title: Morning or evening administration of nasal calcitonin? Effects on biochemical markers of bone turnover.
abstract: The purpose of this study was to examine the effect of intranasal salmon calcitonin (sCT) administration (200 IE), given either in the morning (8:00) or evening (21:00), on the known circadian variation in biochemical markers of bone turnover. An open, placebo-controlled, randomized, crossover study, with three 24 h studies of blood samples drawn every third hour and urine collected in 3 h aliquots was undertaken. Subjects consisted of nine healthy postmenopausal women, aged 58 +/- 7 years. Urinary CrossLaps (a measure of bone resorption) was measured by ELISA and corrected for creatinine (Cr). Serum osteocalcin (sOC) was measured by radioimmunoassay (RIA). The first 24 h study was performed without intervention. Prior to this control study the participants were randomized to either morning (8:00) or evening (21:00) sCT (200 IE). sCT administrations were given 4-5 days prior to and during the second study. After a washing-out period of 2 weeks the participants were given 200 IE of sCT at the reverse time of the day 5 days prior to and during the third study. At all timepoints, urinary CrossLaps/Cr exhibited a significant (p < 0.001) circadian rhythm with its zenith in early morning and nadir in late afternoon. Both morning and evening administration of sCT significantly decreased the urinary excretion of CrossLaps/Cr approximately 3-6 h after administration with a subsequent rebound effect. sOC did not exhibit a significant circadian variation and was not affected by the calcitonin. The 24 h mean urinary CrossLaps/Cr and sOC remained unchanged. Both morning and evening sCT significantly decreased the urinary excretion of CrossLaps/Cr 3-6 h after administration, with a rebound effect approximately 12 h later. However, the present study does not indicate that neither evening nor twice-daily administration is superior to morning administration.
authors.affiliation: Center for Clinical & Basic Research, Ballerup Byvej, Ballerup, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Schlemmer
authors.forename: P
authors.initials: P
authors.lastname: Ravn
authors.forename: C
authors.initials: C
authors.lastname: Hassager
authors.forename: C
authors.initials: C
authors.lastname: Christiansen
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D000368:Aged; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood* / Q000652:urine; D002116:Calcitonin / Q000008:administration & dosage / Q000494:pharmacology*; D002940:Circadian Rhythm / Q000187:drug effects; D018592:Cross-Over Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D011863:Radioimmunoassay
chemical_list: D000700:Analgesics; D015415:Biomarkers; D015675:Osteocalcin; C028815:salmon calcitonin; D002116:Calcitonin