Circadian rhythmicity is an essential feature of bone metabolism. The assessment of diurnal variation in bone resorption and formation markers in cancer patients with bone metastases could provide further insights on tumor induced derangement in bone turnover. Twenty-one ambulatory breast cancer patients with bone metastases and 20 agematched control subjects entered the study. Breast cancer patients were assessed at baseline conditions before starting any antineoplastic treatment of metastatic disease. After fasting from 10.00 pm the evening before experimentation, blood specimens in both patients and controls were collected at 8.00 am, 12.00 am, 4.00 pm, 8.00 pm, 12.00 pm, 2.00 am, 4.00 am, 6.00 am and 8.00 am to determine alkaline phosphatase (ALP), calcium (Ca), albumin, and cortisol. Urine samples were collected at 8.00 am, 12.00 am, 4.00 pm, 8.00 pm, 12.00 pm, 4.00 am and 8.00 am to determine the excretion of deoxypyridinolines (DPD) and N-telopeptide (NTX). Serum cortisol showed a marked circadian rhythm either in control subjects: MESOR 116 ng/dl, amplitude 60.9 ng/dl, acrophase at 6.00 am (P < 0.001) or in cancer patients: MESOR 103.1 ng/dl, amplitude 54.8 ng/dl, acrophase at 11.00 am (P < 0.001). Also albumin showed a rhythm in both subsets: MESOR 4.1 g/l, amplitude 0.21 g/l, Acrophase at 5.50 pm (P = 0.04) and MESOR 3.8 g/l, amplitude 0.40 g/l, acrophase at 4.50 pm (P < 0.001), respectively. Neither serum ALP nor serum calcium showed a significant circadian rhythm. Urinary DPD showed a significant circadian rhythm either in patients: MESOR 6.6 mmol, amplitude 0.96 mmol, acrophase at 8.30 am (P = 0.002) or in controls: MESOR 9.0 mmol, amplitude 1.36 mmol, acrophase at 9.50 am (P = 0.01); whereas urinary NTX showed a diurnal rhythm in control subjects MESOR 37.4 nmol BCE/mmol, amplitude 12 nmol BCE/mmol, acrophase at 7.45 am (P < 0.0001), but only a trend (not significant) was observed in cancer patients. These data indicate that bone resorption markers maintain a circadian rhythmicity in cancer patients. The determination of DPD and NTX in urine collected over a 4 h time span could account for the low amplitude observed. Data on serum cross laps will be provided at the meeting.
CIRCADIAN RHYTHM OF BONE TURNOVER MARKERS INBREAST CANCER PATIENTS WITH METASTATIC BONE DISEASE ANDIN CONTROL SUBJECTS
BERRUTI, Alfredo;TAMPELLINI, MARCO;ANGELI, Alberto;DOGLIOTTI, Luigi
2004-01-01
Abstract
Circadian rhythmicity is an essential feature of bone metabolism. The assessment of diurnal variation in bone resorption and formation markers in cancer patients with bone metastases could provide further insights on tumor induced derangement in bone turnover. Twenty-one ambulatory breast cancer patients with bone metastases and 20 agematched control subjects entered the study. Breast cancer patients were assessed at baseline conditions before starting any antineoplastic treatment of metastatic disease. After fasting from 10.00 pm the evening before experimentation, blood specimens in both patients and controls were collected at 8.00 am, 12.00 am, 4.00 pm, 8.00 pm, 12.00 pm, 2.00 am, 4.00 am, 6.00 am and 8.00 am to determine alkaline phosphatase (ALP), calcium (Ca), albumin, and cortisol. Urine samples were collected at 8.00 am, 12.00 am, 4.00 pm, 8.00 pm, 12.00 pm, 4.00 am and 8.00 am to determine the excretion of deoxypyridinolines (DPD) and N-telopeptide (NTX). Serum cortisol showed a marked circadian rhythm either in control subjects: MESOR 116 ng/dl, amplitude 60.9 ng/dl, acrophase at 6.00 am (P < 0.001) or in cancer patients: MESOR 103.1 ng/dl, amplitude 54.8 ng/dl, acrophase at 11.00 am (P < 0.001). Also albumin showed a rhythm in both subsets: MESOR 4.1 g/l, amplitude 0.21 g/l, Acrophase at 5.50 pm (P = 0.04) and MESOR 3.8 g/l, amplitude 0.40 g/l, acrophase at 4.50 pm (P < 0.001), respectively. Neither serum ALP nor serum calcium showed a significant circadian rhythm. Urinary DPD showed a significant circadian rhythm either in patients: MESOR 6.6 mmol, amplitude 0.96 mmol, acrophase at 8.30 am (P = 0.002) or in controls: MESOR 9.0 mmol, amplitude 1.36 mmol, acrophase at 9.50 am (P = 0.01); whereas urinary NTX showed a diurnal rhythm in control subjects MESOR 37.4 nmol BCE/mmol, amplitude 12 nmol BCE/mmol, acrophase at 7.45 am (P < 0.0001), but only a trend (not significant) was observed in cancer patients. These data indicate that bone resorption markers maintain a circadian rhythmicity in cancer patients. The determination of DPD and NTX in urine collected over a 4 h time span could account for the low amplitude observed. Data on serum cross laps will be provided at the meeting.
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