TY - JOUR
T1 - Metabolomics analysis in adults with High Bone Mass identifies a relationship between bone resorption and circulating citrate which replicates in the general population
AU - Hartley, April
AU - Paternoster, Lavinia
AU - Evans, David M.
AU - Fraser, William D.
AU - Tang, Jonathan C. Y.
AU - Lawlor, Debbie A.
AU - Tobias, Jon H.
AU - Gregson, Celia L.
PY - 2020/1
Y1 - 2020/1
N2 - Objective: Bone turnover, which regulates bone mass, may exert metabolic consequences, particularly on markers of glucose metabolism and adiposity. To better understand these relationships, we examined cross-sectional associations between bone turnover markers (BTMs) and metabolic traits in a population with high bone mass (HBM, BMD Z-score>+3.2).
Design: β-C-terminal telopeptide of type-I collagen (β-CTX), procollagen type-1 amino-terminal propeptide (P1NP) and osteocalcin were assessed by electrochemiluminescence immunoassays. Metabolic traits, including lipids and glycolysis-related metabolites, were measured using Nuclear Magnetic Resonance spectroscopy. Associations of BTMs with metabolic traits were assessed using Generalized Estimating Equation linear regression, accounting for within-family correlation, adjusting for potential confounders (age, sex, height, weight, menopause, bisphosphonate and oral glucocorticoid use).
Results: 198 adults with HBM had complete data, mean [SD] age 61.6 [13.7] years; 77% female. Of 23 summary metabolic traits, citrate was positively related to all BTMs: adjusted ββ-CTX=0.050 (95% CI 0.024,0.076),p=1.71x10-4, βosteocalcin=6.54x10-4 (1.87x10-4,0.001),p=0.006 and βP1NP=2.40x10-4 (6.49x10-5,4.14x10-4),p=0.007 (β= increase in citrate (mmol/L) per 1μg/L BTM
increase). Inverse relationships of β-CTX (β=-0.276 -0.434,-0.118],p=6.03x10-4) and osteocalcin (-0.004 [-0.007,-0.001],p=0.020) with triglycerides were also identified. We explored the generalizability of these associations in 3,664 perimenopausal women (age 47.9 [4.4] years) from a UK family cohort. We confirmed a positive, albeit lower magnitude, association between β-CTX
and citrate (adjusted βwomen=0.020 [0.013,0.026],p=1.95x10-9) and an inverse association of similar magnitude between β-CTX and triglycerides (β=-0.354 [-0.471,-0.237],p=3.03x10-9).
Conclusions: Bone resorption is positively related to circulating citrate and inversely related to triglycerides. Further studies are justified to determine whether plasma citrate or triglyceride concentrations are altered by factors known to modulate bone resorption, such as bisphosphonates.
AB - Objective: Bone turnover, which regulates bone mass, may exert metabolic consequences, particularly on markers of glucose metabolism and adiposity. To better understand these relationships, we examined cross-sectional associations between bone turnover markers (BTMs) and metabolic traits in a population with high bone mass (HBM, BMD Z-score>+3.2).
Design: β-C-terminal telopeptide of type-I collagen (β-CTX), procollagen type-1 amino-terminal propeptide (P1NP) and osteocalcin were assessed by electrochemiluminescence immunoassays. Metabolic traits, including lipids and glycolysis-related metabolites, were measured using Nuclear Magnetic Resonance spectroscopy. Associations of BTMs with metabolic traits were assessed using Generalized Estimating Equation linear regression, accounting for within-family correlation, adjusting for potential confounders (age, sex, height, weight, menopause, bisphosphonate and oral glucocorticoid use).
Results: 198 adults with HBM had complete data, mean [SD] age 61.6 [13.7] years; 77% female. Of 23 summary metabolic traits, citrate was positively related to all BTMs: adjusted ββ-CTX=0.050 (95% CI 0.024,0.076),p=1.71x10-4, βosteocalcin=6.54x10-4 (1.87x10-4,0.001),p=0.006 and βP1NP=2.40x10-4 (6.49x10-5,4.14x10-4),p=0.007 (β= increase in citrate (mmol/L) per 1μg/L BTM
increase). Inverse relationships of β-CTX (β=-0.276 -0.434,-0.118],p=6.03x10-4) and osteocalcin (-0.004 [-0.007,-0.001],p=0.020) with triglycerides were also identified. We explored the generalizability of these associations in 3,664 perimenopausal women (age 47.9 [4.4] years) from a UK family cohort. We confirmed a positive, albeit lower magnitude, association between β-CTX
and citrate (adjusted βwomen=0.020 [0.013,0.026],p=1.95x10-9) and an inverse association of similar magnitude between β-CTX and triglycerides (β=-0.354 [-0.471,-0.237],p=3.03x10-9).
Conclusions: Bone resorption is positively related to circulating citrate and inversely related to triglycerides. Further studies are justified to determine whether plasma citrate or triglyceride concentrations are altered by factors known to modulate bone resorption, such as bisphosphonates.
KW - bone turnover
KW - metabolomics
KW - high bone mass
KW - citrate
KW - ALSPAC
KW - Triglycerides
KW - triglycerides
KW - TURNOVER
KW - BIOCHEMICAL MARKERS
KW - SENSITIVITY
KW - PUBERTAL CHANGES
KW - BIOMARKERS
KW - INDIVIDUALS
KW - MAGNETIC-RESONANCE METABOLOMICS
KW - OSTEOCALCIN
KW - EPIDEMIOLOGY
KW - FAT MASS
UR - http://www.scopus.com/inward/record.url?scp=85075240904&partnerID=8YFLogxK
U2 - 10.1111/cen.14119
DO - 10.1111/cen.14119
M3 - Article
C2 - 31667854
SN - 0300-0664
VL - 92
SP - 29
EP - 37
JO - Clinical Endocrinology
JF - Clinical Endocrinology
IS - 1
ER -