Findings

What do systematic reviews say?

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Evidence found and GRADE certainty

114 questions · 197 findings · 18 reviews · All outcomes

No studies found 0 · 0%GRADE not reported 180 · 91.4%Very low 0 · 0%Low 5 · 2.5%Moderate 5 · 2.5%High 7 · 3.6%

Higher national income (GNI per capita) vs Lower national income (GNI categories: middle <=$15,000 / high $15,001-25,000 / very high >$25,000)

Odds of higher caries (DMFT) category · 12-year-old children across European countries (national/regional epidemiological surveys, 2011-2022)

Higher national income was strongly associated with lower odds of poor oral health (OR 0.10, 95% CI 0.03 to 0.37; about 90% lower odds); not GRADE-rated.

1 finding from 1 review

Lower unemployment rate vs Higher unemployment rate (low <=5% / medium >5-10% / high >10%)

Odds of higher caries (DMFT) category · 12-year-old children across European countries (national/regional epidemiological surveys, 2011-2022)

Unemployment rate was not independently associated with DMFT category in the adjusted model (OR 0.99, 95% CI 0.44 to 2.23); not GRADE-rated.

1 finding from 1 review

Higher number of lost teeth (per one additional lost tooth) vs Fewer lost teeth (continuous, per-tooth increment)

All-cause mortality (ACM) · Adults (any age) with a known number of remaining teeth, followed prospectively in cohort studies

Each additional lost tooth was associated with a multivariable-adjusted HR of 1.02 (95% CI 1.01 to 1.03) for all-cause mortality (11 studies, I2=89%), statistically significant; GRADE per-analysis ratings reported in Supplementary File 7 (not available in provided sources).

3 findings from 1 review

Higher number of lost teeth (per one additional lost tooth) vs Fewer lost teeth (continuous, per-tooth increment)

Atherosclerotic cardiovascular disease (ACVD)-related events (morbidity and mortality) · Adults (any age) with a known number of remaining teeth, followed prospectively in cohort studies

Each additional lost tooth was associated with a multivariable-adjusted HR of 1.02 (95% CI 1.01 to 1.03) for ACVD-related events (13 studies, I2=75%), statistically significant; GRADE per-analysis ratings reported in Supplementary File 7 (not available in provided sources).

3 findings from 1 review

Higher waist circumference vs Lower waist circumference

Dental caries in children · Children (approx. 4-18 years)

Waist circumference was not significantly associated with childhood dental caries (pooled OR 1.08, 95% CI 0.90 to 1.30; I2=47.7%); ungraded.

1 finding from 1 review

Higher dental caries experience vs Caries-free controls

Poor oral health-related quality of life (OHRQoL) · Children aged 3-12 years

Higher dental caries experience was associated with substantially higher odds of poor OHRQoL (OR 1.66, 95% CI 1.43-1.88; 6 studies; high heterogeneity I2=83.5%; ungraded).

1 finding from 1 review

Higher parental education (tertiary) vs Lower parental education (reference)

Early childhood caries (ECC) · Children aged 0-5 years in North Africa

Paternal tertiary education was associated with lower odds of ECC (OR 0.381).

3 findings from 1 review

Higher mean patient age (per 1 year) vs Lower mean patient age (per 1-year decrement)

Spontaneous space closure · Children and adolescents after extraction of a mandibular permanent first molar (before eruption of the second molar)

In the mandible, mean patient age was not significantly associated with space closure odds (OR 0.59 per year; not GRADE-rated).

1 finding from 1 review

Higher parental / maternal education vs Lower parental education (reference)

Oral health-related quality of life · Adolescents (10-19 years)

Higher parental education is associated with better OHRQoL in adolescents (narrative synthesis; no pooled estimate or GRADE rating).

1 finding from 1 review
  • Oral-health-related quality of life in adolescents: umbrella review. 2023 All outcomes
    Community/school/clinic settings; adolescents 10-19 years; included reviews conducted in multiple countries
    Adolescents from families with higher incomes and higher levels of maternal education have better OHRQoL scores [34]. Children from families with high income, parental education and family economy had better OHRQoL [42].
    Studies not reported
    GRADE not reported

Higher circulating 25-hydroxyvitamin D (25(OH)D) concentration vs Lower circulating 25-hydroxyvitamin D (25(OH)D) concentration

Alzheimer’s disease · Participants in observational studies

The meta-analysis of observational studies reported a SMD (to OR) of 0.08 (95% CI 0.01 to 0.63) for higher versus lower circulating vitamin D concentration.

1 finding from 1 review

Higher circulating 25-hydroxyvitamin D (25(OH)D) concentration vs Lower circulating 25-hydroxyvitamin D (25(OH)D) concentration

Aggressive prostate cancer · Participants in observational studies

The meta-analysis of observational studies reported a OR of 0.88 (95% CI 0.68 to 1.15) for higher versus lower circulating vitamin D concentration.

1 finding from 1 review

Higher circulating 25-hydroxyvitamin D (25(OH)D) concentration vs Lower circulating 25-hydroxyvitamin D (25(OH)D) concentration

Tuberculosis · Participants in observational studies

The meta-analysis of observational studies reported a SMD (to OR) of 0.29 (95% CI 0.19 to 0.46) for higher versus lower circulating vitamin D concentration.

1 finding from 1 review

Higher circulating 25-hydroxyvitamin D (25(OH)D) concentration vs Lower circulating 25-hydroxyvitamin D (25(OH)D) concentration

Fracture · Participants in observational studies

The meta-analysis of observational studies reported a SMD (to OR) of 0.31 (95% CI 0.23 to 0.42) for higher versus lower circulating vitamin D concentration.

1 finding from 1 review

Higher circulating 25-hydroxyvitamin D (25(OH)D) concentration vs Lower circulating 25-hydroxyvitamin D (25(OH)D) concentration

All cause mortality (in CKD patients) · Participants in observational studies

The meta-analysis of observational studies reported a RR of 0.88 (95% CI 0.81 to 0.93) for higher versus lower circulating vitamin D concentration.

1 finding from 1 review

Higher drinking-water fluoride exposure vs Null / lowest drinking-water fluoride exposure (reference)

Fracture · general population

Non-linear positive dose-response: little change in overall fracture risk below ~1.5 mg/L drinking-water fluoride, with risk increasing above that threshold (RR 1.06, 1.19, 1.35 at 2.0, 3.0, 4.0 mg/L vs null); ungraded (4 studies).

4 findings from 1 review
Show 1 more finding

Higher drinking-water fluoride exposure vs Null / lowest drinking-water fluoride exposure (reference)

Risk of femoral fractures · general population

Femoral-fracture risk was mildly U-shaped: RR 0.86 at 0.5 mg/L rising to 1.06 at 1.8 mg/L drinking-water fluoride vs null; risk mostly below null across the range; ungraded.

2 findings from 1 review
  • The association of fluoride exposure with bone density and fracture risk: a dose-response meta-analysis. 2025 All outcomes
    Long-term / lifetime fluoride exposure · General population; 37 observational studies (1944-2024), predominantly North America (USA, Canada) and Northern Europe (Finland, Sweden), plus UK, Poland, Italy, Germany, China, Taiwan, South Korea, Ethiopia; exposure mainly community drinking-water fluoride · Drinking-water fluoride 1.8 mg/L vs null
    RR 1.06 [0.67, 1.69]
    Studies not reported
    GRADE not reported
  • The association of fluoride exposure with bone density and fracture risk: a dose-response meta-analysis. 2025 All outcomes
    Long-term / lifetime fluoride exposure · General population; 37 observational studies (1944-2024), predominantly North America (USA, Canada) and Northern Europe (Finland, Sweden), plus UK, Poland, Italy, Germany, China, Taiwan, South Korea, Ethiopia; exposure mainly community drinking-water fluoride · Drinking-water fluoride 0.5 mg/L vs null
    RR 0.86 [0.71, 1.05]
    Studies not reported
    GRADE not reported

Higher drinking-water fluoride exposure vs Null / lowest drinking-water fluoride exposure (reference)

Risk of fragility fractures · Male participants

In males (7 studies), fragility-fracture risk generally decreased with increasing fluoride: RR 0.83 (95% CI 0.72-0.97) at 0.57 mg/L to 0.87 (0.48-1.58) at 1.8 mg/L vs null; ungraded.

2 findings from 1 review
  • The association of fluoride exposure with bone density and fracture risk: a dose-response meta-analysis. 2025 All outcomes
    Long-term / lifetime fluoride exposure · General population; 37 observational studies (1944-2024), predominantly North America (USA, Canada) and Northern Europe (Finland, Sweden), plus UK, Poland, Italy, Germany, China, Taiwan, South Korea, Ethiopia; exposure mainly community drinking-water fluoride · Males: drinking-water fluoride 1.8 mg/L vs null
    RR 0.87 [0.48, 1.58]
    7 studies
    GRADE not reported
  • The association of fluoride exposure with bone density and fracture risk: a dose-response meta-analysis. 2025 All outcomes
    Long-term / lifetime fluoride exposure · General population; 37 observational studies (1944-2024), predominantly North America (USA, Canada) and Northern Europe (Finland, Sweden), plus UK, Poland, Italy, Germany, China, Taiwan, South Korea, Ethiopia; exposure mainly community drinking-water fluoride · Males: drinking-water fluoride 0.57 mg/L vs null
    RR 0.83 [0.72, 0.97]
    7 studies
    GRADE not reported

Higher drinking-water fluoride exposure vs Null / lowest drinking-water fluoride exposure (reference)

Risk of fragility fractures · general population

Fragility-fracture risk overall was slightly U-shaped: RR 0.93 up to 0.9 mg/L, ~1.00 at 1.48 mg/L, 1.05 at 1.8 mg/L drinking-water fluoride vs null; ungraded.

5 findings from 1 review
  • The association of fluoride exposure with bone density and fracture risk: a dose-response meta-analysis. 2025 All outcomes
    Long-term / lifetime fluoride exposure · General population; 37 observational studies (1944-2024), predominantly North America (USA, Canada) and Northern Europe (Finland, Sweden), plus UK, Poland, Italy, Germany, China, Taiwan, South Korea, Ethiopia; exposure mainly community drinking-water fluoride · Drinking-water fluoride up to 0.9 mg/L vs null
    RR 0.93 [0.84, 1.02]
    Studies not reported
    GRADE not reported
  • The association of fluoride exposure with bone density and fracture risk: a dose-response meta-analysis. 2025 All outcomes
    Long-term / lifetime fluoride exposure · General population; 37 observational studies (1944-2024), predominantly North America (USA, Canada) and Northern Europe (Finland, Sweden), plus UK, Poland, Italy, Germany, China, Taiwan, South Korea, Ethiopia; exposure mainly community drinking-water fluoride · Drinking-water fluoride 1.8 mg/L vs null
    RR 1.05 [0.82, 1.35]
    Studies not reported
    GRADE not reported
  • The association of fluoride exposure with bone density and fracture risk: a dose-response meta-analysis. 2025 All outcomes
    Long-term / lifetime fluoride exposure · General population; 37 observational studies (1944-2024), predominantly North America (USA, Canada) and Northern Europe (Finland, Sweden), plus UK, Poland, Italy, Germany, China, Taiwan, South Korea, Ethiopia; exposure mainly community drinking-water fluoride · Sensitivity (excluding high risk-of-bias studies): 0.8-1.5 mg/L vs null
    RR 0.93 [0.72, 1.21]
    Studies not reported
    GRADE not reported
Show 2 more findings
  • The association of fluoride exposure with bone density and fracture risk: a dose-response meta-analysis. 2025 All outcomes
    Long-term / lifetime fluoride exposure · General population; 37 observational studies (1944-2024), predominantly North America (USA, Canada) and Northern Europe (Finland, Sweden), plus UK, Poland, Italy, Germany, China, Taiwan, South Korea, Ethiopia; exposure mainly community drinking-water fluoride · Drinking-water fluoride 1.48 mg/L vs null
    RR 1.00 [0.82, 1.21]
    Studies not reported
    GRADE not reported
  • The association of fluoride exposure with bone density and fracture risk: a dose-response meta-analysis. 2025 All outcomes
    Long-term / lifetime fluoride exposure · General population; 37 observational studies (1944-2024), predominantly North America (USA, Canada) and Northern Europe (Finland, Sweden), plus UK, Poland, Italy, Germany, China, Taiwan, South Korea, Ethiopia; exposure mainly community drinking-water fluoride · Sensitivity (excluding high risk-of-bias studies): 1.8 mg/L vs null
    RR 0.95 [0.70, 1.29]
    Studies not reported
    GRADE not reported

Higher drinking-water fluoride exposure vs Null / lowest drinking-water fluoride exposure (reference)

Lumbar spine bone mineral density (BMD) · general population

Spine BMD showed an inverted U-shaped association with fluoride (peak ~0.6 mg/L); excluding high risk-of-bias studies gave small positive MDs (e.g., 0.05 g/cm2, 95% CI 0.01-0.10, up to 2.27 mg/L); ungraded.

4 findings from 1 review
  • The association of fluoride exposure with bone density and fracture risk: a dose-response meta-analysis. 2025 All outcomes
    Long-term / lifetime fluoride exposure · General population; 37 observational studies (1944-2024), predominantly North America (USA, Canada) and Northern Europe (Finland, Sweden), plus UK, Poland, Italy, Germany, China, Taiwan, South Korea, Ethiopia; exposure mainly community drinking-water fluoride · Sensitivity (excluding high risk-of-bias studies): 1.27 to 2.27 mg/L vs null
    MD 0.05 [0.01, 0.10]
    Studies not reported
    GRADE not reported
  • The association of fluoride exposure with bone density and fracture risk: a dose-response meta-analysis. 2025 All outcomes
    Long-term / lifetime fluoride exposure · General population; 37 observational studies (1944-2024), predominantly North America (USA, Canada) and Northern Europe (Finland, Sweden), plus UK, Poland, Italy, Germany, China, Taiwan, South Korea, Ethiopia; exposure mainly community drinking-water fluoride · Sensitivity (excluding high risk-of-bias studies): 0.60 mg/L vs null
    MD 0.06 [-0.02, 0.13]
    Studies not reported
    GRADE not reported
  • The association of fluoride exposure with bone density and fracture risk: a dose-response meta-analysis. 2025 All outcomes
    Long-term / lifetime fluoride exposure · General population; 37 observational studies (1944-2024), predominantly North America (USA, Canada) and Northern Europe (Finland, Sweden), plus UK, Poland, Italy, Germany, China, Taiwan, South Korea, Ethiopia; exposure mainly community drinking-water fluoride · Both sexes, main dose-response
    Inverted U-shaped association in both males and females, highest value around 0.6 mg/L (no numeric MD reported in text for main analysis)
    Studies not reported
    GRADE not reported
Show 1 more finding
  • The association of fluoride exposure with bone density and fracture risk: a dose-response meta-analysis. 2025 All outcomes
    Long-term / lifetime fluoride exposure · General population; 37 observational studies (1944-2024), predominantly North America (USA, Canada) and Northern Europe (Finland, Sweden), plus UK, Poland, Italy, Germany, China, Taiwan, South Korea, Ethiopia; exposure mainly community drinking-water fluoride · Sensitivity (excluding high risk-of-bias studies): above 2.27 mg/L vs null
    MD 0.04 [-0.21, 0.30]
    Studies not reported
    GRADE not reported