RECENT ADVANCES IN SKELETAL MATURITY STUDIES

JERUN JOSE

INTRODUCTION HISTORY METHODS TO STUDY GROWTH RECENT ADVANCES IN GROWTH STUDIESModified CVMIModified Hagg and TarangerMaxillary canine eruption and skeletal maturity

CONTENTS

Serum Dehydroepiandrosterone and skeletal maturitySerum PTHrP and skeletal maturityIGF-1 and skeletal maturityGCF and Alkaline phosphatase activity in skeletal maturityMasseter muscle conduction velocity and direction of mandibular growth

CONCLUSION REFERENCES

Growth of the craniofacial skeleton is a complex mechanism. In growth studies we are assessing pattern of growth, sites of growth, amount and rate of growth, direction and factors influencing growth.

INTRODUCTION

Proffit

1. Measurement approaches

2. Experimental approaches

METHODS TO STUDY GROWTH

Text book of craniofacial growth , Sridhar Premkumar

Measurement approaches

Measurements taking from living animals. Do not harm animal or human beings

1. Craniometry

2. Anthropometry

3. Cephalometry

4. 3D imaging

Experimental approaches

Procedure is invasive, cause harm to the animals1. Vital staining 2. Radioactive tracer3. Autoradiography4. Implant radiography

Sarnat in 1986 classified the growth measurement methods as1. Direct measurements2. Indirect measurements

Direct measurements Anthropometry Vital staining Histological methods Histochemical methods Implants

Indirect measurements Impressions and casts Photographs Radioautographs Radiographs Serial cephalometric radiography and

implantation

Hippocratus in BC 450 studied about human skull forms.

Leminus in 1567 first mentioned the red staining properties of root of madder in bone.

Duhamel introduced implants in the study of growth of bones in 1742

History

Robinson and Sarnat in 1955 used serial cephalometric radiography along with implant in pig for growth study of mandible.

Mcnamara and Graber (1975) and Bjork in 1963 used implants in humans for growth study.

CVM indicators by Lamparski in 1972 Leonard s Fishman, in 1982 developed skeletal

maturity indicator using handwrist radiography.

RECENT ADVANCES IN GROWTH STUDIES

Proposed by Lamparski (1972) 1st modification by Hassel and Farman in

1995 The method of Hassel and Farman uses the

second through the fourth vertebrae to avoid the defect in the original method.

Modified cervical vertebrae maturation

Skeletal maturation evaluation using cervical vertebrae.AJODO, Jan 1995

SEMIN IN ORTHOD- 2005

Cervical stage 1 (CS1). The lower borders of all the three vertebrae (C2-C4)are flat. The bodies of both C3 and C4 are trapezoid in

shape (the superior border of the vertebral body is tapered from posterior to anterior.

The peak in mandibular growth will occur on average 2 years after this stage.

Cervical stage 2 (CS2). A concavity is present at the lower border of C2. The bodies of both C3 and C4 are still trapezoid

in shape. The peak in mandibular growth will occur on

average 1 year after this stage.

Cervical stage3 (CS3). Concavities at the lower borders of both C2 and C3

are present. The bodies of C3 and C4 may be either trapezoid

or rectangular horizontal in shape. The peak in mandibular growth will occur during

the year after this stage.

Cervical stage 4 (CS4) Concavities at the lower borders of C2, C3, and

C4 now are present. The bodies of both C3 and C4 are rectangular

horizontal in shape. The peak in mandibular growth has occurred

within 1 or 2 years before this stage.

Cervical stage 5 (CS5) The concavities at the lower borders of C2, C3, and C4

still are present. At least one of the bodies of C3 and C4 is squared in

shape. If not squared, the body of the other cervical vertebra still

is rectangular horizontal. The peak in mandibular growth has ended atleast 1 year

before this stage.

Cervicalstage6(CS6) The concavities at the lower borders of C2, C3, and

C4 still are evident. At least one of the bodies of C3 and C4 is

rectangular vertical in shape. If not rectangular vertical, the body of the other

cervical vertebra is squared The peak in mandibular growth has ended at least 2

years before this stage.

By Rajagopal et al (2002) Additional bone stage between MP3-H and

MP3-I, which is called MP3-HI stage has been added.

Modified Hagg and Taranger

A comparison of modified MP3 stages and the cervical vertebrae as growth indicators. JCO -2002 Jul;36(7):398-406

Comprises 6 stages, 1.MP3-F stage is the start of the curve of pubertal growth

spurt: the epiphysisis as wide as the metaphysis The ends of the epiphysis are tapered and rounded; the

metaphysis shows no undulation; and the radiolucent gap (representing the cartilaginous epiphyseal growth plate) between the epiphysis and the metaphysisis wide

2.MP3-FG stage is the acceleration of the curve of the pubertal growth spurt: the epiphysisis as wide as the metaphysis the metaphysis begins to show as light undulation radiolucent gap between the metaphysis and the

epiphysisis wide.

3.MP3-G stage is the maximum point of the pubertal growth spurt: the sides of the epiphysis have thickened and cap its metaphysis, forming a sharp distal edge on at least 1side; marked undulations in the metaphysis give it a “Cupid's bow” appearance. The radiolucent gap between the epiphysis and the

metaphysisis moderate.

4.MP3-H stage is the deceleration of the curve of the pubertal growth spurt

fusion of the epiphysis and the metaphysis begins

5.MP3-Hi stage is the maturation of the curve of the pubertal growth spurt The superior surface of the epiphysis has a smooth

concavity The metaphysis shows a smooth,convex surface

6.MP3-I stage is the end of the pubertal growth spurt fusion of the epiphysis and the metaphysis is

complete. There is no radiolucent gap between the

metaphysis and the epiphysis.

Hagg and Taranger reported that all canines and premolars are usually erupted by the end of the pubertal growth spurt .

This was confirmed with the hand wrist.

Eruption of maxillary canine and skeletal maturity

AJODO 2008

CS1 and CS2 –Prepubertal stages CS3 and CS4 – Pubertal stages CS5 and CS6 – Post pubertal stages

Digramatic representn of 6 stages of CVM, SEMIN IN ORTHOD- 2005

Erupting permanent canine in a 12 year 9 month old patient with CS3 stage .

In 56.6% of patients, the canine erupts in the dental arch at least 1 year before the pubertal growth spurt.

Puberty is a neuro endocrinal event with the pituitary and hypothalamus playing a major role in its initation.

Both the pituitary and hypothalamus are together called gonadostat.

In puberty, gonadotropin releasing hormone is secreted from the hypothalamus, which stimulates the pituitary to secrete gonadotropins (FSH, LH)

SERUM DEHYDRO EPIANDROSTERONE SULPHATE AND SKELETAL MATURATION

EJO- 2012, VOL 34

These gonadotropins stimulate the gonads to secrete the sex steroids testosterone and estrogen, which inturn affects skeletal maturity in puberty.

For the gondaotropins to iniate its action, it requires stimulation from the adrenal gland.

Adrenal gland secretes steroids like dehydroepiandrosterone (DHEA) and its sulphated conjugate dehydroepiandrosterone sulphate (DHEAS). Auches and Rainey 2004

They are present in circulation approximately 3 years prior to puberty.

This period is termed as adrenarche These steroids can stimulate growth and

proliferation of epiphyseal cartilage and potentiate action of growth hormone (GH)

DHEAS has been foud to enhance bone deposition to increse bone mineral density, and to maintain the cancellous and cortical bone mass by way of protective action in osteoblasts.

Serum levels of DHEAS are high in neonates, after which there is a decrease , then a rapid increase in the serum levels from 7 years of age in females and 8 years of age in males, with a gradual increase until it attains adult value.

Serum PTHrP and skeletal maturation

Parathyroid hormone related protein (PTHrP) regulate multiple steps in the development of the growth plate and seconadary cartilage at the head of condyle during skeletal morphogenesis.

2013,vol- 143

Compared with Bacceti`s cervical vertebrae stages. There were low levels of serum PTHrP levels at the pre

pubertal stage (CS1) of circumpubertal development with an increase in the mean serum PTHrP levels from CS1 to peak levels in late puberty(CS5).

There was a decline between CS5 andCS6, with the values at the post pubertal stage (CS6) less than those values at the pre pubertal stage (CS1)

Normal assay range of PTHrP was 0.5-15ng/mL. ELISA test was used in the study. Also found that serum PTHrP levels were at their

peak 2 years later than the peak height velocity. Showed a reduction in the mean serum PTHrP levels

from 14.5ng per milli liter of blood in the late pubertal stage to 8.3ng per milli liter in the post pubertal stage.

Insulin-like growth factorI (IGF-I) is a polypeptide hormone synthesized mainly by the liver.

It is a member of a group of hormones termed insulin-like growth factors.

Insulin like growth factor 1 and skeletal maturity

2012, Vol 142

It is considered a mediator of growth-hormone function.

It is involved in the growth of almost every organ and plays a major role in postnatal growth and precisely in the process of longitudinal bone growth.

Salmon and Daughaday were the first to discover IGF-I as a mediator of growth-hormone function, which was termed the sulphation factor.

Several studies reported that its serum levels in children and adolescents followed a pattern that was closely related to the pubertal growth curve.

Low in the prepubertal stages followed by a sharp increase at puberty and, after pubertal growth had ceased, returning to lower base line values.

ELISA is used for detection of IGF 1 Masoud et al used radioimmuno assay for

detection of IGF1 in their studies.AJODO- 2009

Different assays were comparably accurate, especially in healthy subjects.

The radioimmunoassay technique requires special laboratories that should have been equipped for radiation control.

IGF-I serum levels peaked at stage 4 of the cervical vertebral maturation index with a mean value of 835.6ng/mL.

IGF-I mean values increased gradually from stage1 (initiation) of cervical vertebral maturation to the peak level at stage4 (deceleration) and then declined gradually to approach base line levels at stage 6 (completion).

Stages 3 and 4 showed a difference between boys and girls. Girls had higher values in stage3 (transition), indicating their earlier onset of puberty, and boys showed higher values in stage 5 (maturation), indicating their more delayed pubertal growth spurt.

Pattern of IGF-I in relation to the stages of the cervical vertebral maturation index.

Gingival crevicular fluid (GCF) is a potential source of biomarkers, with molecular constituents that derive mainly from serum, and also from the interstitial fluids of periodontal tissues.

Gingival crevicular fluid protein content and alkaline phosphatase

activity in relation to pubertal growth phase

ANGLE ORTHOD-2012

ALP is an enzyme that is necessary for bone mineralization, with its activity shown to be correlated with local tissue remodeling during orthodontic tooth movement and periodontal inflammation.

This study was proposed as a non invasive diagnostic aid for the determination of optimal treatment timing in functional jaw orthopedics.

Both the volume and total protein content of the GCF have been used extensively to calculate the concentrations of the different GCF constituents, for their normalization.

Total GCF protein content is not a reliable indicator of the different growth phases. While confirming that total GCF ALP activity would be a reliable biologic indicator of skeletal maturation.

GCF ALP activity is a promising diagnostic tool for identification of the growth phases in individual subjects when expressed as the total, rather than the normalized

Moss and Rankow reported that the function of the stomatognathic muscle affects the growing cranioface and plays a role in its morphogenesis

Masseter muscle conduction velocity and direction of mandibular growth

AJODO- 2005

Human skeletal muscle fibers are classified into 2 types—-fast-twitch (F type or type 1) and slow twitch (S type or type 2) —based on contractility and tissue images, and muscle function is characterized by the composition ratio of these types of muscle fibers.

There is a strong correlation between the muscle conduction velocity (MCV) measured by using an electromyogram and the muscle fiber composition,

MCV increases as the proportion of type II fibers increases.

It has been reported that the diameter of muscle fiber is proportional to MCV

Ogata et al reported that a long face, in which the lower facial height is long, has a lower conduction velocity of the masseter muscle in maximum voluntary contraction and more type 1 fibers than a short face.

Therefore, by understanding the muscle fiber composition of the masseter muscle in childhood, it might be possible to predict the direction of growth of the mandible or vertical craniofacial morphology with non invasive methods.

PROCEDURE The subjects sat on a dental chair in a shielded room, and

head positions were adjusted so that the Frankfort horizontal plane became parallel to the floor.

They were asked not to change their head positions on biting. Once they were relaxed, they were asked to perform 100%

maximum voluntary contraction (MVC) to measure the MCV of the masseter muscle.

Bite-taking was done before performing MVC by using a silicon impression in the rest position of the mandible.

The MCV of the masseter muscle was measured when the subject clenched the silicon, to protect the teeth and periodontium and to increase the reproducibility of occlusion and muscle position.

After the skin over the masseter muscle was thoroughly cleaned with rubbing alcohol on cotton to decrease impedance, the electrodes were attached to the skin with electrode paste.

The position and direction of the left masseter muscle were confirmed through manipulation when the subject clenched her teeth, and electrodes were attached to the center of the left masseter muscle and at a point where the bottom of the electrode reached 5 mm above the mandibular plane.

The long axes of the electrode arrays were arranged to be parallel to the running direction of the masseter muscle.

The subjects were asked to continuously perform voluntary contraction for approximately 3 seconds, and wave forms of the action potential were recorded.

Measurement of propagation delay

MCV of the masseter muscle was low in a long face, when the lower facial height is long, compared with that in a short face.

A strong correlation between MCV and the composition ratio of muscle fibre.

The proportion of type I fibers might be higher in a long face than in a short face.

For growth modification to be successful, it is absolutely essential that it start at the right time. So we need more accurate growth assessment methods in our profession.

CONCLUSION

Text book of craniofacial growth by Sridhar Premkumar. Tiziano Baccetti, Lorenzo Franchi, Simona De Lisa,

Veronica Giuntin.Eruption of the maxillary canines in relation to skeletal maturity. Am J Orthod Dentofacial Orthop 2008;133:748-51

SophieGray, Hamza Bennani. Morphometric analysis of cervical vertebrae in relation to mandibular growth. Am J Orthod Dentofacial Orthop 2016;149:92-8

REFERENCES

Ramy Abdul Rahman Ishaq, Sanaa Abou Zeid Soliman. Insulin-like growth factor I: A biologic maturation indicator. Am Jorthod Dentofacial Orthop 2012; 142: 654 -61

Masakatsu Konno, Koshi Sato. Relationship between the direction of mandibular growth and masseter muscle conduction velocity. Am J Orthod Dentofacial Orthop 2005; 128:35-44

Mohammed Zahid Hussain, Ashok Kumar Talapaneni. Serum PTHrP level as a biomarker in assessing skeletal maturation during circumpubertal development.

Sharmila Surendran and Eapen Thomas. Tooth mineralization stages as a diagnostic tool for assessment of skeletal maturity. AmJ Orthod Dentofacial Orthop 2014;145:7-14

Rajagopal and Kansal. A comparison of modified MP3 stages and the cervical vertebrae as growth indicators. JCO -2002 Jul;36(7):398-406

Sridhar premkumar, Bhadrinadh. Assesment of DHEAS in subjects during pre pubertal, pubertal and adult stages of skeletal maturation. EJO 2002, vol 34

Hassal and Farman , Skeletal maturation evaluation using cervical vertebrae. AJODO, Jan 1995

BaccettiT, FranchiL, McNamaraJA. The cervical vertebral maturation method for the assessment of optimal treatment timing in dentofacialorthopedics. SeminOrthod 2005; 11: 119-29.