Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis

Abstract

Changes of bone turnover with aging are responsible for bone loss and play a major role in osteoporosis. Although an increase of bone turnover has been documented at the time of menopause, the subsequent abnormalities of bone resorption and formation and their potential role in determining bone mass in the elderly have not been investigated. To address this issue, we have measured a battery of new sensitive and specific markers of bone turnover in a population-based study of 653 healthy women analyzed cross-sectionally, including 432 women postmenopausal from 1 to 40 years, and the data were correlated with bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) at different skeletal sites. Bone formation was assessed by serum osteocalcin (OC), serum bone-specific alkaline phosphatase (B-ALP), serum C-propeptide of type I collagen (PICP), and bone resorption by the urinary excretion of two pyridinoline cross-linked peptides (NTX and CTX). Bone turnover increased in perimenopausal women with both irregular menses and elevated serum follicle stimulating hormone (FSH). Menopause induced a 37-52% and 79-97% increase in the bone formation and bone resorption marker levels, respectively (p < 0.0001 except for PICP). In postmenopausal women, bone formation markers did not decrease with age. When resorption markers were corrected by whole body bone mineral content (BMC), the fraction of bone resorbed per day was not correlated with age in postmenopausal women and remained elevated for up to 40 years after menopause. In premenopausal women, the bone turnover rate accounted for only 0-10% of the variation in whole body BMC, total hip, distal radius, and lumbar spine BMD. With increasing time after menopause, the importance of the bone turnover rate as a determinant of bone mass increased at all sites and accounted for up to 52% of the BMD variance in elderly women. Thus, in women 20 years or more postmenopause, bone turnover was higher in those in the lowest quartile than in those in the highest quartile of BMD. In elderly women, 20 years since menopause and over, but not in younger ones, serum PTH was negatively correlated with serum 25-hydroxyvitamin D (r = -0.22, p < 0.05) and explained only 5-8% of the bone turnover variance (p < 0.01-0.001). These data indicate that the overall rates of both bone formation and bone resorption remain high in elderly women. The rate of bone turnover appears to play an increasing role as a determinant of bone mass with increasing time since menopause with a high bone turnover rate being associated with a low bone mass. Thus assessing bone marker levels may be useful in the evaluation of osteoporosis risk. In elderly women, secondary hyperparathyroidism caused in part by reduced serum 25-hydroxyvitamin D appears to be a marginal determinant of an increased bone turnover rate.

Improvement of Bone-Sparing Effect of Soy Isoflavones by Pre- and Probiotics in Postmenopausal women

“…On another hand, in late postmenopausal women, resorption was more important than that observed in early postmenopausal women. These data are in accordance with these obtained by Garnero et al (1996) in elderly women, a high bone turnover rate was being associated with a low bone mass. Moreover, Cheong et al (2007) showed that soy protein containing up to 135.5 mg isofl avones/day for 50 days, did not suppress bone resorption in late postmenopausal women (Ͼ6 years since menopause).…”

The FRAX tool in French women: How well does it describe the real incidence of fracture in the OFELY cohort

“…The OFELY cohort has been described elsewhere. (16,17) Briefly, OFELY is an ongoing prospective study of the determinants of bone loss in 1039 volunteer women, recruited between February 1992 and December 1993, 31 to 89 years of age, randomly selected from the affiliates of a large health insurance company (Mutuelle Gé né rale de l'Education Nationale) from the Rhô ne District (ie, Lyon and its surroundings in France), with an annual follow-up. Written informed consent was obtained from each woman, and the study was approved by the local ethics committee.…”

Iron and Menopause: Does Increased Iron Affect the Health of Postmenopausal Women?

“…Moreover, overall bone turnover is significantly increased in peri-and postmenopausal women but in an imbalanced fashion. Bone resorption increases, at 90%, and bone formation increases at only 45%, resulting in a net loss of bone mineral density (11). The exact mechanism through which bone formation after menopause cannot keep up with bone resorption remains unknown.…”