Revista de Osteoporosis y Metabolismo Mineral

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Category: 5

Interdisciplinary prevention of hip fracture

Spain has one of the highest hospital costs relating to hip fracture, at 9,936 euros for an admission related to this pathology1. To these economic-health costs we must add those arising in the patient’s environment and, above all, the non-quantitative costs arising from the changes in lifestyle and the loss of productivity which fragility fractures produce, both for the patient, as well as for their families, and for society as a whole. These are difficult to quantify, pending the results of the ICUROS and PROA2 studies, which have estimating these costs as their objectives.
If we take into account the high number of hip fractures treated annually, 720 cases annually for every 100,000 people over 60 years of age, it is not difficult to understand the serious public health problem this represents. However, the true problem is not the financial costs, but in the personal cost which results, and which is translated into raised levels of morbimortality.
Hip fracture, the outcome of loss of femoral resistance, and in many cases, of a fall, is the most serious example of the complications of osteoporosis. Its treatment should be based on resolving the functional problem, improving the nutritional and metabolic state of the injured person, on avoiding new falls and trying to recuperate and reinforce the bone structure.
If these actions are not carried out diligently the clinical and life prognosis will become more serious.

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Checklist for prevention of new hip fractures

Introduction: Hip fracture is the worst complication of osteoporosis and especially affects postmenopausal women in the developed world. Previous studies have shown low rates of initiating osteoporosis treatment during hip fracture hospitalization.
Objective: To probe the effectiveness of the so-called hip fracture checklist in increasing the rate of the initiation of osteoporosis treatment compared with the previous two years.
Methods: Rates of initiating treatment among a population of one hundred postmenopausal women over 60 years of age surgically treated after suffering a hip fracture. Comparison of rates of prescription in our hospital before and after initiating the current study.
Results: In 2006, 1.66% of the patients were discharged from hospital with a new treatment for osteoporosis. In 2007, the rate was 6.9%. The age of our patients was 80.4 years. All of them were diagnosed during hospitalization with either osteoporosis (61.9%) or osteopenia (38.1%), but only 13% of them were previously diagnosed with osteoporosis, 10% of them were taking calcium and vitamin D, and 2% bisphosphonates. At the time of discharge, we prescribed calcium and vitamin D to all the patients (100%), and bisphosphonates (oral or parenteral) to the 94.6% of them.
Conclusions: The results show a significant increase in rates of antiosteoporotic drugs prescription compared with the previous two years. The implementation of the hip fracture checklist clearly increases the likelihood of starting osteoporosis treatment post hip fragility fracture.

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Inadequate levels of D: not a D-elicious perspective

In the last few decades clinical research in large population studies has revealed the high prevalence of insufficient levels of vitamin D across the globe1,which, combined with its effects on bone, the muscular-skeletal system, innate and acquired immunity, the cardiovascular system, and the development and function of cells, makes this a first order problem in public health. In fact, low levels of vitamin D are associated significantly with all the causes of morbimortality2.

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Prevalence of hypovitaminosis D and secondary hyperparathyroidism in the Spinal Cord Injury Unit in Gran Canaria. Preliminary study

Background: vitamin D deficiency is very common, and has been demonstrated in multiple studies in both the general population and in patients with different pathologies. However, it has been little studied in patients affected by spinal injury.

Objective: to study the prevalence of hypovitaminosis D and the possible development of secondary hyperparathyroidism in a population of patients with spinal injury.

Material and method: transverse descriptive study carried out in 104 patients affected by spinal injury. A clinical history was taken, a detailed physical examination carried out and a blood sample while fasting taken, with the least possible compression, from all patients. The analytical parameters were analysed using automated techniques and the determination of 25-hydroxyvitamin D (25HCC) and parathyroid hormone (PTH) was performed using electroimmunochemiluminescence (ECLIA).

Results: the global mean value of 25-hydroxyvitamin D was 20.1 ± 11.6 n/ml. 84.6% of the patients had blood values of 25-hydroxyvitamin D lower than 30 ng/ml and 62% of all patients showed values lower than 20 ng/ml. The prevalence of vitamin D deficiency was similar in men and women. However, although we found an inverse correlation between levels of PTH and hydroxyvitamin D, only 5.8% of patients ended up developing secondary hyperparathyroidism.

Conclusions: there is a high prevalence of hypovitaminosis D in patients with spinal injury. It is advisable, therefore, to include a study of this metabolite in the care protocol of these patients to correct these deficiencies as and when they are found.

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Effects of calcium and vitamin D, with and without lactulose, in bone mineral density on postmenopausal women with osteopenia: Pilot randomized controlled trial

We report the results of a randomized, double-blind, double-dummy, multicenter, parallel group pilot study, the objective of which was to assess whether the addition of lactulose to vitamin D and calcium supplementation for 12 months contributed to bone mineral density (BMD) maintenance in postmenopausal women with osteopenia (T-score –1 to –2.5 SD). Women in the lactulose group (n=19) received lactulose 15 mL/day (equivalent to 10.05 g), vitamin D3 400 IU/day and calcium carbonate 500 mg/day, and women (n=22) in the placebo group were administered lactulose placebo, vitamin D3 400 IU/day and calcium carbonate 1,000 mg/day. The baseline daily calcium intake was similar in both study groups. The primary endpoint was the BMD in the lumbar spine at the final visit. A generalized liner model was used to assess final versus baseline differences in BMD in both study groups. Differences in least-square means of BMD between lactulose and placebo were not statistically significant both in the per-protocol data set (–0.012, 95% CI –0.031 to 0.007, P=0.224) and in the intention-to-treat population (–0.005, 95% CI –0.025 to 0.016, P=651). As we have not found differences within the two study groups, the addition of lactulose to 500 mg of calcium carbonate associated with vitamin D supplementation could have similar effects on lumbar BMD as 1.000 mg of calcium carbonate. These findings may indicate that lactulose may improve calcium absorption in postmenopausal women. A long follow-up study with a greater number of subjects would be necessary to confirm these preliminary observations.

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Osteoporosis and steroid antagonists of the Wnt way

The association between an excess of glucocorticoids and osteoporosis was indicated more than 80 years ago by Harvey Cushing when describing the disease which takes his name. Subsequently, after the introduction of the glucocorticoids as anti-inflammatory drugs, it was confirmed that exogenous hypercortisolism was also detrimental to the skeleton, in such a way that steroidal osteoporosis is now considered to be the most common form of secondary osteoporosis in our ambit1. Osteopenia induced by corticoids affects predominantly trabecular bone and is most intense during the first months of treatment, when more than 10% of bone mass may be lost2. In addition to inducing the loss of bone, the glucocorticoids alter its quality, which would explain the notable increase in fractures (nearly 75%) during the first three months of treatment, even before bone mineral density falls.

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Risk of fracture associated with states prior to the diagnosis of diabetes mellitus type 2: Nested case-controlled study (DIAFOS cohort)

Summary

Backgound: In phases prior to the diagnosis of diabetes mellitus type 2 there is an increased risk of cardiovascular disease, but it is not known if this is the case in relation to the risk of fractures.

Objective: To compare the prevalence of fracture in cases of diabetes mellitus and in matched controls.

Material and method: Nested case-control study in a population-based cohort. All patients diagnosed with type 2 diabetes in the period 2006-2011 were included, as were, for each of these patients, two control subjects of the same age, gender, and from the same medical centre, without diabetes. Any fractures, cerebro-vascular accidents and ischemic cardiopathy prevalent in these patients were identified using ICD codes 10. The prevalence of osteoporotic, major and hip fractures, and of cardiovascular disease at the time of diagnosis for the diabetic subjects, and on the same date for the matched controls, were calculated. Using conditional logistical regression the odds ratios (OR) were calculated, adjusting for body mass index, smoking, alcoholism, use of statins, cardiovascular disease and diabetic complications.

Results: 58,931 diabetic patients and 117,862 controls were identified. At the date of diagnosis the diabetic patients had a higher prevalence of cerebro-vascular accident (4.9% vs 3.5%; p< 0.001) and ischemic cardiopathy (8.1% vs 4.7%; p< 0.001). On the other hand, the prevalence of osteoporotic fracture (2.8% vs 2.7%; p= 0.22), hip fracture (0.4% vs 0.4%; p=0.63) and major fracture (1.5% vs 1.5%; p=0.97) was similar in both groups. The adjusted ORs were: 1.2 (CI 95%: 0.96-1.09), 1.08 (CI 95%: 0.90-1.28), and 0.99 (CI 95%: 0.91-1.09), respectively.

Conclusions: The type 2 diabetic patients had a higher prevalence of cardiovascular disease at the time of diagnosis. However, their risk of fracture was similar to the non-diabetic control subjects.

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PINP in patients with hepatic insufficiency: Comparison of two methods of measurement and association with different biochemical parameters

Introduction: N-terminal propeptide of type 1 collagen (PINP) is a marker for bone formation. Blood PINP is found in trimeric and monomeric forms. There are two automated methods for its determination. R-PINP (Roche Diagnostics) determines both forms (Total PINP). IDS-PINP (IDS iSYS N-Mid® Vitro) determines the trimeric part (Intact PINP).
Objective: To compare the two methods.
Material and method: 81 patients (64 men and 17 women, average age of 53 ± 8 years) with terminal hepatic insufficiency were recruited. Creatinine, PTH, 25-OH-vitamin D, beta-crosslaps (β-CTX), desoxypyridinoline (Dpyr), hepatic function and PINP with both methods, were measured. Bone mineral density (BMD) was measured (Hologic®, QDR 4500) in the lumbar spine and femoral neck. The comparison between the two methods was carried out using a Bland-Altman and Passing’Bablok analysis.
Results: R-PINP showed higher values than IDS-PINP (85.03 ± 56.67 vs. 55.22 ± 32.81 ng/mL, p<0,001). The correlation between the two methods was r= 0.81 (p<0.01) and the Passing-Bablok regression analysis Y = 0.570 [0.475-0.669] X + 7.724 [2.130-12.542].
Conclusion: There is a good correlation between the two methods in patients with hepatic insufficiency, although not proportional or interchangeable.

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Epidemiology of hip fracture in Gran Canaria over the five year period of 2007-2011

Background: Hip fracture is the most serious clinical complication of osteoporosis, due to its raised morbidity and mortality.
Method: We have studied the epidemiological and demographic characteristics of all the fragility fractures of the hip occurring in patients of &Ge; 50 years of age recorded in Gran Canaria during the 5 year period of 2007-2011 from the admission, coding, emergency and traumatology services of all the hospitals in Gran Canaria, in both the public and private healthcare sectors.
Results: A total of 2,222 hip fractures were recorded, of which 1,593 (71.7%) occurred in women and 629 (28.3%) in men. The female/male ratio was 2.53. The average age at which the fractures occurred was 79 ± 9.7 years. Over the 5 years, the total number of fractures (men and women) varied between 402 (in 2007) and 504 (in 2010). The number of fractures increased with age up to the 90s. The annual global incidence was 150 cases/100,000 inhabitants &Ge; 50 years: in women 205.4 cases with respect to the population of this sex and age, and in men, 89.1 with respect to the population of men &Ge; 50 years. During the winter months 29.7% of the total fractures occurred, 7.5% more than those happening during the summer months (22.2%).
Conclusions: During the period 2007-2011 the incidence of hip fracture in Gran Canaria remained more or less stable, in every year being greater in women than in men, and increasing with age up until the 90s. The greatest number of hip fractures occurred during the winter months, with similar numbers in spring, summer or autumn.

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Blood sclerostin and Dkk-1 in patients who start treatment with glucocorticoids. Preliminary results

Background and objectives: The Wnt pathway and its inhibitors (sclerostin and Dkk-1) have a primary role in the regulation of bone mass and osteoblastogenesis. The objective of this study was to analyse the effect of treatment with glucocorticoids (GCC) on the inhibitors of the Wnt pathway and their relationship with bone mass and the parameters for bone turnover.
Methods: A transverse study including 15 patients (9 women and 6 men) with an mean age of 51±21 years at the start of treatment with GCC (≥ 7.5 mg/day, ≤ 6 months). Levels of sclerostin, blood Dkk-1 and blood markers for bone turnover (procollagen 1 N-terminal propeptide [P1NP], osteocalcin [OC], and carboxy-terminal telopeptide of collagen type 1 [CTX] ) were determined, and bone densitometry ( DXA) in the lumbar spine was carried out, in all patients. The results were compared with a control group.
Results: The mean dose of glucocorticoids was 58 ± 21 mg/day, in the majority of patients (73%) indicated by idiopathic thrombocytopenic purpura. The patients treated with glucocorticoids had a reduction in the parameters for bone formation compared with a control group (OC: 7.4 ± 2.8 vs 24.4 ± 6.2 ng/ml, p<0.01) and a reduction in blood Dkk-1 (29.6 ± 23.6 vs 48.3 ± 15.6 pmol/L, p=0.02). No significant differences were observed in values for blood sclerostin, although this correlated positively with the dose of GCC received and lumbar bone mineral density.

Conclusion: Contrary to what is seen in experimental studies, the start of treatment with glucocorticoids is associated with a reduction in blood levels of Dkk-1. These results indicate the necessity of analysing these inhibitors and their relationship with remodelling and bone mass during this process over the long term.

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Divergent effects of TGF-beta; inhibition in bone metastases in breast and lung cancer

Background: The objective of this study lies in the determination of the validity of transforming growth factor β (TGF-β) as a therapeutic target in models of metastasis deriving from different histological types of lung cancer.

Material and methods: 4-week-old immunodeficient mice inoculated with lung and breast cancer lines were treated with cytokine inhibitor peptide, control peptide or placebo. Weekly bioluminescence and microradiographic measurements were taken to determine the effects of the treatment on tumor burden and metastatic lesions in the long bones.

Results: Treatment with the specific peptide against TGF-β has a protector effect in the bone of animals inoculated with the breast cancer lines, unlike what happens in the control peptide and placebo groups. However, the anti-TGF-β treatment lacks the significant therapeutic effects on the bone metastases which develop in lung cancer bearing animals.

Conclusions: The role of TGF-β as a potential therapeutic target in bone metastasis is highly dependent on the histopathological type and subtype of tumor.

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Increased bone modelling as a presentation of Graves’ disease

The adverse effects of hyperthyroidism on bone have been described for years. Thyroid hormones are necessary for growth, maturation, metabolism and bone remodelling. However, untreated thyrotoxicosis causes increased remodelling, osteopenia or osteoporosis and increased fracture risk. Since the introduction of antithyroid drugs and radioiodine, hyperthyroid bone disease is less common. Here we present a rare case of an asymptomatic patient with thyrotoxicosis making its debut as increased bone remodelling.

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Osteology images
Poster Communications
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