Genetic effects on bone loss in peri- and postmenopausal women: a longitudinal twin study.
This longitudinal twin study was designed to assess the heritability of bone loss in peri- and postmenopausal women. A sample of 724 female twins was studied. Baseline and repeat BMD measurements were performed. Results of genetic model-fitting analysis indicated genetic effects on bone loss account for approximately 40% of the between-individual variation in bone loss at the lumbar spine, forearm, and whole body.


BACKGROUND
BMD and bone loss are important predictors of fracture risk. Although the heritability of peak BMD is well documented, it is not clear whether bone loss is also under genetic regulation. This study was designed to assess the heritability of bone loss in peri- and postmenopausal women.


METHODS
A sample of 724 female twins (177 monozygotic [MZ] and 185 dizygotic [DZ] pairs), 45-82 yr of age, was studied. Each individual had baseline BMD measurements at the lumbar spine, hip, forearm, and total body by DXA and at least one repeat measure, on average 4.9 yr later. Change in BMD (DeltaBMD) was expressed as percent of gain or loss per year. Intraclass correlation coefficients for DeltaBMD were calculated for MZ and DZ pairs. Genetic model-fitting analysis was conducted to partition the total variance of DeltaBMD into three components: genetic (G), common environment (C), and specific environment, including measurement error (E). The index of heritability was estimated as the ratio of genetic variance over total variance.


RESULTS
The mean annual DeltaBMD was -0.37 +/- 1.43% (SD) per year at the lumbar spine, -0.27 +/- 1.32% at the total hip, -0.77 +/- 1.66% at the total forearm, -0.36 +/- 1.56% at the femoral neck, and -0.16 +/- 0.81% at the whole body. Intraclass correlation coefficients were significantly higher in MZ than in DZ twins for all studied parameters, except at the hip sites. Results of genetic model-fitting analysis indicated that the indices of heritability for DeltaBMD were 0.38, 0.49, and 0.44 for the lumbar spine, total forearm, and whole body, respectively. However, the genetic effect on DeltaBMD at all hip sites was not significant.


CONCLUSIONS
These data suggest that, although genetic effects on bone loss with aging are less pronounced than on peak bone mass, they still account for approximately 40% of the between-individual variation in bone loss for the lumbar spine, total forearm, and whole body in peri- and postmenopausal women. These findings are relevant for studies aimed at identification of genes that are involved in the regulation of bone loss.
Makovey
Joanna
J
Institute of Bone and Joint Research, Royal North Shore Hospital, University of Sydney, Sydney, Australia. jmakovey@med.usyd.edu.au
Nguyen
Tuan V
TV
Naganathan
Vasi
V
Wark
John D
JD
Sambrook
Philip N
PN
D015519:Bone Density / Q000235:genetics*; D001842:Bone and Bones / Q000000981:diagnostic imaging; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000235:genetics*; D047648:Perimenopause; D017698:Postmenopause; D011859:Radiography