Polymorphism of LRP5 gene and emphysema severity are associated with osteoporosis in Japanese patients with or at risk for COPD

Shotaro Chubachi, Hidetoshi Nakamura, Mamoru Sasaki, Mizuha Haraguchi, Masaki Miyazaki, Saeko Takahashi, Kyuto Tanaka, Yohei Funatsu, Koichiro Asano, Tomoko Betsuyaku

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background and objective Osteoporosis is an important systemic comorbidity of chronic obstructive pulmonary disease (COPD). However, neither its mechanisms nor its risk factors have been fully elucidated. With regard to genetic factors, low-density lipoprotein receptor-related protein 5 (LRP5) A1330V is known to be associated with osteoporosis in the general population, but the influence of this polymorphism in COPD is unknown. The aim of this study was to investigate the potential risk factors of COPD-related bone loss and fracture. Methods Keio University and affiliated hospitals have enrolled an observational cohort to investigate the management of COPD comorbidities. To assess risk factors for osteopenia and osteoporosis, bone mineral density (BMD) of the hip and lumbar spine, presence of vertebral fracture, quantitative data on emphysema and airway wall on computed tomography, as well as LRP5 genotype were analysed in patients with or at risk for COPD (n = 270). Results The percentage of subjects with osteoporosis (T-score ≤ -2.5), osteopenia (T-score between -1 and -2.5) and a normal BMD (T-score ≥ -1) was 15.2%, 35.9% and 48.9%, respectively. T-score was significantly decreased in subjects with LRP5 TT genotype (n = 15) compared with that in those with CC/CT genotype (n = 255) (-1.83 vs. -0.98, P = 0.0167). On multivariate logistic regression analysis, female gender (odds ratio (OR) 10.4; P < 0.0001), severe emphysema (OR 2.3; P = 0.013) and LRP5 TT genotype (OR 3.7; P = 0.031) independently increased the risk of osteopenia/osteoporosis. Conclusions This study confirmed the complex pathophysiology of COPD-related osteoporosis, including the influence of gender, clinical phenotype and genetic factors. Risk factors for COPD-associated osteoporosis are not fully elucidated. This observational COPD cohort study demonstrates that a polymorphism in low-density lipoprotein receptor-related protein 5 gene, female gender and the presence of severe emphysema are independent risk factors for low bone mineral density in patients with or at risk for COPD.

Original languageEnglish
Pages (from-to)286-295
Number of pages10
JournalRespirology
Volume20
Issue number2
DOIs
Publication statusPublished - 2015 Feb 1

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Low Density Lipoprotein Receptor-Related Protein-5
Emphysema
Chronic Obstructive Pulmonary Disease
Osteoporosis
Genes
Metabolic Bone Diseases
Genotype
Bone Density
Odds Ratio
Comorbidity
Bone Fractures
Hip
Spine
Cohort Studies
Logistic Models

Keywords

  • bone mineral density
  • chronic obstructive pulmonary disease
  • genetic polymorphism
  • low-density lipoprotein receptor-related protein 5
  • osteoporosis

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Polymorphism of LRP5 gene and emphysema severity are associated with osteoporosis in Japanese patients with or at risk for COPD. / Chubachi, Shotaro; Nakamura, Hidetoshi; Sasaki, Mamoru; Haraguchi, Mizuha; Miyazaki, Masaki; Takahashi, Saeko; Tanaka, Kyuto; Funatsu, Yohei; Asano, Koichiro; Betsuyaku, Tomoko.

In: Respirology, Vol. 20, No. 2, 01.02.2015, p. 286-295.

Research output: Contribution to journalArticle

Chubachi, S, Nakamura, H, Sasaki, M, Haraguchi, M, Miyazaki, M, Takahashi, S, Tanaka, K, Funatsu, Y, Asano, K & Betsuyaku, T 2015, 'Polymorphism of LRP5 gene and emphysema severity are associated with osteoporosis in Japanese patients with or at risk for COPD', Respirology, vol. 20, no. 2, pp. 286-295. https://doi.org/10.1111/resp.12429
Chubachi, Shotaro ; Nakamura, Hidetoshi ; Sasaki, Mamoru ; Haraguchi, Mizuha ; Miyazaki, Masaki ; Takahashi, Saeko ; Tanaka, Kyuto ; Funatsu, Yohei ; Asano, Koichiro ; Betsuyaku, Tomoko. / Polymorphism of LRP5 gene and emphysema severity are associated with osteoporosis in Japanese patients with or at risk for COPD. In: Respirology. 2015 ; Vol. 20, No. 2. pp. 286-295.
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abstract = "Background and objective Osteoporosis is an important systemic comorbidity of chronic obstructive pulmonary disease (COPD). However, neither its mechanisms nor its risk factors have been fully elucidated. With regard to genetic factors, low-density lipoprotein receptor-related protein 5 (LRP5) A1330V is known to be associated with osteoporosis in the general population, but the influence of this polymorphism in COPD is unknown. The aim of this study was to investigate the potential risk factors of COPD-related bone loss and fracture. Methods Keio University and affiliated hospitals have enrolled an observational cohort to investigate the management of COPD comorbidities. To assess risk factors for osteopenia and osteoporosis, bone mineral density (BMD) of the hip and lumbar spine, presence of vertebral fracture, quantitative data on emphysema and airway wall on computed tomography, as well as LRP5 genotype were analysed in patients with or at risk for COPD (n = 270). Results The percentage of subjects with osteoporosis (T-score ≤ -2.5), osteopenia (T-score between -1 and -2.5) and a normal BMD (T-score ≥ -1) was 15.2{\%}, 35.9{\%} and 48.9{\%}, respectively. T-score was significantly decreased in subjects with LRP5 TT genotype (n = 15) compared with that in those with CC/CT genotype (n = 255) (-1.83 vs. -0.98, P = 0.0167). On multivariate logistic regression analysis, female gender (odds ratio (OR) 10.4; P < 0.0001), severe emphysema (OR 2.3; P = 0.013) and LRP5 TT genotype (OR 3.7; P = 0.031) independently increased the risk of osteopenia/osteoporosis. Conclusions This study confirmed the complex pathophysiology of COPD-related osteoporosis, including the influence of gender, clinical phenotype and genetic factors. Risk factors for COPD-associated osteoporosis are not fully elucidated. This observational COPD cohort study demonstrates that a polymorphism in low-density lipoprotein receptor-related protein 5 gene, female gender and the presence of severe emphysema are independent risk factors for low bone mineral density in patients with or at risk for COPD.",
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author = "Shotaro Chubachi and Hidetoshi Nakamura and Mamoru Sasaki and Mizuha Haraguchi and Masaki Miyazaki and Saeko Takahashi and Kyuto Tanaka and Yohei Funatsu and Koichiro Asano and Tomoko Betsuyaku",
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T1 - Polymorphism of LRP5 gene and emphysema severity are associated with osteoporosis in Japanese patients with or at risk for COPD

AU - Chubachi, Shotaro

AU - Nakamura, Hidetoshi

AU - Sasaki, Mamoru

AU - Haraguchi, Mizuha

AU - Miyazaki, Masaki

AU - Takahashi, Saeko

AU - Tanaka, Kyuto

AU - Funatsu, Yohei

AU - Asano, Koichiro

AU - Betsuyaku, Tomoko

PY - 2015/2/1

Y1 - 2015/2/1

N2 - Background and objective Osteoporosis is an important systemic comorbidity of chronic obstructive pulmonary disease (COPD). However, neither its mechanisms nor its risk factors have been fully elucidated. With regard to genetic factors, low-density lipoprotein receptor-related protein 5 (LRP5) A1330V is known to be associated with osteoporosis in the general population, but the influence of this polymorphism in COPD is unknown. The aim of this study was to investigate the potential risk factors of COPD-related bone loss and fracture. Methods Keio University and affiliated hospitals have enrolled an observational cohort to investigate the management of COPD comorbidities. To assess risk factors for osteopenia and osteoporosis, bone mineral density (BMD) of the hip and lumbar spine, presence of vertebral fracture, quantitative data on emphysema and airway wall on computed tomography, as well as LRP5 genotype were analysed in patients with or at risk for COPD (n = 270). Results The percentage of subjects with osteoporosis (T-score ≤ -2.5), osteopenia (T-score between -1 and -2.5) and a normal BMD (T-score ≥ -1) was 15.2%, 35.9% and 48.9%, respectively. T-score was significantly decreased in subjects with LRP5 TT genotype (n = 15) compared with that in those with CC/CT genotype (n = 255) (-1.83 vs. -0.98, P = 0.0167). On multivariate logistic regression analysis, female gender (odds ratio (OR) 10.4; P < 0.0001), severe emphysema (OR 2.3; P = 0.013) and LRP5 TT genotype (OR 3.7; P = 0.031) independently increased the risk of osteopenia/osteoporosis. Conclusions This study confirmed the complex pathophysiology of COPD-related osteoporosis, including the influence of gender, clinical phenotype and genetic factors. Risk factors for COPD-associated osteoporosis are not fully elucidated. This observational COPD cohort study demonstrates that a polymorphism in low-density lipoprotein receptor-related protein 5 gene, female gender and the presence of severe emphysema are independent risk factors for low bone mineral density in patients with or at risk for COPD.

AB - Background and objective Osteoporosis is an important systemic comorbidity of chronic obstructive pulmonary disease (COPD). However, neither its mechanisms nor its risk factors have been fully elucidated. With regard to genetic factors, low-density lipoprotein receptor-related protein 5 (LRP5) A1330V is known to be associated with osteoporosis in the general population, but the influence of this polymorphism in COPD is unknown. The aim of this study was to investigate the potential risk factors of COPD-related bone loss and fracture. Methods Keio University and affiliated hospitals have enrolled an observational cohort to investigate the management of COPD comorbidities. To assess risk factors for osteopenia and osteoporosis, bone mineral density (BMD) of the hip and lumbar spine, presence of vertebral fracture, quantitative data on emphysema and airway wall on computed tomography, as well as LRP5 genotype were analysed in patients with or at risk for COPD (n = 270). Results The percentage of subjects with osteoporosis (T-score ≤ -2.5), osteopenia (T-score between -1 and -2.5) and a normal BMD (T-score ≥ -1) was 15.2%, 35.9% and 48.9%, respectively. T-score was significantly decreased in subjects with LRP5 TT genotype (n = 15) compared with that in those with CC/CT genotype (n = 255) (-1.83 vs. -0.98, P = 0.0167). On multivariate logistic regression analysis, female gender (odds ratio (OR) 10.4; P < 0.0001), severe emphysema (OR 2.3; P = 0.013) and LRP5 TT genotype (OR 3.7; P = 0.031) independently increased the risk of osteopenia/osteoporosis. Conclusions This study confirmed the complex pathophysiology of COPD-related osteoporosis, including the influence of gender, clinical phenotype and genetic factors. Risk factors for COPD-associated osteoporosis are not fully elucidated. This observational COPD cohort study demonstrates that a polymorphism in low-density lipoprotein receptor-related protein 5 gene, female gender and the presence of severe emphysema are independent risk factors for low bone mineral density in patients with or at risk for COPD.

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