abnormally low blood levels of calcium
Betts, J. G., Young, K. A., Wise, J. A., Johnson, E., Poe, B., Kruse, D. H., … DeSaix, P. (n.d.). Anatomy and Physiology. Houston, Texas: OpenStax. Access for free at: https://openstax.org/details/books/anatomy-and-physiology
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A Simple-to-Use Score for Identifying Individuals at High Risk of Denosumab-Associated Hypocalcemia in Postmenopausal Osteoporosis: A Real-World Cohort Study
Since denosumab-associated hypocalcemia occurs infrequently, data on its incidence and risk factors are limited. We aimed to evaluate risk factors and develop a useful score for identifying individuals at risk of denosumab-associated hypocalcemia. In this retrospective cohort, 790 consecutive female patients who received 60 mg denosumab at least once between 2016 and 2017 were analyzed. Based on biochemical records from a large-scale single-center, mild and moderate hypocalcemia were defined as albumin-corrected calcium (cCa) levels < 8.5 and < 8.0 mg/dL (< 2.12 and < 2.0 mmol/L), respectively. Mild and moderate hypocalcemia were observed in 8.2% and 1.0% patients, respectively. Patients who developed mild hypocalcemia had lower baseline cCa (8.9 vs. 9.3 mg/dL and 2.22 vs. 2.32mmo/L) and estimated glomerular filtration rate (75.0 vs. 83.2 mL/min/1.73 m2) and more frequent loop diuretic use (10.8% vs. 4.4%; all p < 0.05). In multivariate analysis, low baseline cCa (OR 1.29; 95% CI 1.20-1.40) and chronic kidney disease (CKD) stages 3b-5 were associated with elevated mild hypocalcemia risk (OR 2.92; 95% CI 1.38-6.20). Loop diuretics use was associated with mild hypocalcemia (OR 2.61; 95% CI 1.11-6.18) by univariate analysis, independent of baseline cCa and CKD stage. A scoring approach identified two risk groups: (1) patients without CKD (eGFR ≥ 45) and cCa < 8.5 mg/dL (2.12 mmol/L) and (2) patients with CKD (eGFR < 45) and cCa < 9.5 mg/dL (2.37 mmol/L).
Hypocalcemia in sepsis: analysis of the subcellular distribution of Ca2+ in septic rats and LPS/TNF-α-treated HUVECs
Introduction: Hypocalcemia has been widely recognized in sepsis patients. However, the cause of hypocalcemia in sepsis is still not clear, and little is known about the subcellular distribution of Ca2+ in tissues during sepsis.
Methodology: We measured the dynamic change in Ca2+ levels in body fluid and subcellular compartments, including the cytosol, endoplasmic reticulum and mitochondria, in major organs of cecal ligation and puncture (CLP)-operated rats, as well as the subcellular Ca2+ flux in HUVECs which treated by endotoxin and cytokines.
Results: In the model of CLP-induced sepsis, the blood and urinary Ca2+ concentrations decreased rapidly, while the Ca2+ concentration in ascites fluid increased. The Ca2+ concentrations in the cytosol, ER, and mitochondria were elevated nearly synchronously in major organs in our sepsis model. Moreover, the calcium overload in CLP-operated rats treated with calcium supplementation was more severe than that in the non-calcium-supplemented rats but was alleviated by treatment with the calcium channel blocker verapamil. Similar subcellular Ca2+ flux was found in vitro in HUVECs and was triggered by lipopolysaccharide (LPS)/TNF-α.
Conclusions: Ca2+ influx from the blood into the intercellular space and Ca2+ release into ascites fluid may cause hypocalcemia in sepsis and that this process may be due to the synergistic effect of endotoxin and cytokines.
Associations between lying behavior and activity and hypocalcemia in grazing dairy cows during the transition period
Hypocalcemia is a common metabolic disorder of transition dairy cows that is considered a gateway disease, increasing the risk of other health disorders and reducing cow performance. Clinical milk fever is associated with long periods of recumbency, and it is plausible that cows experiencing non-paretic hypocalcemia may spend more time lying; hence, lying behavior and activity measures may be useful in identifying at-risk cows. The objective of this study was to describe associations among blood calcium (Ca) status at calving and lying behavior and activity measures during the transition period in grazing dairy cows. Blood was sampled on the day of calving (d 0), and d 1, 2, 3, and 4 postcalving, and analyzed for total plasma Ca concentration. Twenty-four multiparous Holstein-Friesian and Holstein-Friesian × Jersey grazing dairy cows were classified, retrospectively, as clinically hypocalcemic (CLIN; blood Ca ≤ 1.4 mmol/L at 1 or more consecutive samplings within 48 h postcalving, but without parturient paresis). These cows were pair-matched (using milk production potential from their estimated breeding value for milk protein, mean body weight at wk -5 and -6 precalving, and, where possible, parity) with 24 cows classified as subclinically hypocalcemic (SUB; blood Ca > 1.4 and < 2.0 mmol/L at 2 consecutive samplings within 48 h postcalving), and 24 cows classified as normocalcemic (NORM; blood Ca ≥ 2.0 mmol/L at 3 consecutive samplings within 72 h postcalving). Lying behavior and activity were monitored using triaxial accelerometers from -21 to +35 d relative to calving. Data were summarized to calculate daily lying time (h/d), daily number of lying bouts (LB; no./d), mean LB duration (min/bout), and the number of steps taken (steps/d). On d 0, the CLIN group were less active and spent approximately 2.6 h longer lying than the SUB and NORM groups, particularly between 0200 and 1400 h. On d 0, the NORM group had fewer LB (16.3/d) than the SUB and CLIN groups (18.2 and 19.2/d, respectively). These differences in behavior were no longer detected 2 d postcalving, and no further differences were observed. The day before calving, the CLIN group spent 1.4 h longer lying down than did the SUB and NORM groups. Further, the relative change in steps from a precalving baseline period (d -14 to -7) until d 0 was positively, linearly associated with blood Ca concentration within 24 h postcalving. Future work should consider daily and temporal changes in behavior in individual cows to determine the potential for these measures to allow early detection of hypocalcemia.