions. Idiopathic juvenile osteoporosis is a primary osteoporosis of unknown aetiology present in previously well children and is a diagnosis of exclusion. We describe a 10-year-old prepubertal boy who presented with back pain of 1-week duration. His spinal X-ray showed generalised loss of vertebral body heights in keeping with osteoporosis. Endocrine and haematological work-up were normal. He was treated with vitamin D supplement and intravenous pamidronate. This case illustrates the general work-up and causes for paediatric osteoporosis, and the management for idiopathic juvenile osteoporosis.

Mid-Term Results of the SL-PLUS Femoral Prosthesis The Influence of Femoral Bone Type.

BACKGROUND: Cementless fixation of the femoral stem has been shown to be durable and predictable in total hip arthroplasty (THA), primarily as a result ofrecent improvements in prosthesis geometry and porous surface. Although patients with osteoporotic bone have been considered poor candidates for the use of a cementless femoral component, some recent studies have indicated satisfactory results. However, the indications and selection criteria of cementless stems based on the morphology of the femoral canal have not been established. PURPOSE: We aimed to assess and compare the mid-term results of cementless THA with an SL-PLUS® femoral component in patients classified as Dorr types A, B, and C. METHODS: We evaluated the clinical and radiographic results of primary THA with the cementless SL-PLUS® stem for 34 hips (25 patients). The preoperative femoral bones were classified as Dorr types A, B, and C in 12, 15, and 7 hips, respectively. Implant survival rates were calculated, hip function was evaluated using the Japanese Orthopaedic Association hip score, and radiographic signs were determined from anteroposterior radiographs. RESULTS: The mean follow-up period was 9.4 years (range: 7 to 13 years), and the mean Japanese Orthopaedic Association hip score improved from 43.8 points preoperatively to 85.3 points at the latest follow-up. The overall implant survival rate was 100% at 10 years; radiographic loosening or revision for any reason was used as the endpoint. Third and fourth degrees of stress shielding were observed in 29.4% of cases and were found to be significantly associated with a low cortical index, a Dorr type C femur, and a larger stem size. CONCLUSIONS: The use of the SL-PLUS® stem provided satisfactory mid-term clinical and radiographic results in patients with any type of femoral canal morphology.

The systemic effects of sclerostin overexpression using ΦC31 integrase in mice.

Sclerostin, encoded by the Sost gene, is mainly produced by osteocytes in bone and antagonizes the Wnt/ß-catenin signaling pathway, which is a requisite for bone formation. Currently, human anti-sclerostin antibodies are being tested in phase III clinical trials. In addition, serum sclerostin levels are reported to be associated with bone mineral density and fracture risk in normal individuals; however, the correlation between serum sclerostin and bone mass remains controversial. To study the effects of the continuous exposure of exogenous sclerostin on bone, a ΦC31 integrase system, which has the characteristics of site-specificity and efficiency, was applied for the delivery of the Sost gene in this study. We injected Sost-attB plasmid with or without ΦC31 integrase plasmid into the mouse tail vein using a hydrodynamic-based method. The site-specific integration of the Sost gene into the mouse genome was confirmed by examining a pseudo-attP site on the hepatic genomic DNA. Sclerostin was expressed in the hepatocytes, secreted into the blood flow, and maintained at high concentrations in the mice with both Sost-attB plasmid and ΦC31 integrase plasmid injections, which was observed by serial measurement. Moreover, the mice with long-term high levels of serum sclerostin showed trabecular bone loss on micro-CT analysis. Peripheral B cell populations were not affected. Our results suggested that sclerostin could be expressed in the liver and sustained successfully at high levels in the blood by using the ΦC31 integrase system, leading to trabecular bone loss. These findings may help to further ascertain the effects of sclerostin introduced exogenously on the skeleton.

Utilização da tomografia computadorizada de feixe cônico na obtenção dos índices radiomorfométricos em mulheres na pré e pós menopausa / Use of cone beam computed tomography in obtaining radiomorphometric index in women in pre and postmenopausal

O rastreio de osteoporose utilizando imagens de tomografia computadorizada de feixe cônico (TCFC) é um procedimento ainda discutível. O objetivo deste estudo foi avaliar a qualidade óssea de mulheres de diversas faixas etárias (AG) através de índices de radiomorfométricos obtidos em TCFC. Setenta e cinco imagens de TCFC de mulheres (idades compreendidas entre 40 - 70 anos) foram avaliadas. Os pacientes foram agrupados de acordo com AG, em três maneiras diferentes, de acordo com a prevalência de osteoporose em mulheres brasileiras. Os índices avaliados foram: índice cortical mandibular (ICM), índice mentual (IM) e os índices de tomografia computadorizada superior e inferior (ITC). Dois examinadores calibrados avaliaram as imagens em três tempos: Abertura / reconstrução de imagens (1), repetindo este procedimento e salvando a reconstrução (2), e a avaliação das imagens reconstruídas (3). As reconstruções panorâmicas (variando as espessuras: 0,30, 10, e 20 mm) e imagens transaxiais foram avaliadas. A concordância intra e inter-examinador foram avaliadas por meio do teste Kappa e estatísticas de coeficiente de correlação intraclasse. A correlação de Pearson foi utilizada para verificar a relação entre os índices avaliados e AG. O teste de quiquadrado foi utilizado para comparar a prevalência de osteoporose de acordo com cada parâmetro e AG. Os índices avaliados não apresentaram correlação com AG. Alta concordância intra e inter-examinador foi encontrada para IM e ITC, mas não para ICM. A prevalência da osteoporose variou grandemente, de acordo com o índice avaliado e o valor de corte utilizado para definir a doença (com base na qualidade do osso). Os índices radiomorfométricos quantitativos obtidos na TCFC podem ser avaliados de uma forma reprodutível. Não houve correlação entre os índices e AG, o que sugere que as imagens de TCFC não devem ser utilizadas para o rastreio de osteoporose.

Screening for osteoporosis using cone beam CT images (CBCT) is a datable procedure. The aim of this study was to evaluate the bone quality of women from diverse age groups (AG) using CBCT-based radiomorphometric indices. Seventy-five CBCT images of women (age range 40 - 70) years were evaluated. Patients were grouped according to AG, in three diverse manners, according to prevalence of osteoporosis in Brazilian women. The mandibular cortical (MCI), mental (MI), and the superior and inferior computed tomography (CTI) indices were assessed. Two calibrated examiners assessed the images in three instances: opening/reconstructing the images (1), repeating this procedure (2), and assessing the reconstructed images once again (3). Panoramic reconstructions (0.30, 10, and 20 mm thicknesses) and cross-sectional images were assessed. Intra and inter-examiner agreement were assessed by means of Kappa and intraclass correlation coefficient statistics. Pearson correlation was used to verify the relationship between the assessed indices and AG. Chi-square statistics was used to compare the prevalence of osteoporosis according to each index and AG. Assessed indices showed no correlation with AG. High intraand inter-examiner agreement was found for MI and CTI but not to MCI. The prevalence of osteoporosis varied widely, according to the assessed index and to the cutoff used to define the disease (based on bone quality). Quantitative CBCT-based radiomorphometric indices can be assessed in a reproducible manner. No correlation between AG and the assessed indices was found, suggesting that CBCT images should not be used for the screening of osteoporosis.

Classification of functioning and assessment of fracture risk of a large Italian osteoporotic population. The Physiatric Approach To Osteoporosis project.

BACKGROUND: Osteoporosis is a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture. Osteoporotic fractures cause significant morbidity, disability, and decrease in quality of life. AIM: The aims of the Physiatric Approach To Osteoporosis (PATO) project were to classify osteoporotic patients with or without fragility fractures, using the Brief ICF (International Classification of Functioning, Disability and Health) Core Set for Osteoporosis and to calculate the fracture risk with the WHO FRAX® (World Health Organization Fracture Risk Assessment Tool) algorithm. DESIGN: Cross-sectional survey. SETTING: Seventy-nine Italian Rehabilitation Services distributed throughout Italy. POPULATION: Osteoporotic patients. METHODS: Each physiatrist involved in the survey was asked systematically to record demographic data, presence of fragility fractures, anamnestic risk factors included in the FRAX® Assessment Tool, ICF categories as they are listed in the Brief ICF Core Set for Osteoporosis, and treatment data of 100 osteoporotic patients (50 with at least a clinical fragility fracture and 50 without). RESULTS: In accordance with the FRAX® algorithm, the 35.22% of the interviewed osteoporotic patients had a FRAX® MAJ≥20.00 and the 70.32% had a FRAX® HIP≥3.00. The most commonly impaired ICF categories were the sensation of pain for the body functions, the structure of the trunk for body structures, lifting and carrying objects for the domain of activities and participation, and products or substances for personal consumption for the environmental factors. CONCLUSION: The FRAX® Assessment tool has been recognized as useful to identify people at high risk of fracture and the Brief ICF Core Set seems to be an important framework to be followed when dealing with osteoporotic patients in an outpatient setting or for clinical studies. CLINICAL REHABILITATION IMPACT: Osteoporosis is well recognized as a disabling disease, posing a significant challenge for the society, therefore physiatrists should always be involved, from prevention to treatment.

Osteoporotic fracture models.

Animal models are widely used to investigate the pathogenesis of osteoporosis and for the clinical testing of anti-resorptive drugs. However, osteoporotic fracture models designed to investigate novel ways to treat fractures of osteoporotic bone must fulfil requirements distinct from those of pharmacological testing. Bone strength and toughness, implant fixation and osteointegration and fracture repair are of particular interest. Osteoporotic models should reflect the underlying clinical scenario be that primary type 1 (post-menopausal) osteoporosis, primary type 2 (senile) osteoporosis or secondary osteoporosis. In each scenario, small and large animal models have been developed. While rodent models facilitate the study of fractures in strains specifically established to facilitate understanding of the pathologic basis of disease, concerns remain about the relevance of small animal fracture models to the human situation. There is currently no all-encompassing model, and the choice of species and model must be individualized to the scientific question being addressed.

Regional migratory osteoporosis and transient osteoporosis of the hip: are they all the same?

We hypothesized that regional migratory osteoporosis (RMO) and transient osteoporosis of the hip (TOH) terms describe a common disease process. Therefore, based on our patient, we aimed to review the pathogenesis, diagnosis, and treatment of both diseases. The patient was a pregnant woman in her third trimester with sacral insufficiency fracture, which was shortly followed by migratory arthralgia of both hips and ankles in a proximal to distal direction. She was operated (core decompression) for both hips and ankles, and she was symptom free at 17th month. RMO and TOH have an unclear etiology, share the similar course, and bear a self-limiting nature. Both disorders may be the same clinical entity with a common pathogenesis. Probably, many of RMO patients were labeled as TOH, and therefore, RMO has been underrepresented. In conclusion, we think that both RMO and TOH describe a common disease process. Either the diagnosis is RMO or TOH, the management will be the same. Finally, the conservative treatment protocol is a better treatment modality and must be obeyed even in resistant cases.

Classifications of glenoid dysplasia, glenoid bone loss and glenoid loosening: a review of the literature.

So far, glenoid implantation still remains a challenge and is technically demanding even for an experienced shoulder surgeon. Each shoulder pathology has its own evolution. In primary glenohumeral osteoarthritis, glenoid involvement and proper morphology vary considerably. Erosion is more posterior and inferior. In rheumatoid arthritis, glenoid erosion is more medial with a very weak and soft bone. In eccentric arthritis, glenoid erosion is most of the time superior. Glenoid component loosening has been recognized as one of the common indications for revision surgery after total shoulder arthroplasty. Scapular notching is specific to the reverse shoulder arthroplasty. Moreover, there is concern about the high frequency of glenoid components that demonstrate radiographic periprosthetic lucencies. There is little information available to guide clinical decision making regarding glenoid surgery. Placement or replacement with a standard glenoid component is usually possible. In some instances, bone graft reconstruction or the use of augmented or custom components can be an option. The purpose of this study is to evaluate the main glenoid erosion classifications.

[Familial exudative vitreoretinopathy].

Familial exudative vitreoretinopathy (FEVR) is a progressive hereditary retinal vascular disorder of unknown etiology. The disease is associated with gene mutation and mainly has an autosomal dominant mode of inheritance. Pathogenesis of the disease consists in abnormal retinal peripheral vasculogenesis. Three classifications, detailed clinical presentation and differential diagnostic criteria of the disease are presented. Surgical options of treatment of potential retinal detachment are discussed.

Correlation of tooth mobility with systemic bone mineral density and periodontal status in Indian women.

Imbalanced bone remodelling associated with osteopaenic or osteoporotic conditions can lead to a net bone loss throughout the skeleton, including the oral cavity, possibly leading to tooth mobility. This study investigated possible associations between systemic bone mineral density and both tooth mobility and periodontal status in peri-menopausal women. Subjects comprised 119 dentate, peri-menopausal Indian women between 40 and 54 years old. Clinical parameters recorded were systemic bone mineral density (BMD), tooth mobility in terms of Periotest value (PTV score), clinical attachment loss (CAL), pocket depth (PD), plaque index (PI) and sulcular bleeding index (SBI). Statistical analysis was performed to assess correlations between PTV score and T-score. PTV score correlated significantly (P < 0.05) with T-score, PD and CAL. The partial correlation coefficient between PTV score and T-score after adjusting for confounders was -0.3676 (P < 0.05). Results of one-way analysis of variance showed a significant difference between mean PTV scores for osteoporotic, osteopaenic and normal patients. In this population of peri-menopausal women, systemic bone mineral density represented an independent factor associated with tooth mobility.