The effect of growth hormone treatment on craniofacial growth in short stature children

Sung-Ho Chung; Jin-Wook Kim; Yong-Hoon Park; Chung-Ju Hwang; Hee-Kyung Lee

doi:10.4041/kjod.2010.40.4.227

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The effect of growth hormone treatment on craniofacial growth in short stature children

Original Article

Korean J Orthod 2010;40(4):227-238.

Published online: 19 January 2010

DOI: https://doi.org/10.4041/kjod.2010.40.4.227

The effect of growth hormone treatment on craniofacial growth in short stature children

Sung-Ho Chung, DDS, MSD, PhD^a, Jin-Wook Kim, DDS, MSD, PhD^b, Yong-Hoon Park, MDS, MSD, PhD^c, Chung-Ju Hwang, DDS, MSD, PhD^d, Hee-Kyung Lee, DDS, MSD, PhD^e

^aPostgraduate Student, Graduate School of Department of Medical Science, Yeungnam University.

^bClinical Professor, Department of Dentistry, College of Medicine, Yeungnam University.

^cProfessor, Department of Pediatrics, College of Medicine, Yeungnam University.

^dProfessor, Department of Orthodontics, College of Dentisrty, Yonsei University.

^eProfessor, Department of Dentistry, College of Medicine, Yeungnam University.

Corresponding author: Hee-Kyung Lee. Department of Dentistry, College of Medicine, Yeungnam University, 317-1 Daemyeong-dong, Nam-gu, Daegu 705-717, Korea. +82 53 620 3281; e-mail, lhk@med.yu.ac.kr.

Received 26 January 2010 Revised 6 June 2010 Accepted 9 June 2010

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective:

The purpose of this study was to analyze the effect of growth hormone treatment (GHT) on craniofacial growth in children of short stature.

Methods:

Nineteen untreated children of short stature were referred from the Pediatric Department, Yeungnam University Hospital as a subject group. All subjects had lateral cephalograms taken before, after 1 year and after 2 years of growth hormone treatment. As a reference group, we selected 19 normal children with paired sampling who matched the subjects' age and sex, from the Department of Orthodontics, Kyungpook National University Hospital.

Results:

Before GHT, anterior cranial base length and upper posterior facial height, posterior total facial height, mandibular ramus length, and mandibular corpus length were significantly smaller in the reference group. In angular craniofacial measurements, saddle angle and mandibular plane angle were larger. SNA and SNB were smaller in the reference group. After two years of GHT, growth hormone accelerated growth in several craniofacial components. The posterior total facial height, the anterior, posterior cranial base length, and the mandibular ramus length were increased. And the difference in mandibular plane angle and ANB values compared with the reference group was decreased.

Conclusions:

GHT over 2 years leads to a craniofacial catch-up growth tendency, which is pronounced in interstitial cartilage and condylar cartilage.

Keywords: Short stature children, Growth hormone therapy, Craniofacial catch-up growth

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Fig 1.

Cephalometric landmarks.

Table 1.

Demographic characteristics of subjects at baseline

	Childrenof shortstature (n=19)	Childrenof normalstature (n=19)
Sex Male(%)	8(42.1)	8(42.1)
Female(%)	11(57.9)	11(57.9)
Age 9-11years(	(%) 11(57.9)	11(57.9)
12-15years	(%) 8(42.1)	8(42.1)
Mean(SD)	11.63(1.89)	11.63(1.89)

Table 2.

Linear and angular craniofacial measurements

Linear	Abbreviation	Cephalometric landmarks	Angular	Abbreviation	Cephalometric landmarks
Anterior cranial base length	ACB	N-S	Saddle angle	SA	N-S-Art
Posterior cranial base length	PCB	S-Ba	Gonialangle	GA	Art-Go-Me
Total cranial base length	TCB	N-Ba	Mandibular plane angle	MPA	S-N-Go-Gn
Upper anterior facial height	UAFH	N-ANS	Position of maxilla	SNA	S-N-A
Upper posterior facial height	UPFH	S-PNS	Position of mandible	SNB	S-N-B
Lower anterior facial height	LAFH	ANS-Me	Maxilla/mandible	ANB	A-N-B
Anterior total facial height	ATFH	N-Me	Posterior position of mandib	ble PPMand	S-N-Art-Go
Posteriortotalfacialheight	PTFH	S-Go	Maxilla length	MaxL	ANS-PNS
Mandibular ramus length	MandRL	Art-Go
Mandibular corpus length	MandCL	Go-Pog
Overall mandibular length	OMandL	Art-Pog

Table 3.

Comparison of raw mean (standard error, SE) for the z scores of weight and height, bone mass index (BMI), and bone age from baseline to after 2 years in children of short stature by age groups

Agegroup	Atbaseline(n=19) Mean(SE)	After1year(n=19) Mean(SE)	After2years(n=19 Mean(SE)	) p^a
9-11years(n=11)
Weight(kg)^∗	26.13(1.09)	32.68(1.32)^b	40.63(1.92)^c	0.001
Weight^†	−1.25(0.10)	−0.94(1.67)^b	−0.49(0.16)^c	0.001
Height(cm)^∗	125.45(1.92)	136.39(1.96)^b	145.33(2.02)^c	0.001
Height^†	−2.14(0.13)	−1.45(0.17)^b	−1.03(0.18)^c	0.001
BMI	16.53(0.28)	17.52(0.45)^b	19.15(0.54)^c	0.001
Boneage(years)	8.09(0.46)	9.86(0.47)^b	11.68(4.23)^c	0.001
12-15years(n=8)
Weight(kg)^∗	39.27(3.39)	45.99(3.53)^b	51.55(3.06)^c	0.001
Weight^†	−1.07(0.24)	−0.81(0.24)^b	−0.51(0.24)^c	0.001
Height(cm)^∗	141.20(2.68)	151.44(2.34)^b	158.50(1.83)^c	0.001
Height^†	−2.30(0.19)	−1.58(0.14)^b	−0.93(0.12)^c	0.001
BMI	19.46(1.17)	19.86(1.04)^b	20.37(1.02)^c	0.001
Boneage(years)	11.13(0.42)	12.63(0.44)^b	14.03(0.38)^c	0.001
Total(n=19)
Weight(kg)^∗	31.66(2.15)	38.28(2.24)^b	45.23(2.22)^c	0.001
Weight^†	−1.17(0.11)	−0.88(0.14)^b	−0.50(0.14)^c	0.001
Height(cm)^∗	132.08(2.39)	142.73(2.28)^b	150.87(2.05)^c	0.001
Height^†	−2.20(0.11)	−1.52(0.11)^b	−0.99(0.11)^c	0.001
BMI	17.77(0.61)	18.51(0.56)^b	19.66(0.53)^c	0.001
Boneage(years)	9.36(0.47)	11.03(0.45)^b	12.67(0.39)^c	0.001

p^a p value of repeated ANOVA; ^b, significant difference between at base line and after 1yearat p ＜ 0.05; ^c, significant difference between after 1year and a fter 2 year sat p＜ 0.05. ∗ rawdata; † z(standard)score.

Table 4.

Comparison of mean of linear and angular measurements between children of short stature and normal stature at baseline by age groups

	Children of short stature			Children of normal stature
Variables	9-11years1	12-15years	Total9	-11years1	2-15years	Total	p^a	p^b
	Mean(SE)	Mean(SE)	Mean(SE)	Mean(SE)	Mean(SE)	Mean(SE)
Linear(mm) ACB	64.82(0.87)	66.94(0.63)	65.71(0.61)	67.00(0.59)	68.06(0.73)	67.45(0.46)	∗	-
PCB	44.79(0.72)	46.63(0.87)	45.56(0.58)	45.09(0.88)	48.94(1.24)	46.71(0.84)	-	-
TCB	100.8(1.06)	104.94(1.60)	102.58(1.01)	103.27(0.98)	106.19(1.35)	104.50(0.85)	-	-
UAFH	51.36(0.67)	54.19(1.27)	52.55(0.72)	52.32(0.64)	56.88(1.10)	54.24(0.78)	-	-
UPFH	46.73(0.42)	47.50(0.82)	47.05(0.42)	47.45(0.57)	51.19(1.31)	49.03(0.76)	∗	-
LAFH	64.45(0.63)	70.13(1.07)	66.84(0.87)	62.91(0.95)	66.60(1.10)	64.46(0.82)	-	-
ATFH	114.7(1.41)	122.31(2.56)	117.92(1.58)	114.27(1.21)	121.70(1.94)	117.40(1.36)	-	-
PTFH	70.95(1.42)	66.56(1.88)	69.11(1.22)	70.73(0.77)	79.01(2.22)	74.22(1.39)	†	-
MaxL	45.09(0.95)	45.81(1.60)	45.40(0.85)	45.05(0.64)	49.56(0.97)	46.95(0.75)	-	-
MandRL	37.95(1.35)	37.56(1.75)	37.79(1.04)	40.45(0.96)	45.56(2.19)	42.61(1.20)	†	-
MandCL	69.91(1.27)	71.31(0.94)	70.50(0.83)	72.73(0.97)	77.25(1.51)	74.63(0.98)	†	-
OMandL	98.23(1.17)	100.81(2.38)	99.32(1.21)	98.23(1.10)	107.13(1.56)	101.97(1.37)	-	-
Angular(°) SA	127.14(1.37)	128.94(2.40)	127.90(1.26)	124.95(1.06)	122.63(0.84)	123.97(0.74)	∗	-
GA	126.86(1.04)	123.81(1.31)	125.58(0.87)	125.41(1.90)	123.75(1.35)	124.71(1.22)	-	-
MPA	38.05(1.15)	37.50(1.60)	37.82(0.92)	34.05(1.70)	32.13(1.46)	33.24(1.15)	†	∗
SNA	79.27(0.83)	77.88(1.34)	78.68(0.74)	79.27(0.43)	83.13(1.09)	80.90(0.67)	∗	-
SNB	75.18(0.96)	74.13(1.19)	74.74(0.74)	76.18(0.35)	79.69(0.69)	77.66(0.53)	†	-
ANB	4.09(0.44)	3.75(0.67)	3.95(0.37)	3.09(0.47)	3.38(0.71)	3.21(0.39)	-	-
PPMand	87.64(1.01)	86.19(1.61)	87.03(0.88)	86.73(1.22)	89.19(1.65)	87.76(1.00)	-	-

p^a, value of independent t-test between childrens of shorts tatureand normals tature at baseline; p^b, value of interaction effects between a geandgroupusingtwo-way ANOVA.-, not significant; ^∗ p ＜ 0.05; ^† p＜ 0.01.SE, Standard error.

Table 5-1.

Comparison of scores for the linear and angular craniofacial variables from baseline to after 2 years among children of short stature

Variables		At baseline(n=19) Mean(SE)	After 1 year(n=19) Mean(SE)	After2years(n=19) p^a Mean(SE)
Linear(mm)	ACB	65.71(0.61)	67.97(0.62)^b	69.63(0.58)^c	0.001
	PCB	45.56(0.58)	47.39(0.52)^b	48.63(0.54)^c	0.001
	TCB	102.58(1.01)	104.05(0.99)^b	105.08(1.04)^c	0.001
	UAFH	52.55(0.72)	53.89(0.73)^b	55.05(0.65)^c	0.001
	UPFH	47.05(0.42)	48.50(0.42)^b	49.92(0.51)^c	0.001
	LAFH	66.84(0.87)	69.39(0.94)^b	71.84(0.96)^c	0.001
	ATFH	117.92(1.58)	121.00(1.53)^b	123.90(1.58)^c	0.002
	PTFH	69.11(1.22)	73.84(1.02)^b	78.16(0.79)^c	0.001
	MaxL	45.40(0.85)	47.63(0.84)^b	48.92(0.76)^c	0.001
	MandRL	37.79(1.04)	42.00(1.01)^b	44.18(0.80)^c	0.001
	MandCL	70.50(0.83)	73.05(0.79)^b	75.53(0.88)^c	0.001
	OMandL	99.32(1.21)	103.29(1.23)^b	106.16(1.20)^c	0.001
Angular(°)	SA	127.90(1.26)	127.08(1.31)	126.37(0.94)	0.572
	GA	125.58(0.87)	125.45(1.22)	126.66(1.14)	0.598
	MPA	37.82(0.92)	36.29(0.95)^b	35.47(0.85)^c	0.001
	SNA	78.68(0.74)	79.39(0.72)	79.24(0.72)	0.167
	SNB	74.74(0.74)	76.16(0.76)^b	76.61(0.71)^c	0.001
	ANB	3.95(0.37)	3.24(0.34)^b	2.53(0.40)^c	0.001
	PPMand	82.97(4.20)	88.24(0.90)	87.45(0.76)	0.390

p^a, p value of repeated ANOVA; ^b, significant difference between at base line and after 1 year at p ＜ 0.05; ^c, significant difference between after 1 year and after 2 years at p ＜ 0.05. SE, Standard error.

Table 5-2.

Comparison of scores for the linear and angular craniofacial variables from baseline to after 2 years among children of short stature by age groups

Age group	Variables	At baseline (n=19) Mean(SE)	After 1 year(n=19) Mean(SE)	After 2 years (n=19) Mean(SE)	p^a
9-11 years (n=8)	Linear(mm)
	ACB	64.81(0.87)	66.95(0.81)^b	68.41(0.76)^c	0.001
	PCB	44.79(0.72)	46.96(0.63)^b	48.09(0.57)^c	0.001
	TCB	100.86(1.06)	102.55(1.07)^b	104.09(1.01)^c	0.001
	UAFH	51.36(0.67)	52.50(0.66)^b	53.82(0.57)^c	0.001
	UPFH	46.73(0.42)	47.82(0.41)^b	49.41(0.61)^c	0.010
	LAFH	64.45(0.63)	66.86(0.72)^b	69.68(1.10)^c	0.001
	ATFH	114.73(1.41)	116.96(1.19)	121.46(2.07)^c	0.042
	PTFH	70.95(1.43)	75.45(1.15)^b	78.95(0.94)^c	0.001
	MaxL	45.09(0.95)	47.18(0.80)^b	48.27(0.72)^c	0.001
	MandRL	37.95(1.35)	42.14(1.34)^b	44.68(1.01)^c	0.001
	MandCL	69.91(1.27)	72.09(1.16)^b	74.59(1.32)^c	0.001
	OMandL	98.23(1.17)	101.96(0.84)^b	105.05(0.98)^c	0.001
	Angular(°)
	SA	127.14(1.37)	126.59(1.35)	126.73(1.43)	0.877
	GA	126.86(1.04)	125.59(1.34)	126.05(1.40)	0.425
	MPA	38.05(1.15)	36.23(1.20)^b	35.27(1.00)^c	0.001
	SNA	79.27(0.83)	80.23(0.79)	80.05(0.76)	0.400
	SNB	75.18(0.96)	76.77(0.99)	77.05(0.85)^c	0.016
	ANB	4.09(0.44)	3.46(0.40)^b	3.00(0.33)^c	0.014
	PPMand	87.64(1.01)	89.50(0.98)	87.00(1.00)	0.182
12-15years(n=11)	Linear(mm)
	ACB	66.94(0.63)	69.37(0.75)^b	71.31(0.43)^c	0.001
	PCB	46.62(0.87)	48.00(0.90)^b	49.37(1.01)^c	0.005
	TCB	104.94(1.60)	106.13(1.66)^b	106.44(2.03)	0.071
	UAFH	54.19(1.27)	55.81(1.23)^b	56.75(1.10)^c	0.002
	UPFH	47.50(0.82)	49.44(0.73)^b	50.63(0.84)^c	0.004
	LAFH	70.12(1.07)	72.88(1.18)^b	74.81(1.05)^c	0.007
	ATFH	122.31(2.56)	126.56(1.95)^b	127.25(2.01)	0.004
	PTFH	66.56(1.88)	71.63(1.58)^b	77.06(1.35)^c	0.001
	MaxL	45.81(1.60)	48.25(1.71)^b	49.81(1.53)^c	0.001
	MandRL	37.56(1.75)	41.81(1.63)^b	43.50(1.35)^c	0.001
	MandCL	71.31(0.94)	74.38(0.83)^b	76.81(0.94)^c	0.001
	OMandL	100.81(2.38)	105.13(2.64)^b	107.69(2.51)^c	0.001
	Angular(°)
	SA	128.94(2.40)	127.75(2.60)	125.88(1.15)	0.663
	GA	123.81(1.31)	125.25(2.34)	127.50(1.97)	0.188
	MPA	37.50(1.60)	36.38(1.63)^b	35.75(1.54)^c	0.006
	SNA	77.88(1.34)	78.25(1.28)	78.13(1.30)	0.258
	SNB	74.13(1.19)	75.31(1.17)^b	76.00(1.25)^c	0.003
	ANB	3.75(0.67)	2.94(0.62)	1.88(0.81)^c	0.007
	PPMand	76.56(9.78)	86.50(1.53)	88.06(1.19)	0.427

p^a p value of repeated ANOVA; ^b, significant difference between at base line and after 1 year at p ＜ 0.05; ^c, significant difference between after 1 year and after 2 year sat p ＜ 0.05.SE, Standard error.

Table 6.

Comparison of scores for the linear and angular craniofacial variables between children of short and normal stature from baseline to after 2 years

	Childrren of short sttature			Children of normal stature
Variables	Atbaseline (n=19) Mean(SE)	After2years (n=19) Mean(SE)	Difference (n=19) Mean(SE)	Atbaseline A (n=19) Mean(SE)	After2years (n=19) Mean(SE)	Difference (n=19) Mean(SE)	p^a	p^b
Linear(mm) ACB	65.71(0.61)	69.63(0.58)	3.92(0.34)	67.45(0.46)	68.71(0.45)	1.26(0.14)	0.001	0.001
PCB	45.56(0.58)	48.63(0.54)	3.07(0.38)	46.71(0.84)	48.50(0.81)	1.79(0.26)	0.018	0.020
TCB	102.58(1.01)	105.08(1.04)	2.50(0.66)	104.50(0.85)	107.08(0.83)	2.58(0.30)	0.628	0.611
UAFH	52.55(0.72)	55.05(0.65)	2.50(0.29)	54.24(0.78)	56.47(0.78)	2.24(0.23)	0.811	0.811
UPFH	47.05(0.42)	49.92(0.51)	2.87(0.43)	49.03(0.76)	50.74(0.75)	1.71(0.29)	0.110	0.120
LAFH	66.84(0.87)	71.84(0.96)	5.00(0.64)	64.46(0.82)	67.11(0.84)	2.65(0.24)	0.001	0.001
ATFH	117.92(1.58)	123.90(1.58)	5.97(1.57)	117.40(1.36)	122.14(1.34)	4.74(0.32)	0.358	0.365
PTFH	69.11(1.22)	78.16(0.79)	9.05(0.86)	74.22(1.39)	79.29(1.45)	5.07(0.36)	0.005	0.005
MaxL	45.40(0.85)	48.92(0.76)	3.53(0.38)	46.95(0.75)	49.25(0.72)	2.31(0.41)	0.096	0.096
MandRL	L 37.79(1.04)	44.18(0.80)	6.40(0.71)	42.61(1.20)	45.68(1.25)	3.08(0.43)	0.011	0.012
MandCL	L 70.50(0.83)	75.53(0.88)	5.03(0.45)	74.63(0.98)	77.89(0.89)	3.26(0.41)	0.078	0.078
OMandL	L 99.32(1.21)	106.16(1.20)	6.84(0.87)	101.97(1.37)	106.24(1.11)	4.26(0.59)	0.061	0.061
Angular(°) SA	127.90(1.26)	126.37(0.94)	-1.53(1.56)	123.97(0.74)	124.00(0.85)	0.03(0.37)	0.344	0.344
GA	125.58(0.87)	126.66(1.14)	1.08(1.32)	124.71(1.22)	124.45(1.37)	-0.26(0.39)	0.269	0.269
MPA	37.82(0.92)	35.47(0.85)	-2.34(0.31)	33.24(1.15)	32.32(1.31)	-0.92(0.28)	0.004	0.004
SNA	78.68(0.74)	79.24(0.72)	0.56(0.50)	80.90(0.67)	81.44(0.69)	0.54(0.29)	0.542	0.542
SNB	74.74(0.74)	76.61(0.71)	1.87(0.42)	77.66(0.53)	78.72(0.55)	1.06(0.22)	0.465	0.482
ANB	3.95(0.37)	2.53(0.40)	-1.42(0.24)	3.21(0.39)	2.72(0.37)	-0.49(0.29)	0.047	0.047
PPMand	d 82.97(4.20)	87.45(0.76)	4.47(4.28)	87.76(1.00)	88.13(0.81)	0.37(0.47)	0.652	0.609

p^a, p value of ANCOVA between children of short and normal stature after 2 years; p^b, p value of ANCOVA between children of short and normal stature for difference values. SE, Standard error.

Table 7.

Correlation among the linear and angular craniofacial variables and the z scores of weight and height, BMI, and the bone age in 19 treated short children; difference from baseline to after 2 years

Variables	Weight			Height			BMI			Boneage
Variables	T0-T1	T1-T2	T0-T2	T0-T1T	T1-T2T	T0-T2	T0-T1	T1-T2	T0-T2	T0-T1	T1-T2	T0-T2
Linear(mm) ACB	-0.28	-0.06	-0.55^∗	-0.27	0.01	-0.34	-0.33	-0.42	-0.41	-0.06	-0.26	-0.12
PCB	0.02	0.07	0.03	-0.15	0.06	-0.41	0.79	-0.08	0.18	-0.15	-0.17	-0.16
TCB	0.20	0.23	0.11	0.11	0.06	0.11	0.07	0.12	-0.03	0.06	0.33	0.35
UAFH	-0.18	0.22	-0.12	0.01	0.13	0.20	-0.25	0.21	-0.13	0.14	0.04	0.09
UPFH	-0.05	-0.06	0.15	0.14	0.01	0.14	-0.01	-0.14	0.08	-0.05	0.27	0.16
LAFH	0.07	0.15	-0.04	-0.14	0.05	-0.10	0.15	0.13	0.11	-0.19	-0.23	-0.48^∗
ATFH	-0.36	0.22	-0.16	-0.35	0.29	0.04	-0.23	0.19	0.02	0.26	-0.16	0.14
PTFH	-0.28	-0.28	-0.47^∗	-0.28	0.33	-0.14	-0.24	-0.33	-0.44	0.42	-0.26	0.14
MaxL	0.13	-0.22	0.02	0.13	0.20	0.19	-0.11	-0.23	-0.10	-0.35	-0.31	-0.25
MandRL	0.19	0.32	0.44	0.13	0.10	0.10	0.20	0.36	0.58^∗	0.30	-0.38	0.05
MandCL	-0.16	0.02	-0.33	-0.18	0.48^∗	0.16	-0.03	-0.10	-0.32	0.15	-0.12	-0.05
OMandL	-0.20	0.09	-0.21	-0.07	0.08	-0.15	-0.03	0.13	-0.05	0.19	-0.47^∗	-0.24
Angular(°) SA	0.15	0.07	-0.25	0.28	-0.22	-0.30	-0.12	0.17	-0.25	0.52^∗	-0.27	0.09
GA	-0.26	0.08	-0.15	-0.12	0.05	0.00	-0.16	-0.08	-0.19	-0.48^∗	-0.04	-0.41
MPA	-0.12	-0.01	-0.19	0.27	0.46^∗	0.42	-0.31	-0.23	-0.41	-0.29	0.04	-0.05
SNA	0.11	-0.22	0.39	0.19	0.13	0.16	0.07	-0.26	0.37	-0.43	0.17	-0.35
SNB	0.22	-0.20	0.57^∗	0.25	0.17	0.24	0.13	-0.35	0.39	-0.41	0.06	-0.27
ANB	-0.22	0.21	-0.12	-0.07	-0.01	-0.08	-0.10	0.28	0.15	-0.21	0.27	-0.10
PPMand	-0.10	-0.39	0.02	0.18	0.33	0.41	-0.19	-0.43	-0.13	0.12	0.11	0.18

To, baseline; T1, after 1 year; T2, after 2 years. ∗ p ＜ 0.05.

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