A Missense Variant in TP53 Could Be a Genetic Biomarker Associated with Bone Tissue Alterations.

Metabolic bone diseases cover a broad spectrum of disorders that share alterations in bone metabolism that lead to a defective skeleton, which is associated with increasing morbidity, disability, and mortality. There is a close connection between the etiology of metabolic bone diseases and genetic factors, with TP53 being one of the genes associated therewith. The single nucleotide polymorphism (SNP) Arg72Pro of TP53 is a genetic factor associated with several pathologies, including cancer, stroke, and osteoporosis. Here, we aim to analyze the influence of the TP53 Arg72Pro SNP on bone mass in humanized Tp53 Arg72Pro knock-in mice. This work reports on the influence of the TP53 Arg72Pro polymorphism in bone microarchitecture, OPG expression, and apoptosis bone status. The results show that the proline variant of the TP53 Arg72Pro polymorphism (Pro72-p53) is associated with deteriorated bone tissue, lower OPG/RANK ratio, and lower apoptosis in bone tissue. In conclusion, the TP53 Arg72Pro polymorphism modulates bone microarchitecture and may be a genetic biomarker that can be used to identify individuals with an increased risk of suffering metabolic bone alterations.

Influence of non-osteoporotic treatments in patients on active anti-osteoporotic therapy: evidence from the OSTEOMED registry.

PURPOSE: To evaluate the effect of different non-osteoporotic drugs on the increase or decrease in the risk of incident fragility fractures (vertebral, humerus or hip) in a cohort of patients diagnosed with osteoporosis on active anti-osteoporotic therapy. METHODS: For this retrospective longitudinal study, baseline and follow-up data on prescribed non-osteoporotic treatments and the occurrence of vertebral, humerus or hip fractures in 993 patients from the OSTEOMED registry were analyzed using logistic regression models. The drugs evaluated with a possible beneficial effect were thiazides and statins, while the drugs evaluated with a possible harmful effect were antiandrogens, aromatase inhibitors, proton pump inhibitors, selective serotonin reuptake inhibitors, benzodiazepines, GnRH agonists, thyroid hormones, and oral and inhaled corticosteroids. RESULTS: Logistic regression analyses indicated that no treatment significantly improved fracture risk, with the only treatments that significantly worsened fracture risk being letrozole (OR = 0.18, p-value = 0.03) and oral corticosteroids at doses ≤ 5 mg/day (OR = 0.16, p-value = 0.03) and > 5 mg/day (OR = 0.27, p-value = 0.04). CONCLUSION: The potential beneficial or detrimental effects of the different drugs evaluated on fracture risk are masked by treatment with anabolic or antiresorptive drugs that have a more potent action on bone metabolism, with two exceptions: letrozole and oral corticosteroids. These findings may have important clinical implications, as patients receiving these treatments are not fully protected by bisphosphonates, which may imply the need for more potent anti-osteoporotic drugs such as denosumab or teriparatide.

Animal Experimental Models in Bone Metabolic Disease.

Bone is a highly specialized and dynamic tissue with several crucial functions, including support, movement support, protection of vital organs, and mineral storage [...].

Genistein supplementation has no effects on vitamin D levels in healthy Spanish postmenopausal women.

Background: In vitro studies have shown that genistein inhibits the CYP240 enzyme, which is involved in the degradation of 1,25-dihydroxycholecalciferol and its precursor 25-hydroxycholecalciferol, and increases their plasma levels. However, no clinical studies have primarily assessed the synergistic effect of isoflavones on vitamin D levels. The aim of this study was to evaluate the possible additive effect of genistein supplementation on vitamin D levels, calcium metabolism and bone remodeling markers in healthy postmenopausal women during the spring-summer months. Patients and methods: We made a prospective, double-blind study with 150 healthy postmenopausal women that were randomized to three groups. One received placebo, another received calcium (1000 mg/day) and vitamin D (cholecalciferol, 800 U/day) and the third received calcium (1000 mg/day), vitamin D (cholecalciferol, 800 U/day) and genistein (90 mg/day). The study period was from May to September (spring-summer). Vitamin D, PTH, CTX and P1NP were determined by electrochemiluminescence at baseline and after 12 weeks. Results: Vitamin D levels increased in all groups: placebo (23±9 ng/ml vs. 29±10 ng/ml, p<0.05), calcium+vitamin D (26±10 ng/ml vs. 33±8 ng/ml, p<0.05) and calcium+vitamin D+genistein (24±9 ng/ml vs. 31±8 ng/l, p<0.05) without between-group differences. At study end, the percentage of women with vitamin D <20 ng/ml (11%) and <30 ng/ml (39%) had fallen without between-group differences. The effects on calcium metabolism and bone remodeling markers were similar between groups: rises in vitamin D were significantly linked to reductions in PTH, CTX and P1NP. Conclusion: Adding genistein to supplementation with calcium and vitamin D provided not additional changes in vitamin D levels, calcium metabolism or bone remodeling markers in healthy Spanish postmenopausal women during the spring-summer months.

Long-Term Treatment and Effect of Discontinuation of Calcifediol in Postmenopausal Women with Vitamin D Deficiency: A Randomized Trial.

Vitamin D plays a major role in bone health and probably also in multiple extraskeletal acute and chronic diseases. Although supplementation with calcifediol, a vitamin D metabolite, has demonstrated efficacy and safety in short-term clinical trials, its effects after long-term monthly administration have been studied less extensively. This report describes the results of a 1-year, phase III-IV, double-blind, randomized, controlled, parallel, multicenter superiority clinical trial to assess the efficacy and safety of monthly calcifediol 0.266 mg versus cholecalciferol 25,000 IU (0.625 mg) in postmenopausal women with vitamin D deficiency (25(OH)D < 20 ng/mL). A total of 303 women were randomized and 298 evaluated. Patients were randomized 1:1:1 to calcifediol 0.266 mg/month for 12 months (Group A1), calcifediol 0.266 mg/month for 4 months followed by placebo for 8 months (Group A2), and cholecalciferol 25,000 IU/month (0.625 mg/month) for 12 months (Group B). By month 4, stable 25(OH)D levels were documented with both calcifediol and cholecalciferol (intention-to-treat population): 26.8 ± 8.5 ng/mL (Group A1) and 23.1 ± 5.4 ng/mL (Group B). By month 12, 25(OH)D levels were 23.9 ± 8.0 ng/mL (Group A1) and 22.4 ± 5.5 ng/mL (Group B). When calcifediol treatment was withdrawn in Group A2, 25(OH)D levels decreased to baseline levels (28.5 ± 8.7 ng/mL at month 4 versus 14.4 ± 6.0 ng/mL at month 12). No relevant treatment-related safety issues were reported in any of the groups. The results confirm that long-term treatment with monthly calcifediol in vitamin D-deficient patients is effective and safe. The withdrawal of treatment leads to a pronounced decrease of 25(OH)D levels. Calcifediol presented a faster onset of action compared to monthly cholecalciferol. Long-term treatment produces stable and sustained 25(OH)D concentrations with no associated safety concerns. © 2023 Faes Farma SA. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Analysis of Bone Histomorphometry in Rat and Guinea Pig Animal Models Subject to Hypoxia.

Hypoxia may be associated with alterations in bone remodeling, but the published results are contradictory. The aim of this study was to characterize the bone morphometry changes subject to hypoxia for a better understanding of the bone response to hypoxia and its possible clinical consequences on the bone metabolism. This study analyzed the bone morphometry parameters by micro-computed tomography (µCT) in rat and guinea pig normobaric hypoxia models. Adult male and female Wistar rats were exposed to chronic hypoxia for 7 and 15 days. Additionally, adult male guinea pigs were exposed to chronic hypoxia for 15 days. The results showed that rats exposed to chronic constant and intermittent hypoxic conditions had a worse trabecular and cortical bone health than control rats (under a normoxic condition). Rats under chronic constant hypoxia were associated with a more deteriorated cortical tibia thickness, trabecular femur and tibia bone volume over the total volume (BV/TV), tibia trabecular number (Tb.N), and trabecular femur and tibia bone mineral density (BMD). In the case of chronic intermittent hypoxia, rats subjected to intermittent hypoxia had a lower cortical femur tissue mineral density (TMD), lower trabecular tibia BV/TV, and lower trabecular thickness (Tb.Th) of the tibia and lower tibia Tb.N. The results also showed that obese rats under a hypoxic condition had worse values for the femur and tibia BV/TV, tibia trabecular separation (Tb.Sp), femur and tibia Tb.N, and BMD for the femur and tibia than normoweight rats under a hypoxic condition. In conclusion, hypoxia and obesity may modify bone remodeling, and thus bone microarchitecture, and they might lead to reductions in the bone strength and therefore increase the risk of fragility fracture.

Treatment of Vitamin D Deficiency with Calcifediol: Efficacy and Safety Profile and Predictability of Efficacy.

Calcifediol (25-OH-vitamin D3) is the prohormone of the vitamin D endocrine system. It is used to prevent and treat vitamin D deficiency. Calcifediol, as well as cholecalciferol (vitamin D3), is efficient and safe in the general population, although calcifediol has certain advantages over cholecalciferol, such as its rapid onset of action and greater potency. This review analyzed studies comparing the efficacy and safety of both calcifediol and cholecalciferol drugs in the short and long term (>6 months). Calcifediol was found to be more efficacious, with no increase in toxicity. We also assessed the predictability of both molecules. A 25OHD increase depends on the dose and frequency of calcifediol administration. In contrast, after cholecalciferol administration, 25OHD increase depends on more factors than dose and frequency of administration, also phenotypic aspects (such as obesity and malabsorption), and genotypic factors impacts in this increase.

Comorbidity and osteoporotic fracture: approach through predictive modeling techniques using the OSTEOMED registry.

PURPOSE: To examine the response to anti-osteoporotic treatment, considered as incident fragility fractures after a minimum follow-up of 1 year, according to sex, age, and number of comorbidities of the patients. METHODS: For this retrospective observational study, data from baseline and follow-up visits on the number of comorbidities, prescribed anti-osteoporotic treatment and vertebral, humerus or hip fractures in 993 patients from the OSTEOMED registry were analyzed using logistic regression and an artificial network model. RESULTS: Logistic regression showed that the probability of reducing fractures for each anti-osteoporotic treatment considered was independent of sex, age, and the number of comorbidities, increasing significantly only in males taking vitamin D (OR = 7.918), patients without comorbidities taking vitamin D (OR = 4.197) and patients with ≥ 3 comorbidities taking calcium (OR = 9.412). Logistic regression correctly classified 96% of patients (Hosmer-Lemeshow = 0.492) compared with the artificial neural network model, which correctly classified 95% of patients (AUC = 0.6). CONCLUSION: In general, sex, age and the number of comorbidities did not influence the likelihood that a given anti-osteoporotic treatment improved the risk of incident fragility fractures after 1 year, but this appeared to increase when patients had been treated with risedronate, strontium or teriparatide. The two models used classified patients similarly, but predicted differently in terms of the probability of improvement, with logistic regression being the better fit.

Molecular Mechanisms Involved in Hypoxia-Induced Alterations in Bone Remodeling.

Bone is crucial for the support of muscles and the protection of vital organs, and as a reservoir of calcium and phosphorus. Bone is one of the most metabolically active tissues and is continuously renewed to adapt to the changes required for healthy functioning. To maintain normal cellular and physiological bone functions sufficient oxygen is required, as evidence has shown that hypoxia may influence bone health. In this scenario, this review aimed to analyze the molecular mechanisms involved in hypoxia-induced bone remodeling alterations and their possible clinical consequences. Hypoxia has been associated with reduced bone formation and reduced osteoblast matrix mineralization due to the hypoxia environment inhibiting osteoblast differentiation. A hypoxic environment is involved with increased osteoclastogenesis and increased bone resorptive capacity of the osteoclasts. Clinical studies, although with contradictory results, have shown that hypoxia can modify bone remodeling.

Improving hip fracture care in Spain: evolution of quality indicators in the Spanish National Hip Fracture Registry.

This study was carried out to analyze the evolution of the quality indicators in the Spanish National Hip Fracture Registry, after disseminating a series of recommendations based on available clinical practice guidelines to the participating hospitals. Six of the seven proposed quality indicators showed a significant improvement. PURPOSE: The Spanish National Hip Fracture Registry (RNFC) arises from the need to know the process and improve the quality of care. Our goal was to analyze the changes in the RNFC's quality indicators after an intervention based on disseminating specific recommendations among the participating hospitals, following available clinical practice guidelines. METHODS: Study comparing before and after performing an intervention in hospitals participating in the RNFC. Data from the hospitals that registered cases in 2017, and that kept registering cases in 2019. Seven quality indicators were chosen, and a standard to be achieved for each indicator was proposed. The intervention consisted in the dissemination of 25 recommendations with practical measures to improve each quality indicator, based on available clinical practice guidelines, by drafting and publishing a scientific paper and sending it via email and printed cards. Fulfilment of each quality indicator was measured after carrying out the intervention. RESULTS: Forty-three hospitals registered 2674 cases between January and May, 2017, and 8037 during 2019. The quality indicators chosen and the degree of compliance were (all with p<0.05): (1) surgery ≤48 h increased from 38.9 to 45.8%; (2) patients mobilised on the first postoperative day increased from 58.9 to 70.3%; (3) patients with anti-osteoporotic medication at discharge increased from 34.5 to 49.8%; (4) patients with calcium supplements at discharge increased from 48.7 to 62.8%; (5) patients with vitamin D supplements at discharge increased from 71.5 to 84.7%; (6) patients developing a grade >2 pressure ulcer during admission decreased from 6.5 to 5.0%; (7) patients able to move on their own at 1 month fell from 58.8 to 56.4%. More than 48% of hospitals improved the proposed indicators. CONCLUSION: Establishing quality indicators and standards and intervening through the dissemination of specific recommendations to improve these indicators achieved an improvement in hospital performance results on a national level.

Vitamin D Receptor (VDR) Gene Polymorphisms Modify the Response to Vitamin D Supplementation: A Systematic Review and Meta-Analysis.

The vitamin D receptor (VDR), a member of the nuclear receptor superfamily of transcriptional regulators, is crucial to calcitriol signalling. VDR is regulated by genetic and environmental factors and it is hypothesised that the response to vitamin D supplementation could be modulated by genetic variants in the VDR gene. The best studied polymorphisms in the VDR gene are Apal (rs7975232), BsmI (rs1544410), Taql (rs731236) and Fokl (rs10735810). We conducted a systematic review and meta-analysis to evaluate the response to vitamin D supplementation according to the BsmI, TaqI, ApaI and FokI polymorphisms. We included studies that analysed the relationship between the response to vitamin D supplementation and the genotypic distribution of these polymorphisms. We included eight studies that enrolled 1038 subjects. The results showed no significant association with the BsmI and ApaI polymorphisms (p = 0.081 and p = 0.63) and that the variant allele (Tt+tt) of the TaqI polymorphism and the FF genotype of the FokI variant were associated with a better response to vitamin D supplementation (p = 0.02 and p < 0.001). In conclusion, the TaqI and FokI polymorphisms could play a role in the modulation of the response to vitamin D supplementation, as they are associated with a better response to supplementation.

Genetic variants in obesity-related genes and the risk of osteoporotic fracture. The Hortega Follow-up Study.

BACKGROUND: Osteoporosis and obesity are major public health problems that are closely correlated, as they share various features, including a genetic predisposition. A genetic correlation between obesity and osteoporosis due to the biological common pathways of bone and fat metabolism, which implies pleiotropic genes regulating has been described. The objective of our study was to analyse whether polymorphisms in obesity-related genes modify the risk of osteoporotic bone fracture. METHODS: We studied 575 subjects from the Hortega Study. The subjects were followed-up for 12-14 years. 202 subjects were overweight, 143 obese and 221 had bone fractures. The distribution of 39 genetic variants in 22 obesity-related genes were studied. RESULTS: The results showed a relationship between polymorphisms in the FTO and NEGR1 genes and the susceptibility to osteoporotic fracture. The variant genotype of the rs2568958 NEGR1 polymorphism and the rs6499649, rs3751812, and rs8044769 genetic variants in FTO were associated with susceptibility to bone fracture. In the best of our knowledge, this is the first time that these variants in NEGR1 and FTO genes have been associated with the susceptibility to osteoporotic bone fracture, supporting the hypothesis that the NEGR1 and FTO genes might be candidates for osteoporosis and bone fracture. CONCLUSIONS: In conclusion, this study associates obesity-related polymorphisms in the NEGR1 and FTO genes with osteoporotic bone fracture, reinforcing the hypothesis that obesity and bone metabolism are closely correlated genetically.

Association between genetic variants in oxidative stress-related genes and osteoporotic bone fracture. The Hortega follow-up study.

The most widely accepted etiopathogenesis hypothesis of the origin of osteoporosis and its complications is that they are a consequence of bone aging and other environmental factors, together with a genetic predisposition. Evidence suggests that oxidative stress is crucial in bone pathologies associated with aging. The aim of this study was to determine whether genetic variants in oxidative stress-related genes modified the risk of osteoporotic fracture. We analysed 221 patients and 354 controls from the HORTEGA sample after 12-14 years of follow up. We studied the genotypic and allelic distribution of 53 SNPs in 24 genes involved in oxidative stress. The results showed that being a carrier of the variant allele of the SNP rs4077561 within TXNRD1 was the principal genetic risk factor associated with osteoporotic fracture and that variant allele of the rs1805754 M6PR, rs4964779 TXNRD1, rs406113 GPX6, rs2281082 TXN2 and rs974334 GPX6 polymorphisms are important genetic risk factors for fracture. This study provides information on the genetic factors associated with oxidative stress which are involved in the risk of osteoporotic fracture and reinforces the hypothesis that genetic factors are crucial in the etiopathogenesis of osteoporosis and its complications.

Ocular Surface Pathology in Patients Suffering from Mercury Intoxication.

PURPOSE: To report the ocular surface pathology of patients suffering from acute/subacute mercury vapor intoxication. DESIGN: Cross-sectional study. PARTICIPANTS: Male workers intoxicated with inorganic mercury referred for ophthalmic involvement and healthy control subjects. METHODS: The following tests were performed: dry eye (DE)-related symptoms indicated by the ocular surface disease (OSDI) index questionnaire; tear osmolarity; analysis of 23 tear cytokine concentrations and principal component and hierarchical agglomerative cluster analyses; tear break-up time (T-BUT); corneal fluorescein and conjunctival lissamine green staining; tear production by Schirmer and tear lysozyme tests; mechanical and thermal corneal sensitivity (non-contact esthesiometry); and corneal nerve analysis and dendritic cell density by in vivo confocal microscopy (IVCM). RESULTS: Twenty-two out of 29 evaluated patients entered the study. Most had DE-related symptoms (OSDI values > 12), that were severe in 63.6% of them. Tear osmolarity was elevated (>308 mOsms/L) in 83.4% of patients (mean 336.23 (28.71) mOsm/L). Corneal and conjunctival staining were unremarkable. T-BUT was low (<7 s) in 22.7% of patients. Schirmer test and tear lysozyme concentration were low in 13.6% and 27.3% of cases, respectively. Corneal esthesiometry showed patient mechanical (mean 147.81 (53.36) mL/min) and thermal thresholds to heat (+2.35 (+1.10) °C) and cold (-2.57 (-1.24) °C) to be significantly higher than controls. Corneal IVCM revealed lower values for nerve density (6.4 (2.94) n/mm2), nerve branching density (2 (2.50) n/mm2), and dendritic cell density (9.1 (8.84) n/mm2) in patients. Tear levels of IL-12p70, IL-6, RANTES, and VEGF were increased, whereas EGF and IP-10/CXCL10 were decreased compared to controls. Based on cytokine levels, two clusters of patients were identified. Compared to Cluster 1, Cluster 2 patients had significantly increased tear levels of 18 cytokines, decreased tear lysozyme, lower nerve branching density, fewer dendritic cells, and higher urine mercury levels. CONCLUSIONS: Patients suffering from systemic mercury intoxication showed symptoms and signs of ocular surface pathology, mainly by targeting the trigeminal nerve, as shown by alterations in corneal sensitivity and sub-basal nerve morphology.

Multiple vertebral fractures after suspension of denosumab. A series of 56 cases.

BACKGROUND: Denosumab is a monoclonal antibody approved for the treatment of postmenopausal osteoporosis. The withdrawal of denosumab produces an abrupt loss of bone mineral density and may cause multiple vertebral fractures (MVF). OBJECTIVE: The objective of this study is to study the clinical, biochemical, and densitometric characteristics in a large series of postmenopausal women who suffered MVF after denosumab withdrawal. Likewise, we try to identify those factors related to the presence of a greater number of vertebral fractures (VF). PATIENTS AND METHODS: Fifty-six patients (54 women) who suffered MVF after receiving denosumab at least for three consecutive years and abruptly suspended it. A clinical examination was carried out. Biochemical bone remodelling markers (BBRM) and bone densitometry at the lumbar spine and proximal femur were measured. VF were diagnosed by magnetic resonance imaging MRI, X-ray, or both at dorsal and lumbar spine. RESULTS: Fifty-six patients presented a total of 192 VF. 41 patients (73.2%) had not previously suffered VF. After discontinuation of the drug, a statistically significant increase in the BBRM was observed. In the multivariate analysis, only the time that denosumab was previously received was associated with the presence of a greater number of VF (P = .04). CONCLUSIONS: We present the series with the largest number of patients collected to date. 56 patients accumulated 192 new VF. After the suspension of denosumab and the production of MVF, there was an increase in the serum values of the BBRM. The time of denosumab use was the only parameter associated with a greater number of fractures.

Calcifediol is superior to cholecalciferol in improving vitamin D status in postmenopausal women: a randomized trial.

Vitamin D has shown to play a role in multiple diseases due to its skeletal and extraskeletal actions. Furthermore, vitamin D deficiency has become a worldwide health issue. Few supplementation guidelines mention calcifediol treatment, despite being the direct precursor of calcitriol and the biomarker of vitamin D status. This 1-year, phase III-IV, double-blind, randomized, controlled, multicenter clinical trial assessed the efficacy and safety of calcifediol 0.266 mg soft capsules in vitamin D-deficient postmenopausal women, compared to cholecalciferol. Results reported here are from a prespecified interim analysis, for the evaluation of the study's primary endpoint: the percentage of patients with serum 25-hydroxyvitamin D (25(OH)D) levels above 30 ng/ml after 4 months. A total of 303 patients were enrolled, of whom 298 were included in the intention-to-treat (ITT) population. Patients with baseline levels of serum 25(OH)D <20 ng/ml were randomized 1:1:1 to calcifediol 0.266 mg/month for 12 months, calcifediol 0.266 mg/month for 4 months followed by placebo for 8 months, and cholecalciferol 25,000 IU/month for 12 months. At month 4, 35.0% of postmenopausal women treated with calcifediol and 8.2% of those treated with cholecalciferol reached serum 25(OH)D levels above 30 ng/ml (p < 0.0001). The most remarkable difference between both drugs in terms of mean change in serum 25(OH)D levels was observed after the first month of treatment (mean ± standard deviation change = 9.7 ± 6.7 and 5.1 ± 3.5 ng/ml in patients treated with calcifediol and cholecalciferol, respectively). No relevant treatment-related safety issues were reported in any of the groups studied. These results thus confirm that calcifediol is effective, faster, and more potent than cholecalciferol in raising serum 25(OH)D levels and is a valuable option for the treatment of vitamin D deficiency. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Utilidad del índice de comorbilidad de Charlson en personas ancianas. Concordancia con otros índices de comorbilidad / Utility of the Charlson Comorbidity Index in older people and concordance with other comorbidity indices

Objetivo: El objetivo principal de nuestro estudio fue evaluar la utilidad actual del índice de comorbilidad de Charlson (CCI) para predecir la mortalidad en personas mayores y la concordancia entre varios índices. Diseño: Estudio observacional, cohorte concurrente. Emplazamiento: Servicio de Medicina Interna de un hospital terciario, pacientes ambulatorios de un centro de salud y residentes de cuatro hogares de ancianos. Participantes: 375 individuos ≥ 65 años, con supervivencia esperada ≥ 6 meses, sin deterioro cognitivo. Mediciones principales: Se realizaron tres índices: CCI, el índice geriátrico de comorbilidad (GIC) y el índice de Kaplan-Feinstein (KF). A los 12 meses, se registró mortalidad. Los datos se analizaron con IBM SPSS Statistics® versión 23.0. Resultados: Edad media: 81,4 años. El CCI mostró comorbilidad baja-media en el grupo ambulatorio de 65-75 años (43 [75,4%]); moderada-alta más común en hospitalizados (19 [61,3%]) y en hogares de ancianos (5 [62,5%]). Al año fallecieron 59 (16,1%) individuos: con CCI: 10 (6,4%) comorbilidad baja-media y 49 (23,3%) moderada-alta, odds ratio (OR) 3,63 (intervalo de confianza [IC] 95% 1,76-7,51); con KF: 27 (13,3%) baja-media y 32 (19,5%) moderada-alta, OR 1,38 (IC 95% 0,78-2,44), y con GIC: 45 (14,1%) baja-media y 14 (29,2%) moderada-alta, OR 2,47 (IC 95% 1,21-5,06). La concordancia entre CCI-KF fue: 65-75 años: K = 0,62, 76-85 años: K = 0,396, y ≥ 86 años: K = 0,255. La concordancia entre CCI-GIC: 65-75 años: K = 0,202, 76-85 años: K = 0,069, y ≥ 86 años: K = 0,118. Conclusión: El CCI es el mejor predictor de mortalidad después de 1 año de seguimiento. Concordancia considerable entre CCI y KF en los individuos de 65-75 años, en el resto de las franjas etarias la correlación con GIC fue insignificante.(AU)

Background: The main aim of our study was to evaluate the current usefulness of the CCI in predicting mortality in older people and the concordance between various comorbidity indices. Design: An observational, concurrent cohort study was performed. Location: Internal Medicine Service of a tertiary hospital, outpatients in a health centre and residents in four nursing homes. Participants: 375 individuals ≥65 years and with expected survival ≥6 months, without cognitive impairment. Main measurements: Three indices, the CCI, the Geriatric Index of comorbidity (GIC), and the Kaplan-Feinstein index (KFI), were administered in all participants. At 12 months, mortality was evaluated. The data were analyzed using the SPSS 23.0 statistical programme. Results: Average age 81.4 years. The CCI revealed low-medium comorbidity in the outpatient group aged 65-75: 43 (75.4%), moderate-high morbidity and more common in hospitalized patients: 19 (61.3%) and nursing homes: 5 (62.5%). At one year follow-up 59 (16.1%) individuals died: CCI: 10 (6.4%) low-medium and 49 (23.3%) moderate-high comorbidity, OR 3.63 (95% CI 1.76-7.51); KF: 27 (13.3%) low-medium and 32 (19.5%) moderate-high comorbidity, OR 1.38 (95% CI 0.78-2.44) and GIC: 45 (14.1%) low-medium and 14 (29.2%) moderate-high comorbidity, OR 2.47 (95% CI 1.21-5.06). The concordance between CCI-KF: 65-75 years K=0.62, 76-85 years: K=0.396 and ≥86 years: K=0.255. Concordance between CCI-GIC was: 65-75 years K=0.202, 76-85 years: K=0.069 and ≥86 years: K=0.118. Conclusion: CCI was found to be the best predictor of mortality after one year of follow up. There was considerable concordance between CCI and KF in the 65-75 years and remaining age groups. Correlation with GIC was low.(AU)

Arsenic, cadmium, and selenium exposures and bone mineral density-related endpoints: The HORTEGA study.

BACKGROUND AND OBJECTIVES: Experimental data suggest that trace elements, such as arsenic (As), cadmium (Cd), and selenium (Se) can influence the bone remodeling process. We evaluated the cross-sectional association between As, Cd, and Se biomarkers with bone mineral density (BMD) measured at the calcaneus, in a representative sample of a general population from Spain. As secondary analyses we evaluated the associations of interest in subgroups defined by well-established BMD determinants, and also conducted prospective analysis of osteoporosis-related incident bone fractures restricted to participants older than 50 years-old. METHODS: In N = 1365 Hortega Study participants >20 years-old, urine As and Cd were measured by inductively coupled-plasma mass spectrometry (ICPMS); plasma Se was measured by atomic absorption spectrometry (AAS) with graphite furnace; and BMD at the calcaneus was measured using the Peripheral Instaneuous X-ray Imaging system (PIXI). As levels were corrected for arsenobetaine (Asb) to account for inorganic As exposure. RESULTS: The median of total urine As, Asb-corrected urine As, urine Cd, and plasma Se was 61.3, 6.53 and 0.39 µg/g creatinine, and 84.9 µg/L, respectively. In cross-sectional analysis, urine As and Cd were not associated with reduced BMD (T-score < -1 SD). We observed a non-linear dose-response of Se and reduced BMD, showing an inverse association below ~105 µg/L, which became increasingly positive above ~105 µg/L. The evaluated subgroups did not show differential associations. In prospective analysis, while we also observed a U-shape dose-response of Se with the incidence of osteoporosis-related bone fractures, the positive association above ~105 µg/L was markedly stronger, compared to the cross-sectional analysis. CONCLUSIONS: Our results support that Se, but not As and Cd, was associated to BMD-related disease. The association of Se and BMD-related disease was non-linear, including a strong positive association with osteoporosis-related bone fractures risk at the higher Se exposure range. Considering the substantial burden of bone loss in elderly populations, additional large prospective studies are needed to confirm the relevance of our findings to bone loss prevention in the population depending on Se exposure levels.