Table 1 Studies Examining Urinary Phthalate Metabolites and Bone Mineral Density
From: Phthalates and bone mineral density: a systematic review
Author, Publication Year | Study Design | Study Population | Phthalate Metabolites Measured | Outcome (Parameterization) | Key Findings |
|---|---|---|---|---|---|
DeFlorio-Barker et al., 2016 [26] | Cross-sectional | 480 postmenopausal women from NHANES 2005-2010 cohort | MEP, MnBP, MiBP, MBzP, MCNP, MCOP, MCPP, MEHP, MEHHP, MEOHP, MECPP, Σ-LMW phthalate metabolitesa, Σ-DEHP metabolitesb, Σ-HMW phthalate metabolitesc, Σ-Anti-androgenic phthalate metabolitesd, Σ-Estrogenic phthalate metabolitese | BMD (g/cm2) measured using DXA scans of the lumbar spine, proximal femur, and femoral neck | Associations of phthalate metabolites (continuous) with BMD: Total spine:  MEP (β = − 0.038, p = 0.001)  Σ-LMW phthalate metabolites (β = − 0.044, p = 0.003)  Σ-Estrogenic phthalate metabolites (β = − 0.046, p = 0.002) Femoral neck:  MCNP (β = 0.024, p = 0.05) |
Min & Min, 2014 [27] | Cross-sectional | 398 postmenopausal women from NHANES 2005-2008 cohort | MnBP, MCPP, MCNP, MCOP, MECPP, MEP, MBzP, MiBP, Σ-DEHP metabolites (MEHP, MEHHP, MEOHP) | BMD (g/cm2) measured using DXA scans of the total hip and femoral neck | Associations of phthalate metabolites with BMD: Total hip:  MnBP (β = − 0.048, p = 0.035) (Q4 vs. Q1)  MCPP (β = − 0.055, p = 0.005) (Q4 vs. Q1)  MBzP (β = − 0.054, p = 0.003) (Q3 vs. Q1) Femoral neck:  MnBP (β = − 0.040, p = 0.046) (Q4 vs. Q1)  MCPP (β = − 0.045, p = 0.041) (Q4 vs. Q1)  MBzP (β = − 0.041, p = 0.024) (Q3 vs. Q1) |
Reeves et al., 2021 [28] | Cross-sectional & Prospective Cohort | 1255 postmenopausal women from the WHI cohort | MEP, MBzP, MCOP, MCNP, MCPP, Σ-DBPf, Σ-DiBPg, Σ-DEHPb, | BMD (g/cm2) measured using DXA scans of the total hip and femoral neck | Longitudinal associations between phthalate biomarkers and 3-year percentage change BMD measures among non-HT users: Total hip:  MCOP (β = − 1.80, 95% CI − 2.81 to − 0.78) (Q4 vs. Q1)  MCNP (β = − 1.84, 95% CI − 2.80 to − 0.89) (Q4 vs. Q1) Femoral neck:  MCNP (β = − 1.53, 95% CI − 2.75 to − 0.31) (Q4 vs. Q1) |
Van Zwol-Janssens et al., 2020 [29] | Prospective cohort | 1362 mother-child pairs from the Generation R Study | Σ-LMW phthalate metabolites (MMP, MEP, MiBP, MnBP), Σ-HMW phthalate metabolites (MBzP, MHP, mono-2-heptyl phthalate), Σ-DEHP (MECPP, MCMHP, MEHHP, MEOHP), Σ-DNOP (MCPP) | BMD (mg/cm2) measured using DXA scans of the whole body (excluding head) | Adjusted associations of maternal phthalate concentrations with childhood total body BMD at age 6 years: Σ-LMW phthalate metabolites:  First trimester (β = − 0.61, 95% CI − 2.89 to 1.67)  Second trimester (β = 0.92, 95% -1.44 to 3.29)  Third trimester (β = 1.81, 95% -0.69 to 4.30) Σ-DEHP metabolites:  First trimester (β = − 0.41, 95% CI − 2.45 to 1.63)  Second trimester (β = 0.13, 95% -1.90 to 2.17)  Third trimester (β = 0.30, 95% -1.82 to 2.41) Σ-HMW (high-molecular-weight) phthalate metabolites:  First trimester (β = − 0.67, 95% CI − 2.74 to 1.41)  Second trimester (β = 0.56, 95% CI − 1.46 to 2.58)  Third trimester (β = − 0.15, 95% CI − 1.98 to 2.28) Σ-DNOP metabolites:  First trimester (β = − 1.48, 95% CI − 3.43 to 0.47)  Second trimester (β = 1.19, 95% CI − 0.95 to 3.34)  Third trimester (β = − 1.39, 95% CI − 3.45 to 0.68) |
Kuiper et al., 2022 [30] | Prospective cohort | 233 mother-child pairs from the HOME Study | MEP, MiBP, MnBP, MBzP, MCPP, Σ-DEHPb | BMD and BMAD (height-for-age adjusted age-, sex-, and population ancestry-specific Z-scores) measured using DXA scans of the whole body (excluding head), lumbar spine, total hip, femoral neck, 1/3rd distal radius, and ultradistal radius | Adjusted mean differences (β and 95% Cis) in BMD Z-score at age 12 associated with a doubling in prenatal phthalate biomarkers: Whole body (excluding head):  MEP (β = 0.11, 95% CI 0.04 to 0.18) in overall sample  MEP (β = 0.15, 95% CI 0.06 to 0.24) in males Total hip:  MEP (β = 0.09, 95% CI 0.01 to 0.18) in overall sample  MEP (β = 0.13, 95% CI 0.01 to 0.24) in males Femoral neck:  MEP (β = 0.13, 95% CI 0.01 to 0.25) in males 1/3rd Distal radius:  MEP (β = 0.09, 95% CI 0.01 to 0.17) in overall sample  MCPP (β = 0.16, 95% CI 0.01 to 0.31) in overall sample Ultradistal radius:  MBzP (β = − 0.10, 95% CI − 0.24 to 0.03) in males  MBzP (β = 0.16, 95% CI − 0.03 to 0.35) in females   P interaction = 0.03  MCPP (β = 0.21, 95% CI 0.04 to 0.38) in overall sample  MCPP (β = − 0.05, 95% CI − 0.27 to 0.17) in males  MCPP (β = 0.41, 95% CI 0.17 to 0.64) in females   P interaction = 0.01 Spine BMAD:  MEP (β = 0.15, 95% CI 0.05 to 0.25) in males  MEP (β = − 0.01, 95% CI − 0.13 to 0.12) in females   P interaction = 0.05  MiBP (β = 0.21, 95% CI 0.04 to 0.39) in females Adjusted mean differences (β and 95% CrIs) in aBMD Z-scores at age 12 associated with the 90th percentile of the maternal urinary phthalate mixture compared to the 50th percentile:  1/3rd distal radius: (β = 0.52, 95% CrI 0.09 to 0.96)  Ultradistal radius: (β = 0.51, 95% CrI 0.03 to 0.98)  Total hip: (β = 0.50, 95% CrI 0.04 to 0.96) |