Not much is known about the relationship between teeth and other growth and developmental processes. To date research has looked into the relationships beween teeth, skeletal development and height. A close associated was found to exist between the classification stages of mandibular cainines and skeletal maturity(1). Other studies have also looked into the correlation between dental development calculated from the number of permanent teeth and other measures of other somatic maturation including age of menarche (r=0.59) (2). Furthermore research by Filipson et al has looked at the relationhsip between dental age and growth trajectories. Results indicated an increase in the difference in time between sexual and dental maturation signifies a greater remaining height growth(2).

Many developmental processes share common pathways and teeth are no different. Prior to eruption process mononuclear cells move to the dental follicle and fuse to produce osteoclasts. Osteoclasts resorb alveolar bone and form an eruption pathway (3). Molecules involved in this process and signalling cascades have been studied using rodent models. Three molecules play a pivotal role in osteoclast formation; Receptor activator of nuclear factor-6B ligand (RANKL), osteoprotegerin (OPG) and CSF-1. RANKL promotes formation of osteoclasts (3). OPG inhibits the function of RANKL and osteoclast differentiation. OPG is expressed in the dental follicle in rats'; however expression of this molecule is reduced when incubated with CSF-1. This inhibition and the cell-cell signalling of RANKL from the alveolar bone enable osteoclast formation leading to an eruption process (3). Genes involved in this eruption process (RANKL/OPG) as also closely associated with bone turnover and bone mineral density.

3. Hypothsis

There is a relationship between tooth development and other aspects of development and bone phenotypes.

4. Aims:

We aim to investigate the relationship between tooth phenotypes and bone outcomes. In doing so we need to take into account any confounders and mediators. We then aim to use results from a previous genome-wide-association of tooth development to conduct some instrumental variable analysis using previosly identified genetic predictors of tooth development and bone outcomes.

Exposure variables:

Number of teeth (15 and 24 months)

Age first tooth at (15 months)

Any milk teeth fallen out (64 months)

Number of milk teeth fallen (64 and 78 months)

Genotype for 'Age at first tooth' (from previous GWAS to use as an instrumental variable)

Genotype for 'number of teeth''(from previous GWAS to use as an instrumental variable)

Outcome variables:

HipDXA (17 years): Standardised hip outcomes individually error corrected:

Femoral neck BMD

Total hip BMD

Minimum neck width

Cross-sectional area

Cross-sectional moment of inertia

Cortical Thickness

Minimum Section Modulus

Maximum buckling ratio

pQCT (17 years): Standardised outcomes individually error corrected:

Cortical area

Cortical content

Cortical density

Periosteal Circumference

Cortical thickness

Endosteal circumference

Confounding variables:

Height

Weight

Total body fat mass

Total body lean mass

BMI

Insulin

Pubic Hair

References:

1. Chertkow S, Tooth mineralization as an indicator os the pubertal growth spurt. American Journal of Orthodontics 7, 79-91 (1980)

2. Filipsson R and Hall K, Correlation between dental maturity, height development and sexual maturation in normal girls. Annals of Human Biology 3, 205-210 (1976)

3. Wise,G.E., Frazier-Bowers,S., & R.N.D'Souza Cellular, Molecular, and Genetic Determinants of Tooth Eruption. Critical Reviews in Oral Biology & Medicine 13, 323-335 (2002).