Gaucher disease (GD) is a congenital fault of the metabolism due to a deficiency in the lysosomal enzyme glucocerebrosidase, also called acid beta glucosidase. This enzyme deficit results in the accumulation of non-metabolised substrate in the lysosomes of various cell lines of the monocyte-macrophage system. The deposit of non-degraded material, a glucocerebroside called glucosylceramide, is an intermediate metabolite in the synthesis and breakdown of glucosphingolipids. These macrophages laden with lipids, called “Gaucher cells” , are involved in the pathogeny of the disease1. GD is a sphingolipidosis, which constitutes the most frequent liposomal deposition disease. GD is a multiethnic disorder which is inherited in a recessive autosomic way1. The Gaucher Registry is the largest co-operative observational register in the world. Up to January 2007, 4,585 patients from 56 countries had been registered (www.gaucherregistry.com). It is estimated that there are currently around 300 diagnosed cases in Spain, although it is calculated that there are many more. In the majority of case, the molecular basis of the disease is made up of mutations in the gene GBA (Glucocerebrosidase beta acid) located in chromosome 1 (1q21) which codes for glucocerebrosidase. GD has three clinical forms, and in all of these there is bone, bone medullar and visceral affectation. The Neuronopathic Gaucher Disease Task Force of the European Working Group on Gaucher Disease classifies the disease as: type 1, or non-neuropathic; type 2, or acute neuropathic; and type 3, or chronic neuropathic2. Type 1 GD is the most common, making up 94% of all cases. Type 2 GD is the form called infantile cerebral. Type 3 GD is very rare and is only seen in the Norrbottnian region in the north of Sweden. For this reason we are always here refering to type 1 GD. GD, as with other rare diseases is characterised by being multisystemic. Notable among its multiple clinical manifestations are osteopenia, bone pain, bone fractures, anaemia, thrombopenia, haemorrhages, delayed growth, hepatomegaly, splenomegaly and changes in liver function tests. The prognosis of GD depends on the degree of affectation of these clinical manifestations. GD is a disease which starts in infancy but which is not usually diagnosed until the age of 16 years2. Even in those patients diagnosed as adults, the signs and symptoms begin in infancy3. This is why each patient is different in terms their age of presentation, symptomology, diagnosis and progression of the disease. Although there is a fulminant presentation form in infancy, the disease may be asymptomatic and diagnosed by chance in adults, in whom it usually takes an insidious and progressive course. Despite being treated as a hereditary disease, the diagnosis of type 1 GD is carried out in 74% of cases at an adult age. And 10% of cases of GD are even diagnosed at over 50 years of age. If it is not brought to mind, it is almost impossible to diagnose. It initially presents as a combination of symptoms such as bone pain, haematomas and asthenia. For this reason it is usually wrongly labelled as a non-specific viral infection, “growing pains”, a crisis of acute bone pain with local inflammation and/or fever with necrosis in the hip categorised as Perthes disease, accidental fractures, recurrent epistaxis due to non-specific alterations in coagulation and splenomegaly.Read More
The paradox of vitamin D deficiency in sunny regions, in young people or in osteoporotic patients treated with vitamin D, could be explained by common genetic variations. Have we found the Rosetta Stone of this apparent contradiction?
The “epidemics” of rickets which devastated humanity appeared to have ended with the discovery of vitamin D at the start of the last century. However, severe and prolonged deficiency of vitamin D, with clinical manifestations of rickets and osteomalacia is rising again, above all in ethnic minorities, in Western countries1.
At present, vitamin D deficiency constitutes a pandemic which affects more than half the population of the whole world2, and is a significant factor in age-related loss of bone and muscle mass , falls and fractures2,3.
In addition, in developed societies, vitamin D deficiency is associated with a higher risk of degenerative and chronic diseases, such as autoimmune diseases: diabetes mellitus, multiple schlerosis; cancer: colon and breast; infectious diseases, such as tuberculosis and seasonal flu; cardiovascular diseases, cardiac insufficiency, hypertension, and acute myocardial infarction, and even a higher risk of cardiovascular death, or death by any other cause2,3. Although, the great majority of the studies are associative and not interventional, the biological plausability generated by knowledge of non-hormonal actions, intracrines and paracrines of the endocrine system of vitamin D, give consistency to the potential problem which, for the public health system, a deficiency or insufficiency of vitamin D may constitute3.
“Vitamin D” in circulation is made up of vitamin D3 and D2, the first mainly acquired by subcutaneous formation by ultraviolet B radiation, and in smaller qualities by ingesting the few natural dietary sources which contain it, as well as fortified foods or supplements, the second solely from these last two sources4. Once acquired, the vitamin D, and later its metabolites, are transported by means of a vitamin D transporter protein, also known as “gc-globulin (group-specific component)”, which also participates in transport within cells2,3.
In the liver, by the action of, above all, the microsomal enzyme CYP2R1, the “vitamin D” is converted in to 25 hydroxyvitamin D (calcifediol), the most stable and abundant metabolite, biomarker for the status of the organism of vitamin D2,3.
Introduction: The bone-related and non bone-related functions of vitamin D are becoming better known by the day. As a result, levels of 25 hydroxyvitamin D (25-HCC) above 30 ng/mL are considered optimum.
Objectives: To study in a population of medical students in Gran Canaria what nutritional and lifestyle factors are associated with high levels of 25-HCC.
Material and method: A transverse study carried out in 98 Medical students of both sexes at the University of Las Palmas de Gran Canaria. All completed a questionnaire about their lifestyles and nutritional habits. A general physical examination was carried out and blood in fasting was taken to determine various biochemical parameters, including markers for remodelled bone, PTH and 25-HCC. In addition, bone mineral density was determined by dual X-ray absorptiometry and using ultrasound parameters in the calcaneum.
Results: We did not find statistically significant differences between thestudents who had levels of 25-HCC higher than 30 ng/mL and those with levels below this figure, in any of the variables studied, with the exception of male sex and the consumption of vitamin supplements.
Conclusions: Male gender in students of medicine in Gran Canaria, and the consumption of vitamin supplements, are associated with levels of vitamin D lower than 30 ng/mL.
Background: The arrival of the biphosphonates signified an advance in the treatment of Pagets’s disease of bone (PDB), but agents which are more efficacious and easier to use are needed to improve the complement of treatments. Zoledronic acid, a biphosphonate administered in the form of a single intravenous perfusion, could satisfy these requirements.
Method: We administered a perfusion of 15 minutes in duration of 5 mg of zoledronic acid to patients with PDB. The principal criterion for evaluating efficacy was the rate of therapeutic response at 6 months and 12 months, defined as a normalisation of the levels of alkaline phosphatase (AP), of amino-terminal propeptide of procollagen type 1 (P1NP), as markers for formation, and of carboxy-terminal telopeptide of collagen type 1 (CTx) as marker for resorption. We also evaluated the response of AP, CTx and P1NP at 18 months and 24 months.
Results: At 6 months and 12 months all the patients who received zoledronic acid presented a therapeutic response with normalisation of levels of AP, P1NP and CTx. The response was maintained at 18 and 24 months, although only one patient showed raised levels of AP at 24 months, coinciding with an elevation of hepatic gamma-glutamyl transpeptidase.
Conclusions: A single perfusion of zoledronic acid produces a rapid, complete and sustained response in PDB.
Over the last decade vertebroplasty and kyphoplasty have become popular as therapeutic options for the treatment of vertebral fractures. In fact, numerous non-controlled studies have indicated that both procedures are very efficacious for the control of pain associated with fractures. However, some recently published randomised trials have cast doubt on the true effectiveness of these procedures. On the other hand, certain observations have suggested that the increase in the rigidity which is produced by the injection of metacrylate into a vertebral body could facilitate the collapse of the adjacent vertebra. Therefore, vertebroplasty and kyphoplasty should not be considered as a routine theraputic measure, but should be limited to carefully selected patients, in whom the potential benefits surpass the risks and costs of the procedure. In any case, the patients should be put on a global treatment programme which includes pharmaceutical measures and non-pharmaceutical care to reduce the risk of future vertebral and peripheral fractures.
Various clinical trials have recently been published which were supposed to be an important contribution to knowledge regarding the effectiveness of vertebroplasty. The results have been rather contradictory both within themselves, and with earlier observational studies. For this reason it is worth reviewing this questions with the intention of helping clinicians who need to take decisions on the treatment of patients with osteoporotic fractures. We have not dealt with the possible utility vertebroplasty in other processes, such as fractures caused by tumours or by trauma.
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.Read More
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.Read More
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.
Current perspectives on the role of vitamin D and calcium in the patient care for osteoporosis: An expert panel discussion
Background: A better knowledge of the wide variety of actions of vitamin D is an essential step to improve the quality of osteoporosis care. This review of the current evidence of the binomiun ‘vitamin D-osteoporosis’ is the result of a one-day expert panel meeting held in Madrid in 2008. The panel consisted of experts in osteoporosis and mineral bone metabolism pertaining to a range of clinical disciplines and drawn from throughout Spain.
Method: A literature search was performed on the MEDLINE database for clinical trials, randomized clinical trials, systematic reviews and meta-analyses for articles published between 2007 and 2008, using the terms osteoporosis, vitamin and calcium. The resulting articles were the material used for small-group discussions at the meeting.
Findings: Oral alendronate and risedronate are the aminobisphosphonates of choice because of their proven efficacy in vertebral, nonvertebral and hip fractures. The adequate dose of vitamin D could be defined as 800 IU/day for healthy adults and as 1000 IU/day for osteoporotic patients, and the adequate amount of calcium intake is 1000-1200 mg/day. The dose required for correct functioning of extraskeletal actions of vitamin D may be higher. Calcium supplementation could be secured through the diet but drug administration is required when vitamin D supplementation is given.
Conclusions: Optimization of the nutritional supply of vitamin D and calcium is the first step in the care of the patient with osteoporosis. Vitamin D supplementation does not exclude the intervention on other factors that may influence the risk of falls.
Consensual conclusions of the I Multidisciplinary Forum on the management of patients with High Risk of osteoporotic Fracture (HRF)
On the 12th and 13th of February this year the first Forum on High Risk of Fracture was held in Madrid, coordinated by Prof. Díaz Curiel under the auspices of SEIOMM, and with the sponsorship of Nycomed. Around 100 specialists in rheumatology, traumatology, rehabilitation, geriatrics, units of bone metabolism, internal medicine and endocrinology discussed, from a multidisciplinary perspective, the presentations prepared by the group coordinators based on the review of data published and having been previously discussed in two meetings by the members of the scientific committee.
With the difficulties consequent to tackling such a complex theme, a consensus document was developed to reflect the clinical and multidisciplinary reality of the concept of “high risk of osteoporotic fracture”. An extract of this document is presented here in summary, with the aim of bringing together the views from the different specialisms involved in the management of disease in this type of at risk patient in our country
To the Director:
The fracture of the proximal extremity of the femur, known also as a hip fracture, constitutes the most serious clinical complication of osteoporosis1, leading to an increase both in the morbidity and the mortality of the patients who suffer it2-4. Practically all hip fractures are admitted to hospital, where they are mostly dealt with by surgical intervention5. For many years, in all the hospitals in our country, a system of coding for diseases is applied, based on the international classification of diseases, or ICD • 9 •6. These codes are applied both in the clinical history and in the databases of hospital archives
It might be thought that the collection of epidemiological data on hip fractures is simple, since by practically all cases being admitted to hospitals, they would be easily identifiable7. However, we believe that in reality this is not the case, and that it is possible that we are losing information on the true prevalence both of fractures of the hip and on osteoporosis and vertebral fractures, because the current coding allows many options.
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