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      Secretion of Parathyroid Hormone Oscillates Depending on the Change in Serum Ionized Calcium during Hemodialysis and May Affect Bone Metabolism

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          Background: The current study was undertaken to clarify the dynamic response of parathyroid hormone (PTH) during hemodialysis and to determine whether or not such dynamic change of PTH affects bone turnover. Methods: Serum ionized calcium (iCa) and intact PTH (iPTH) were measured in 66 dialysis patients before (basal) and after each hemodialysis. The changes of iCa (ΔiCa) and iPTH (ΔiPTH) were defined as [postdialysis iCa – basal iCa] m M, and [(postdialysis iPTH – basal iPTH)/basal iPTH] × 100%, respectively. We also investigated the data of the patients divided into four groups based on their basal iPTH levels; group 1 (iPTH <60 pg/ml, n = 17), 2 (≧60 to <150, n = 20), 3 (≧150 to <300, n = 15), and 4 (≧300, n = 14). Results: While iCa and iPTH changed variably during each hemodialysis procedure, there was a highly significant inverse correlation between ΔiCa and ΔiPTH (r = –0.761, p < 0.0001). Regression coefficients between ΔiPTH and ΔiCa were –519.1, –311.2, –268.1, and –194.6%/m M in groups 1–4, respectively. The difference in the regression coefficient was statistically significant between group 1 and 2 (F = 3.69, p < 0.05, ANCOVA), group 1 and 3 (F = 5.599, p < 0.05), and group 1 and 4 (F = 10.853, p < 0.005). This suggested that patients with higher basal iPTH responded poorly to modulate serum PTH levels by sensing the change of iCa. However, after an intensified oral calcitriol therapy to reduce iPTH, the PTH response in group 4 patients was restored to levels comparable with those observed in patients having lower basal iPTH. We also demonstrate that the ΔiPTH of patients of group 1 but not of other groups was significantly correlated with serum markers for bone metabolism; osteocalcin (r = 0.535, p < 0.05) and collagen type I C-terminal telopeptide (r = –0.575, p < 0.05). Conclusions: Our findings suggest that secretion of PTH is dynamically regulated by ΔiCa during hemodialysis and such oscillated PTH secretion may affect bone metabolism in a subset of dialysis patients.

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          Most cited references 15

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          Parathyroid hormone stimulates the bone apposition rate independently of its resorptive action: differential effects of intermittent and continuous administration.

          The deposition of mineralized bone matrix by differentiated osteoblasts was studied in rats in vivo by labeling the bone with three doses of tetracycline given at 48-h intervals. Only bone formation loci bearing all three tetracycline doses were measured, thus eliminating sites where bone formation was not continuous during the labeling period. Using this technique, the effects of intact bovine parathyroid hormone [bPTH-(1-84)] and of a synthetic amino-terminal fragment of human PTH [hPTH-(1-34)] were measured in thyroparathyroidectomized animals. bPTH-(1-84), administered sc, and hPTH-(1-34), administered iv, caused a dose-dependent increase in the bone apposition. Subcutaneous administration of hPTH-(1-34) in doses varying from 2.7-173.0 pmol/rat.day had no effect, probably due to the degradation of the hormone when administered this way. We also compared the effects of bPTH-(1-84) when administered by either daily sc injections or continuous infusion. Continuous infusion of bPTH-(1-84) resulted in an increased apposition rate. Using a morphometric technique, we also found an increase in both formation and resorption surfaces and a net decrease in the trabecular bone volume in this group. Daily injection of the hormone caused an increase in the bone apposition rate, accompanied by an increase in the formation surface without an increase in the resorption surface. This resulted in a net increase in trabecular bone volume. The results thus suggest that the resorptive effects of bPTH-(1-84) can be separated from the effects of the hormone on the apposition rate.
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            Anabolic and catabolic bone effects of human parathyroid hormone (1-34) are predicted by duration of hormone exposure.

            Parathyroid hormone (PTH)(1-34), given once daily, increases bone mass in a variety of animal models and humans with osteoporosis. However, continuous PTH infusion has been shown to cause bone loss. To determine the pharmacokinetic profile of PTH(1-34) associated with anabolic and catabolic bone responses, PTH(1-34) pharmacokinetic and serum biochemical profiles were evaluated in young male rats using dosing regimens that resulted in either gain or loss of bone mass. Once-daily PTH(1-34) or 6 PTH(1-34) injections within 1 h, for a total daily dose of 80 microg/kg, induced equivalent increases in proximal tibia bone mass. In contrast, 6 PTH(1-34) injections/day over 6 h for a total dose of 80 microg/kg/day or 3 injections/day over 8 h for a total of 240 microg/kg/day decreased tibia bone mass. The PTH(1-34) pharmacokinetics of the different treatment regimens were distinctive. The magnitude of the maximum serum concentrations (Cmax) of PTH(1-34) and area under the curve (AUC) did not predict the catabolic bone outcome. Compared to the anabolic pharmacokinetic profile of a transient increase in PTH(1-34) with rapid decreases in serum calcium and phosphate, the catabolic regimen was associated with PTH(1-34) concentrations remaining above baseline values during the entire 6-h dosing period with a trend toward an increase in serum calcium and a prolonged decrease in phosphate. The pharmacokinetic profiles suggest that the anabolic or catabolic response of bone to PTH(1-34) is determined primarily by the length of time each day that serum concentrations of PTH(1-34) remain above baseline levels of endogenous PTH and only secondarily by the Cmax or AUC of PTH(1-34) achieved.
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              Diurnal variation of bone mineral turnover in elderly men and women.

              The diurnal variation of markers of bone mineral metabolism have been documented in pre- and early postmenopausal women. Such rhythms have clinical implications for timing of sample collection and assessment of therapeutic intervention. To examine the diurnal variation of bone turnover in the elderly, we examined markers of bone formation [serum osteocalcin (OC) and bone-specific alkaline phosphatase (B-ALP)]; a marker of bone resorption (urinary N-telopeptide cross-linked collagen type 1 [NTX]); and serum calcium and parathyroid hormone (PTH) over 24 hours. Subjects were healthy community-dwelling elderly who were on no medications known to significantly alter bone mineral metabolism. Subjects included 14 women [74 +/- 6 years (mean +/- SD)] and 14 men (80 +/- 5 years). Over the 24-hour sampling period, mean serum OC, B-ALP, and calcium values were similar in elderly men and women. However, mean serum PTH was significantly higher in elderly men compared with women (P < 0.05). The magnitude of the diurnal variation of urinary NTX was significantly higher in women compared with men (P < 0.05). There was a significant diurnal variation for serum OC, B-ALP, calcium, PTH, and urinary NTX in both elderly men and women. The magnitude of the diurnal variation was approximately 10-20% of mean value for OC and B-ALP, 30% for PTH, and up to 40% for urinary NTX. We conclude that there is significant diurnal variation in the markers of bone mineral metabolism for elderly men and women. The peak value, which on average would be 20% higher than the mean value for urinary NTX, highlights the importance of the timing of sample collection for appropriate interpretation of therapeutic response. In addition, gender-related differences, including relatively higher levels of serum PTH and lower levels of urinary NTX in elderly men, may help explain differences in rates of bone loss in this age group.

                Author and article information

                Nephron Clin Pract
                Nephron Clinical Practice
                S. Karger AG
                September 2005
                11 May 2005
                : 101
                : 1
                : c9-c17
                Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi, Japan
                85706 Nephron Clin Pract 2005;101:c9–c17
                © 2005 S. Karger AG, Basel

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                Page count
                Figures: 5, Tables: 2, References: 23, Pages: 1
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/85706
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