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Hyponatremia and osteoporosis: reappraisal of a novel association.

ABSTRACT: Age was a modifier of the independent association between hyponatremia and osteoporosis (OP). Risk of OP was the highest in the youngest age group as compared to older patients. A longer duration of hyponatremia revealed a similar association with OP in all anatomical sites.Epidemiologic studies provide conflicting results on the relationship between hyponatremia and OP. Our aim is to test the modification effect of age on the relationship between hyponatremia and OP at various anatomical sites in a large patient population.This is a cross-sectional observation of consecutive patients with available bone densitometry, demographic, clinical, and laboratory data from 2001 to 2013 at a single center. OP was defined as a bone mineral density of ?2.5 standard deviations below the mean peak bone mass of young, healthy adults. Hyponatremia was defined as serum sodium ?135 mmol/L. Multiple logistic regressions were used to calculate adjusted odds ratio (OR).Overall, 24,784 patients were included. There were 4549 males (18.4 %). Hyponatremia was present in 703 patients (2.8 %), femoral neck OP in 2603 (10.5 %), total hip OP in 1885 (7.5 %), and lumbar OP in 4830 (19.5 %). Total hip OP occurred in 17.6 % (n?=?124) of patients with hyponatremia as compared to 6.6 % (n?=?880) of patients with sodium level of "140-145" mmol/L (P?67 years (age-sodium category interaction P value?=?0.002).Age appeared as a modifier of the independent association between hyponatremia and OP. Risk of OP was the highest in the youngest age group as compared to older patients.

SUBMITTER: Afshinnia F

PROVIDER: S-EPMC4856473 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Hyponatremia and osteoporosis: reappraisal of a novel association.

Afshinnia F F Sundaram B B Ackermann R J RJ Wong K K KK

Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 20150326 9

<h4>Unlabelled</h4>Age was a modifier of the independent association between hyponatremia and osteoporosis (OP). Risk of OP was the highest in the youngest age group as compared to older patients. A longer duration of hyponatremia revealed a similar association with OP in all anatomical sites.<h4>Introduction</h4>Epidemiologic studies provide conflicting results on the relationship between hyponatremia and OP. Our aim is to test the modification effect of age on the relationship between hyponatr ...[more]

PMID: 25807914

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Project description:Combinations of anabolic and antiresorptive agents have potential to improve bone density and bone strength more than either agent alone. A large number of relatively small clinical trials have been performed evaluating combinations of PTH1-34 or PTH1-84 with a variety of antiresorptives, including hormone/estrogen therapy, raloxifene, alendronate (Aln), risedronate, ibandronate, zoledronic acid and denosumab (Dmab). Most of the studies evaluate dual-X-ray densitometry outcomes, with a few trials reporting volumetric bone mineral density (BMD) by quantitative computed tomography followed by finite element modeling of bone strength. None of the studies has been powered to assess differences in fracture incidence between combination therapy and monotherapy. BMD outcomes vary depending on the timing of introduction of the anabolic agent (before, during or after antiresorptive treatment), as well as according to the specific anabolic and antiresorptive used. Furthermore, effects of combination therapies are site dependent. The most consistent effect of combining antiresorptive agents with parathyroid hormone (PTH) is a superior hip BMD outcome compared with PTH alone. This is most evident when PTH is combined with a bisphosphonate or Dmab. In contrast to findings in the hip, in the majority of studies there is no benefit to spine BMD with combination therapy when compared with monotherapy. The two exceptions to this are when PTH is combined with Dmab and when PTH is given as monotherapy first for 9 months followed by the addition of Aln and continuation of PTH as combination treatment. On the basis of what we now know, in patients on bisphosphonates who suffer hip fractures or who have very low hip BMD, strong consideration should be given to starting teriparatide and continuing a bisphosphonate (possibly switching to zoledronic acid or even Dmab) to maximize hip BMD and strength. Furthermore, in treatment-naive individuals with very severe osteoporosis, such as those with spine and hip fractures, combination therapy with PTH and Dmab or PTH followed by combination treatment with a potent bisphosphonate or Dmab should be considered to maximize early increases in BMD.

Project description:In this study, we integrated large-scale GWAS summary data and used the predicted transcriptome-wide association study method to discover novel genes associated with osteoporosis. We identified 204 candidate genes, which provide novel clues for understanding the genetic mechanism of osteoporosis and indicate potential therapeutic targets.IntroductionOsteoporosis is a highly polygenetic disease characterized by low bone mass and deterioration of the bone microarchitecture. Our objective was to discover novel candidate genes associated with osteoporosis.MethodsTo identify potential causal genes of the associated loci, we investigated trait-gene expression associations using the transcriptome-wide association study (TWAS) method. This method directly imputes gene expression effects from genome-wide association study (GWAS) data using a statistical prediction model trained on GTEx reference transcriptome data. We then performed a colocalization analysis to evaluate the posterior probability of biological patterns: associations characterized by a single causal variant or multiple distinct causal variants. Finally, a functional enrichment analysis of gene sets was performed using the VarElect and CluePedia tools, which assess the causal relationships between genes and a disease and search for potential gene's functional pathways. The osteoporosis-associated genes were further confirmed based on the differentially expressed genes profiled from mRNA expression data of bone tissue.ResultsOur analysis identified 204 candidate genes, including 154 genes that have been previously associated with osteoporosis, 50 genes that have not been previously discovered. A biological function analysis found that 20 of the candidate genes were directly associated with osteoporosis. Further analysis of multiple gene expression profiles showed that 15 genes were differentially expressed in patients with osteoporosis. Among these, SLC11A2, MAP2K5, NFATC4, and HSP90B1 were enriched in four pathways, namely, mineral absorption pathway, MAPK signaling pathway, Wnt signaling pathway, and PI3K-Akt signaling pathway, which indicates a causal relationship with the occurrence of osteoporosis.ConclusionsWe demonstrated that transcriptome fine-mapping identifies more osteoporosis-related genes and provides key insight into the development of novel targeted therapeutics for the treatment of osteoporosis.

Project description:Background and objectivesOsmotic demyelination syndrome is the most concerning complication of severe hyponatremia, occurring with an overly rapid rate of serum sodium correction. There are limited clinical tools to aid in identifying individuals at high risk of overcorrection with severe hyponatremia.Design, setting, participants, & measurementsWe identified all patients who presented to a tertiary-care hospital emergency department in Ottawa, Canada (catchment area 1.2 million) between January 1, 2003 and December 31, 2015, with serum sodium (corrected for glucose levels) <116 mmol/L. Overcorrection was determined using 14 published criteria. Latent class analysis measured the independent association of baseline factors with a consensus overcorrection status on the basis of the 14 criteria, and was summarized as a risk score, which was validated in two cohorts.ResultsA total of 623 patients presented with severe hyponatremia (mean initial value 112 mmol/L; SD 3.2). The prevalence of no, unlikely, possible, and definite overcorrection was 72%, 4%, 10%, and 14%, respectively. Overcorrection was independently associated with decreased level of consciousness (2 points), vomiting (2 points), severe hypokalemia (1 point), hypotonic urine (4 points), volume overload (-5 points), chest tumor (-5 points), patient age (-1 point per decade, over 50 years), and initial sodium level (<110 mmol/L: 4 points; 110-111 mmol/L: 2 points; 112-113 mmol/L: 1 point). These points were summed to create the Severe Hyponatremic Overcorrection Risk (SHOR) score, which was significantly associated with overcorrection status (Spearman correlation 0.45; 95% confidence interval, 0.36 to 0.49) and was discriminating (average dichotomized c-statistic 0.77; 95% confidence interval, 0.73 to 0.81). The internal (n=119) and external (n=95) validation cohorts had significantly greater use of desmopressin, which was significantly associated with the SHOR score. The SHOR score was significantly associated with overcorrection status in the internal (P<0.001) but not external (P=0.39) validation cohort.ConclusionsIn patients presenting with severe hyponatremia, overcorrection was common and predictable using baseline information. Further external validation of the SHOR is required before generalized use.

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Hyponatremia and osteoporosis: reappraisal of a novel association.

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Hyponatremia and osteoporosis: reappraisal of a novel association.

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