Revista de Osteoporosis y Metabolismo Mineral

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Category: 12

Methodology to improve the efficiency in the migration and detection of mesenchymal stem cells in murine models

Osteoporosis is a generalised disease of the skeletal system characterised by an imbalance between the bone formation and resorption that leads to bone mass loss and to the deterioration of the microarchitecture of the bone tissue, compromising bone resistance and therefore resulting in a higher bone fragility and an increased susceptibility to fractures [1].
Two stem cells coexist in the bone cavity (bone marrow): the hematopoietic stem cell, which generates all the blood and immune system cells, and the mesenchymal stem cell, responsible for the formation of the skeleton. Osteoblasts or bone-forming cells originate from the differentiation of mesenchymal stem cells. These pluripotent cells can create a wide variety of cell types such as osteoblasts, adipocytes, or chondrocytes [2-4]. This characteristic makes them highly interesting candidates for regenerative medicine given their ability to migrate to injured areas to promote the de novo generation of bone [5].

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A sensitive method for monitoring the migration of mesenchymal stem cells from bone marrow in murine models

Osteoporosis is the most frequent bone disease, characterized by low bone mass and alteration of the microstructure. This is due to an imbalance between bone formation and bone resorption that causes loss of connections among the different bone trabeculae, a greater thinning and cortical bone porosity. Consequently, there is greater bone fragility and an increased risk of fractures (Fx) [1,2].
Osteoblasts, cells specialized in bone formation, originate from the differentiation of mesenchymal stem cells (MSCs) [3]. These cells are multipotent and can differentiate into a wide variety of mesoderm cell types, such as osteoblasts, adipocytes, or chondrocytes. MSCs are highly interesting candidates for regenerative medicine, because they migrate to skeletal lesions where they have the capacity to form new bone [4]. The many relevant published studies show the importance of MSCs in tissue engineering and regenerative medicine [5,6]. In addition, there are currently more than 250 clinical trials with MSCs, as reflected in the clinical trial database (clinicaltrials.gov).

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Can 3D measurements obtained by lumbar DXA predict fractures in the dorsal vertebrae?

Every year 8.9 million osteoporosis-related fractures occur worldwide, representing one fracture every 3 seconds [1], with vertebral being the most common osteoporotic fractures [2].
Dual-energy X-ray absorptiometry (DXA) is the standard test for diagnosing osteoporosis and evaluating fracture risk [3,4], as it is a low-radiation, inexpensive technique. The DXA provides two-dimensional (2D) images that measure the bone mineral density of the area (aBMD) projected along the anteroposterior (AP) direction. Various studies show that a low aBMD value, measured in AP DXA explorations, is among the highest fracture risks [3-5]. The decrease of the aBMD standard deviation leads to an increase from 1.5 up to 3.0 times the risk of fracture, depending on its location and its measurement’s location [5]. Nevertheless, a low BMD value is not enough to explain every fracture. Recent studies suggest that the risk of fracture is high when the BMD value is low, but this does not mean that fracture risk is negligible when the BMD value is normal [3-8].
Most osteoporosis-related vertebral fractures are located in the vertebral body [9]. In AP DXA images of the spinal column, the vertebral body overlaps the posterior vertebral elements, so the BMD in the vertebral body cannot be estimated separately. On the other hand, the risk of fracture depends on the architecture of the trabecular bone and the thickness of the cortical bone [10]. However, the trabecular and cortical bone compartments are difficult to assess separately on AP DXA scans.

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Impact of vascular calcification on bone health and mortality in kidney transplant patients

Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD), was defined in 2009 as a set of systemic disorders of the bone and mineral metabolism due to chronic kidney disease, resulting in a combination of the following manifestations [1,2]:
I) Abnormalities of the metabolism of calcium, phosphorus, paratohormone or vitamin D.
II) Anomalies of bone remodeling, mineralization, volume, linear growth or resistance.
III) Vascular and other soft tissue calcifications.
This recently updated definition [3], and the consensus documents of various scientific societies [4], have highlighted the importance of the role of vascular calcification in the morbidity and mortality of patients with chronic kidney disease.

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Relative fragility of osteoporotic femurs assessed with DXA and simulation of finite element falls guided by emergency X-rays

The increase in the elderly population and the growing concern about the consequences of fractures, together with insufficient rates of detection of situations of bone fragility [1,2], has increased the indication of the assessment of fracture risk in people of both sexes older than 64 years [3]. The dual-energy X-ray absorptiometry (DXA) technique is currently the clinical standard for this type of bone measurement.
Nowadays, when evaluating the risk of fracture, different methods are applied, although the most widely used include the presence of clinical risk factors and the measurement of areal bone mineral density (BMD). Bone measurements are made in the proximal femur and lumbar spine using DXA. However, BMD only allows a limited assessment of the mechanical determinants of bone fracture [4,5].
Finite element analysis (FE) has been applied to assess bone resistance in volumetric bone models, based on computed tomography (CT) scans, precisely identifying the subject-specific mechanical determinants of fracture. This type of analysis includes the three-dimensional geometry of the bone, the quantity and distribution of bone tissue, and the loads to which the bone is subjected [6]. With this process, the limitations of the BMDa are overcome. CT-based models of FE have been extensively validated ex vivo [7-12], and have shown better performance compared to a BMD in predicting proximal femur resistance in vitro [6,13]. A significant association between bone fractures and estimated resistance with FE has also been reported in an in vivo study [14].

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Postoperative thyroid hypocalcemia diagnosis and management protocol

Transient hypocalcaemia due to hypoparathyroidism is the most common complication of cervical surgery (thyroid and parathyroid) and also of reoperations. The deficiency of parathyroid hormone (PTH) secretion causes postoperative hypocalcemia due to an inhibition of bone resorption, a decrease in the synthesis of 1-25-dihydroxy vitamin D by the kidney and reduced intestinal calcium absorption. Some associated comorbidities, such as malabsorption, gastric bypass, and bisphosphonate therapy, may promote parathyroid failure. When PTH secretion is insufficient, hypocalcemia develops. Hypocalcaemia due to hypoparathyroidism is associated with few symptoms, if the hypocalcaemia is mild. In severe cases, symptoms include seizures, heart failure, or laryngospasm. In addition to the magnitude of hypocalcemia, the speed of establishment determines its clinical expression [1].
The removal or inadvertent damage of the parathyroids or the alteration of their blood supply are the responsible causes. Both transient and permanent hypoparathyroidism can have important repercussions on patients’ health and establishing appropriate protocols for their prevention, evaluation and treatment are needed [2].

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Bone protection during breast cancer treatment

Few medical areas have changed as much through the last decades as the treatment of breast cancer (BC). From Halsted’s theory of the progression of an initially local disease, with a first loco-regional and then metastatic extension, to the most recent studies in molecular biology that identify the gene personality of each tumor, there have been many advances. Old TNM classification originally designed for solid tumors have been abandoned and all areas related to hormonal dependence and gene expression of each tumor have grown in importance. All this is aimed at better facing a global therapeutic approach.
Almost 20 years ago, an important biological research laboratory provided us with a detailed study of the basal estradiol levels of the patients in the placebo group of the MORE study [1]. An increased risk of breast cancer associated with raised serum estradiol levels was demonstrated, confirming the previous results on the hormonal dependence of this neoplasm. With the introduction of chemotherapy (QMT) in the final decade of the last century, the general mortality of women from breast cancer was reduced in all western countries. At the time, and just a few years later, the implementation of massive early detection programs at the population level facilitated an increase in the diagnosis of tumors in early stages.

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Risk factors for incident fracture in patients with breast cancer treated with aromatase inhibitors: B-ABLE cohort

Currently, aromatase inhibitors (AI) are used as first-line adjuvant therapy for women diagnosed with breast cancer with positive hormonal receptors. Although its effectiveness in reducing the risk of recurrence and mortality is well known [1], AIs have also been associated with side effects that can negatively affect the patient’s quality of life, adherence to treatment and associated mortality [2].
In AI treatment, there is a marked reduction in circulating estrogens in postmenopausal women by blocking the conversion by the enzyme aromatase from androgens to estrogens. This action leaves the woman without residual estrogens, such as estradiol and estrone, after menopause. One of the most common side effects is accelerated bone loss, which is associated with an increased risk of osteoporotic fractures [3,4]. Along these lines, there are different meta-analyzes that include randomized controlled clinical trials that have shown an association between prolonged treatment with AI and an increased risk of bone fractures, with an increase between 34% and 59% [5,6].

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Differences in bone mineral metabolism normocalcemic primary hyperparathyroidism with respect to classical primary hyperparathyroidism

Primary hyperparathyroidism (HPT) is a very common bone mineral metabolic disease consisting of autonomous overproduction of parathyroid hormone (PTH), which leads to an increase in serum calcium [1]. It is the most frequent cause of hypercalcemia.
A lesser known clinical variant of HPT is the so-called “normocalcemic primary hyperparathyroidism” (NHPT), which has normal blood calcium levels and elevated parathyroid hormone (PTH) values, not knowing the mechanism by which this differential fact occurs [2-4]. These patients do not have clear causes that justify secondary elevations of PTH such as chronic renal damage [5], vitamin D deficiency (less than 30 ng/ml) [6], renal hypercalciuria or drugs [7]. Although NHPT was first formally recognized in the Third International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism in 2008 [8], all clinical features are not yet known, particularly with regard to its epidemiology, natural history, management and prognosis [9,10]. Therefore, this clinical variety of the disease is less studied [11] and there is less bibliography. All of which has motivated us to carry out this study.

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Effects of bazedoxifene treatment on the bone quality of ovariectomized rats

Selective estrogen-receptor modulators (SERMs) are synthetic, nonsteroidal agents with estrogenic agonist-antagonist activity in different target tissues [1]. Their estrogenic responses are mediated by estrogen receptors (α and β). SERMs may present agonistic or antagonistic behavior depending on the tissue type [2,3]. In general, SERMs exhibit agonist activity in the liver, the digestive tube, the skeleton and the heart, but antagonist activity in the breast. In the uterus some SERMs manifest agonist activity while others show an antagonist behavior [1]. Several co-regulatory proteins modify the behavior of the SERMs on gene expression and contribute to their tissue-selective pharmacology.
Tamoxifen is a SERM used as a mammary antiestrogen for preventing and treating breast cancer with estrogen agonistic activity in the uterus. Raloxifene has been used for the prevention and treatment of osteoporosis and prevents breast cancer but presents some estrogenic activity [4]. Bazedoxifene is a 3rd generation SERM with agonistic effects on the bone and additional positive effects on lipids, the uterus and the breast tissue [5,6].

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Influence of high-concentration hyperbaric oxygen therapy on bone metabolism

Oxygen is required to produce cellular energy and is involved in numerous processes, such as enzymatic activation, molecular signaling and regulation of gene expression [1]. Also in angiogenesis, the maintenance of hematopoietic stem cells and bone formation [2]. In fact, changes in the partial pressure of oxygen can influence the function of osteoblasts and osteoclasts [3]. In hypoxia, bone formation and mineralization decreases, while resorption increases [4-6]. In the opposite direction, hyperoxia could have a beneficial effect on the bone. Treatment with high concentration of oxygen in the hyperbaric chamber has proven useful in osteomyelitis and osteonecrosis of the jaw caused by radiotherapy or by the use of bisphosphonates [7-9]. HC accelerates osteogenic differentiation of mesenchymal cells and decreases the activation of osteoclasts [10-12].
In this work we wanted to analyze the actions of oxygen at high concentration in HBO on the expression of genes related to bone metabolism in osteoblastic cell lines and human bone [5,6,13,14].

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Assessment of bone mass density in the surgical indication. New tool

To the Editor:

Current scientific evidence and practical clinical guidelines recommend primary and secondary prevention of fragility fractures in geriatric patients [1,2]. A personal history of fragility fractures significantly increases the risk of new fractures. Up to 33% of patients with a femur fracture had suffered a previous fracture. Among the various fractures due to fragility, the femur is the most prevalent and presents the most repercussions (clinical, functional and social) in patients over 65 years of age, with the resulting depletion of health resources [3]. The worldwide trend is estimated to rise from 1.7 million femoral fractures in 1990 to 6 million in 2050 [4].
In 2011, the Fractures Working Group of the Scientific Advisory Committee of the International Osteoporosis Foundation stressed the importance of coordination between orthopedics, osteoporosis services, fall units, patient, family, geriatrician and Primary Care physician. This multidisciplinary action was consolidated in the so-called “coordinated services for the treatment of fractures” or Fracture Liaison Services (FLS) that were initially implemented in the United Kingdom, Europe, Australia, Canada and the USA [5], with very good results.

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Clinical Notes
Committees
Editorial
English
Index of Authors
Index of Communications
Letter to the Director
Oral Communications
Original Articles
Osteology images
Poster Communications
Presentation
Reviews
SIBOMM News
Special Article
Special Documents

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