On 14th November 1877, the British doctor James Paget presented to the Medical and Surgical Society of London five cases of a condition which was called “Osteitis Deformans”, a slowly developing bone disease characterised by the lengthening, softening and deformation of the bones, above all affecting the cranial bones and the long bones of the lower limbs. He published the first report in Medical-Surgical Transactions in 1877, in which he described in detail a man he had treated over a period of 20 years 1. He subsequently published, more cases in 1882 as well as saying that he had not known that Czerney had used the term “Osteitis Deformans” in 1873.Read More
Primary health care (PHC) is the first point of contact for patients in the health care system and is key to the suspicion of osteoporosis in postmenopausal women (PMO), as well as in the approach to its diagnosis and treatment and the establishment of the risk of fracture.
Osteoporosis is the most common bone metabolic disease in our environment, representing a serious public health problem world-wide 1, and specifically in our country 2. The prevalence of osteoporosis determined by bone densitometry in the lumbar spine is especially high after the menopause 3,4. It is estimated that in Spain, one in three women over 50 years of age suffer from osteoporosis, increasing to one in two for those over 70 years of age. Most of these patients are located in the 55-80 years age range 3,4, and it is estimated that 4% of those patients over 50 years of age with a hip fracture will die during hospitalisation, and 24% in the first year after fracture 5. Vertebral fracture is the most common, and that of the hip the most serious and with a greater cost to the health system, while there may also be other fragility fractures such as the distal radius, humerus, rib and tibia 6.Read More
Study of the deletions in the GSTM1 and GSTT1 genes and of the Ile105Val polymorphism of the GSTP1 gene in patients with Paget’s disease of bone
Background: Paget’s disease of bone (PDB) is a disorder focussed on the bone with an increase in the number, size and activity of the osteoclasts. Some epidemiological data support the theory of its relationship with toxic or infectious environmental agents, whose interaction with some predisposing genetic alterations may lead to PDB. The glutathione S-transferases (GST) are involved in the metabolism of toxins, by catalysing the nucleophilic attack of the physiological substrate, reduced glutathione or GSH (g-Glu-Cys-Gly) on the electrophilic centre of a great number of toxic structures. We studied whether the variability of the GSTM1, GSTP1 and GSTT1 genes is related to the risk of developing PDB.
Patients and methods: We analysed 148 patients diagnosed with PDB, and 207 control individuals matched in sex and age with no history of bone alterations. Using genomic DNA obtained from peripheral blood the presence-absence of the GSTM1 and GSTT1 genes was studied by means of multiplex PCR. The study of the Ile105Val GSTP1 gene was carried out using PCR and subsequent digestion with the restriction enzyme BsmAI. The distribution of genotypes was analysed by means of the Pearson chi-square test. When statistically significant differences were found we carried out a multivariate logistical regression to determine the risk which the presence of a particular genotype could generate. We used the CSPSS 21.0 program. Differences were considered to be statistically significant when the value of p<0.05. Results: We found differences in the distribution of the presence-absence of the deletion in the GSTM1 gene; not being a carrier for the deletion or being a heterozygous carrier in the GSTM1 gene confers a lower risk of developing PDB (OR=0.56, 95% CI: 0.36-0.87; p=0.011). In the study of the GSTT1 and GSTP1 genes there were no significant differences. Conclusion: The detoxifying activity diminishes when two copies of the GSTM1 gene with deletions are inherited by reducing in enzyme activity, which has been associated with a greater susceptibility to some cancers, alcoholic hepatopathy and other inflammatory problems. We are not aware of any description of its association with PDB. PDB is observed more frequently in carriers of the homozygous deletion in the GSTM1 gene. This fact could explain the epidemiological findings which link PDB to exposure to certain environmental agents.Read More
Analysis of epigenetic modifications in bone cells: osteoblasts are osteoblasts isolated from bone a good model to study changes in DNA methylation?
Epigenetics is the study of the mechanisms which regulate gene expression in a stable and hereditary way, but without altering the DNA sequence 1. This field of research has gained importance in recent years and it is postulated that it may explain the process of differentiation of bone cells, the appearance of bone metabolic diseases, as well the inheritability of certain pathologies (for recent reviews, see 1-3). Epigenetic mechanisms include post-translational modification in histones, regulation of protein synthesis by means of microRNA and DNA methylation.Read More
Knowledge of osteoporosis, and the pharmaceutical expenditure it entails, in the primary health care system of the Canary Islands
Background: Osteoporosis is a disease which can be managed by different specialisms, one of which is the family doctor. In this study we analyse the knowledge of osteoporosis, and the diagnostic and therapeutic approach taken to this disease, among primary care doctors in the Canarian archipelago, as well as making a first approximation of the expenditure on drugs used to treat this disease in 2013.
Material and method: Observational, descriptive, transverse study conducted between May 2013 and May 2014 with all primary care doctors in the Canarian health service. An anonymous survey covering 13 points was developed. The capture of the data about expenditure on drugs was facilitated by the service for the control of supply and rational use of medicines of the Canarian health service.
Results: 28.60% of primary care doctors in the Canarian archipelago responded to the survey. Of these, 75.30% reported using risk factors in evaluating the risk of fractures. Not a very high percentage, approximately half of the respondents, request densitometries, while 28.60% routinely use scales for the evaluation of risk of fracture and 32.80% use them occasionally. 90% of the professionals recommend non-pharmacological measures for the prevention of fractures in their patients, although 91% do not normally request a determination of blood levels of vitamin D.
In 2013 the expenditure on drugs for osteoporosis by the Canarian health service amounted to € 7,684,393.61, of which € 7,265,491.06 was in primary care.
Conclusions: The Canarian primary care doctors who responded to the survey had, in general, a good knowledge of osteoporosis, and of its risk factors, but focussed their professional activity more on prevention than treatment. The drug most commonly used in the treatment of osteoporosis in primary care is risedronate. Expenditure on drugs for osteoporosis in the Canarian archipelago in 2013 amounted to € 7,684,393.61, 94% of which was in primary care.
Effect of spinal cord injury recently in bone turnover and in bone mass evolution of complete motor. Preliminary findings
Background and aim: Spinal cord injury (SCI) has been associated with a marked increase in bone loss and a higher incidence of skeletal fractures, however the pathogenesis and clinical management of this condition remains unclear. The aim of this study was to analyze the bone mineral density (BMD) evolution in patients with complete SCI and its relationship with parameters of bone metabolism and bone turnover markers. Methods: Patients with a recent complete motor SCI (ASIA A)(<6 months) were prospectively included. Bone metabolism parameters (calcium, phosphate, PTH and 25-OHD), bone turnover markers (bone formation: procollagen type 1 aminoterminal propeptide -P1NP-, bone alkaline phosphatase -bone AP-, osteocalcin -OC-; bone resorption: C-telopeptides of type I collagen -CTx-) and BMD were assessed in all patients at baseline and at 6 months. The results were compared with a control group. Results: 23 men with complete SCI (ASIA A) and a mean age of 38<15 years were included at 102<33 days of SCI onset. 52% had paraplegia. 12 patients were assessed at 6 months of follow-up. Patients with SCI showed a significant increase in bone turnover markers, especially P1NP and CTx, compared to controls (P1NP: 191±90 vs 51±19 ng/ml, <0.001; CTx: 1.37±0.49 vs 0.51±0.23 ng/ml, <0.001). At 6 months, bone turnover markers decreased (P1NP: -34%, p=0.005 and CTx: -26%, p=0.002) and BMD had a mean decrease of 12% at total femur (p=0.002) compared to baseline, with osteoporosis development in 50% of patients. Bone markers (bone AP, P1NP and OC) were negatively correlated with total femur BMD values. Conclusions: Patients with complete SCI show a marked increase in bone turnover and bone loss, especially at the proximal femur, with the development of osteoporosis being observed in 50% of these patients at 6 months of follow-up. These findings indicate the need to implement preventive measures within the therapeutic approach in these patients.
The Journal of Osteoporosis and Mineral Metabolism (Revista de Osteoporosis y Metabolismo Mineral) was first published in March 2009. It has now, therefore, completed its first five years. Born out of the need of the Spanish Society for Bone and Mineral Metabolism Research (Sociedad Española de Investigación Ósea y Metabolismo Mineral (SEIOMM) ) to have its own official organ to disseminate its scientific activities, taking over this role from the Revista Española de Enfermedades Metabólicas Óseas (REEMO) given the insoluble difficulties which the management committee of SEIOMM then found in reaching an agreement with the editors of REEMO, both from an economic point of view and, more importantly, regarding the management of the Journal.Read More
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.Read More
Objectives: Epigenetic mechanisms, and in particular cytosine methylation in the promoter regions, modulate the expression of many genes. However, their role in skeletal homeostasis has scarcely been studied. In particular, it is not known if the patterns of methylation of bone cells in culture are a good reflection of that which occurrs in bone tissues. The aim of this work was to explore the possible differences in cytosine methylation in human bone and in osteoblasts.
Material and methods: To achieve this we carried out a genome-wide study, analysing the degree of methylation of 23,667 loci and comparing the results in samples of bone tissue and in cultures of primary osteoblasts.
Results: Overall, we observed a good correlation between the two sample types, both in the whole group of loci (r2=0,87; p<10-50), and in those located in genes involved in bone metabolism. However, some of the loci (7-8%) deviated from this general tendency and showed differences in methylation greater than 20%.
Conclusions: These results indicate that the methylation data obtained in cultures are not necessarily a true reflection of that which occurs in tissues, which means that care should be taken when extrapolating such results to an in vivo situation.
The main aim of the treatment of a patient with osteoporosis is to avoid the appearance of osteoporotic fractures and, in the case in which it has already occurred, to avoid a new one. To achieve this is it important that in each specific case the risk of fracture is evaluated at the time and, as a function of its degree, low, medium or high, set out the preventative and therapeutic strategies necessary to reduce the risk of fracture in this specific person 1,2,3. One of the great challenges that still arises in daily clinical practice is to improve the adherence of patients to the various recommendations and treatments counselled by the health professionals.Read More
Risk of major osteoporotic or hip fracture in patients with cerebrovascular accident in the acute phase. Multicentre prospective study
Objetives: Hemiplegic patients are considered to be a population at risk of suffering osteoporotic fractures. The aim of this work is to understand the absolute risk of fragility fracture in patients with cerebrovascular accident (CVA) and the osteometabolic state of patients with ictus in the acute phase, as well as confirming if there are baseline differences compared to a control group without cerebrovascular pathology.
Patients and method: Multicentre prospective study carried out in five Spanish hospitals. Two groups were established: a) patients with ictus of less than three months development, and b) a control group from a population without cerebrovascular disease. History of fragility fractures, number of falls in the previous year, bone mineral density (BMD) in the hip, FRAX® index, determinations of biochemistry and bone markers – calcium, phosphorus, alkaline phosphatase, vitamin D, parathormone (PTH), and carboxy-terminal telopeptide of collagen type I (CTX) – were analysed.
Results: A total of 82 patients were studied: 50 patients with CVA and 32 controls. 12% of those patients with CVA had an increased risk of suffering a hip fracture, and 8% an increased risk of a major osteoporotic fracture. In the control group the risk was greater. The hemiplegic patients had BMD in the hip lower than those in the control group, although the differences in both variables were not statistically significant.
The levels of CTX were higher in patients with CVA, this being the sole determination which showed a statistical difference between the two groups studied.
Conclusions: The patients with CVA had values of markers for bone resorption (CTX) significantly higher and a BMD in the hip lower than those in the control group.
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.Read More
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