Revista de Osteoporosis y Metabolismo Mineral

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Category: Reviews

Pathophysiology of osteoporosis in chronic inflammatory joint diseases

Chronic inflammation is a nonspecific response against aggressor agents mediated by the body’s immune system. In such a scenario, an infiltrate of predominantly mononuclear cells, such as lymphocytes, macrophages and plasma cells, is produced. Under certain conditions or when the aggressor agent persists, a sustainable accumulation and activation of immune cells occurs. Then, the secretion of cytokines, agents that prolong the life of lymphocytes and macrophages, is increased, what leads to chronic inflammation.
Inflammation is the main mechanism involved in bone destruction in chronic inflammatory diseases (CIDs) [1], such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), systemic lupus erythematosus (SLE), multiple sclerosis and/or inflammatory bowel disease (IBD). These diseases show a chronic systemic inflammation that can affect different organs, caused by an alteration of the immune system [2].

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Osteocalcin: from marker of bone formation to hormone; and bone, an endocrine organ

Osteocalcin is a protein synthesized by the osteoblast. It was identified in the late 1970s and in humans contains 49 amino acids [1]. Before being released into the extracellular matrix, osteocalcin undergoes gamma-carboxylation, as gamma-carboxy-glutamic acid binds at positions 17, 21 and 24. A gamma-carboxylase is involved in this reaction and the presence of vitamin K is required (Figure 1). The presence of the two carboxyl groups causes gamma-carboxylated osteocalcin to have a high affinity for calcium and, when released into the extracellular environment, binds in a large proportion to hydroxyapatite in bone. A part of this gamma-carboxylated osteocalcin and also non-carboxylated osteocalcin remain in the circulation [2]. Only 10-30% of the synthesized osteocalcin reaches the circulation, and the rest remains attached to the bone matrix. Non-carboxylated osteocalcin represents 1/3 of total osteocalcin. During resorption, when the bone matrix is destroyed, part of the osteocalcin that is bound to the bone passes into the circulation [2]. Osteocalcin is only synthesized by osteoblasts and is the most abundant non-collagenous protein in the extracellular matrix and is the tenth most abundant protein in vertebrates [3]. Since first reported, its levels were correlated with bone formation [4]. For all researchers working in bone metabolism, having a new bone formation marker was a breakthrough when the only markers of remodeling that were available up to that time were hydroxyproline and total alkaline phosphatase. The bone isoenzyme of alkaline phosphatase could also be measured by a rather complex method by electrophoresis. Osteocalcin has been used for many years as a marker of bone formation in practically all the work carried out in this regard. It is used less since 2011 when the International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) recommended that the N-terminal propeptide of type I collagen (PINP) be used as a marker of formation and the C-terminal β-telopeptide of type I collagen or β-crosslaps (β-CTX) as a marker of resorption in clinical studies on osteoporosis [5].

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Olive oil and bone health

Osteoporosis is the bone disease that most affects humans and predisposes a person to fractures. It constitutes a serious public health problem due to its impact on patients’ quality of life and the economic burden it represents. Osteoporosis reportedly affects more than 200 million people [1]. Therefore, it is extremely important to take all possible measures to mitigate its development.
Along with other factors, bone modeling and remodeling are determined by nutritional status [2]. Nutrition has relevant effects on peak bone mass, bone loss with age, and muscle strength [3]. Of course, the main nutrients for bone are calcium and vitamin D [4], since calcium is the major component of bone and its contribution is regulated by vitamin D, thus optimizing peak bone mass. However, the European Union has indicated the relevance of other nutrients on bone development and the advisability of conducting research into these on bone development [5]. The main advantage of nutrition in assessing its importance for bone health is that it can be modified.
The Mediterranean diet is characterized by a high intake of fruits, vegetables, and olive oil. The incidence of osteoporosis and associated fractures seems to be less in countries where the Mediterranean diet is predominant [6].

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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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Vitamin D and heart failure. Pathophysiology, prevalence, and prognostic association

Heart failure (HF) is a major public health problem characterized by high mortality, frequent hospitalizations and deterioration in the quality of life, with a prevalence and incidence that is increasing worldwide [1,2]. Although the prognosis has improved in recent decades thanks to the diagnostic and therapeutic improvement of cardiovascular diseases, the morbidity and mortality of these patients remains high [3]. All this implies that new objectives and treatment options are still needed.
Vitamin D had traditionally been associated only with bone health, accepting that vitamin D deficiency caused osteomalacia and osteoporosis in adults and rickets in children [4,5]. However, data obtained in recent years indicate that vitamin D is an important micronutrient for optimal function of many organs and tissues throughout the body, including the cardiovascular system [6,7]. It has been suggested that vitamin D deficiency may be an important factor both in the genesis of risk factors and cardiovascular disease [7] as a prognostic marker in HF. Pathophysiological data indicate that vitamin D deficiency may be very harmful for patients with HF and that vitamin D supplementation can be potentially beneficial, although all this is not without controversy [8].

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Free vitamin D: an increasing determination

In recent decades, vitamin D has attracted growing interest, not only in the medical field, but also among the general population. Initially, the evaluation of vitamin D was part of bone metabolism assessment when, for example, rickets or osteomalacia were suspected, or in populations at risk of osteoporosis [1]. 25-hydroxyvitamin D (25-OHD) is the circulating metabolite of higher concentration and longer half-life, used to monitor the body status of vitamin D. Patients with chronic kidney disease and undergoing dialysis treatment are also controlled by measurements of the evaluation of this state [2]. In this case, in addition to 25-OHD, the active metabolite of vitamin D, 1,25-dihydroxyvitamin D (1,25- (OH) 2D), produced mainly in the cells of the proximal tubule of the nephron.

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Isoflavones and bone health

Phytoestrogens are a family of plant-derived components that present a steroid structure and can act in the estrogen receptor. They contain both estrogenic and antiestrogenic properties, depending on the tissue in which they act.
The potential mechanisms by which phytoestrogens can affect cell activities have been divided into genomic and non-genomic effects. The former act through estrogen receptors, and the latter are mediated by cellular proteins. The active mechanism of soy isoflavones in bone may be beneficial, as they act by stimulating the activity of the osteoblasts. On the other hand, through the RANK-L/OPG system they bring about a decrease in osteoclast survival and activity. This article reviews in vitro studies, in animals and humans, that involve isoflavones and bone health to ascertain how these substances affect those postmenopausal women who use them in treatment or prevention of the climacteric syndrome.
In general, the global assessment of human studies shows variability in the design, in the variety of isoflavone sources, in the time of the analysis and in the dose. In addition, the variability in the bioavailability and metabolism of isoflavones between the subjects must be considered. All this makes it difficult to obtain consistent conclusions.
To sum up, some positive results justify the need for further research. From a clinical point of view, isoflavones are used in women with climacteric symptoms who cannot or do not wish to undergo hormone therapy. They would not be indicated for treating osteoporosis, but those women who use them at the right doses and time can expect a benefit in maintaining bone mass.

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Importance of the type of formulation of the preparations of calcium and vitamin D in the prevention and treatment of osteoporosis

Most Europeans do not meet the adequate intake for calcium and vitamin D; supplementation of both can help to meet requirements. Inappropriate intake can lead to reduced calcium absorption, higher bone remodeling rates and increased bone mass loss. Also, vitamin D deficit has been linked to reduced muscle function and increased risk of falling. Calcium from carbonate is the most common form, due to its cost-effectiveness profile, of calcium supplement for choice. Calcium lactate and gluconate are less concentrated forms of calcium and are not practical oral supplements. The purpose of the present article is to examine the importance of the combination calcium-vitamin D its role in the prevention and management of osteoporosis and the most common and useful formulations for its clinical use.

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Bone mineral metabolism in inflammatory bowel disease

Ulcerous colitis and Crohn’s disease constitute the principal components of inflammatory bowel disease (IBD). Osteoporosis is a well-known complication of IBD presenting a multifactorial etiology, although the importance of the inflammatory process in itself seems to be ever greater. The end of this article reviews the existing data on bone mineral metabolism in these patients, both in relation to the prevalence of the loss of bone mass, as in the situation of the markers for bone turnover, the factors involved, as well as the risk factors. In this way, it is intended to shine a light on the importance of osteoporosis in IBD.

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Advances in the study of the mechanisms involved in the modulation of the expression of sclerostin in human cells

Sclerostin plays an important role in the regulation of bone metabolism, as is shown in the dramatic changes in bone mass which occur when its activity is inhibited by means of monoclonal antibodies. However, the mechanisms which regulate its expression are still not well-understood. Various studies have shown an association between polymorphisms of the SOST gene promoter (which codes for sclerostin) and bone mineral density. Also, the degree of methylation of a CpG island near the start of the transcription is associated with marked changes in the expression of the gene. Therefore, it appears that the production of sclerostin is influenced by both genetic and epigenetic mechanisms, in addition to other hormonal and mechanical factors. A greater knowledge of these mechanisms would not only contribute to a better understanding of bone biology, but could open up new therapeutic opportunities.

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920191101-en
Clinical Notes
Committees
Editorial
English
Index of Authors
Index of Communications
Letter to the Director
Oral Communications
Original Articles
Osteology images
Position Paper
Poster Communications
Presentation
Reviews
SIBOMM News
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