Findings

What do systematic reviews say?

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Evidence found and GRADE certainty

24 questions · 27 findings · 5 reviews · Oral and maxillofacial surgery

No studies found 0 · 0%GRADE not reported 22 · 81.5%Very low 0 · 0%Low 5 · 18.5%Moderate 0 · 0%High 0 · 0%

Age 8-10 years vs Age >10 years

Spontaneous space closure · Children and adolescents with maxillary permanent first molar extraction

In the maxilla, age 8-10 years was not associated with a statistically significant difference in space closure odds.

1 finding from 1 review

Extraction at patient age <8 years vs Extraction at patient age >10 years

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

In the mandible, extraction before age 8 (vs after 10) increases odds of space closure (OR 5.01; low certainty).

1 finding from 1 review

Age 8-10 years vs Extraction at patient age >10 years

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

In the mandible, extraction at age 8-10 (vs after 10) increases odds of space closure (OR 3.32; low certainty).

1 finding from 1 review

Extraction at patient age 11-12 years vs Extraction at patient age 8-10 years

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

In the mandible, extraction at 11-12 vs 8-10 years showed no significant difference in one analysis (OR 0.82; not GRADE-rated).

2 findings 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

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

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

Risk of fragility fractures · Females aged over 50 years

In females over 50, fragility-fracture risk rose steeply from ~0.5 mg/L: RR 0.98 at 0.25, 1.00 at 0.45, and 1.26 (95% CI 1.10-1.46) at 1.0 mg/L drinking-water fluoride vs null; ungraded.

3 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 over 50 years: drinking-water fluoride 0.45 mg/L vs null
    RR 1.00 [0.80, 1.24]
    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 over 50 years: drinking-water fluoride 0.25 mg/L vs null
    RR 0.98 [0.83, 1.14]
    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 over 50 years: drinking-water fluoride 1.0 mg/L vs null
    RR 1.26 [1.10, 1.46]
    Studies not reported
    GRADE not reported

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

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

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

Lumbar spine bone mineral density (BMD) · Females aged over 50 years

In females over 50, spine BMD showed an inverted U-shaped curve with a downward trend beginning at lower fluoride concentrations than in the overall analysis; no numeric MD reported in text; 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 · Females >50, spine BMD dose-response
    Inverted U-shaped curve with a downward trend starting at lower fluoride concentrations than the overall analysis (no numeric MD reported in text)
    Studies not reported
    GRADE not reported

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

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

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

No difference in mean Streptococcus mutans presence was reported; GRADE was not reported.

1 finding from 1 review

Bilateral extraction of compromised mandibular first permanent molars vs Age- and gender-matched non-extraction controls

Lower incisor inclination (lingual tipping and retrusion) · Children (approximately 11 years or older) with compromised mandibular first permanent molars

Bilateral lower first permanent molar extraction was associated with lingual tipping and retrusion of the lower incisors in one case-control study; ungraded.

1 finding from 1 review

Extraction of a maxillary first permanent molar vs Extraction of a mandibular first permanent molar

Spontaneous space closure · Children aged 5 to 15 years undergoing first permanent molar extraction

Spontaneous post-extraction space closure did not differ significantly between the maxilla and mandible (pooled OR 2.06, 95% CI 0.46 to 9.28; 3 studies; I2 = 72%); ungraded.

1 finding from 1 review

Bilateral extraction of compromised mandibular first permanent molars vs Age- and gender-matched non-extraction controls

Skeletal development (occlusal plane rotation, facial height) · Children (approximately 11 years or older) with compromised mandibular first permanent molars

Bilateral lower first permanent molar extraction was associated with counter-clockwise rotation of the occlusal plane and a mild decrease in lower anterior face height in one case-control study; ungraded.

1 finding from 1 review