Findings

What do systematic reviews say?

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Evidence found and GRADE certainty

21 questions · 23 findings · 4 reviews · Oral and maxillofacial surgery

No studies found 0 · 0%GRADE not reported 20 · 87%Very low 0 · 0%Low 3 · 13%Moderate 0 · 0%High 0 · 0%

Cleft lip and/or palate (CL/P) vs Healthy controls without cleft

Oral microbiota composition · Individuals assessed for oral microbiota (mainly children and adolescents)

Oral microbiota composition differs between persons with orofacial cleft and healthy controls, synthesized qualitatively across 8 studies but not meta-analyzed (ungraded).

1 finding from 1 review

Non-syndromic cleft lip and palate (CLP) status and its oral microbiota (exposure/grouping) vs Children and adolescents aged 0-18 years without CLP (controls)

Dental caries · Children and adolescents aged 0-18 years with non-syndromic cleft lip and palate (CLP)

Pooling 3 studies, children/adolescents with CLP were about 2.03 times more likely to have dental caries than non-CLP controls (p<0.005; low heterogeneity), though most included studies were at high risk of bias; the evidence is ungraded.

1 finding from 1 review

Non-syndromic cleft lip and palate (CLP) status and its oral microbiota (exposure/grouping) vs Children and adolescents aged 0-18 years without CLP (controls)

Lactobacillus spp. salivary/plaque counts (cariogenic microbiota) · Children and adolescents aged 0-18 years with non-syndromic cleft lip and palate (CLP)

A meta-analysis found no significant difference in mean Lactobacillus spp. levels between children with and without CLP, with high heterogeneity; the evidence is ungraded.

1 finding from 1 review

Non-syndromic cleft lip and palate (CLP) status and its oral microbiota (exposure/grouping) vs Children and adolescents aged 0-18 years without CLP (controls)

Streptococcus mutans count · Children and adolescents aged 0-18 years with non-syndromic cleft lip and palate (CLP)

A meta-analysis of 2 studies found no difference in mean Streptococcus mutans levels between children with and without CLP, with very high heterogeneity; the evidence is ungraded.

1 finding from 1 review

Non-syndromic cleft lip and palate (CLP) status and its oral microbiota (exposure/grouping) vs Children and adolescents aged 0-18 years without CLP (controls)

Periodontal conditions (gingival inflammation, bleeding on probing, probing depth, clinical attachment loss) · Children and adolescents aged 0-18 years with non-syndromic cleft lip and palate (CLP)

Narrative synthesis of 6 studies suggests children/adolescents with CLP have poorer periodontal status (higher gingival and plaque indices, deeper probing, more bleeding and attachment loss) and harbor periodontopathogens; no pooled estimate and the evidence is ungraded.

1 finding from 1 review

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

Genetically predicted periodontitis vs Lower genetically predicted periodontitis liability

Femoral neck bone mineral density (FN-BMD) · European-ancestry adults

Genetically predicted periodontitis had no causal effect on femoral neck BMD.

1 finding from 1 review

Genetically predicted DMFS (dental caries) vs Reference (1-SD lower genetically predicted DMFS)

Femoral neck bone mineral density (FN-BMD) · European-ancestry adults

Genetically predicted dental caries (DMFS) had no causal effect on femoral neck BMD.

1 finding from 1 review

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

Hip/femoral bone mineral density (BMD) · general population

Hip BMD increased with fluoride in both sexes (linearly in males, non-linearly above ~1.2 mg/L in females); no numeric MD reported in text for the main analysis; ungraded.

1 finding 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 · Both sexes, main dose-response
    Hip BMD increased in both sexes, linearly in males and non-linearly (starting above 1.2 mg/L) in females (no numeric MD reported in text for main analysis)
    Studies not reported
    GRADE not reported

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

Hip/femoral bone mineral density (BMD) · Females (all ages)

In females (low-to-moderate risk-of-bias studies), hip BMD rose monotonically above ~0.9 mg/L: MD 0.04 g/cm2 (95% CI -0.03-0.12) up to ~2.3 mg/L and 0.09 (-0.09-0.27) at 4.0 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 · Females, low-to-moderate risk-of-bias studies: up to ~2.3 mg/L vs null
    MD 0.04 [-0.03, 0.12]
    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 · Females, low-to-moderate risk-of-bias studies: 4.0 mg/L vs null
    MD 0.09 [-0.09, 0.27]
    Studies not reported
    GRADE not reported

Cleft lip and/or palate (CL/P) vs Healthy controls without cleft

Gingival index (GI) · Individuals assessed for periodontal health (mainly children and adolescents, age >2 years)

Persons with orofacial cleft have a higher gingival index than healthy controls (MD 0.15, 95% CI 0.11 to 0.19; low certainty).

1 finding from 1 review

Cleft lip and/or palate (CL/P) vs Healthy controls without cleft

Clinical attachment level (CAL) · Individuals assessed for periodontal health (mainly children and adolescents, age >2 years)

Clinical attachment level loss is greater in persons with orofacial cleft than in healthy controls (p<0.00001), but no pooled effect size was reported (ungraded).

1 finding from 1 review

Cleft lip and/or palate (CL/P) vs Healthy controls without cleft

Bleeding Index (BI) · Individuals assessed for periodontal health (mainly children and adolescents, age >2 years)

Bleeding index is significantly higher in persons with orofacial cleft than in healthy controls (p<0.0001), but no pooled effect size was reported (ungraded).

1 finding from 1 review

Unilateral cleft lip and palate (UCLP) vs Bilateral cleft lip and palate (BCLP)

Plaque · Patients with cleft lip and palate (CLP)

Plaque index does not differ significantly between unilateral and bilateral cleft lip and palate (MD -0.13, 95% CI -0.38 to 0.12; ungraded).

1 finding from 1 review

Cleft lip and/or palate (CL/P) vs Healthy controls without cleft

Probing pocket depth · Individuals assessed for periodontal health (mainly children and adolescents, age >2 years)

Persons with orofacial cleft have a greater probing pocket depth than healthy controls (MD 0.88, 95% CI 0.82 to 0.95; low certainty).

1 finding from 1 review

Cleft lip and/or palate (CL/P) vs Healthy controls without cleft

Plaque · Individuals assessed for periodontal health (mainly children and adolescents, age >2 years)

Persons with orofacial cleft have a higher plaque index than healthy controls (MD 0.29, 95% CI 0.24 to 0.34; low certainty).

1 finding from 1 review

Cleft lip and/or palate (CL/P) vs No cleft lip and/or palate (non-CL/P)

Lactobacillus spp. mean levels/counts · Children and adolescents aged 0-18 years with non-syndromic cleft lip and palate (CLP)

No significant difference in Lactobacillus spp. presence was reported; GRADE was not reported.

1 finding from 1 review