Osteoporosis (OP) is a highly prevalent chronic disease which constitutes a public health problem, with significant medical and socioeconomic repercussions due, respectively, to the morbid-mortality which it brings and the direct and indirect costs which it generates. It is expected that with demographic changes which are happening, and the aging of the population, if there is no immediate intervention in clinical practice, the number of patients who will suffer at least one fracture will become greater.<Read More
The appearance of scales for the prediction of the absolute risk of fragility fracture and the consequent definition of thresholds for pharmacological intervention has significantly limited the number of women eligible for treatment among those who are in their first years of the menopause. What is certain is the deterioration that many of them suffer in terms of bone metabolism as a consequence of rapid hypogonadism, but there are no defined strategies for the use of drugs to limit this phenomenon. In its day, hormone therapy solved this problem, but its limitations to use in women with symptoms sufficient to affect quality of life has left many users without an efficacious option. It is true that life style changes, especially diet and exercise, alleviate the problem, but they are not an entirely satisfactory solution. The advances which are being made in the action mechanism of plant extracts, both in the form of pure molecules prepared to the equal quality of medicines, or foods in which they are found in sufficient concentrations (functional foods), are raising new expectations. There has been significant progress in the knowledge of the molecular mechanisms of many of these substances, especially the isoflavones. Although there are differences between their components, we know that they are capable of activating estrogen receptors, particularly isoform β, and that this is followed by the activation of different signalling pathways in various experimental models, essentially cellular. The fundamental question, however, is what is their true clinical significance.
On this point the evidence is more limited and to date, still confusing. On the one hand is the unfinished business of the symptoms, where there are few clinical studies of quality, and those that there are present difficulties derived from their inclusion of groups with low numbers of participants or of other methodological drawbacks. On the other, there is the question of their eventual efficacy in limiting chronic diseases which more or less clearly have their roots in hypogonadism, such as cardiovascular disease or osteoporosis. The questions in relation to the former have recently been reviewed1, and with respect to the latter, particularly welcome is the article by García-Martín et al. in this issue2.
Background: To assess the appropriateness of the prescription of antiresorptive drugs according to the Guide to Osteoporosis of the Spanish Society for Family and Community Medicine (SEMFYC).
Material and methods: Descriptive transversal study carried out in two urban primary care centres. Out of all those patients who had taken an antiresorptive drug and/or had a diagnosis of osteoporosis, a sample of 411 patients was studied. Those who took the drug for other reasons (13), with diagnostic errors (8), exitus (3), or lacking clinical history (16) were excluded. Variables were recorded: age, sex, personal and family history of fractures, T and Z densitometric scores, type of antiresorptive drug, calcium and vitamin D supplements, and the specialist who initially indicated treatment. The appropriateness of the prescription was assessed according to whether or not it complied with the criteria in the SEMFYC Guide.
Results: 371 patients complied with the inclusion criteria. Of these, 96.5% were women. The average age was 68 years (standard deviation -SD-: 9.4). In 288 patients (77.6%) the personal antecedence of fractures was assessed, and in 21 (5.7%), that of the family. Densitometry had been carried out in 65.5% of patients. 65.2% had taken biphosphonates, and 14.8%, raloxifene. 72.8% were receiving vitamin D supplements, and 76%, calcium. In 30.5% of cases the treatment was initiated by the family doctor, in 21% by a traumatologist and in 14.3%, by a gynaecologist. In 204 patients (55%) the antiresorptive prescription was appropriate, in 113 cases (30.5%) it was not possible to determine the appropriateness, and in 51 (13.7%) it was inappropriate.
Conclusions: The prescription was inappropriate in fewer than 15% of patients, with biphosphonates the drugs most commonly used. In a third of patients densitometry was not carried out.
Maxillary osteonecrosis (MON) is a disease which has appeared recently as a serious complication in patients suffering from neoplasms or other chronic diseases. MON has been associated with the use of powerful diphosphonates, for which reason many authors have named the disease secondary osteonecrosis of the mandible due to biphosphonates1-5.
This is a relatively new disease, which means that there is not yet unanimity on many of its aspects. For a start, there is no clear and universally accepted definition of MON. A panel of experts from the American Society of Bone and Mineral Research (ASBMR)2 recently recommended using the definition “an area of exposed bone which persists for more than 8 weeks in the absence of earlier irradiation and/or metastasis in the mandible”. The American Academy of Mouth and Maxillofacial Surgeons published a similar definition: a patient may have MON if they comply with 3 requirements: 1) current or previous use of biphosphonates; 2) the presence exposed or necrotic bone for a minimum of 8 weeks; and 3) an absence of maxillary radiotherapy. At this point should insist that the correct name for the disease is maxillary necrosis and not necrosis of the mandible, given that there is frequently also affectation of the upper maxilla6.
Changes in bone metabolism markers and ultrasound parameters in postmenopausal women induced by soy isoflavones
Introduction: The results of the works published on the role of isoflavones in the prevention of postmenopausal osteoporosis are contradictory. The objective of our study is to evaluate the effects of nutritional intervention with a milk product enriched with soy isoflavones on bone metabolism in Spanish postmenopausal women.
Subjects and methods: A randomised controlled double blind trial was carried out in 99 postmenopausal women who were allocated to two groups: group S (n=48), with a consumption of a milk product enriched with soy isoflavones (50mg/day), and group C (n=51), with a consumption of a control milk product over 12 months. Hormone parameters and markers for bone metabolism were assessed at the baseline and at one year. Ultrasound of the calcaneum (QUS, Hologic Sahara®, North Carolina, US.) was used as the evaluation tool for bone mass.
Results: At 12 months, a decrease in blood levels of tartrate-resistant acid phosphatase and osteoprotegerin occurred (2.18 ± 0.8 vs 1.76 ± 0.54 U/l, p<0.001, and 5.21 ± 3.36 vs 3.89 ± 1.47 pmol/L, p=0.007, respectively), as well as an increase in 25-OH-vitamin D (24.48 ± 9.85 vs 28.18 ± 10.45 ng/ml, p<0.001 ) with no differences between the groups. There were no significant changes in hormone parameters and the rest of the bone markers. In terms of the QUS, in the total sample there was an increase in the sound velocity [SOS] (1517.86 ± 38.13 vs 1525.11 ± 35.6 m/s, p=0.036), QUI (76.37 ±19.87 vs 80.82 ± 18.26, p=0.012 ), estimated bone mineral density [Est. BMD] (0.408 ± 0.13 vs 0.435 ± 0.12 g/cm², p=0.013) and T-score (-1.55 ± 1.12 vs -1.31 ± 1.03, p=0.019). In group S, positive changes occurred in QUI (74.37 ± 18.87 vs 78.83 ± 13.68, p=0.032) and Est. BMD (0.397 ± 0.12 vs 0.423 ± 0.09 g/cm², p=0.04), whilst in group C there were no significant differences.
Conclusions: The daily consumption of these milk products increases levels of 25-OH-vitamin D and results in a decrease in markers for bone metabolism. A diet rich in soy isoflavones may be an option as a preventative measure against the effects of the menopause on bone.
Introduction: The objective of this study is to analyse the bone microarchitecture in rheumatoid arthritis (RA) in a series of biopsies of the iliac crest carried out previously in patients not having had earlier treatment with glucocorticoids, using microCT analysis.
Material and method: 14 bone specimens were obtained, taken from the iliac crest of patients with RA with no previous treatment with glucocorticoids. None of these patients was diagnosed with a disease or was taking medicines which could compromise bone mineral metabolism. A complete clinical history was taken, and a blood analysis carried out, including the rheumatoid factor. The specimens were embedded in methyl-methacrylate and studied with a microCT eXplorer Locus SP scanner. The acquisition parameters were: 80 kVp/80 μA, thickness of aluminium filter:10-3 inches, FOV ≈ 2×2 cm, mode of acquisition of 360°, 720 views, 4 frame averages/view, exposure time 1.700 ms, voxel resolution: 28 μm. A region of interest (ROI) was selected by means of interpolation, avoiding cortical bone. An automatic segmentation process (thresholding) was used to differentiate and segment the hematopoietic bone tissue. The microarchitectural parameters were generated automatically by computer using parallel-plate algorithms. The results were compared with 14 specimens from healthy controls of similar age and sex using Student’s test for unpaired samples. The statistical significance was p< 0.05.
Results: The fraction of bone volume (BV/TV) was significantly lower in those patients with RA than in the healthy controls (p< 0.05). The trabecular thickness (Tb.Th) was higher in the controls. The trabecular separation (Tb.Sp) was higher in those specimens with RA (p< 0.05). The trabecular connectivity (Tb.N) was significantly greater in the control specimens (p< 0.05).
Conclusions: The patients with RA have worse trabecular bone quality and low trabecular connectivity. The microCT scanner is a quick and powerful tool for the study of trabecular microstructure.
The FRAX® tool has been developed as an aid to predict the 10-year probability of hip and major osteoporotic fracture using country-specific data. This algorithm combines clinical risk factors with or without the bone mineral density (BMD) measurement to identify subjects in high risk of fragility fracture. The aim of this study was to challenge the Spanish version of the WHO fracture risk assessment tool FRAX® on a cohort of women with BMD measurement indication.
Methods:Clinical and BMD data from a large population cohort taken from metropolitan area of Barcelona were used for this study. Inclusion criteria were: age range 40-90 yrs, clinical risk factors, femoral neck BMD T-score available and follow-up longer than 7 years. Main outcome was: major osteoporotic fracture at least 7 years after the first BMD measurement. The total number of predicted fractures by the FRAX algorithm was compared with the total number of new registered fractures during the follow-up time in the study population and expressed as observed – expected fracture (O/E) ratio. Results were stratified by age; BMD results and number of clinical risk factors were included in the FRAX algorithm.
Results: 8450 women were included, 69% were under 60 years and 14% presented a previous fracture. After follow-up, 10% had a major osteoporotic fracture. Wrist was the most incident fracture site and hip accounted only for 0.9% of the total. The 52% of the main fractures happened in women with none or only one risk factor. The fracture ratio (O/E) was 0.8 [CI 95%: 0.7 ; 1.1] for hip fractures and 3.1 [CI 95%: 2.8 ; 3.5] for the main osteoporotic fractures. The O/E ratio was lower as higher was the age of women (for those older than 70 O/E=1.9 [CI 95%: 1.6 ; 4.3]), longer the follow-up time (for those with more than 10 years O/E=2.7 [CI 95%: 2.2 ; 3.4]) or fewer number of risk factors (O/E=3.2 [CI 95%: 2.7 ; 3.9]).
Conclusions: The Spanish version of the FRAX® algorithm for this population is reasonably well adjusted to predict hip fractures but underestimates the observed main osteoporotic fracture incidence, independently of the T-score, and number of risk factors.
FRAX® index is a prognostic tool to assess the risk of osteoporotic fracture. Although ethanol ingestion, liver disease and body mass index are considered independent prognostic factors in the FRAX® score, we have observed that in chronic alcoholics there are several variables not included in the FRAX® index, which show a relation with prevalent fractures and/or low BMD. Therefore, in this study we compare the relation of FRAX® index with those of other variables, such as lean and fat mass, liver function parameters, and amount of ethanol consumed, with the presence or not of prevalent fractures in 57 chronic alcoholic men, older than 40 years, drinkers of more than 200 g ethanol/day during a long time. We found that FRAX® index was significantly higher among those with any fracture, but the same happened with BMI, total fat amount, and fat amount at arms, as well as total amount of ethanol. The FRAX® index did not show differences among those with or without vertebral fractures, or rib fractures. Patients with rib fractures showed differences in total fat amount and right arm fat amount when compared with patients without rib fractures. Therefore, these results suggest that in the alcoholic, other variables, such as amount of ethanol consumed and fat mass, should be considered, in addition to FRAX®, in the prediction of fractures.Read More
Structural study using micro-CT of the femur of Goto-Kakizaki rats, experimental model for non-overweight type 2 diabetes
Background: The effects of type 2 diabetes on the microstructure and mass of bone are not clearly defined. The objective of this study has been to assess the microstructural properties and volumetric bone mineral density of Goto-Kazizaki rats, the rat model for non-overweight type 2 diabetes which tries to circumvent the influence of obesity on bone mass.
Material and methods: An experimental study was designed using Goto-Kazizaki rats compared with a control group of non-diabetic Wistar rats of similar weight and with normal glycemia, with densitometric and microstructural studies being carried out on the distal region of the femur using computerised X-ray microtomography (micro-CT).
Results: In the volumetric densitometry no significant differences were found between the two groups. The microstructural study showed that the BV/TV and trabecular connectivity were reduced in the diabetic rats, while the tube-like trabeculae increased to the detriment of plaque-like trabeculae.
Conclusion: The deterioration trabecular bone quality could explain the decrease in biomechanical bone resistance in type 2 diabetes.
Risk of fracture according to FRAX®, hypovitaminosis D, and quality of life in a population with osteoporotic fracture cared for in primary care: baseline description of the VERFOECAP cohort
Background: the patient with an osteoporotic fracture cared for in primary care has seldom been studied. The VERFOECAP study has dual objectives: to estimate if the risk of fracture (FRAX®) in fractured patients is different in patients with or without a re-fracture; and to study the prevalence of hypovitaminosis D and the impact of the fracture on quality of life. We present a baseline description.
Material and method: design and ambit: multicentred prospective cohort study in primary care (12 centres in Catalonia). Population: random sample of patients with a history of principal osteoporotic fracture between 2006 and 2008 cared for in primary care. Information gathering: at initial inclusion meetings clinical information was gathered, quality of life questionnaires ECOS16 (specific) and EuroQol-5D (generic) completed, spinal X-ray carried out, and levels of vitamin D in the blood measured. Subjects were followed up for two years. Analysis: comparison between two groups using T-test or chi-squared test. Prevalence of hypovitaminosis D and confidence interval using binomial test.
Results: 194 patients were included. The average risk (standard deviation) of fracture of the hip, according to FRAX® was calculated as: 6.9% (6.4), and of principal osteoporotic fractures: 14.8% (8.6). EuroQol-5D showed frequent limitations to walking (47.6%) and to daily activities (45.5%); 55.0% reported moderate pain, and 41.0% anxiety/depression. The ECOS-16 score was higher in patients with a history of vertebral fracture (p<0.001). The prevalence of hypovitaminosis D was 61.4% (CI 95%: 53.6%-68.9%).
Conclusions: the VERFOECAP cohort includes patients with osteoporotic fractures cared for in primary care at high risk of re-fracture with significant deterioration in quality of life. In these patients vitamin D deficiency is highly prevalent.
Evaluation of the risedronate efficiency 75 mgs versus generic alendronate 70 mgs, in women with post-menopausal osteoporosis and previous vertebral fractures in Spain
Introduction: The objective is to assess the cost-effectiveness of risedronate 75 mg 2 consecutive days/month vs generic alendronate 70 mg weekly, during one year in 75 years old females with post-menopausal osteoporosis and previous vertebral fracture.
Methods: A cost-effectiveness analysis under Health National System perspective has been developed to assess clinical (hip fracture prevention and quality adjusted life years gained) and economic consequences (€ 2010) during 5 years following one year treatment with both alternatives. Drug effect has been considered during the one year of drug administration. Epidemiology data and unitary costs were derived from Spanish literature.
Results: In a cohort of 1.000 females, (75 years old) with post-menopausal osteoporosis and vertebral fractures, risedronate 75 mg vs alendronate avoid 10 hip fractures, with 9.983€/hip fracture avoided cost. Aditional QALY gained are 4 with an incremental cost of 99,83€. Incremental cost-effectiveness ratio (ICER) is 24.957€ per QALY gained with risedronate 75 mg vs generic alendronate 70 mg.
Conclusion: In the treatment of females with post-menopausal osteoporosis and previous vertebral fracture, risedronate 75 mg 2 consecutive days/month compared to generic alendronate 70 mg weekly is an efficient strategy in Spain.
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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