The objective of this study was to determine the effect of oral contraceptive pills on bone turnover. The design consisted of a cross-sectional analysis of a prospective cohort. There were 52 women taking oral contraceptives and 156 nonuser controls from a large cohort of 1039 healthy women, aged 31-89 years (OFELY study). Most users were taking combined oral contraceptives containing 30 micrograms ethinyl estradiol and the mean duration of pill use was 6.7 +/- 6.4 years. Users and nonusers were matched for age [mean age (years): 39.3 +/- 3.5 vs. 40.5 +/- 4.3, range 35-49 years for both]. Main outcome measures included three markers of bone formation (serum osteocalcin, bone-specific alkaline phosphatase, and C-terminal propeptide of type I collagen) and two markers of bone resorption that are pyridinoline crosslinked peptides (Crosslaps and NTX). Users and nonusers did not differ for weight, height, alcohol and tobacco use, dietary calcium intake, parity, exercise activity, body fat and lean composition, and calcium chemistry tests. In pill users all bone formation and resorption markers were decreased compared with controls: osteocalcin, 7.7 +/- 2.7 vs. 10.1 +/- 3.1 ng/mL (-24%, p < 0.001); bone-specific alkaline phosphatase, 7.5 +/- 2.3 vs. 8.8 +/- 2.7 ng/mL (-15%, p < 0.003); C-terminal propeptide of type I collagen, 77.2 +/- 93.1 vs. 93.1 +/- 31.9 ng/mL (-17%, p = 0.001); Crosslaps: 175 +/- 91 vs. 211 +/- 105 micrograms/mmol Cr (-17%, p = 0.03); and NTX, 16.2 +/- 5.9 vs. 22.5 +/- 9.4 nmol of bone collagen equivalent/mmol Cr (-28%, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)