In this large population-based study in young men, we show that the COMT val158met polymorphism modulates the association between physical activity, aBMD (DXA), and trabecular vBMD (pQCT).

Introduction: Peak BMD is an important predictor of future risk of osteoporosis and is largely determined by genetic factors but also by environmental factors, among which physical activity (PA) is a strong contributor. Estrogens are believed to influence the mechanical strain signal generated by bones subjected to mechanical loading. Catechol-O-methyltransferase (COMT) is involved in the degradation of estrogens. A functional polymorphism in the COMT gene (val158met), results in a 60–75% difference in enzyme activity between the val (high activity = H) and met (low activity = L) variants. The aim of this study was to determine if the COMT val158met polymorphism modulates the association between PA and BMD in young men.

Materials and Methods: The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study consists of 1068 men (age, 18.9 ± 0.6 yr). Areal BMD (aBMD) was measured by DXA, whereas cortical and trabecular volumetric BMD (vBMD) were measured by pQCT. Study subjects were genotyped and classified as COMT^LL, COMT^HL, or COMT^HH. The amount (h/wk) of PA was determined through questionnaires.

Results: Using a linear regression model (including age, height, weight, smoking, and calcium intake as covariates), significant interactions between the COMT genotype and PA were seen for aBMD at all sites and for trabecular vBMD in both the radius and the tibia. The difference in adjusted aBMD and trabecular vBMD between high (≥4 h/wk) and low PA (<4 h/wk) was greater in COMT^LL subjects than in subjects homozygous for the COMT^HH (total body aBMD: COMT^LL 4.2% versus COMT^HH 1.5%, p = 0.02; lumbar spine aBMD: COMT^LL 7.8% versus COMT^HH 3.9%, p = 0.04; tibia trabecular vBMD: COMT^LL 7.1% versus COMT^HH 1.0%, p < 0.01). The COMT polymorphism was associated with aBMD, at all sites and with trabecular vBMD in the low-PA subjects, but not in their high-PA counterparts.

Conclusions: We show that the COMT val158met polymorphism modulates the association between PA, aBMD, and trabecular vBMD, suggesting that this polymorphism is of importance for BMD in subjects with a low level of PA.