The University of Southampton
University of Southampton Institutional Repository

Genetic influence on bone turnover in postmenopausal twins

Genetic influence on bone turnover in postmenopausal twins
Genetic influence on bone turnover in postmenopausal twins

Postmenopausal bone mass is determined by both peak bone mass and subsequent bone loss. Previous studies have shown that peak bone mass is under genetic influence mediated partly by factors affecting bone formation. The rate of bone loss increases markedly after the menopause, but is highly variable from subject to subject. The aims of this study were to determine whether postmenopausal bone turnover was under genetic control, which should be linked to the genetic influence on the rate of postmenopausal bone loss. A classical twin study was performed that compared the intraclass correlations in monozygotic (MZ) twins with those in dizygotic (DZ) twins, with any difference assumed to be due to genetic factors. Markers of bone formation and resorption were measured in 240 untreated postmenopausal twins, aged 45-69 yr, on the average 12.3 yr (SD, 6.0) postmenopause, including 61 MZ pairs and 59 DZ pairs. The intraclass correlation coefficient of MZ twin pairs, rMZ (95% confidence interval), for 2 specific markers of bone formation, serum osteocalcin and bone-specific alkaline phosphatase, were higher than the corresponding rDZ [0.67 (range, 0.59-0.75) vs. 0.48 (range, 0.35-0.61; P = 0.06) for osteocalcin and 0.53 (range, 0.41-0.65) vs. 0.21 (range, 0.01-0.41; P = 0.02) for bone-specific alkaline phosphatase]. For serum propeptide of type I collagen, a type I collagen synthesis marker that exhibits only a slight increase after menopause, a high proportion of its variance was explained by genetic factors [rMZ = 0.82 (0.77-0.87), rDZ = 0.33 (0.16-0.50); P < 0.001]. The correlations for bone resorption measured by three distinct urinary markers, total deoxypyridinoline and two cross-linked type I collagen peptides (CrossLaps and NTX), that increase markedly after menopause were higher in MZ than in DZ pairs, but the difference reached significance only for NTX (P = 0.03). For urinary free dexoypyridinoline, a marker reflecting bone collagen degradation that increases moderately after menopause, the proportion of the variance explained by genetic factors was highly significant (P = 0.002). In conclusion, our data indicate that a proportion of the variance in postmenopausal levels of both bone formation and resorption markers are explained by genetic factors, but this contribution was clearly significant only for markers that do not change markedly at the menopause. These data suggest that the contribution of genetic factors to overall postmenopausal bone turnover and possibly bone loss is likely to be small.

Aged, Bone Development, Bone Resorption, Female, Humans, Middle Aged, Osteoporosis, Postmenopausal, Postmenopause, Twins, Journal Article, Research Support, Non-U.S. Gov't
0021-972X
140-146
Garnero, P
d7dae9ce-5510-4b3b-a820-97e2f8fcb2c0
Arden, N K
23af958d-835c-4d79-be54-4bbe4c68077f
Griffiths, G
7fd300c0-d279-4ff6-842d-aa1f2b9b864d
Delmas, P D
788d83fc-6eb8-41ac-a72b-d0c7c304db1f
Spector, T D
29debf10-949d-4094-8f5f-9a8614511ccb
Garnero, P
d7dae9ce-5510-4b3b-a820-97e2f8fcb2c0
Arden, N K
23af958d-835c-4d79-be54-4bbe4c68077f
Griffiths, G
7fd300c0-d279-4ff6-842d-aa1f2b9b864d
Delmas, P D
788d83fc-6eb8-41ac-a72b-d0c7c304db1f
Spector, T D
29debf10-949d-4094-8f5f-9a8614511ccb

Garnero, P, Arden, N K, Griffiths, G, Delmas, P D and Spector, T D (1996) Genetic influence on bone turnover in postmenopausal twins. Journal of Clinical Endocrinology & Metabolism, 81 (1), 140-146. (doi:10.1210/jcem.81.1.8550741).

Record type: Article

Abstract

Postmenopausal bone mass is determined by both peak bone mass and subsequent bone loss. Previous studies have shown that peak bone mass is under genetic influence mediated partly by factors affecting bone formation. The rate of bone loss increases markedly after the menopause, but is highly variable from subject to subject. The aims of this study were to determine whether postmenopausal bone turnover was under genetic control, which should be linked to the genetic influence on the rate of postmenopausal bone loss. A classical twin study was performed that compared the intraclass correlations in monozygotic (MZ) twins with those in dizygotic (DZ) twins, with any difference assumed to be due to genetic factors. Markers of bone formation and resorption were measured in 240 untreated postmenopausal twins, aged 45-69 yr, on the average 12.3 yr (SD, 6.0) postmenopause, including 61 MZ pairs and 59 DZ pairs. The intraclass correlation coefficient of MZ twin pairs, rMZ (95% confidence interval), for 2 specific markers of bone formation, serum osteocalcin and bone-specific alkaline phosphatase, were higher than the corresponding rDZ [0.67 (range, 0.59-0.75) vs. 0.48 (range, 0.35-0.61; P = 0.06) for osteocalcin and 0.53 (range, 0.41-0.65) vs. 0.21 (range, 0.01-0.41; P = 0.02) for bone-specific alkaline phosphatase]. For serum propeptide of type I collagen, a type I collagen synthesis marker that exhibits only a slight increase after menopause, a high proportion of its variance was explained by genetic factors [rMZ = 0.82 (0.77-0.87), rDZ = 0.33 (0.16-0.50); P < 0.001]. The correlations for bone resorption measured by three distinct urinary markers, total deoxypyridinoline and two cross-linked type I collagen peptides (CrossLaps and NTX), that increase markedly after menopause were higher in MZ than in DZ pairs, but the difference reached significance only for NTX (P = 0.03). For urinary free dexoypyridinoline, a marker reflecting bone collagen degradation that increases moderately after menopause, the proportion of the variance explained by genetic factors was highly significant (P = 0.002). In conclusion, our data indicate that a proportion of the variance in postmenopausal levels of both bone formation and resorption markers are explained by genetic factors, but this contribution was clearly significant only for markers that do not change markedly at the menopause. These data suggest that the contribution of genetic factors to overall postmenopausal bone turnover and possibly bone loss is likely to be small.

Full text not available from this repository.

More information

Published date: January 1996
Keywords: Aged, Bone Development, Bone Resorption, Female, Humans, Middle Aged, Osteoporosis, Postmenopausal, Postmenopause, Twins, Journal Article, Research Support, Non-U.S. Gov't
Organisations: Human Development & Health, Clinical Trials Unit

Identifiers

Local EPrints ID: 406323
URI: https://eprints.soton.ac.uk/id/eprint/406323
ISSN: 0021-972X
PURE UUID: 9fbea04d-5fc7-4f06-9868-89146b307613
ORCID for G Griffiths: ORCID iD orcid.org/0000-0002-9579-8021

Catalogue record

Date deposited: 10 Mar 2017 10:44
Last modified: 12 Nov 2019 01:36

Export record

Altmetrics

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×