Osteoporotic patients treated with bisphosphonates do not show the increased mortality observed in those untreated.

INTRODUCTION: Osteoporosis has been said to be associated with increased mortality. On the other hand, it is debated whether treatment with bisphosphonates may reduce mortality in osteoporotic patients. To contribute to the clarification of these issues, we have studied in a prospective cohort the mortality in people without osteoporosis and in patients with osteoporosis, untreated or treated with bisphosphonates MATERIAL AND METHODS: At their inclusion in the cohort, four groups of participants were identified: (a) people without osteoporosis (group 1); (b) osteoporotic patients treated with bisphosphonates (group 2); (c) osteoporotic patients who refused to be treated (group 3); and (d) patients who met osteoporosis diagnostic criteria but were not treated because their risk of fracture was considered to be low (group 4). To compare all four groups, unadjusted Kaplan-Meier estimates of survivorship were obtained and they were compared using log-rank test. Hazard ratios were then estimated via Cox regression adjusting for the main confounders. A comparison among the osteoporotic groups was made by means of a Cox regression analysis performed using only these three groups, adjusting for propensity scores. RESULTS: Two thousand six hundred and sixty-five people were included. In the unadjusted analysis, mortality in group 3 was higher than in the other groups (p < 0.001). Taking group 1 as a reference, Cox regression analysis showed the following mortality HRs for groups 2, 3, and 4 after adjusting for confounding factors: 0.82 (0.41-1.63), 1.37 (0.90-2.10), and 0.69 (0.46-1.02). In the analysis of the osteoporotic groups with the PS generated for them, and taking group 2 as a reference, the HRs were as follows: group 3, 2.38 (1.34-4.22); group 4, 1.45 (0.61-3.43). CONCLUSION: Mortality in osteoporotic patients who refused treatment is higher than in osteoporotic patients treated with bisphosphonates. In unadjusted analysis, it was also higher than in non-osteoporotic people; however, this difference disappeared after adjustment for confounding factors.

Serum 25-hydroxyvitamin D, parathyroid hormone, calcium intake, and bone mineral density in Spanish adults.

UNLABELLED: Vitamin D insufficiency is very common among Spanish community-dwelling adult subjects. A threshold of serum 25(OH)D around 30 ng/ml would be necessary for the prevention of secondary hyperparathyroidism and hip bone loss in our population, regardless of the dairy calcium ingestion. INTRODUCTION: This study aims to assess 25-hydroxyvitamin D-25(OH)D-status in Spanish adult subjects and to analyze its relationships with serum PTH levels, calcium intake, and bone mineral density (BMD). METHODS: A total of 1811 individuals (1154 postmenopausal women and 657 men) aged 44-93 years participated in the study. Serum 25(OH)D, intact parathyroid hormone (PTH), aminoterminal propeptide of type I collagen (P1NP), and C-terminal telopeptide of type I collagen (ß-CTX) levels were measured by electrochemiluminescence. BMD was determined by dual x-ray absorptiometry (DXA) at lumbar spine, femoral neck, and total hip. RESULTS: Serum 25(OH)D levels were below 10, 20, and 30 ng/ml in 5, 40, and 83 % of participants, respectively. There was a significant seasonal difference in mean serum 25(OH)D, with higher levels in summer-autumn. In multivariate analysis, 25(OH)D levels were negatively correlated with age, serum PTH and creatinine, body mass index, smoking, alcohol intake, and a number of chronic diseases, but positively with dairy calcium intake. The magnitude of the difference in serum PTH according to 25(OH)D quartiles was not influenced by calcium intake. A threshold of serum 25(OH)D around 30 ng/ml was observed for serum PTH and hip BMD. CONCLUSIONS: Vitamin D insufficiency is very common among Spanish community-dwelling adult subjects. A threshold of serum 25(OH)D around 30 ng/ml would be necessary for the prevention of secondary hyperparathyroidism and hip bone loss in our population, regardless of the dairy calcium ingestion. Programs to improve vitamin D status may be required in our country.

Serum uric acid is associated with quantitative ultrasound parameters in men: data from the Camargo cohort.

UNLABELLED: This study analyzes the association between serum uric acid levels and heel quantitative ultrasound (QUS) parameters in men aged 50 or more from the Camargo cohort. We found that higher serum uric acid levels are positively associated with all QUS measurements, suggesting a better bone quality in men with elevated serum uric acid values. INTRODUCTION: Higher serum uric acid concentrations have been associated with higher bone mineral density and lower prevalence of fractures. However, there are no studies that have assessed the bone quality properties in Caucasians. Therefore, we have analyzed the association between quantitative ultrasound (QUS) and serum uric acid levels in adult men from a population-based cohort. METHODS: A total of 868 men older than 50 were recruited from a larger cohort (Camargo Cohort) after excluding those with any known condition or drug treatment with a possible influence on bone metabolism, or those with a previous diagnosis of gout or taking hipouricemic agents. Bone turnover markers (PINP and CTX), 25OH-vitamin D and PTH levels were measured by electrochemiluminiscence. BMD was determined by DXA, and heel QUS with a gel-coupled device. RESULTS: Lumbar, femoral neck and total hip BMD was significantly higher in men with higher serum uric acid levels. QUS parameters were also significantly higher in men with high uric acid levels than those with lower values, and increased continuously across quartiles after adjustment for confounding variables. In multiple regression analysis, serum uric acid was significantly associated with all QUS parameters. Finally, men with serum acid levels above median showed higher values in all the QUS parameters than men with lower values. CONCLUSIONS: Higher serum uric acid levels in men older than 50 years are positively associated with QUS parameters. These data might suggest a better bone quality in men with elevated serum uric acid values.

Predictive ability of heel quantitative ultrasound for incident fractures: an individual-level meta-analysis.

UNLABELLED: The relationship between bone quantitative ultrasound (QUS) and fracture risk was estimated in an individual level data meta-analysis of 9 prospective studies of 46,124 individuals and 3018 incident fractures. Low QUS is associated with an increase in fracture risk, including hip fracture. The association with osteoporotic fracture decreases with time. INTRODUCTION: The aim of this meta-analysis was to investigate the association between parameters of QUS and risk of fracture. METHODS: In an individual-level analysis, we studied participants in nine prospective cohorts from Asia, Europe and North America. Heel broadband ultrasonic attenuation (BUA dB/MHz) and speed of sound (SOS m/s) were measured at baseline. Fractures during follow-up were collected by self-report and in some cohorts confirmed by radiography. An extension of Poisson regression was used to examine the gradient of risk (GR, hazard ratio per 1 SD decrease) between QUS and fracture risk adjusted for age and time since baseline in each cohort. Interactions between QUS and age and time since baseline were explored. RESULTS: Baseline measurements were available in 46,124 men and women, mean age 70 years (range 20-100). Three thousand and eighteen osteoporotic fractures (787 hip fractures) occurred during follow-up of 214,000 person-years. The summary GR for osteoporotic fracture was similar for both BUA (1.45, 95 % confidence intervals (CI) 1.40-1.51) and SOS (1.42, 95 % CI 1.36-1.47). For hip fracture, the respective GRs were 1.69 (95 % CI, 1.56-1.82) and 1.60 (95 % CI, 1.48-1.72). However, the GR was significantly higher for both fracture outcomes at lower baseline BUA and SOS (p < 0.001). The predictive value of QUS was the same for men and women and for all ages (p > 0.20), but the predictive value of both BUA and SOS for osteoporotic fracture decreased with time (p = 0.018 and p = 0.010, respectively). For example, the GR of BUA for osteoporotic fracture, adjusted for age, was 1.51 (95 % CI 1.42-1.61) at 1 year after baseline, but at 5 years, it was 1.36 (95 % CI 1.27-1.46). CONCLUSIONS: Our results confirm that quantitative ultrasound is an independent predictor of fracture for men and women particularly at low QUS values.

The impact of common co-morbidities (as measured using the Charlson index) on hip fracture risk in elderly men: a population-based cohort study.

UNLABELLED: We used a large population-based health care database to determine the impact of common co-morbidities on hip fracture risk amongst elderly men. We demonstrated that diabetes, chronic obstructive pulmonary disease, renal failure, HIV infection, dementia, and cerebrovascular disease are independent predictors of hip fracture, as is a Charlson score of ≥ 3. INTRODUCTION: Risk factors for hip fractures in men are still unclear. We aimed to identify common co-morbidities (amongst those in the Charlson index) that confer an increased risk of hip fracture amongst elderly men. METHODS: We conducted a population-based cohort study using data from the SIDIAP (Q) database. SIDIAP(Q) contains primary care and hospital inpatient records of a representative 30% of the population of Catalonia, Spain (>2 million people). All men aged ≥ 65 years registered on 1 January 2007 were followed up until 31 December 2009. Both exposure (co-morbidities in the Charlson index) and outcome (incident hip fractures) were ascertained using ICD codes. Poisson regression models were fitted to estimate the effect of (1) each individual co-morbidity and (2) the composite Charlson index score, on hip fracture risk, after adjustment for age, body mass index, smoking, alcohol drinking, and use of oral glucocorticoids. RESULTS: We observed 186,171 men for a median (inter-quartile range) of 2.99 (2.37-2.99) years. In this time, 1,718 (0.92%) participants had a hip fracture. The following co-morbidities were independently associated with hip fractures: diabetes mellitus, chronic obstructive pulmonary disease (COPD), renal failure, HIV infection, dementia, and cerebrovascular disease. A Charlson score of ≥ 3 conferred an increased hip fracture risk. CONCLUSION: Common co-morbidities including diabetes, COPD, cerebrovascular disease, renal failure, and HIV infection are independently associated with an increased risk of hip fracture in elderly men. A Charlson score of 3 or more is associated with a 50% higher risk of hip fracture in this population.

Bone mass and vitamin D levels in women with a diagnosis of fibromyalgia.

UNLABELLED: No differences in either bone mineral density or serum 25OHD levels have been found between 205 women with fibromyalgia (both pre- and postmenopausal) and their controls. However, a lack of the expected 25OHD summer rise was observed in patients. INTRODUCTION: Contradictory data have been published regarding a possible association between fibromyalgia and osteoporosis or hypovitaminosis D. Most studies, however, have been performed in small size samples and have excluded postmenopausal women. We decided to study this association in a larger sample of fibromyalgia patients including both pre- and postmenopausal women. METHODS: Two hundred five patients were recruited from a clinic specializing in fibromyalgia and 205 healthy controls were enrolled from the census of a Primary Care Center. Controls were matched with patients by age and the time of the year they were included in the study. Bone mineral density (BMD) was measured by DXA. Serum 25OHD, iPTH, P1NP, and CTX were also determined. RESULTS: BMD was similar in both groups (lumbar spine, 0.971 ± 0.146 g/cm(2) in patients and 0.970 ± 0.132 g/cm(2) in controls; femoral neck, 0.780 ± 0.122 g/cm(2) and 0.785 ± 0.117 g/cm(2), respectively). 25OHD levels were also similar: 23.0 ± 9.5 ng/ml and 24.1 ± 9.6 ng/ml. However, while controls showed the usual summer rise in 25OHD, fibromyalgia patients did not. PTH did not show seasonal changes, but on average was higher in patients (51 pg/ml vs. 48 pg/ml; p = 0.034). P1NP or CTX were similar in both groups. CONCLUSIONS: No differences in BMD were found between patients and controls. As for 25OHD, a lack of its expected summer rise was observed. It is doubtful whether this has any homeostatic consequence. We consider that the association reported in other studies is merely circumstantial, and not due to the intrinsic characteristics of these disorders.

Missense polymorphisms of the WNT16 gene are associated with bone mass, hip geometry and fractures.

UNLABELLED: Two missense polymorphisms of WNT16 were associated with hip bone mineral density (BMD), the buckling ratio of the femoral neck, calcaneal ultrasound and hip fractures in individuals under 80 years of age. These results confirm the association of the WNT16 gene with bone mass and osteoporotic fractures. INTRODUCTION: Osteoporosis has a strong genetic component. Wnt ligands stimulate the differentiation of osteoblast precursors and play a major role in skeletal homeostasis. Therefore, the aim of this study was to explore the association of allelic variants of the WNT16 gene with BMD, other structural parameters of bone and osteoporotic hip fractures. METHODS: Six single nucleotide polymorphisms were analysed in 1,083 Caucasian individuals over 49 years of age. RESULTS: Two missense polymorphisms (rs2908004 and rs2707466) were associated with femoral neck BMD, with average differences across genotypes of 35 mg/cm(2) (p = 0.00037 and 0.0015, respectively). Likewise, the polymorphisms were associated with calcaneal quantitative ultrasound parameters (p = 0.00004 and 0.0014, respectively) and the buckling ratio, an index of cortical instability of the femoral neck (p = 0.0007 and 0.0029, respectively). Although there were no significant differences in the genotype frequency distributions between 294 patients with hip fractures and 670 controls, among the subgroup under 80 years of age, TT genotypes were underrepresented in patients with fractures (odds ratio 0.50; CI 0.27-0.94). CONCLUSION: Common missense polymorphisms of the WNT16 gene are associated with BMD at the hip, calcaneal ultrasound and the buckling ratio of the femoral neck, as well as with hip fractures in individuals under 80 years of age. Overall, these results confirm the association of the WNT16 locus with BMD identified in genome-wide association studies and support its role in determining the risk of osteoporotic fractures.

Common allelic variants of the farnesyl diphosphate synthase gene influence the response of osteoporotic women to bisphosphonates.

Farnesyl diphosphate synthase (FDPS) is necessary for osteoclast survival and activity and is considered as a major molecular target of aminobisphosphonates. Our objective was to analyze the influence of FDPS polymorphisms on bone mineral density (BMD) and the response to antiresortive drugs. Three single-nucleotide polymorphisms of FDPS were analyzed in 1186 postmenopausal women. There was only a marginally significant association of baseline hip BMD with rs11264359 alleles (P=0.043). However, among 191 women receiving antiresortive therapy, there was a very significant association between rs2297480 or rs11264359 alleles and the BMD changes after aminobisphosphonate therapy for an average period of 2.5 years (P=0.001). The genotype explained 7.2% of the variance in the BMD response. On the other hand, there was no association between the BMD changes after raloxifene therapy and any of the polymorphisms studied. These results suggest that common polymorphisms of the FDPS gene influence the response to aminobisphosphonates.

Treatment failure in osteoporosis.

UNLABELLED: Guidelines concerning the definition of failure of therapies used to reduce the risk of fracture are provided. INTRODUCTION: This study aims to provide guidelines concerning the definition of failure of therapies used to reduce the risk of fracture. METHODS: A working group of the Committee of Scientific Advisors of the International Osteoporosis Foundation was convened to define outcome variables that may assist clinicians in decision making. RESULTS: In the face of limited evidence, failure of treatment may be inferred when two or more incident fractures have occurred during treatment, when serial measurements of bone remodelling markers are not suppressed by anti-resorptive therapy and where bone mineral density continues to decrease. CONCLUSION: The provision of pragmatic criteria to define failure to respond to treatment provides an unmet clinical need and may stimulate research into an important issue.

Executive summary clinical practice guideline of postmenopausal, glucocortcioid-induced and male osteoporosis (2022 update). Spanish Society for Bone and Mineral Metabolism Investigation (SEIOMM).

This updated version of the Spanish Society for Research in Osteoporosis and Mineral Metabolism (SEIOMM) osteoporosis guides incorporate the most relevant information published in the last 7 years, since the 2015 guides, with imaging studies, such as vertebral fracture assessment and bone trabecular score analysis. In addition, therapeutic advances include new anabolic agents, comparative studies of drug efficacy, and sequential and combined therapy. Therefore, therapeutic algorithms are also updated.

Wnt pathway genes in osteoporosis and osteoarthritis: differential expression and genetic association study.

UNLABELLED: In comparison with hip fractures, increased expression of genes in the Wnt pathway and increased Wnt activity were found in bone samples and osteoblast cultures from patients with osteoarthritis, suggesting the involvement of this pathway in subchondral bone changes. No consistent differences were found in the genetic association study. INTRODUCTION: This study aims to explore the allelic variations and expression of Wnt pathway genes in patients with osteoporosis and osteoarthritis. METHODS: The expression of 86 genes was studied in bone samples and osteoblast primary cultures from patients with hip fractures and hip or knee osteoarthritis. The Wnt-related activity was assessed by measuring AXIN2 and in transfection experiments. Fifty-five SNPs of the LRP5, LRP6, FRZB, and SOST genes were analyzed in 1,128 patients. RESULTS: Several genes were differentially expressed in bone tissue, with the lowest values usually found in hip fracture and the highest in knee osteoarthritis. Overall, seven genes were consistently upregulated both in tissue samples and in cell cultures from patients with knee osteoarthritis (BCL9, FZD5, DVL2, EP300, FRZB, LRP5, and TCF7L1). The increased expression of AXIN2 and experiments of transient transfection of osteoblasts with the TOP-Flash construct confirmed the activation of Wnt signaling. Three SNPs of the LRP5 gene and one in the LRP6 gene showed marginally significant differences in allelic frequencies across the patient groups, but they did not resist multiple-test adjustment. CONCLUSIONS: Genes in the Wnt pathway are upregulated in the osteoarthritic bone, suggesting their involvement not only in cartilage distortion but also in subchondral bone changes.

Relationship between bone quantitative ultrasound and mortality: a prospective study.

UNLABELLED: In a cohort of 5,201 women [72.3 +/- 5.3 years] from 58 primary care centers in Spain, followed for three years, no relationship between heel QUS parameters and overall mortality was found. However, a significant relationship between a low speed of sound (SOS) and vascular mortality was observed. INTRODUCTION: An inverse relationship between mortality and bone mineral density measured by dual-energy absorption densitometry or quantitative bone ultrasound (QUS) has been described. The aim of the present study was to test this relationship in the ECOSAP cohort, a 3-year prospective study designed to assess the ability of heel QUS and clinical risk factors to predict non-vertebral fracture risk in women over 64. METHODS: A cohort of 5,201 women [72.3 +/- 5.3 years] was studied. QUS was assessed with the Sahara(R) bone sonometer. Women attended follow-up visits every 6 months. Physicians recorded if the patient died and cause of death. Hazard rates (HR) of all-cause and vascular mortality per one standard deviation reduction in QUS parameters were determined. RESULTS: One hundred (1.9%) women died during a median of 36.1 months follow-up, for a total of 14,999 patient-years, 42 because of vascular events (both cardiovascular and cerebrovascular). After adjusting for age, none of the QUS variables showed statistically significant differences between the patients who died and the survivors. In the final multivariate model, adjusted for age, current thyroxine and hypoglycaemic drug use, chronic obstructive pulmonary disease and decreased visual acuity, SOS was marginally non-significant: (HR: 1.19; 0.97-1.45). However, each 1 SD reduction in SOS was associated with a 39% increase in vascular mortality (HR: 1.39; 1.15-1.66). CONCLUSIONS: In our cohort, SOS was related with vascular mortality, but not overall mortality.

Inadequate responders to osteoporosis treatment: proposal for an operational definition.

UNLABELLED: The concept of inadequate response to osteoporosis treatment is not clear. In the literature several criteria have been used. We propose an operational definition of an inadequate responder based on the changes observed in bone mineral density and incident fractures while on therapy. INTRODUCTION: Fractures may occur in compliant patients even while on active treatment. These cases have been defined as inadequate responders (IR). METHODS: We reviewed the basis for this concept and propose an operational definition for IR. RESULTS: Good compliance and adequate calcium and vitamin D supplementation are the first requirement. The second requirement is a treatment period of at least 1 year, since before that time treatment may not have been fully effective. Fractures are the gold standard for measuring efficacy and changes in bone density and turnover markers may be surrogates. We propose classifying patient response as: Inadequate--incident fracture and a decrease in BMD greater than a significant change (Trend Assessment Margin or TAM); Possibly inadequate--incident fracture or a decrease in BMD greater than a significant change (TAM); and Appropriate--no fracture and no decrease in BMD greater than a significant change (TAM). Additional criteria (biochemical markers, bone quality parameters) may be taken into account. CONCLUSION: A wide consensus on the IR concept is required given its clinical, regulatory, and reimbursement implications.

Surgical site infections in cardiac surgery after a hospital catastrophe.

On 2 November 1999, one of the main hospital façades adjoining cardiovascular surgery collapsed in a 900-bed teaching hospital in Santander, Spain. The purpose of this study was to determine whether the accident affected the safety of patients by increasing the risk for nosocomial and surgical site infections (SSI). Measures for the prevention of nosocomial infections were immediately reinforced. A total of 217 consecutive patients were operated on before 2 November 1999, with another 296 after this date. Patients in both study periods showed similar severity of illness, complexity of surgical procedure and length of hospital stay. The overall rate of nosocomial infection before and after the accident was 28.1% and 24.7%, respectively (P=0.381). The rates of respiratory infection, urinary infection and bacteraemia were also similar. A statistically significant reduction in the SSI rate in the second period was observed (14.8% vs 4.4%, P=0.008). The collapse of the façade was not associated with any increase in nosocomial infection rates, but there was a significant reduction of SSI rates in relation to intensive infection control measures implemented after the collapse.

Bone mass in young adults with Down syndrome.

BACKGROUND: Down syndrome (DS) is a frequent cause of intellectual disability. With the increasing life expectancy of these patients, concerns have been raised about the risk of osteoporosis. In fact, several investigators have reported a reduced bone mass in DS. However, the results may be confounded by comorbid diseases, and differences in lifestyle habits and body size. Therefore, we planned to determine anthropometric and lifestyle factors influencing bone mineral density (BMD) in young adults with DS. METHODS: Thirty-nine patients with DS (mean age 26 years) and 78 controls were studied. Areal BMD was measured by dual x-ray densitometry (DXA); volumetric BMD at the lumbar spine and femoral neck was estimated with published formulae. RESULTS: DS patients had lower areal BMD than controls at all regions (spine, hip and total body). Height and projected bone area were also lower. There were no differences between both groups regarding estimated volumetric BMD at the femoral neck. However, spine volumetric BMD was also lower in DS than controls. In multivariate analysis, DS, male sex, little physical activity and low sunlight exposure were associated with lower spine volumetric BMD; on the other hand, fat mass and sunlight exposure were associated with femoral neck volumetric BMD. CONCLUSION: This study shows that patients with DS had a reduced areal BMD, but it is in part a consequence of the reduced body size, particularly at the femoral neck. Physical activity and sunlight exposure are associated to volumetric BMD and should be stimulated in order to maintain an adequate bone mass in these patients.

Ventilation/Perfusion SPECT lung scintigraphy and computed tomography pulmonary angiography in patients with clinical suspicion of pulmonary embolism.

UNLABELLED: The aim was to compare ventilation/perfusion SPECT lung scintigraphy (V/Q-SPECT) and computed tomography pulmonary angiography (CTPA) in patients with suspicion of pulmonary embolism (PE). MATERIAL AND METHODS: This prospectively designed study included 53 patients with intermediate or high clinical probability of PE. A V/Q-SPECT and CTPA was performed on all patients. The V/Q-SPECT was interpreted according to the European Association of Nuclear Medicine and Molecular Imaging (EANMMI) guidelines. CTPA was reported as positive, negative, or indeterminate. RESULTS: CTPA was positive in 22 cases, negative in 28, and indeterminate in 3. V/Q-SPECT was positive in 27 cases, negative in 24, and non-diagnostic in 2. In the 22 with positive CTPA, V/Q-SPECT was positive in 18, negative in 3, and non-diagnostic in 1. In the 28 with negative CTPA, V/Q-SPECT was positive in 8, negative in 19, and non-diagnostic in 1. In the 3 with indeterminate CTPA, V/Q-SPECT was positive in 1 and negative in 2. In the 2 non-diagnostic cases V/Q-SPECT, CTPA was positive in 1 and negative in one. In the 10 high clinical probabilities, CTPA and V/Q-SPECT were positive in 7, negative in 2, and in 1, CTPA was positive and V/Q-SPECT negative. In the 38 intermediate probability group, CTPA and V/Q-SPECT were positive in 11, negative in 17, with CTPA negative and V/Q-SPECT positive in 8, and in 2 CTPA was positive and V/Q-SPECT negative. The results show that V/Q-SPECT detected PE in 5 patients more than CTPA. CONCLUSION: Our results show a 77% concordance of both techniques. Overall V/Q-SPECT detected PE in 18% more patients than CTPA in the intermediate group. Both techniques have a complementary role when a diagnosis cannot be made with one of them.

Evaluation of the Duke criteria in 93 episodes of prosthetic valve endocarditis: could sensitivity be improved?

BACKGROUND: Since publication of the Duke criteria for diagnosing endocarditis, several articles have confirmed their sensitivity when native and prosthetic valves are considered together. OBJECTIVES: To compare the differences between the older von Reyn criteria and the Duke criteria in prosthetic valve endocarditis only, and to determine if the latter's sensitivity could be improved by adding 2 minor criteria: new-onset heart failure and presence of conduction disturbances. METHODS: We retrospectively evaluated 93 episodes of prosthetic valve endocarditis from January 1986 to January 1998 in a teaching hospital, and then analyzed the 76 surgically confirmed episodes to compare the differences between the von Reyn and Duke diagnostic criteria. RESULTS: The von Reyn criteria rejected the diagnosis in 16 of the confirmed episodes, compared with 1 diagnosis missed by the Duke criteria and 1 missed using our suggested modifications. Definite diagnosis (Duke) was established in 60 episodes, compared with a diagnosis of probable (von Reyn) in 36 episodes (P<.001). Our modifications improved the sensitivity of the Duke criteria, diagnosing 70 episodes as definite (P = .02). CONCLUSIONS: As was the case with native valve endocarditis, the Duke criteria proved to be more sensitive than the von Reyn criteria in prosthetic valve endocarditis. The addition of 2 minor criteria (new-onset heart failure and presence of conduction disturbances) could improve the diagnostic sensitivity of the Duke criteria.

Clinical practice guidelines for posmenopausal, glucocorticoid-induced and male osteoporosis. Spanish Society for Research on Bone and Mineral Metabolism (3rd updated version 2014).

These guidelines update issues covered in previous versions and introduce new ones that have arisen in recent years. The former refer mainly to the therapeutic developments that have been made during this time (zoledronate, denosumab, bazedoxifene), which have led to a change in the drug selection algorithm. The latter deal with therapeutic management, the description of new adverse effects (which have led to changes in therapeutic behaviour patterns, as is the case with atypical fracture of the femur), treatment duration (with consideration for the so-called "therapeutic holidays"), the so-called sequential treatment and changes in treatment imposed by certain circumstances. A new algorithm has been introduced for sequential treatment. Attention has also been paid to vertebroplasty and kyphoplasty.

Effects of interleukin-4 on the formation of macrophages and osteoclast-like cells.

The lymphokine interleukin-4 (IL-4) is an important lymphocyte growth factor, and it also has a modulatory role on hematopoiesis. It was recently reported that IL-4 has an inhibitory effect on bone resorption in vitro, but the underlying mechanisms are not well known. We studied its effects on the formation of osteoclast-like cells in mouse bone marrow cultures and in cocultures of spleen cells and stromal cells. The addition of recombinant mouse IL-4 (0.01-10 ng/ml) induced a marked dose-dependent inhibition on the formation of TRAP-positive multinucleated cells (MNC) in bone marrow cultures. The effect was blocked by anti-IL-4 antibodies and was not related to a decreased production of IL-6. The inhibitory effect required the presence of IL-4 during the second half of the culture period. Time course experiments showed that IL-4 impaired the formation of osteoclast-like cells rather than inducing the disappearance of previously formed cells. This inhibitory effect was associated with increased numbers of esterase-positive cells. Moderately high doses of IL-4 (1-10 ng/ml) also induced the formation of abundant macrophage polykaryons that did not form resorption pits. IL-4 had a similar inhibitory effect on the formation of osteoclast-like cells in cocultures of mouse spleen cells and stromal cells. Our results suggest that IL-4 acts on uncommitted macrophage-osteoclast precursors, inducing a preferential differentiation toward the macrophage lineage and thus decreasing the formation of osteoclast-like cells.

Seasonal deficiency of vitamin D in children: a potential target for osteoporosis-preventing strategies?

Peak bone mass attained after skeletal growth is a major determinant of the risk of developing osteoporosis later in life, hence the importance of nutritional factors that contribute to bone mass gain during infancy and adolescence. An adequate supply of vitamin D is essential for normal bone homeostasis. This study was undertaken to determine what the levels are of 25-hydroxyvitamin D (25(OH)D) that may be considered desirable in children and to assess if normal children maintain these levels throughout the year. Vitamin D metabolites and parathyroid hormone (PTH) serum levels were measured in 21 children in March and October, prior to and after the administration of a daily supplement of 25(OH)D (40 microg for 7 consecutive days). There were inverse correlations between basal 25(OH)D levels and supplementation-induced changes in serum 1,25(OH)2D (r = 0.57, p < 0.05) and PTH (r = 0.41, p < 0.05). When basal levels of 25(OH)D were below 20 ng/ml, the supplement induced an increase in serum 1,25(OH)2D; with basal 25(OH)D under 10-12 ng/ml, the supplement also decreased serum PTH. The lowest serum level of 25(OH)D in 43 normal children studied in summer was 13 ng/ml. Those results suggested that the lowest limit for desirable levels of 25(OH)D in children was somewhere between 12 and 20 ng/ml. However, 31% of 51 normal children studied in winter had levels below 12 ng/ml, and 80% had levels lower than 20 ng/ml. Those children are likely to have suboptimal bioavailability of vitamin D, which might hamper their achievement of an adequate peak bone mass. Since cutaneous synthesis of vitamin D is rather limited in winter, oral vitamin D supplementation should be considered.