J Bone Miner Metab DOI 10.1007/s00774-014-0630-6
ORIGINAL ARTICLE
Association between delivery at an advanced maternal age and osteoporosis in elderly Korean women Eunju Ahn · Jungkwon Lee · Yong Soon Park · Hye-Mi Noh · Bo Ha Kim
Received: 5 June 2014 / Accepted: 18 August 2014 © The Japanese Society for Bone and Mineral Research and Springer Japan 2014
Abstract Although several reproductive factors have been associated with low bone mineral density (BMD) in elderly women, few studies have evaluated the long-term effects of delivery at a high-risk maternal age on BMD. Using nationally representative survey data collected from 736 women aged 65 years or older, we evaluated the relationship between delivery during adolescence or at an age of 35 years or older and osteoporosis in elderly women. Data regarding demographic and socioeconomic characteristics, medical history, lifestyle risk factors, reproductive history, and history of osteoporosis and fracture were collected by administration of self-report questionnaires. Anthropometric
E. Ahn Health Screening Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Yongin, Republic of Korea J. Lee (*) Department of Family Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-gu, Seoul 135-710, Republic of Korea e-mail: [email protected] Y. S. Park (*) Department of Family Medicine, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, 77 Sakju-ro, Chuncheon, Gangwon-do 200-704, Republic of Korea e-mail: [email protected] H.-M. Noh Department of Family Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea B. H. Kim Health Screening Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
data and BMD were measured in accordance with standardized guidelines. Independent determinants of BMD were identified by stepwise multiple linear regression analysis, and the resulting model was used to evaluate the risk of osteoporosis according to delivery during adolescence or at an advanced age. Of the 736 subjects, 426 (60.1 %) were found to have osteoporosis (T score ≤ −2.5), and 19.2 and 38.9 % reported delivery during adolescence and at an advanced age, respectively. The incidence of delivery during adolescence or at an advanced age was significantly higher in subjects with osteoporosis than in those without osteoporosis. After adjustment for covariates, multiple logistic regression analysis revealed that elderly women with a history of delivery at an advanced maternal age are at an increased (2.164fold greater) risk of osteoporosis (95 % confidence interval 1.109–4.223) compared with elderly women without a history of delivery at an advanced age. However, a history of delivery during adolescence did not affect the risk. Keywords Bone mineral density · Korea National Health and Nutrition Examination Survey · Maternal age · Osteoporosis · Parity
Introduction Osteoporosis is a systemic skeletal system disease that is characterized by low bone mass, microarchitectural disruption, and skeletal fragility, which result in an increased risk of fracture [1]. Osteoporosis in the elderly population and its association with fragility fractures have become major public health issues because of their relationship with increased mortality and functional impairment, decreased quality of life, and high financial and social burden [2]. As the incidence of osteoporosis and resulting osteoporotic
13
fracture is expected to increase in parallel with increasing life expectancy, the extent of these public health problems is expected to become even more significant. Several factors that affect bone mass and bone loss are currently being investigated to identify their potential role in primary and secondary prevention of osteoporotic fracture. These include predictors of low bone mass, such as female sex, advanced age, low body mass index (BMI), inadequate physical activity, vitamin D deficiency, and premature ovarian failure [1]. Among these factors, sex hormones, particularly estrogen, have been found to strongly affect female bone health, either directly or indirectly [3]. Estrogen deficiency is considered an important cause of both the early accelerated and the late slow phases of bone loss in postmenopausal women [4]. Of the reproductive factors closely related to estrogen level in women, late menarche, early menopause, and low endogenous estrogen level have been associated with low bone mineral density (BMD) [5, 6]. However, the relationship between low BMD and reproductive factors, including pregnancy and delivery, is unclear and controversial. Several studies have reported that some reproductive factors, such as the number of pregnancies and the duration of breast-feeding, may affect peak bone mass and bone loss [7, 8]. Although pregnancy has been identified as a risk factor in the development of osteoporosis, the results of previous studies have been inconsistent regarding the association between pregnancy and osteoporosis, and the data collected regarding the association between BMD and the long-term effects of pregnancy are conflicting [9]. Furthermore, few studies have evaluated the long-term effects of maternal age on BMD. Although Cho et al. [10] reported that a history of pregnancy during adolescence is associated with an increased risk of osteoporosis after menopause, it is unclear how delivery at an advanced maternal age affects BMD and osteoporosis after menopause. Pregnancies during adolescence and pregnancies at an advanced maternal age may result in unfavorable birth outcomes as well as maternal complications, including adverse bone health effects. Despite these potential risks, little research has examined whether maternal age at the first and/or last delivery affects the risk of osteoporosis after menopause, regardless of parity. Moreover, to the best of our knowledge, no research has examined the relationship between delivery at an advanced maternal age, defined here as delivery at the age of 35 years or older, and osteoporosis in elderly women, defined here as women aged 65 years or older. To fill these study gaps, this study evaluated the relationship between delivery during adolescence or at an advanced age, stages of life that have been associated with high-risk pregnancy, and osteoporosis in elderly Korean women using nationally representative survey data.
13
J Bone Miner Metab
Materials and Methods Study subjects The data examined in this study were collected during the fifth Korea National Health and Nutrition Examination Survey (KNHANES) conducted in 2010 (KNHANES V-1). KNHANES has been conducted periodically since 1998 to assess the health and nutritional status of the civilian, noninstitutionalized Korean population. KNHANES V-1 is a cross-sectional and nationally representative survey that was conducted by the Korea Centers for Disease Control and Prevention (KCDC) from 2010 to 2012. Using a stratified, multistage probability sampling design, the KCDC selected 10,938 individuals from 3,840 households for possible participation in KNHANES V-1. Of these 10,938 individuals, 8,958 agreed to participate, yielding a response rate of 81.9 %. The current study examined KNHANES V-1 participants who met the inclusion criteria of female sex and age of 65 years or older (n = 829) and did not meet the exclusion criterion of incomplete BMD data (n = 93). All of the 736 enrolled subjects submitted a written informed consent form before participating, and approval for the study was obtained from the Institutional Review Board of the Samsung Medical Center (Institutional Review Board approval number 2012-03-071) before study initiation. Data collection and measurement The KNHANES V-1 data were collected through standardized health examinations in mobile examination centers equipped especially for the study as well as face-to-face interviews within households. The sequence of the health survey was intake, receipt of written informed consent, anthropometric measurements, blood sampling and BMD measurements, and completion of the questionnaire. A standardized questionnaire collecting data regarding demographic and socioeconomic characteristics, medical history, medication use, lifestyle risk factors, and reproductive history was prepared by the KCDC. A self-reported questionnaire was administered to collect data regarding past or current diseases, including rheumatoid arthritis and thyroid disease. Data regarding history of osteoporosis and fracture were collected by asking the participants whether they had been diagnosed with fracture of the vertebra, hip, forearm, or other sites. Data regarding reproductive factors were collected by asking the participants to recall the age at menarche, at first and last delivery, and at menopause; gravidity; parity; oral contraceptive and hormone replacement therapy (HRT) use; and duration of breast-feeding. Nutrient intake, including total calorie and calcium intake, was assessed using a 24-h dietary recall questionnaire
J Bone Miner Metab
administered by a trained dietician performing house-tohouse enquiries. Anthropometric data were collected in accordance with standardized guidelines. Height and body weight were measured by a nurse who had received special training regarding the use of a stadiometer (SECA 225; Vogel & Halke, Hamburg, Germany) and scale (GL-6000-20; CAS Korea, Seoul, South Korea). BMI was calculated by dividing the body weight in kilograms by the square of the height in meters. Laboratory parameters were assessed via year-round collection of blood samples after a fast of at least 8 h. After collection, blood samples were immediately processed, refrigerated, and transported in cold storage within 24 h to the central testing institute (NeoDin Medical Institute, Seoul, South Korea) for analysis. Serum vitamin D (25-hydroxyvitamin D) level was measured with a radioimmunoassay kit (DiaSorin, Stillwater, MN, USA) using a gamma counter (1470 Wizard; PerkinElmer, Turku, Finland). Fasting plasma glucose level was measured using an autoanalyzer (model 7600 automatic analyzer, Hitachi, Tokyo, Japan). Calculation and definition of variables Household equivalent income was calculated by summing the monthly income of all household members and dividing this sum by the square root of the household size. Smoking status was defined as current smoker, ex-smoker, or nonsmoker. High-risk alcohol consumption was defined as consumption of five or more alcoholic drinks per day at least twice per week. Engaging in physical activity was defined as walking for 30 min or longer at least five times per week. A family history of osteoporosis was defined as having at least one parent diagnosed with osteoporosis or osteoporotic fracture. Diabetes mellitus was defined as a fasting plasma glucose level of 126 mg/dL or higher or use of medication for previously diagnosed diabetes. Menopause was defined as amenorrhea for 12 months following the final menstrual period. Gravidity was defined as the reported number of pregnancies, and parity was defined as the reported number of live births. Oral contraceptive and HRT use was defined as either ever or never. The duration of breast-feeding was calculated by summing the periods during which the subject breast-fed each child. BMD measurement and diagnosis of osteoporosis BMD (g/cm2) was measured at the lumbar spine (L1-L4), femoral neck, and total hip by dual-energy X-ray absorptiometry (DISCOVERY-W fan-beam densitometer; Hologic, Bedford, MA, USA). The coefficients of variation, which were 1.9 % for the lumbar spine BMD, 2.5 % for the femoral neck BMD, and 1.8 % for the total hip BMD, were
obtained by scanning 30 randomly selected subjects who had undergone two scans on the same day, getting on and off the table between examinations. The BMD measurement provided absolute values for each anatomic site, and the T score, defined as the standard deviation of a participant’s BMD from the weight-adjusted average peak BMD of a healthy population- and sex-matched East Asian (Japanese) sample, was used. According to World Health Organization guidelines, osteoporosis is diagnosed with a T score of −2.5 or lower at any of the sites: lumbar spine, femoral neck, or total hip. Statistical analysis All estimates were calculated on the basis of sample weights, which were evaluated taking into consideration the sampling rate, response rate, and age and sex proportions of the reference population. The analysis was adjusted for the complex sample design of the survey, which could aid in determining statistical reliability. Continuous variables were tested for normality using graphical tools and the Kolmogorov–Smirnov test. The values of total energy intake, calcium intake, serum vitamin D level, and household equivalent income were log-transformed to improve the normality of the distribution. Continuous data are expressed as the mean and standard error (SE) and categorical data are expressed as the frequency and SE, as appropriate. Student’s t test or analysis of covariance was used to compare continuous variables, and the chi square test was used to compare categorical variables between two groups. To establish independent determinants of BMD, stepwise multiple linear regression analysis was conducted with BMD as the dependent variable and potentially significant factors, including delivery at an advanced maternal age, as independent variables. A model based on the results of the multiple logistic regression analysis was developed to evaluate the risk of osteoporosis according to delivery during adolescence or at an advanced maternal age. All tests were two-sided, and P
ORIGINAL ARTICLE
Association between delivery at an advanced maternal age and osteoporosis in elderly Korean women Eunju Ahn · Jungkwon Lee · Yong Soon Park · Hye-Mi Noh · Bo Ha Kim
Received: 5 June 2014 / Accepted: 18 August 2014 © The Japanese Society for Bone and Mineral Research and Springer Japan 2014
Abstract Although several reproductive factors have been associated with low bone mineral density (BMD) in elderly women, few studies have evaluated the long-term effects of delivery at a high-risk maternal age on BMD. Using nationally representative survey data collected from 736 women aged 65 years or older, we evaluated the relationship between delivery during adolescence or at an age of 35 years or older and osteoporosis in elderly women. Data regarding demographic and socioeconomic characteristics, medical history, lifestyle risk factors, reproductive history, and history of osteoporosis and fracture were collected by administration of self-report questionnaires. Anthropometric
E. Ahn Health Screening Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Yongin, Republic of Korea J. Lee (*) Department of Family Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-gu, Seoul 135-710, Republic of Korea e-mail: [email protected] Y. S. Park (*) Department of Family Medicine, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, 77 Sakju-ro, Chuncheon, Gangwon-do 200-704, Republic of Korea e-mail: [email protected] H.-M. Noh Department of Family Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea B. H. Kim Health Screening Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
data and BMD were measured in accordance with standardized guidelines. Independent determinants of BMD were identified by stepwise multiple linear regression analysis, and the resulting model was used to evaluate the risk of osteoporosis according to delivery during adolescence or at an advanced age. Of the 736 subjects, 426 (60.1 %) were found to have osteoporosis (T score ≤ −2.5), and 19.2 and 38.9 % reported delivery during adolescence and at an advanced age, respectively. The incidence of delivery during adolescence or at an advanced age was significantly higher in subjects with osteoporosis than in those without osteoporosis. After adjustment for covariates, multiple logistic regression analysis revealed that elderly women with a history of delivery at an advanced maternal age are at an increased (2.164fold greater) risk of osteoporosis (95 % confidence interval 1.109–4.223) compared with elderly women without a history of delivery at an advanced age. However, a history of delivery during adolescence did not affect the risk. Keywords Bone mineral density · Korea National Health and Nutrition Examination Survey · Maternal age · Osteoporosis · Parity
Introduction Osteoporosis is a systemic skeletal system disease that is characterized by low bone mass, microarchitectural disruption, and skeletal fragility, which result in an increased risk of fracture [1]. Osteoporosis in the elderly population and its association with fragility fractures have become major public health issues because of their relationship with increased mortality and functional impairment, decreased quality of life, and high financial and social burden [2]. As the incidence of osteoporosis and resulting osteoporotic
13
fracture is expected to increase in parallel with increasing life expectancy, the extent of these public health problems is expected to become even more significant. Several factors that affect bone mass and bone loss are currently being investigated to identify their potential role in primary and secondary prevention of osteoporotic fracture. These include predictors of low bone mass, such as female sex, advanced age, low body mass index (BMI), inadequate physical activity, vitamin D deficiency, and premature ovarian failure [1]. Among these factors, sex hormones, particularly estrogen, have been found to strongly affect female bone health, either directly or indirectly [3]. Estrogen deficiency is considered an important cause of both the early accelerated and the late slow phases of bone loss in postmenopausal women [4]. Of the reproductive factors closely related to estrogen level in women, late menarche, early menopause, and low endogenous estrogen level have been associated with low bone mineral density (BMD) [5, 6]. However, the relationship between low BMD and reproductive factors, including pregnancy and delivery, is unclear and controversial. Several studies have reported that some reproductive factors, such as the number of pregnancies and the duration of breast-feeding, may affect peak bone mass and bone loss [7, 8]. Although pregnancy has been identified as a risk factor in the development of osteoporosis, the results of previous studies have been inconsistent regarding the association between pregnancy and osteoporosis, and the data collected regarding the association between BMD and the long-term effects of pregnancy are conflicting [9]. Furthermore, few studies have evaluated the long-term effects of maternal age on BMD. Although Cho et al. [10] reported that a history of pregnancy during adolescence is associated with an increased risk of osteoporosis after menopause, it is unclear how delivery at an advanced maternal age affects BMD and osteoporosis after menopause. Pregnancies during adolescence and pregnancies at an advanced maternal age may result in unfavorable birth outcomes as well as maternal complications, including adverse bone health effects. Despite these potential risks, little research has examined whether maternal age at the first and/or last delivery affects the risk of osteoporosis after menopause, regardless of parity. Moreover, to the best of our knowledge, no research has examined the relationship between delivery at an advanced maternal age, defined here as delivery at the age of 35 years or older, and osteoporosis in elderly women, defined here as women aged 65 years or older. To fill these study gaps, this study evaluated the relationship between delivery during adolescence or at an advanced age, stages of life that have been associated with high-risk pregnancy, and osteoporosis in elderly Korean women using nationally representative survey data.
13
J Bone Miner Metab
Materials and Methods Study subjects The data examined in this study were collected during the fifth Korea National Health and Nutrition Examination Survey (KNHANES) conducted in 2010 (KNHANES V-1). KNHANES has been conducted periodically since 1998 to assess the health and nutritional status of the civilian, noninstitutionalized Korean population. KNHANES V-1 is a cross-sectional and nationally representative survey that was conducted by the Korea Centers for Disease Control and Prevention (KCDC) from 2010 to 2012. Using a stratified, multistage probability sampling design, the KCDC selected 10,938 individuals from 3,840 households for possible participation in KNHANES V-1. Of these 10,938 individuals, 8,958 agreed to participate, yielding a response rate of 81.9 %. The current study examined KNHANES V-1 participants who met the inclusion criteria of female sex and age of 65 years or older (n = 829) and did not meet the exclusion criterion of incomplete BMD data (n = 93). All of the 736 enrolled subjects submitted a written informed consent form before participating, and approval for the study was obtained from the Institutional Review Board of the Samsung Medical Center (Institutional Review Board approval number 2012-03-071) before study initiation. Data collection and measurement The KNHANES V-1 data were collected through standardized health examinations in mobile examination centers equipped especially for the study as well as face-to-face interviews within households. The sequence of the health survey was intake, receipt of written informed consent, anthropometric measurements, blood sampling and BMD measurements, and completion of the questionnaire. A standardized questionnaire collecting data regarding demographic and socioeconomic characteristics, medical history, medication use, lifestyle risk factors, and reproductive history was prepared by the KCDC. A self-reported questionnaire was administered to collect data regarding past or current diseases, including rheumatoid arthritis and thyroid disease. Data regarding history of osteoporosis and fracture were collected by asking the participants whether they had been diagnosed with fracture of the vertebra, hip, forearm, or other sites. Data regarding reproductive factors were collected by asking the participants to recall the age at menarche, at first and last delivery, and at menopause; gravidity; parity; oral contraceptive and hormone replacement therapy (HRT) use; and duration of breast-feeding. Nutrient intake, including total calorie and calcium intake, was assessed using a 24-h dietary recall questionnaire
J Bone Miner Metab
administered by a trained dietician performing house-tohouse enquiries. Anthropometric data were collected in accordance with standardized guidelines. Height and body weight were measured by a nurse who had received special training regarding the use of a stadiometer (SECA 225; Vogel & Halke, Hamburg, Germany) and scale (GL-6000-20; CAS Korea, Seoul, South Korea). BMI was calculated by dividing the body weight in kilograms by the square of the height in meters. Laboratory parameters were assessed via year-round collection of blood samples after a fast of at least 8 h. After collection, blood samples were immediately processed, refrigerated, and transported in cold storage within 24 h to the central testing institute (NeoDin Medical Institute, Seoul, South Korea) for analysis. Serum vitamin D (25-hydroxyvitamin D) level was measured with a radioimmunoassay kit (DiaSorin, Stillwater, MN, USA) using a gamma counter (1470 Wizard; PerkinElmer, Turku, Finland). Fasting plasma glucose level was measured using an autoanalyzer (model 7600 automatic analyzer, Hitachi, Tokyo, Japan). Calculation and definition of variables Household equivalent income was calculated by summing the monthly income of all household members and dividing this sum by the square root of the household size. Smoking status was defined as current smoker, ex-smoker, or nonsmoker. High-risk alcohol consumption was defined as consumption of five or more alcoholic drinks per day at least twice per week. Engaging in physical activity was defined as walking for 30 min or longer at least five times per week. A family history of osteoporosis was defined as having at least one parent diagnosed with osteoporosis or osteoporotic fracture. Diabetes mellitus was defined as a fasting plasma glucose level of 126 mg/dL or higher or use of medication for previously diagnosed diabetes. Menopause was defined as amenorrhea for 12 months following the final menstrual period. Gravidity was defined as the reported number of pregnancies, and parity was defined as the reported number of live births. Oral contraceptive and HRT use was defined as either ever or never. The duration of breast-feeding was calculated by summing the periods during which the subject breast-fed each child. BMD measurement and diagnosis of osteoporosis BMD (g/cm2) was measured at the lumbar spine (L1-L4), femoral neck, and total hip by dual-energy X-ray absorptiometry (DISCOVERY-W fan-beam densitometer; Hologic, Bedford, MA, USA). The coefficients of variation, which were 1.9 % for the lumbar spine BMD, 2.5 % for the femoral neck BMD, and 1.8 % for the total hip BMD, were
obtained by scanning 30 randomly selected subjects who had undergone two scans on the same day, getting on and off the table between examinations. The BMD measurement provided absolute values for each anatomic site, and the T score, defined as the standard deviation of a participant’s BMD from the weight-adjusted average peak BMD of a healthy population- and sex-matched East Asian (Japanese) sample, was used. According to World Health Organization guidelines, osteoporosis is diagnosed with a T score of −2.5 or lower at any of the sites: lumbar spine, femoral neck, or total hip. Statistical analysis All estimates were calculated on the basis of sample weights, which were evaluated taking into consideration the sampling rate, response rate, and age and sex proportions of the reference population. The analysis was adjusted for the complex sample design of the survey, which could aid in determining statistical reliability. Continuous variables were tested for normality using graphical tools and the Kolmogorov–Smirnov test. The values of total energy intake, calcium intake, serum vitamin D level, and household equivalent income were log-transformed to improve the normality of the distribution. Continuous data are expressed as the mean and standard error (SE) and categorical data are expressed as the frequency and SE, as appropriate. Student’s t test or analysis of covariance was used to compare continuous variables, and the chi square test was used to compare categorical variables between two groups. To establish independent determinants of BMD, stepwise multiple linear regression analysis was conducted with BMD as the dependent variable and potentially significant factors, including delivery at an advanced maternal age, as independent variables. A model based on the results of the multiple logistic regression analysis was developed to evaluate the risk of osteoporosis according to delivery during adolescence or at an advanced maternal age. All tests were two-sided, and P
