Perimenopausal Bone Loss Is Associated with Ovulatory Activity—Results of the PeKnO Study (Perimenopausal Bone Density and Ovulation)

Abstract

Background: During the menopausal transition, around 25% of women experience a particularly accelerated loss of bone mineral density. These so-called “fast bone losers” represent a group of patients with an increased risk of osteoporosis. The precise mechanisms underlying this extraordinary level of bone mass reduction have not yet been conclusively elucidated. The PeKnO study (Perimenopausale Knochendichte und Ovulation; Perimenopausal Bone Density and Ovulation) was a 2-year prospective study investigating menstrual cycle changes, hormonal levels, markers of bone metabolism, and changes in bone mineral density (BMD) in perimenopausal women. The PeKnO study specifically focused on the questions of when the maximum of bone loss occurs, whether the decreasing number of ovulatory cycles correlates with increased bone density loss, and which hormones play a role during these processes. Methods: Healthy women aged ≥45 years with menstrual cycles of ≤42 days and without any exogenous hormonal intake continually self-assessed the lengths of their menstrual cycles and the occurrence of LH peaks with the help of a commercially available electronic fertility monitoring device. At baseline and at 6, 12, 18, and 24 months, hormones (LH, FSH, 17β-estradiol, progesterone, cortisol) and markers of bone metabolism (bone-specific alkaline phosphatase (BAP), osteocalcin (OC), and CTX (C-terminal telopeptide) were assessed during the luteal phase. Trabecular bone density was measured in the lumbar spine (vertebrae L1 through L3) by means of quantitative computed tomography (QCT) at the beginning and at the end of the 2-year study period. Patients were divided into 3 groups according to the changes in bone mineral density (BMD) that occurred within the period of 2 years: group I with an increase in BMD, group II with a decrease in BMD of ≤7%, and group III with a decline in BMD of >7%. Women in the latter group were defined as fast bone losers. Results: From a total of 72 recruited patients with an average age of 48.1 (±2.4) at baseline, complete 2-year data were available from 49 participants. Over the course of 24 months, mean bone mineral density decreased by −4.26 (±4.65). In the same time period, the proportion of ovulatory cycles declined from 67% to 33%. The decrease in the ovulatory rate significantly correlated with an enhanced BMD loss (r = 0.68; p < 0.05). Twelve of the forty-nine participants (24.3%) showed a BMD loss of >7% and were identified as fast bone losers. Levels of the luteal phase hormones LH, FSH, 17β-estradiol, and progesterone were significantly different between the three groups. Conclusion: The PeKnO study confirms a marked decline of the ovulatory rate during perimenopause, which is associated with an increased bone density loss while estrogen levels are still adequate.