Clinical Endocrinology (2015) 83, 173–179
doi: 10.1111/cen.12755
ORIGINAL ARTICLE
The association between serum dehydroepiandrosterone Sulphate (DHEA-S) level and bone mineral density in Korean men Dain Lee*,1, Hyeonmok Kim*,1, Seong Hee Ahn*, Seung Hun Lee*, Sung Jin Bae†, Eun Hee Kim†, Hong-Kyu Kim†, Jae Won Choe†, Beom-Jun Kim* and Jung-Min Koh* *Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, and †Health Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Summary Context Many lines of evidence indicate that dehydroepiandrosterone (DHEA) plays a distinct role in bone metabolism and that its sulphated form (DHEA-S), which is easily measured in blood, may be a potential biomarker of osteoporosis-related phenotypes. However, most previous epidemiologic studies focused on postmenopausal women and reported conflicting results. Objective We aimed to investigate the association between the serum DHEA-S level and bone mass in men. Design and Methods This large cross-sectional study included 1089 healthy Korean men who participated in a routine health screening examination. Bone mineral density (BMD) at the lumbar spine, total femur, femur neck, and trochanter and serum DHEA-S level were obtained in all subjects. Results After adjustment for age, body mass index, lifestyle factors and serum levels of calcium, phosphorus, testosterone, 25-OH-vitamin D3 and cortisol, higher serum DHEA-S concentrations were associated with higher BMD values at all skeletal sites. Consistently, compared to the subjects in the highest DHEA-S quartile (Q4), those in the lowest DHEA-S quartile (Q1) showed significantly lower BMD values. Multiple logistic regression analyses revealed that the odds ratios for the risk of lower BMD (T-score < 1) increased in a dose-dependent manner across decreasing DHEA-S quartiles and the odds for the risk of lower BMD were 259-fold higher in Q1 than in Q4. Conclusion These findings support previous evidences that DHEA-S has favourable effects on bone mass in men and suggest that a low serum DHEA-S level may be a potential risk factor for male osteoporosis. (Received 25 November 2014; returned for revision 19 December 2014; finally revised 25 January 2015; accepted 13 February 2015) Correspondence: Beom-Jun Kim, Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap2-Dong, Songpa-Gu, Seoul 138-736, Korea. Tel.: +82-2-3010-5876; Fax: +82-2-3010-6962; E-mail: [email protected] 1
These authors contributed equally to this work.
© 2015 John Wiley & Sons Ltd
Introduction Osteoporosis is a skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue, leading to an increase in bone fragility and susceptibility to fracture. Although osteoporosis has long been considered a disease of postmenopausal women, male osteoporosis and related fractures are becoming recognized as important public health concerns. More than one in four men over the age of 50 will sustain an osteoporotic fracture during their remaining lifetime,1 and 20–35% of all femoral fractures and 33–50% of all vertebral fractures occur in men.2,3 Moreover, men suffering any major osteoporotic fracture have a markedly higher mortality rate than women.4,5 With increasing life expectancies in men, male osteoporosis will likely further become a significant burden on society and healthcare systems in the future.6 Therefore, more effort to elucidate the risk factors and the underlying pathogenic mechanism of osteoporosis in men is needed to effectively prevent this condition. Dehydroepiandrosterone (DHEA) is the most abundant circulating C19 steroid in humans, derived primarily from the adrenal glands,7 and exists predominantly in a sulphated form (DHEAS). Peak serum levels of DHEA and DHEA-S are achieved in early adulthood and decline steadily thereafter,7 suggesting that these factors may be implicated in a variety of age-related pathologic conditions including osteoporosis. Indeed, many lines of evidence indicate that DHEA plays a distinct role in bone metabolism. Although the effect of DHEA on bone is traditionally thought to be primarily mediated through conversion to sex hormone,8 in vitro studies showed that DHEA can directly affect bone formation and bone resorption.9–11 Furthermore, intervention studies have reported positive effects of DHEA administration on bone mass in humans.12,13 These findings suggest that serum DHEA-S, which is easily measured in blood, may be a potential biomarker to predict osteoporosis-related phenotypes. However, most previous epidemiologic studies relating serum DHEA-S level to bone health were mainly focused on postmenopausal women and showed conflicting results.14–16 Therefore, we 173
174 D. Lee et al. performed a large cross-sectional study in healthy Korean men to clarify whether low serum DHEA-S level is a risk factor for male osteoporosis.
Methods Study participants The study population consisted of 1300 consecutive Korean men who had undergone comprehensive health examinations at the health promotion centre of the Asan Medical Center (AMC, Seoul, Korea) between January 2010 and December 2011 and in whom bone mineral density (BMD) and serum DHEA-S concentrations were measured. Visitors to our centre are usually healthy and receive extensive screening tests for early detection of malignancy, diabetes, osteoporosis and other age-related diseases. Among them, subjects with serum liver enzyme (aspartate aminotransferase and alanine aminotransferase) activities twofold above the upper normal limits, increased serum creatinine levels [>14 mg/dl (>1238 lmol/l)], abnormal thyroid function (serum thyrotropin 50 mU/l) or elevated rheumatic factor levels (>20 IU/ml) were excluded from this study. In addition, subjects were excluded if they suffered from any diseases that might affect bone metabolism, such as asthma/chronic obstructive pulmonary disease (COPD), thyroid diseases, neoplastic diseases or rheumatoid arthritis. Men who had suffered a stroke or dementia were also excluded because of concerns related to their limited physical activity. Finally, subjects were excluded if they had taken drugs, such as bisphosphonates or glucocorticoids, which may affect bone metabolism for more than 6 months or within the previous 12 months. Some subjects met two or more exclusion criteria. The remaining 1089 men were enrolled in the study. This study was approved by the local Institutional Review Board of the AMC. All subjects enrolled in this study provided written informed consent. All participants were interviewed and examined by physicians in the health promotion centre. Information on history of previous medical or surgical diseases for each subject was obtained. As there was no item regarding DHEA supplementation in the questionnaires, we could not determine whether one was actually taking oral DHEA. Smoking and drinking habits were categorized into three (never, past and current) and two (
doi: 10.1111/cen.12755
ORIGINAL ARTICLE
The association between serum dehydroepiandrosterone Sulphate (DHEA-S) level and bone mineral density in Korean men Dain Lee*,1, Hyeonmok Kim*,1, Seong Hee Ahn*, Seung Hun Lee*, Sung Jin Bae†, Eun Hee Kim†, Hong-Kyu Kim†, Jae Won Choe†, Beom-Jun Kim* and Jung-Min Koh* *Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, and †Health Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Summary Context Many lines of evidence indicate that dehydroepiandrosterone (DHEA) plays a distinct role in bone metabolism and that its sulphated form (DHEA-S), which is easily measured in blood, may be a potential biomarker of osteoporosis-related phenotypes. However, most previous epidemiologic studies focused on postmenopausal women and reported conflicting results. Objective We aimed to investigate the association between the serum DHEA-S level and bone mass in men. Design and Methods This large cross-sectional study included 1089 healthy Korean men who participated in a routine health screening examination. Bone mineral density (BMD) at the lumbar spine, total femur, femur neck, and trochanter and serum DHEA-S level were obtained in all subjects. Results After adjustment for age, body mass index, lifestyle factors and serum levels of calcium, phosphorus, testosterone, 25-OH-vitamin D3 and cortisol, higher serum DHEA-S concentrations were associated with higher BMD values at all skeletal sites. Consistently, compared to the subjects in the highest DHEA-S quartile (Q4), those in the lowest DHEA-S quartile (Q1) showed significantly lower BMD values. Multiple logistic regression analyses revealed that the odds ratios for the risk of lower BMD (T-score < 1) increased in a dose-dependent manner across decreasing DHEA-S quartiles and the odds for the risk of lower BMD were 259-fold higher in Q1 than in Q4. Conclusion These findings support previous evidences that DHEA-S has favourable effects on bone mass in men and suggest that a low serum DHEA-S level may be a potential risk factor for male osteoporosis. (Received 25 November 2014; returned for revision 19 December 2014; finally revised 25 January 2015; accepted 13 February 2015) Correspondence: Beom-Jun Kim, Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap2-Dong, Songpa-Gu, Seoul 138-736, Korea. Tel.: +82-2-3010-5876; Fax: +82-2-3010-6962; E-mail: [email protected] 1
These authors contributed equally to this work.
© 2015 John Wiley & Sons Ltd
Introduction Osteoporosis is a skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue, leading to an increase in bone fragility and susceptibility to fracture. Although osteoporosis has long been considered a disease of postmenopausal women, male osteoporosis and related fractures are becoming recognized as important public health concerns. More than one in four men over the age of 50 will sustain an osteoporotic fracture during their remaining lifetime,1 and 20–35% of all femoral fractures and 33–50% of all vertebral fractures occur in men.2,3 Moreover, men suffering any major osteoporotic fracture have a markedly higher mortality rate than women.4,5 With increasing life expectancies in men, male osteoporosis will likely further become a significant burden on society and healthcare systems in the future.6 Therefore, more effort to elucidate the risk factors and the underlying pathogenic mechanism of osteoporosis in men is needed to effectively prevent this condition. Dehydroepiandrosterone (DHEA) is the most abundant circulating C19 steroid in humans, derived primarily from the adrenal glands,7 and exists predominantly in a sulphated form (DHEAS). Peak serum levels of DHEA and DHEA-S are achieved in early adulthood and decline steadily thereafter,7 suggesting that these factors may be implicated in a variety of age-related pathologic conditions including osteoporosis. Indeed, many lines of evidence indicate that DHEA plays a distinct role in bone metabolism. Although the effect of DHEA on bone is traditionally thought to be primarily mediated through conversion to sex hormone,8 in vitro studies showed that DHEA can directly affect bone formation and bone resorption.9–11 Furthermore, intervention studies have reported positive effects of DHEA administration on bone mass in humans.12,13 These findings suggest that serum DHEA-S, which is easily measured in blood, may be a potential biomarker to predict osteoporosis-related phenotypes. However, most previous epidemiologic studies relating serum DHEA-S level to bone health were mainly focused on postmenopausal women and showed conflicting results.14–16 Therefore, we 173
174 D. Lee et al. performed a large cross-sectional study in healthy Korean men to clarify whether low serum DHEA-S level is a risk factor for male osteoporosis.
Methods Study participants The study population consisted of 1300 consecutive Korean men who had undergone comprehensive health examinations at the health promotion centre of the Asan Medical Center (AMC, Seoul, Korea) between January 2010 and December 2011 and in whom bone mineral density (BMD) and serum DHEA-S concentrations were measured. Visitors to our centre are usually healthy and receive extensive screening tests for early detection of malignancy, diabetes, osteoporosis and other age-related diseases. Among them, subjects with serum liver enzyme (aspartate aminotransferase and alanine aminotransferase) activities twofold above the upper normal limits, increased serum creatinine levels [>14 mg/dl (>1238 lmol/l)], abnormal thyroid function (serum thyrotropin 50 mU/l) or elevated rheumatic factor levels (>20 IU/ml) were excluded from this study. In addition, subjects were excluded if they suffered from any diseases that might affect bone metabolism, such as asthma/chronic obstructive pulmonary disease (COPD), thyroid diseases, neoplastic diseases or rheumatoid arthritis. Men who had suffered a stroke or dementia were also excluded because of concerns related to their limited physical activity. Finally, subjects were excluded if they had taken drugs, such as bisphosphonates or glucocorticoids, which may affect bone metabolism for more than 6 months or within the previous 12 months. Some subjects met two or more exclusion criteria. The remaining 1089 men were enrolled in the study. This study was approved by the local Institutional Review Board of the AMC. All subjects enrolled in this study provided written informed consent. All participants were interviewed and examined by physicians in the health promotion centre. Information on history of previous medical or surgical diseases for each subject was obtained. As there was no item regarding DHEA supplementation in the questionnaires, we could not determine whether one was actually taking oral DHEA. Smoking and drinking habits were categorized into three (never, past and current) and two (
