Breastfeeding duration is associated with favorable body composition and lower glycoprotein acetyls in later life.

OBJECTIVE: The aim of the present study was to investigate associations between lifetime breastfeeding behaviors and cardiovascular risk in later reproductive years. METHOD: This was a prospective 10-year longitudinal cohort study of 168 parous women. Health, lifestyle and infant feeding questionnaires, blood samples, anthropometry and body composition were collected. Cardiovascular risk was estimated using QRISK®3 and hierarchical multiple linear regression analysis performed. RESULTS: Mean age was 42.4 years (SD 3.8; range 31-50) and 98.7% (n = 156/158) were premenopausal. Ever breastfeeding rates were 72.6% (n = 122/168) and 37.5% (n = 63/168) lifetime ≥12 months breastfeeding duration. Median durations were 5.5 weeks for exclusive breastfeeding (IQR 35.8; range 0-190) and 30.5 weeks for any breastfeeding (IQR 84.0; range 0-488). Breastfeeding duration was not associated with QRISK®3 scores in adjusted models. Lower glycoprotein acetyls were associated with ever breastfeeding (P = 0.03), and lifetime breastfeeding ≥12 months (P = 0.001). Lifetime breastfeeding ≥12 months and longer exclusive breastfeeding were associated with lower fat mass index (P = 0.03, P = 0.01), tissue percentage fat (P = 0.02, P = 0.009) and visceral adipose tissue volume (P = 0.04, P = 0.025) after correcting for confounders including body mass index. CONCLUSION: Longer breastfeeding is associated with favorable body composition and lower glycoprotein acetyls, a novel inflammatory biomarker associated with cardiometabolic risk. Breastfeeding is a low-cost, health promoting behavior for women and infants. Pregnant women, especially those at higher risk of cardiovascular disease, should be counseled about the potential benefits of exclusive and longer breastfeeding duration.

The impact of macrosomia on cardiometabolic health in preteens: findings from the ROLO longitudinal birth cohort study.

BACKGROUND: Macrosomia (birthweight ≥ 4 kg or ≥ 4.5 kg) is strongly associated with a predisposition to childhood obesity, which in turn is linked with adverse cardiometabolic health. Despite this, there is a lack of longitudinal investigation on the impact of high birthweight on cardiometabolic outcomes in youth. The preteen period represents an important window of opportunity to further explore this link, to potentially prevent cardiometabolic profiles worsening during puberty. METHODS: This is a secondary analysis of 9-11-year-olds (n = 405) born to mothers in the ROLO longitudinal birth cohort study, who previously delivered an infant with macrosomia. Preteens were dichotomised into those born with and without macrosomia, using two common cut-off criteria (birthweight ≥ 4 kg (n = 208) and < 4 kg; ≥ 4.5 kg (n = 65) and < 4.5 kg). Cardiometabolic health was assessed using anthropometry, dual-energy x-ray absorptiometry, blood pressure, heart rate, cardiorespiratory endurance (20-m shuttle run test), and non-fasting serum biomarkers for a subgroup (n = 213). Statistical comparisons between the two groups were explored using independent t-tests, Mann-Whitney U tests, and Chi-square tests. Crude and adjusted linear regression models investigated associations between macrosomia and preteen cardiometabolic outcomes. RESULTS: In total, 29.3% (n = 119) of preteens had overweight/obesity based on their BMI z-score. Preteens born ≥ 4 kg had lower median (IQR) C3 concentrations (1.38 (1.22, 1.52) g/L vs. 1.4 (1.26, 1.6) g/L, p = 0.043) and lower median (IQR) ICAM-1 concentrations (345.39 (290.34, 394.91) ng/mL vs. 387.44 (312.91, 441.83) ng/mL, p = 0.040), than those born < 4 kg. Those born ≥ 4.5 kg had higher mean (SD) BMI z-scores (0.71 (0.99) vs. 0.36 (1.09), p = 0.016), and higher median (IQR) lean mass (24.76 (23.28, 28.51) kg vs. 23.87 (21.9, 26.79) kg, p = 0.021), than those born < 4.5 kg. Adjusted linear regression analyses revealed birthweight ≥ 4 kg was negatively associated with C3 concentration (g/L) (B = - 0.095, 95% CI = - 0.162, - 0.029, p = 0.005) and birthweight ≥ 4.5 kg was positively associated with weight z-score (B = 0.325, 95% CI = 0.018, 0.633, p = 0.038), height z-score (B = 0.391, 95% CI = 0.079, 0.703, p = 0.014), lean mass (kg) (B = 1.353, 95% CI = 0.264, 2.442, p = 0.015) and cardiorespiratory endurance (B = 0.407, 95% CI = 0.006, 0.808, p = 0.047). CONCLUSION: This study found no strong evidence to suggest that macrosomia is associated with adverse preteen cardiometabolic health. Macrosomia alone may not be a long-term cardiometabolic risk factor. Trial registration ISRCTN54392969 registered at  www.isrctn.com .

N-glycans from serum IgG and total serum glycoproteins specific for endometriosis.

Endometriosis is a chronic inflammatory gynaecological disease characterized by the growth of endometrial tissue outside the uterine cavity. There are currently no definitive non-invasive diagnostic tools. Glycosylation is the most common posttranslational modification of proteins and altered glycosylation has been found in many diseases, including chronic inflammatory conditions and cancer. Sialylation and galactosylation on serum IgG have previously been found to be altered in endometriosis and serum sialylation changed after Zoladex (Goserelin Acetate) therapy. Using IgG and whole serum glycoproteins, we investigated N-glycosylation in two clinical cohorts of women with and without endometriosis. PNGase F-digested serum samples were fluorescently labelled and N-glycans were profiled by ultra-performance liquid chromatography. Clinical data was collected to link glycomic findings with metabolic and hormonal profiles. Total serum glycoprotein and IgG glycosylation differed in patients with endometriosis compared to control cases. The most significantly altered was glycan peak 3 from IgG, containing bisected biantennary glycans, which was decreased in the endometriosis cohorts (p = 0.0000005-0.018). In conclusion, this is the first pilot study to identify changes in N-glycans from whole serum glycoproteins associated with endometriosis. A larger validation study is now warranted and such studies should include the follow-up of surgically and pharmacologically treated patients.

Wilson's disease: best practice.

Wilson's disease is an autosomal recessive disorder arising from pathogenic variants in the Atp7b gene on chromosome 13. The defective translated ATPase copper (Cu) transport protein produced leads to Cu accumulation, initially affecting the liver but eventually affecting other cells. It is just over 20 years since the last Best Practice on this topic in this journal. This review is an update on this, covering new disease biomarkers, pathogenesis, assumptions around clinical features and developments in therapy.

Maternal Glycaemic and Insulinemic Status and Newborn DNA Methylation: Findings in Women With Overweight and Obesity.

CONTEXT: Maternal dysglycaemia and prepregnancy obesity are associated with adverse offspring outcomes. Epigenetic mechanisms such as DNA methylation (DNAm) could contribute. OBJECTIVE: To examine relationships between maternal glycaemia, insulinemic status, and dietary glycemic indices during pregnancy and an antenatal behavioral-lifestyle intervention with newborn DNAm. METHODS: We investigated 172 women from a randomized controlled trial of a lifestyle intervention in pregnant women who were overweight or obese. Fasting glucose and insulin concentrations and derived indices of insulin resistance (HOMA-IR), ß-cell function (HOMA-%B), and insulin sensitivity were determined at baseline (15) and 28 weeks' gestation. Dietary glycemic load (GL) and index (GI) were calculated from 3-day food diaries. Newborn cord blood DNAm levels of 850K CpG sites were measured using the Illumina Infinium HumanMethylationEPIC array. Associations of each biomarker, dietary index and intervention with DNAm were examined. RESULTS: Early pregnancy HOMA-IR and HOMA-%B were associated with lower DNAm at CpG sites cg03158092 and cg05985988, respectively. Early pregnancy insulin sensitivity was associated with higher DNAm at cg04976151. Higher late pregnancy insulin concentrations and GL scores were positively associated with DNAm at CpGs cg12082129 and cg11955198 and changes in maternal GI with lower DNAm at CpG cg03403995 (Bonferroni corrected P < 5.99 × 10-8). These later associations were located at genes previously implicated in growth or regulation of insulin processes. No effects of the intervention on cord blood DNAm were observed. None of our findings were replicated in previous studies. CONCLUSION: Among women who were overweight or obese, maternal pregnancy dietary glycemic indices, glucose, and insulin homeostasis were associated with modest changes in their newborn methylome. TRIAL REGISTRATION: ISRCTN29316280.

COVID-19 pandemic and vitamin D: rising trends in status and in daily amounts of vitamin D provided by supplements.

OBJECTIVES: Since the onset of the COVID-19 pandemic in 2020, there have been plausible suggestions about the need to augment vitamin D intake by supplementation in order to prevent SARS-CoV2 infection and reduce mortality. Some groups have advocated supplementation for all adults, but governmental agencies have advocated targeted supplementation. We sought to explore the effect of the COVID-19 pandemic on both vitamin D status and on the dose of new-to-market vitamin D supplements. SETTING: University hospital, Dublin, Ireland. PARTICIPANTS: Laboratory-based samples of circulating 25-hydroxyvitamin D (25OHD) (n=100 505). PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes: comparing yearly average 25OHD prior to the pandemic (April 2019 to March 2020) with during the pandemic (April 2020 to March 2021) and comparing the dose of new-to-market vitamin D supplements between 2017 and 2021 (n=2689). SECONDARY OUTCOME: comparing prevalence of vitamin D deficiency and vitamin D excess during the two time periods. RESULTS: The average yearly serum 25OHD measurement increased by 2.8 nmol/L (61.4, 95% CI 61.5 to 61.7 vs 58.6, 95% CI 58.4 to 58.9, p<0.001), which was almost threefold higher than two similar trend analyses that we conducted between 1993 and 2016. There was a lower prevalence of low 25OHD and a higher prevalence of high 25OHD. The dose of new-to-market vitamin D supplements was higher in the years 2020-2021 compared with the years 2017-2019 (p<0.001). CONCLUSIONS: We showed significant increases in serum 25OHD and in the dose of new-to-market vitamin D supplements. The frequency of low vitamin D status reduced indicating benefit, but the frequency of vitamin D excess increased indicating risk of harm. Rather than a blanket recommendation about vitamin D supplementation for all adults, we recommend a targeted approach of supplementation within current governmental guidelines to at-risk groups and cautioning consumers about adverse effects of high dose supplements on the market.

Higher Inflammation Is Associated with Cardiometabolic Phenotype and Biochemical Health in Women with Obesity.

INTRODUCTION: Metabolic or inflammatory markers may predict adverse outcomes in women with obesity. We sought to describe metabolic-obesity phenotypes of women using novel staging tools and investigate relationships with inflammation. METHODS: In a cross-sectional study, we collected fasting blood samples from sixty-four females with body mass index (BMI) ≥28 kg/m2. Participants were classified as metabolically healthy or metabolically unhealthy obesity (MUO) using the cardiometabolic disease staging system (CMDS) and Edmonton obesity staging system (EOSS). Data were analyzed using independent sample t tests, Pearson's correlations, and multiple logistic regression. RESULTS: Mean (SD) age was 40.2 (9.3) years with median (IQR) BMI 31.8 (30.3-35.7) kg/m2. The prevalence of MUO was 46.9% and 81.3% using CMDS and EOSS criteria, respectively. Women with raised CMDS scores had higher C3 (1.34 [0.20] vs. 1.18 [0.15], p = 0.001) and C-reactive protein (CRP) (2.89 [1.31-7.61] vs. 1.39 [0.74-3.60], p = 0.034). C3 correlated with insulin (r = 0.52), hemoglobin A1c (r = 0.37), and C-peptide (r = 0.58), all p < 0.05. C3 above the median (>1.23 g/L) increased odds of raised CMDS score, when controlled for age, BMI, ethnicity, and smoking (OR = 6.56, 95% CI: 1.63, 26.47, p = 0.008). CONCLUSION: The prevalence of MUO was lower using CMDS than EOSS. C3 and CRP may be useful clinical biomarkers of risk or treatment targets in women with obesity.

Assessment of serum total 25-hydroxyvitamin D assays for Vitamin D External Quality Assessment Scheme (DEQAS) materials distributed at ambient and frozen conditions.

The Vitamin D External Quality Assessment Scheme (DEQAS) distributes human serum samples four times per year to over 1000 participants worldwide for the determination of total serum 25-hydroxyvitamin D [25(OH)D)]. These samples are stored at -40 °C prior to distribution and the participants are instructed to store the samples frozen at -20 °C or lower after receipt; however, the samples are shipped to participants at ambient conditions (i.e., no temperature control). To address the question of whether shipment at ambient conditions is sufficient for reliable performance of various 25(OH)D assays, the equivalence of DEQAS human serum samples shipped under frozen and ambient conditions was assessed. As part of a Vitamin D Standardization Program (VDSP) commutability study, two sets of the same nine DEQAS samples were shipped to participants at ambient temperature and frozen on dry ice. Twenty-eight laboratories participated in this study and provided 34 sets of results for the measurement of 25(OH)D using 20 ligand binding assays and 14 liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. Equivalence of the assay response for the frozen versus ambient DEQAS samples for each assay was evaluated using multi-level modeling, paired t-tests including a false discovery rate (FDR) approach, and ordinary least squares linear regression analysis of frozen versus ambient results. Using the paired t-test and confirmed by FDR testing, differences in the results for the ambient and frozen samples were found to be statistically significant at p < 0.05 for four assays (DiaSorin, DIAsource, Siemens, and SNIBE prototype). For all 14 LC-MS/MS assays, the differences in the results for the ambient- and frozen-shipped samples were not found to be significant at p < 0.05 indicating that these analytes were stable during shipment at ambient conditions. Even though assay results have been shown to vary considerably among different 25(OH)D assays in other studies, the results of this study also indicate that sample handling/transport conditions may influence 25(OH)D assay response for several assays.

Clinical Implementation and Initial Experience of Neutrophil Gelatinase-Associated Lipocalin Testing for the Diagnostic and Prognostic Assessment of Acute Kidney Injury Events in Hospitalized Patients.

INTRODUCTION: The use of novel kidney injury biomarkers has been shown to improve diagnostic assessment and prognostic prediction in various populations with acute kidney injury (AKI), but their use in a standard clinical practice have been rarely reported. METHODS: We reported the clinical implementation of neutrophil gelatinase-associated lipocalin (NGAL) measurement for routine AKI diagnostic workup of patients receiving nephrology consultation in a tertiary academic centre. Specific focus was made on the diagnostic performance to discriminate functional ("pre-renal") from intra-renal AKI and to predict AKI progression. RESULTS: Forty-five urine NGAL (uNGAL) and 25 plasma NGAL (pNGAL) samples in the first 50 consecutive patients were analysed. KDIGO Stage 1, 2, 3 AKI, and renal replacement therapy occurred in 10%, 40%, 50%, and 24% of cases, respectively. The uNGAL was lower in patients with transient AKI (<48 h) and no sign of urinary tract infections (37 [25-167] ng/mL) than sustained or progressive AKI (298 [74-1,308] ng/mL) (p = 0.016), while pNGAL did not discriminate transient (264 [100-373] ng/mL) from persistent AKI (415 [220-816] ng/mL) (p = 0.137). The median uNGAL level was 63 (35-1,123) ng/mL for functional/pre-renal AKI and 451 (177-1,315) ng/mL for intra-renal AKI (p = 0.043), while the pNGAL was 264 (114-468) and 415 (230-816) ng/mL (p = 0.235), respectively. CONCLUSION: NGAL, as part of the routine workup, is useful for diagnostic and prognostic assessment of new-onset AKI in clinical practice. Interpretation of an increased NGAL level should be clinically evaluated in its clinical context, particularly considering concomitant infection (urinary or systemic). Clinical adoption of emerging AKI biomarkers as diagnostic tests in clinical practice should be further encouraged.

Interlaboratory comparison of 25-hydroxyvitamin D assays: Vitamin D Standardization Program (VDSP) Intercomparison Study 2 - Part 2 ligand binding assays - impact of 25-hydroxyvitamin D2 and 24R,25-dihydroxyvitamin D3 on assay performance.

An interlaboratory comparison study was conducted by the Vitamin D Standardization Program (VDSP) to assess the performance of ligand binding assays (Part 2) for the determination of serum total 25-hydroxyvitamin D [25(OH)D]. Fifty single-donor samples were assigned target values for concentrations of 25-hydroxyvitamin D2 [25(OH)D2], 25-hydroxyvitamin D3 [25(OH)D3], 3-epi-25-hydroxyvitamin D3 [3-epi-25(OH)D3], and 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] using isotope dilution liquid chromatography-tandem mass spectrometry (ID LC-MS/MS). VDSP Intercomparison Study 2 Part 2 includes results from 17 laboratories using 32 ligand binding assays. Assay performance was evaluated using mean % bias compared to the assigned target values and using linear regression analysis of the test assay mean results and the target values. Only 50% of the ligand binding assays achieved the VDSP criterion of mean % bias ≤ |± 5%|. For the 13 unique ligand binding assays evaluated in this study, only 4 assays were consistently within ± 5% mean bias and 4 assays were consistently outside ± 5% mean bias regardless of the laboratory performing the assay. Based on multivariable regression analysis using the concentrations of individual vitamin D metabolites in the 50 single-donor samples, most assays underestimate 25(OH)D2 and several assays (Abbott, bioMérieux, DiaSorin, IDS-EIA, and IDS-iSYS) may have cross-reactivity from 24R,25(OH)2D3. The results of this interlaboratory study represent the most comprehensive comparison of 25(OH)D ligand binding assays published to date and is the only study to assess the impact of 24R,25(OH)2D3 content using results from a reference measurement procedure.

High bone turnover and hyperparathyroidism after surgery for tumor-induced osteomalacia: A case series.

Tumor-induced osteomalacia (TIO) is an ultrarare disorder that is caused by renal phosphate wasting due to uncontrolled tumoral production of fibroblast growth factor 23 (FGF23) from phosphaturic mesenchymal tumors. Surgical removal of the tumor is curative. There is limited information on the biochemical changes in mineral metabolism and bone remodeling activity after surgery, but it is reported that surgery is followed by a hungry bone syndrome (HBS) with hypocalcemia and secondary hyperparathyroidism. We report the biochemical response to surgery in two patients, who presented with severe TIO, as manifested by proximal myopathy, multiple stress fractures, high FGF23, low serum phosphate, low maximum renal phosphate reabsorption threshold (TmP/GFR), and low 1,25-dihydroxy-vitamin D (1,25(OH)2D). Prior to surgery, both patients developed secondary hyperparathyroidism and one case had progressed to tertiary hyperparathyroidism. After surgery there was normalization of FGF23, TmP/GFR, and phosphate. High 1,25(OH)2D was recorded. One patient had hypocalcaemia and worsening secondary hyperparathyroidism consistent with HBS; the other patient did not have hypocalcemia but had worsening tertiary hyperparathyroidism that only resolved with cinacalcet. There was a marked increase in bone remodeling markers, both resorption and formation, consistent with a high bone turnover state. There was a different pattern of change in bone specific alkaline phosphatase, reflecting healing of osteomalacia. Biochemical monitoring in the post-surgical management of TIO is warranted for guiding adjustments in medical intervention, both short-term and long-term. Future use of burosumab prior to surgery for TIO may ameliorate the immediate post-surgery effects.

No effect of calcium and vitamin D intake on maternal blood pressure in a healthy pregnant population.

OBJECTIVES: Clinical studies have reported an inverse relationship between calcium and vitamin D intake and hypertensive disorders of pregnancy (HDP). The aim of this study was to investigate if there was an association between calcium/vitamin D intake, and vitamin D (25OHD) status, and maternal blood pressure (BP), during pregnancy and at 5-year follow-up. STUDY DESIGN: This was an observational study of 415 women who participated in the ROLO (Randomised cOntrolled trial of LOw glycaemic index diet for the prevention of recurrence of macrosomia) study. Maternal BP measurements were taken during each trimester and at 5-year follow-up. Calcium and vitamin D intake were determined at each trimester and 25OHD was measured in early and late pregnancy. RESULTS: Over two-thirds of the cohort were vitamin D sufficient (25OHD > 30 nmol/L) and had adequate calcium intake (>750 mg/day). There was no correlation between calcium intake or vitamin D intake and maternal BP in trimester 1 to 3 or at 5-year follow-up. Vitamin D status at 13 weeks' gestation negatively correlated with mean arterial pressure in trimester 1 (r = -0.152, p = 0.044). There was no correlation however between 25OHD at 28 weeks' gestation and BP at 28 or 34 weeks' gestation or 25OHD and BP at 5-year follow-up. CONCLUSIONS: In a healthy population of women with adequate calcium and vitamin D intake, no clinically significant correlation existed between calcium and vitamin D and maternal BP.

Assessment of serum total 25-hydroxyvitamin D assay commutability of Standard Reference Materials and College of American Pathologists Accuracy-Based Vitamin D (ABVD) Scheme and Vitamin D External Quality Assessment Scheme (DEQAS) materials: Vitamin D Standardization Program (VDSP) Commutability Study 2.

An interlaboratory study was conducted through the Vitamin D Standardization Program (VDSP) to assess commutability of Standard Reference Materials® (SRMs) and proficiency testing/external quality assessment (PT/EQA) samples for determination of serum total 25-hydroxyvitamin D [25(OH)D] using ligand binding assays and liquid chromatography-tandem mass spectrometry (LC-MS/MS). A set of 50 single-donor serum samples were assigned target values for 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] using reference measurement procedures (RMPs). SRM and PT/EQA samples evaluated included SRM 972a (four levels), SRM 2973, six College of American Pathologists (CAP) Accuracy-Based Vitamin D (ABVD) samples, and nine Vitamin D External Quality Assessment Scheme (DEQAS) samples. Results were received from 28 different laboratories using 20 ligand binding assays and 14 LC-MS/MS methods. Using the test assay results for total serum 25(OH)D (i.e., the sum of 25(OH)D2 and 25(OH)D3) determined for the single-donor samples and the RMP target values, the linear regression and 95% prediction intervals (PIs) were calculated. Using a subset of 42 samples that had concentrations of 25(OH)D2 below 30 nmol/L, one or more of the SRM and PT/EQA samples with high concentrations of 25(OH)D2 were deemed non-commutable using 5 of 11 unique ligand binding assays. SRM 972a (level 4), which has high exogenous concentration of 3-epi-25(OH)D3, was deemed non-commutable for 50% of the LC-MS/MS assays.

Renal Phosphate Handling: Independent Effects of Circulating FGF23, PTH, and Calcium.

Excess fibroblast growth factor 23 (FGF23), excess PTH, and an increase in extracellular calcium cause hypophosphatemia by lowering the maximum renal phosphate reabsorption threshold (TmP/GFR). We recently reported two cases of X-linked hypophosphatemia (XLH) with severe tertiary hyperparathyroidism who had normalization of TmP/GFR upon being rendered hypoparathyroid following total parathyroidectomy, despite marked excess in both C-terminal FGF23 (cFGF23) and intact FGF23 (iFGF23). We explored the effects of FGF23, PTH, and calcium on TmP/GFR in a cross-sectional study (n = 74) across a spectrum of clinical cases with abnormalities in TmP/GFR, PTH, and FGF23. This comprised three groups: FGF23-dependent hypophosphatemia (n = 27), hypoparathyroidism (HOPT; n = 17), and chronic kidney disease (n = 30). Measurements included TmP/GFR, cFGF23, PTH, ionized calcium, vitamin D metabolites, and bone turnover markers. The combined effect of cFGF23, PTH, and ionized calcium on TmP/GFR was modeled using hierarchical multiple regression and was probed by moderation analysis with PROCESS. Modeling analysis showed independent effects on TmP/GFR by cFGF23, PTH, and ionized calcium in conjunction with a weak but significant effect of the interaction term for PTH and FGF23; probing showed that the effect was most prominent during PTH deficiency. Teriparatide 20 µg daily was self-administered for 28 days by one case of X-linked hypophosphatemia with hypoparathyroidism (XLH-HOPT) to assess the response of TmP/GFR, cFGF23, iFGF23, nephrogenous cyclic adenosine monophosphate (NcAMP), vitamin D metabolites, and bone turnover markers. After 28 days, TmP/GFR was lowered from 1.10 mmol/L to 0.48 mmol/L; this was accompanied by increases in NcAMP, ionized calcium, and bone turnover markers. In conclusion, the effect of FGF23 excess on TmP/GFR is altered by PTH such that the effect is ameliorated by hypoparathyroidism and the effect is augmented by hyperparathyroidism. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

The effects of acute hyponatraemia on bone turnover in patients with subarachnoid haemorrhage: A preliminary report.

CONTEXT: Animal data and cross-sectional human studies have established that chronic hyponatraemia predisposes to osteoporosis; the effects of acute hyponatraemia on bone turnover have not been determined. Our objective was to test the hypothesis that acute hyponatraemia leads to dynamic effects on bone turnover. DESIGN: A prospective observational pilot study. METHODS: Bone turnover markers [C-terminal crosslinking telopeptide of type 1 collagen (CTX-1), N-propeptide of type 1 collagen (P1NP) and osteocalcin] were measured prospectively over one week in 22 eunatraemic patients with subarachnoid haemorrhage. Patients treated with glucocorticoids were excluded. RESULTS: Eight patients developed acute hyponatraemia, median nadir plasma sodium concentration 131 mmol/L (IQR 128-132), and 14 remained eunatraemic, nadir plasma sodium concentration 136 mmol/L (IQR 133-137). Significant main effects of hyponatraemia were found for P1NP (p = .02) and P1NP:CTX-1 ratio (p = .02), both fell in patients with acute hyponatraemia, with significant interaction between hyponatraemia and time from baseline for P1NP (p = .02). Significant main effects of time from baseline (p < .001) but not hyponatraemia (p = .07) were found for osteocalcin. For CTX-1, significant main effects of time from baseline (p = .001) but not hyponatraemia (p = .65) were found. There was a positive correlation between change in P1NP:CTX-1 ratio and nadir plasma sodium concentration, r = +.43, p = .04. Median serum cortisol (measured on days 1, 3 and 7) was higher in the hyponatraemia group than in those who remained eunatraemic, 545 nmol/L (IQR 373-778) versus 444 nmol/L (IQR 379-542) p = .03. CONCLUSION: These data suggest that acute mild hyponatraemia is associated with a reduction in bone formation activity.