Revista de Osteoporosis y Metabolismo Mineral

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Category: Reviews

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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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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Cardiovascular disease, type 2 diabetes and osteoporosis

In recent years various epidemiological studies have shown an independent association of age between type 2 diabetes and osteoporosis, as well as an increase in cardiovascular mortality in patients with a reduction in BMD and/or osteoporotic fracture. The most recent research has focussed on factors involved in the physiopathology of the two diseases. In general, the studies which have investigated the relationship between cardiovascular risk factors, bone metabolism, bone mass and risk of fracture have shown inconclusive and contradictory results. In patients with DM2 there is an increase in risk of fractures in spite of a higher BMD, caused essentially by an increased risk of falls associated with the presence of vascular complications, although changes in bone quality are also a determining factor. Knowledge of the physiopathological mechanisms common to these pathologies will not only help better management of patients, but also could contribute to the development of drugs which would act on the two processes.

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Vertebroplasty: An alternative therapy for painful osteoporotic vertebral fractures which do not respond to conservative treatment? Review and update

Purpose: To review and update the available literature of vertebroplastia: a procedure for treating painful compression fractures of the thoracic and lumbar spine that don’t have responded to a conservative treatment.
Material and methods: A review of the literature was performed about the procedure, indications, complications and results based on PubMed and academic Google using the following keywords: vertebroplasty, compression vertebral fractures, polimetilmetacrilato, PMMA and osteoporosis.
Results: Description of the procedure, indications and complications. Several studies with few number of patients have indicated a high rate of successes an a low rate of complications. Recently, two double blind, randomized clinical trials have been published, comparing vertebroplasty with a simulation of it. The results of these studies don´t support the realization of vertebroplasty for the treatment of pain in osteoporotic compression fractures.
Conclusions: The clinical results of vertebroplasty were promising. Recently, the publication of two randomized clinical trials with greater evidence than previous ones, contradicts it.
Several questions without answer arise: Can this procedure be effective in a subgroup of patients? Could be effective in medium-long term? Are there other options to treat patients that don´t respond to conventional treatment?

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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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Determining the principal metabolites of vitamin D in the blood through on-line solid phase extraction with liquidchromatography-mass spectrometry in tandem

The determination of metabolites of vitamin D is very important in bone metabolism, in coronary disease, cancer, innate immunology, etc. Unfortunately, variation in methods for determining the metabolites of vitamin D limits the ability of clinicians to monitor the status, supplementation and toxicity of vitamin D.
In this work, an automatic method of determining the most important metabolites of vitamin D is presented. 0.2 ml of serum is injected into an XLC-MS/MS (eXtraction Liquid Chromatography-tandem Mass Spectrometry) platform to be cleaned and preconcentrated through extraction in the solid phase (SPE). The analytes retained in the SPE cartridge are eluated directly by the mobile chromatographic phase containing 10% water in methanol, with 5 mM of ammonium formate as ionizing agent, at a flow of 0.3 ml/min for the separation of the analytes, and their later detection through triple quadrupole mass spectrometry (MS/MS).
The limits of detection varied between 3.5 and 8.2 pg/ml. The coefficients of variation within the trial varied between 1.5 and 2.3% during the same day, and between 2.5-3.9% over a week. The recuperation varied between 97 and 99.7% for all analytes. The total time taken for the analysis was 20 minutes.
Thus, the proposed method is robust, cheap and appropriate for use in clinical and research laboratories.

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Osteoclasts: much more than bone remodelling cells

The osteoclast has been considered classically as a cell with the exclusive function of bone remodelling, with a gregarious behaviour.

However, advances which have been made in recent years have changed this concept drastically, and we now know that this multinuclear cell is subject to complex biological regulation, necessary for it to exert a multifunctional role of unknown dimensions.

In addition to its participation as the only cell capable of reabsorbing the calcified bone matrix, the osteoclast is one of the cellular elements effective in the immune system, a function still little-known but expected, given its belonging to the monocyte-macrophage lineage. Its role in other processes, both local, such as as a collaborative element in osteoformation and hematopoietic stem cell niche maintenance, and systemic, is also beginning to be understood.

In this review the most significant findings contributing to our understanding of the biology of the osteoclast are analysed, with an eminently practical content and an approach aimed at understanding the possible molecular targets which will allow a better therapeutic treatment of such important diseases as osteoporosis, arthritis or cancer.

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Bone disease following liver transplant

Liver transplant is now well established in the management of chronic terminal hepatopathy. With the follow up of these patients, we are getting to know pathologies derived from their earlier diseases and those from the organ transplant, among which are those produced by the immunosuppression (cyclosporine, FK506, sirolimus, glucocorticoids) necessary for their treatment. Among these complications with affect the quality of life in these patients are osteoporosis and fractures, which can appear mainly in the first 6-12 months after transplant, but which can continue to a lesser extent in the following years. Vertebral fractures, and those of the ribs, are the most frequent, in 65% and 24% of patients, with negative prognostic factors such as age and primary biliary cirrhosis. So, it is a severe form of osteoporosis which is analysed in this work, and to which we bring our therapeutic experience. With antiresorptive drugs, positive results have been reported for the prevention and treatment of this bone loss.

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Nutrition and osteoporosis. Calcium and vitamin D

Calcium and vitamin D are essential nutritional elements in bone health throughout life, in the attainment and maintenance of peak bone mass. In the treatment of osteoporosis, an adequate intake of calcium and the repletion of vitamin D are critical for the maximisation, in terms of antifractural efficacy, of the response to osteo-active treatments: anticatabolics and anabolics.
The daily requirement for calcium is estimated to be between 1,000 and 1,200 mg and may be obtained relatively easily through a normal diet, or by means of food supplements. However, a substantial section of the population does not attain these required levels. In addition, patients with intolerance to milk, with limited gastric secretion due to their age, for autoimmune reasons, or due to the use of agents such as proton pumps which limit it, gastrectomy or other reasons, or malabsorption, make calcium supplements, nutritional or pharmacological, necessary. The requirements for vitamin D are estimated at 800-1,000 UI, but few foods contain this vitamin, and cutaneous synthesis, even in sunny regions, is insufficient to obtain blood levels of 25 (OH)D [marker for the status of vitamin D in the body] above the 30 ng/mL necessary for an optimum biological response in the bone and other target organs and tissues. This means that it is practically always necessary to supplement it through reinforced foods or with pharmacological vitamin D.

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Role of DNA methylation in the regulation of osteogenesis

Recent studies suggest that epigenetic mechanisms, such as the methylation of DNA, play a critical role in cellular differentiation. Osteoclasts are cells with the capability of reabsorbing bone. Their differentiation is strictly regulated by the RANKL-OPG-RANK signalling pathway. Recently, our group has reported that the expression of RANKL and OPG by cells of the osteoblastic lineage is regulated by the methylation of the promoter regions of those genes. This review summarizes current knowledge about the influence of DNA methylation on the regulation of osteoclastogenesis.

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Treatment of Paget’s disease of bone


Paget’s disease of bone (PDB) is a chronic and focussed skeletal disorder, whose cause is unknown. The disease is located in the osteoclasts, which increase in number, size and activity. Bone turnover accelerates, with an increase in bone resorption, followed by excessive and disorganised formation. The result is bone which is not laminar (plexiform bone) highly vascularised, increased in volume, less compact and more susceptible to fracture or deformation. It is usually diagnosed at over 60 years of age, being infrequent below 40 years of age. It slightly predominates in males. It is the most common metabolic bone disease after osteoporosis1.
It is considered to be a multifactorial disease with the involvement of environmental and genetic factors.
Its main clinical manifestations are bone deformity and pain. During its evolution various complications may appear, the most frequent being degenerative arthropathy in its vicinity, neurological changes due to compression, fractures, cardiac pathology, disorders of the metabolism and of bone remodelling.
The diagnosis is based on clinical manifestations, raised levels of biochemical markers for bone remodelling (essentially, alkaline phosphatase – AP) and radiology.
There is no curative treatment, but the anti-resorptives, especially the diphosphonates, are efficacious in controlling the activity and progression of the disease. The therapeutic objectives are to eliminate bone pain, normalise bone remodelling, re-establish normal bone structure and prevent recurrence and complications.

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