Prevalence of ankylosing spondylitis in Spain: EPISER2016 Study.

Objective: The aim of this study was to estimate the prevalence of ankylosing spondylitis (AS) in Spain.Method: This is a cross-sectional, population-based study of people aged 20 years or older in Spain. Randomly selected individuals were contacted by telephone and rheumatic disease screening was performed. If the first screening was positive, medical records were then reviewed and/or a telephone questionnaire was conducted by a rheumatologist, followed by an appointment if necessary. Cases had to fulfil the modified New York (mNY) criteria.Results: In total, 4916 individuals were included, of whom 355 had a positive screening result for AS. Of these, 11 were classified as AS. An additional individual who reported a prior diagnosis of rheumatoid arthritis had a diagnosis of AS confirmed on review of the medical records. Estimated prevalence was 0.26% (95% CI 0.14-0.49).Conclusion: EPISER2016 is the first population-based study to estimate the prevalence of AS in Spain, which has been estimated as being similar to that in other European countries.

Determinants of survival after severe acute respiratory syndrome coronavirus 2 infection in Mexican outpatients and hospitalised patients.

OBJECTIVES: This study aimed to evaluate the association of chronic diseases and indigenous ethnicity on the poor prognosis of outpatients with coronavirus disease 2019 (COVID-19) and hospitalised patients in Mexico. STUDY DESIGN: The study design is an observational study of consecutive COVID-19 cases that were treated in Mexican healthcare units and hospitals between February 27 and April 27, 2020. METHODS: Epidemiological, clinical and sociodemographic data were analysed from outpatients and hospitalised patients. Cox regression models were used to analyse the risk of mortality after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. RESULTS: In total, 15,529 patients with COVID-19 were characterised; 62.6% of patients were aged older than 40 years, 57.8% were men and 1.4% were of indigenous ethnicity. A high proportion had a history of diabetes (18.4%), hypertension (21.9%) and obesity (20.9%). Among hospitalised patients, 11.2% received health care in the intensive care unit. Advanced age, male sex, indigenous ethnicity and having a history of chronic diseases, such as hypertension, diabetes and obesity, were significantly associated with a high risk of death after SARS-CoV-2 infection. Diabetes and obesity were the comorbidities most highly associated with death through the models used in this study. Moreover, living in Mexico City and Mexico State (where there is easy access to medical services) and walking (rather than driving or getting public transport) were negatively associated with mortality after SARS-CoV-2 infection. CONCLUSIONS: Diabetes, hypertension and obesity combined with older age, male sex and indigenous ethnicity increase the risk of death after SARS-CoV-2 infection in the Mexican population. It is recommended that the incidence of COVID-19 is monitored in indigenous communities, and access to health services is increased nationwide.

Biochemical markers of bone turnover and clinical outcome in patients with renal cell and bladder carcinoma with bone metastases following treatment with zoledronic acid: The TUGAMO study.

BACKGROUND: Levels of bone turnover markers (BTM) might be correlated with outcome in terms of skeletal-related events (SRE), disease progression, and death in patients with bladder cancer (BC) and renal cell carcinoma (RCC) with bone metastases (BM). We try to evaluate this possible correlation in patients who receive treatment with zoledronic acid (ZOL). METHODS: This observational, prospective, and multicenter study analysed BTM and clinical outcome in these patients. Serum levels of bone alkaline phosphatase (BALP), procollagen type I amino-terminal propeptide (PINP), and beta-isomer of carboxy-terminal telopeptide of type I collagen (ß-CTX) were analysed. RESULTS: Patients with RCC who died or progressed had higher baseline ß-CTX levels and those who experienced SRE during follow-up showed high baseline BALP levels. In BC, a poor rate of survival was related with high baseline ß-CTX and BALP levels, and new SRE with increased PINP levels. Cox univariate analysis showed that ß-CTX levels were associated with higher mortality and disease progression in RCC and higher mortality in BC. Bone alkaline phosphatase was associated with increased risk of premature SRE appearance in RCC and death in BC. CONCLUSION: Beta-isomer of carboxy-terminal telopeptide of type I collagen and BALP can be considered a complementary tool for prediction of clinical outcomes in patients with BC and RCC with BM treated with ZOL.

Usefulness of bone turnover markers as predictors of mortality risk, disease progression and skeletal-related events appearance in patients with prostate cancer with bone metastases following treatment with zoledronic acid: TUGAMO study.

BACKGROUND: Owing to the limited validity of clinical data on the treatment of prostate cancer (PCa) and bone metastases, biochemical markers are a promising tool for predicting survival, disease progression and skeletal-related events (SREs) in these patients. The aim of this study was to evaluate the predictive capacity of biochemical markers of bone turnover for mortality risk, disease progression and SREs in patients with PCa and bone metastases undergoing treatment with zoledronic acid (ZA). METHODS: This was an observational, prospective and multicenter study in which ninety-eight patients were included. Patients were treated with ZA (4 mg every 4 weeks for 18 months). Data were collected at baseline and 3, 6, 9, 12, 15 and 18 months after the beginning of treatment. Serum levels of bone alkaline phosphtase (BALP), aminoterminal propeptide of procollagen type I (P1NP) and beta-isomer of carboxiterminal telopeptide of collagen I (ß-CTX) were analysed at all points in the study. Data on disease progression, SREs development and survival were recorded. RESULTS: Cox regression models with clinical data and bone markers showed that the levels of the three markers studied were predictive of survival time, with ß-CTX being especially powerful, in which a lack of normalisation in visit 1 (3 months after the beginning of treatment) showed a 6.3-times more risk for death than in normalised patients. Levels of these markers were also predictive for SREs, although in this case BALP and P1NP proved to be better predictors. We did not find any relationship between bone markers and disease progression. CONCLUSION: In patients with PCa and bone metastases treated with ZA, ß-CTX and P1NP can be considered suitable predictors for mortality risk, while BALP and P1NP are appropriate for SREs. The levels of these biomarkers 3 months after the beginning of treatment are especially important.

Risk in dosing regimens for 25-OH vitamin D supplementation in chronic haemodialysis patients.

INTRODUCTION: 25-OH vitamin D (25-OHvitD) insufficiency or deficiency should be treated in haemodialysis (HD) patients, although the 25-OHvitD target, drug or dosing regimens are unclear. AIMS: To describe factors associated with 25-OHvitD levels in HD patients and to assess the effect of three dosing regimens to supplement 25-OHvitD (calcifediol) on serum calcium (Ca), phosphate (P), parathyroid hormone (PTH), 25-OHvitD and 1,25-OHvitD. METHODS: Two hundred and seventeen patients from three HD units were studied. Demographic and biochemical data were collected at baseline. Two different 25-OHvitD assays were used. One hundred and sixty-seven patients were treated with various calcifediol dosing regimens. The same biochemical determinations were repeated after 3 months of treatment. RESULTS: At baseline, 12.9% of patients had 25-OHvitD <10 ng/ml. In multivariate linear regression, the season (lower in winter) and the assay method were determinants of 25-OHvitD concentration. Following calcifediol supplementation, 25-OHvitD, calcium and phosphate increased, while PTH diminished with statistical significance. After treatment, there were positive correlations between 25-OHvitD and Ca (r = 0.28, p < 0.0001) or 1,25-OHvitD (r = 0.75, p < 0.0001) that were not observed in the baseline dataset. High concentrations of post-treatment 25-OHvitD were associated with higher 1,25-OHvitD levels. Calcemia increased more in those treated with concomitant active vitamin D or those having suppressed baseline PTH, while PTH decreased more in those having above-target PTH levels. CONCLUSIONS: Standardisation of methods to determine 25-OHvitD blood levels is needed. In HD patients, calcifediol increased 25-OHvitD, calcemia and phosphatemia and lowered PTH. Caution should be exercised with the higher calcifediol dosing regimens, especially in patients with suppressed PTH or on vitamin D receptor activators.

[High resolution surgery: one more step in out-patient surgery]. / Cirugía de alta resolución: un paso más en la cirugía ambulatoria.

OBJECTIVES: One stop surgery (CAR: Cirugía Alta Resolución) is a step forward in outpatient surgery. The new scheme simplifies ambulatory conventional surgery, achieves more satisfaction between patients and optimizes health resources. METHODS: By One stop surgery we mean the performance in the same day of both pre-surgery assessment and surgical procedure. This new working way allows performing a surgical procedure in only one visit to the hospital, instead of the average four visits used before for surgical outpatients. Diagnosis, presurgery assessment and post surgery progress are made by the primary care paediatricians at theirs NHS offices. It is essential to maintain a close relationship between the Paediatric surgeons, the primary care paediatricians as well as with paediatric anaesthesiologists and nurses. An autoevaluation is made once a year in which quality survey results are made public and possible areas for improvement are identified, following the model proposed by the European Foundation for Quality Management (EFQM). RESULTS: We present 416 children treated following this scheme since 2008. Surgery is performed on the abdominal wall, genitals, skin and soft tissues. Families are satisfied with the quality of the whole medical and nursery received care as they qualified it with a 99% satisfaction index. Complications developed in less than 3%. CONCLUSIONS: One stop surgery is a progress in the outpatient surgery and, for us, it is a consolidated, continuously growing and constantly improving scheme of providing medical care.

Clinical factors associated with discontinuation of ts/bDMARDs in rheumatic patients from the BIOBADASER III registry.

Biologic and targeted synthetic disease-modifying antirheumatic drugs (ts/bDMARDs) play a pivotal role in the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). Persistence of therapy provides an index of a drug's overall effectiveness. The objective of the study was to identify factors associated with discontinuation of ts/bDMARDs in a real-world dataset. The study population comprised patients diagnosed with RA, PsA, and AS included in the BIOBADASER registry for whom follow-up data were available until November 2019. Patient features and treatment data were included in the analysis. The Kaplan-Meier method was used to study survival of the different drugs according to the reason for discontinuation. Factors associated with discontinuation were studied using Cox regression models and bivariate and multivariate analyses. P values of less than 0.05 were regarded as statistically significant. The study population comprised 4,752 patients who received a total of 8,377 drugs, of which 4,411 (52.65%) were discontinued. The Kaplan-Meier curves showed that survival for first-line treatment was greater in all 3 groups (p < 0.001). Patients with RA had a greater risk of discontinuation if they were younger (HR, 0.99; 95% CI 0.99-1.00), if they were receiving anti-TNFα agents (HR, 0.61; 95% CI 0.54-0.70), and if they had more comorbid conditions (HR, 1.09; 95% CI 1.00-1.17). Patients with PsA had a higher risk if they were women (HR, 1.36; 95% CI 1.15-1.62) and if they were receiving other ts/bDMARDs (HR, 1.29; 95% CI 1.05-1.59). In patients with AS, risk increased with age (HR, 1.01; 95% CI 1.00-1.02), as did the number of comorbid conditions (HR, 1.27; 95% CI 1.12-1.45). The factors that most affected discontinuation of ts/bDMARDs were line of treatment, age, type of drug, sex, comorbidity and the year of initiation of treatment. The association with these factors differed with each disease, except for first-line treatment, which was associated with a lower risk of discontinuation in all 3 diseases.

The effectiveness of intermittent rat parathyroid hormone (1-34) treatment on low bone mass due to oestrogen or androgen depletion in skeletally mature rats.

Rat parathyroid hormone (PTH) 1-34 (4 microg/kg/day) was applied for 2.5 months to 9 month-old rats immediately after ovariectomy or orchidectomy or to 15 month-old rats with low bone mass which had been castrated 6 months before in order to know the effects on serum biochemistry parameters, lumbar and femoral bone mineral density, histology, cancellous and cortical bone histomorphometry, mineralisation content profile in cortical bone by backscattered-electron microscopy, and femoral torsion biomechanical testing. In ovariectomised rats, preventive PTH treatment avoided cancellous bone loss in tibial metaphysis and partially in lumbar vertebra, while in cortical bone, PTH increased endosteal resorption and periosteal formation. In intervention study, PTH did not restore cancellous bone but a strong endosteal and periosteal new bone formation was detected. In orchidectomised rats, PTH, in preventive study, avoided cancellous bone loss in metaphysis and lumbar vertebra, and a mild new bone formation in cortical bone was found. In intervention study, PTH maintained baseline cancellous bone mass, but in cortical bone a strong endosteal and periosteal new bone formation was detected. The PTH-induced new bone formation was confirmed by histology and by mineral content profiles. After castration, biomechanical properties were affected in females but not in male rats and PTH reverted this effect.

Bone disease induced by phenytoin therapy: clinical and experimental study.

Previous studies have made references to prolonged treatment with phenytoin as a possible risk factor in the development of osteoporosis and/or osteomalacia. We studied a group of 30 epileptic patients who were under long-term treatment with phenytoin (DPH) in an ambulatory regimen. We found the prevalence of osteoporosis to be 3.3% and of osteopenia to be 56.6%, affecting predominantly the femur, without any significant decrease in bone mineral density of the lumbar spine. These patients were showing signs of bone turnover uncoupling with increases in bone resorption markers. At this time, they also exhibited slight alterations in their phosphocalcium metabolism with trends to hypocalcemia and secondary hyperparathyroidism that was found not to be caused by a vitamin D deficiency as the serum levels of 25(OH)D and 1,25(OH)(2)D were normal. With the aims of corroborating these results and to investigate the physiopathological effects on the bone induced by anticonvulsant drugs we developed a further experimental study in which we administered DPH over a 6-week period with a dose of 5 g/kg/day to male Wistar rats that were in the growth phase. This treatment produced a decrease in overall BMD and bone mineral content in the femur. We did not find osteomalacia in the vertebral biopsy, but the administration of DPH to these animals decreased trabecular volume as well as lessened the thickness of osteoid edges together with an uncoupling in bone turnover. There was also a marked decrease in bone formation and a tendency towards increased bone resorption. We have also found a decrease in resistance to fracture by torsion in the biomechanical assay, which translates into an increase in bone fragility. In these male Wistar rats, the administration of DPH produced a tendency towards increasing the markers of resorption and, though changes in serum levels of calcium and phosphorus were not observed, to provoke an increase in the parathyroid hormone levels; with normal levels of 1,25(OH)(2)D which has produced the same inclination in rats as in humans.

Effect of risedronate on bone mass, remodelling and biomechanical strength in orchidectomized rats.

BACKGROUND: The ability of risedronate to prevent and/or treat orchidectomy-induced osteoporosis in male rats was studied. METHODS: Ninety-five 10-week-old male Wistar rats were sham-operated or orchidectomized. Prevention study: Sham: sham-operated rats; ORX: orchidectomized rats; ORX + RSD: orchidectomized rats, treated for 6 weeks with risedronate. Animals were sacrificed 6 weeks after surgery. Treatment study: Sham(1) and ORX(1): sham and orchidectomized rats sacrificed 3 months after orchidectomy; Sham(2), ORX(2) and ORX(2) + RSD: sham-operated, and orchidectomized rats treated with placebo or risedronate for 6 weeks starting 3 months after orchidectomy, and then sacrificed. Risedronate (0.5 mg/kg/day) and placebo (saline) were administered via oral gavage. After sacrifice, bone mineral density by DEXA, bone volume (BV/TV), osteocalcin (BGP), and serum carboxyterminal telopeptide of collagen type I (CTX) were measured. Femur low-rate torsion testing was performed. RESULTS: Orchidectomy produced an increase in bone remodelling with loss of BV/TV, without effects on torsional strength. Risedronate treatment partially prevented these effects. In the treatment study, risedronate reduced bone remodelling and restored BV/TV to levels higher than those of the sham group, improving biomechanical parameters. CONCLUSIONS: These results suggest that risedronate could be used as a prevention or treatment of male osteoporosis due to hypogonadism.

Effects of Cyclosporine, Tacrolimus, and Rapamycin on Osteoblasts.

PURPOSE: One factor that can contribute to severe bone loss after transplantation is the direct action of immunosuppressants on bone cells. The aim of this work was to study the effects of cyclosporine (CsA), tacrolimus (FK-506), and rapamycin (RAPA) on the release of three local factors directly implicated in bone-remodeling regulation and apoptosis of human osteoblasts: interleukin (IL)-6, osteoprotegerin, and receptor activator of nuclear factor κß (RANKL). BASIC PROCEDURES: Human osteoblasts were obtained from five different patients who underwent orthopedic surgery. These cells were treated with what are considered to be a clinically high dose and an acceptable dose of each immunosuppressant-RAPA 50 ng/mL and 12 ng/mL, FK-506 20 ng/mL and 5 ng/mL, CsA 1000 ng/mL and 250 ng/mL-or vehicle. Apoptotic cell death was quantified using flow cytometry of DNA content in permeabilized, propidium iodide-stained cells. IL-6 was measured using enzyme-linked immunosorbent assay (ELISA; Quantikine Human IL6, R&D Systems, Minneapolis, Minn, United States). Messenger RNA (mRNA) expression of osteoprotegerin, RANKL, and IL-6 was measured using quantitative RT-PCR. MAIN FINDINGS: A significant increase in IL-6 (mRNA and released protein) was observed in the presence of FK-506 and RAPA. Addition of RAPA to the cultures of osteoblasts produced a significant increase in the OPG/RANKL ratio. A significant increase in osteoblast apoptosis was observed in the cells treated with FK-506 and RAPA 24 hours after the addition of immunosuppressants. CsA did not produce any significant changes in osteoblasts. PRINCIPAL CONCLUSIONS: These results suggest that an increase in osteoblast apoptosis by osteoblasts may be one of the mechanisms by which bone loss occurs after RAPA and FK-506 treatments.

The use of lactic acid bacteria to reduce mercury bioaccessibility.

Mercury in food is present in either inorganic [Hg(II)] or methylmercury (CH3Hg) form. Intestinal absorption of mercury is influenced by interactions with other food components. The use of dietary components to reduce mercury bioavailability has been previously proposed. The aim of this work is to explore the use of lactic acid bacteria to reduce the amount of mercury solubilized after gastrointestinal digestion and available for absorption (bioaccessibility). Ten strains were tested by addition to aqueous solutions containing Hg(II) or CH3Hg, or to food samples, and submission of the mixtures to gastrointestinal digestion. All of the strains assayed reduce the soluble fraction from standards of mercury species under gastrointestinal digestion conditions (72-98%). However their effectiveness is lower in food, and reductions in bioaccessibility are only observed with mushrooms (⩽68%). It is hypothesized that bioaccessible mercury in seafood forms part of complexes that do not interact with lactic acid bacteria.

La osteocalcina: de marcador de formación ósea a hormona; y el hueso, un órgano endocrino / Osteocalcin: from marker of bone formation to hormone; and bone, an endocrine organ

La osteocalcina es una proteína sintetizada por el osteoblasto. Antes de ser liberada a la matriz extracelular, la osteocalcina humana sufre una gamma-carboxilación, al unirse en las posiciones 17, 21 y 24 el ácido gamma-carboxi-glutámico. A la circulación pasa parte de osteocalcina carboxilada y descarboxilada. Desde su descubrimiento a finales de los años 70, se ha utilizado como marcador de formación ósea al ser un producto osteoblástico, y desconociéndose su papel en el organismo. En estos últimos años se ha descubierto que la osteocalcina es, en realidad, una hormona, y el hueso un órgano endocrino. La osteocalcina que actúa como hormona es la forma descarboxilada. La osteocalcina interviene en la homeostasis de la glucosa, en el funcionamiento del músculo esquelético, en el desarrollo cerebral, la fertilidad masculina, la esteatosis hepática y la calcificación arterial. En realidad todos estos hechos se han probado en ratones, pero existen indicios importantes de que esto podría ocurrir en humanos. Nos encontramos ante hechos que, de probarse, tendrían una enorme trascendencia clínica. (AU)

Osteocalcin is a protein synthesized by the osteoblast. Before being released into the extracellular matrix, human osteocalcin undergoes gamma-carboxylation, as gamma-carboxy-glutamic acid binds at positions 17, 21 and 24. Part of the carboxylated and decarboxylated osteocalcin passes into the circulation. Since its discovery in the late 70s, it has been used as a marker of bone formation as it is an osteoblastic product and its role in the body is unknown. In recent years, osteocalcin has been identified as a hormone. Bone is considered an endocrine organ. Osteocalcin acting as a hormone is the decarboxylated form. Osteocalcin is involved in glucose homeostasis, skeletal muscle function, brain development, male fertility, hepatic steatosis, and arterial calcification. All of these facts have actually been tested in mice, but there is strong evidence that this could occur in humans. We are faced with facts that, if proven, would have enormous clinical significance. (AU)

Aceite de oliva y salud ósea / Olive oil and bone health

OBJETIVO: Existen en la literatura una serie de trabajos que demuestran que la incidencia de osteoporosis y fracturas asociadas es menor en países en los que la dieta mediterránea es predominante. El aceite de oliva es la principal característica común de toda la dieta mediterránea suponiendo un tercio de la ingesta de grasas vegetales. Se ha realizado una amplia revisión de trabajos que demuestran que la ingesta de aceite de oliva, tanto en animales de experimentación, en especial ratas ovariectomizadas, como en humanos, produce acciones positivas sobre el hueso. Se han revisado los efectos de diferentes componentes del aceite de oliva virgen como la oleuropeína, un compuesto fenólico, y otros alcoholes fenólicos como el tirosol y el hidrotirosol. La oleuropeína no sólo ejerce acciones sobre el hueso de ratas ovariectomizadas, sino que produce acciones sobre la formación de osteoblastos y desciende la formación de células "osteoclasto-like". Los compuestos fenólicos del aceite de oliva han demostrado ejercer acciones anti-oxidantes in vitro e in vivo. El tirosol y el hidrotirosol ejercen acciones sobre la pérdida de hueso en ratas ovariectomizadas e inhiben la formación de osteoclastos de modo dosis-dependiente. Un trabajo realizado por nuestro grupo ha demostrado que el aceite de oliva virgen ejerce también acciones sobre los parámetros biomecánicos del hueso como el módulo de Young y la dimensión fractal en ratas ovariectomizadas. Los resultados de esta revisión muestran que el aceite de oliva ejerce una acción positiva sobre la salud ósea. Sus componentes poseen propiedades anti-oxidantes y anti-inflamatorias, siendo candidatos potenciales para la prevención de la osteoporosis

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Toxic trace elements at gastrointestinal level.

Many trace elements are considered essential [iron (Fe), zinc (Zn), copper (Cu)], whereas others may be harmful [lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As)], depending on their concentration and chemical form. In most cases, the diet is the main pathway by which they enter our organism. The presence of toxic trace elements in food has been known for a long time, and many of the food matrices that carry them have been identified. This has led to the appearance of legislation and recommendations concerning consumption. Given that the main route of exposure is oral, passage through the gastrointestinal tract plays a fundamental role in their entry into the organism, where they exert their toxic effect. Although the digestive system can be considered to be of crucial importance in their toxicity, in most cases we do not know the events that occur during the passage of these elements through the gastrointestinal tract and of ascertaining whether they may have some kind of toxic effect on it. The aim of this review is to summarize available information on this subject, concentrating on the toxic trace elements that are of greatest interest for organizations concerned with food safety and health: Pb, Cd, Hg and As.