Background: Longitudinal bone growth is regulated by multiple endocrine signals (e.g., growth hormone, insulin-like growth factor I, estrogen, and androgen) and local factors (e.g., fibroblast growth factors and their receptors and the C-natriuretic peptide/natriuretic peptide receptor-B pathway). Summary: Abnormalities in both endocrine and local regulation of growth plate physiology cause many disorders of human skeletal growth. Knowledge of these pathways creates therapeutic potential for sustaining or even augmenting linear growth. Key Message: During the past 4 decades, advances in understanding growth plate physiology have been accompanied by development and implementation of growth-promoting treatments that have progressed in both efficacy and specificity of action. This paper reviews the history and continuing evolution of growth plate therapeutics.

1.
Ağırdil
Y
.
The growth plate: a physiologic overview
.
EFORT Open Rev
.
2020
;
5
(
8
):
498
507
. .
2.
Lui
JC
,
Nilsson
O
,
Baron
J
.
Growth plate senescence and catch-up growth
.
Endocr Dev
.
2011
;
21
:
23
9
. .
3.
Wang
J
,
Zhou
J
,
Bondy
CA
.
IGF1 promotes longitudinal bone growth by insulin-like actions augmenting chondrocyte hypertrophy
.
FASEB J
.
1999
;
13
(
14
):
1985
90
. .
4.
Nilsson
O
,
Marino
R
,
De Luca
F
,
Phillip
M
,
Baron
J
.
Endocrine regulation of the growth plate
.
Horm Res
.
2005
;
64
(
4
):
157
65
.
5.
Oz
OK
,
Millsaps
R
,
Welch
R
,
Birch
J
,
Zerwekh
JE
.
Expression of aromatase in the human growth plate
.
J Mol Endocrinol
.
2001
;
27
(
2
):
249
53
.
6.
Abu
EO
,
Horner
A
,
Kusec
V
,
Triffitt
JT
,
Compston
JE
.
The localization of androgen receptors in human bone
.
J Clin Endocrinol Metab
.
1997
;
82
(
10
):
3493
7
.
7.
Keenan
BS
,
Richards
GE
,
Ponder
SW
,
Dallas
JS
,
Nagamani
M
,
Smith
ER
,
Androgen-stimulated pubertal growth: the effects of testosterone and dihydrotestosterone on growth hormone and insulin-like growth factor-I in the treatment of short stature and delayed puberty
.
J Clin Endocrinol Metab
.
1993
;
76
(
4
):
996
1001
.
8.
Stevens
DA
,
Hasserjian
RP
,
Robson
H
,
Siebler
T
,
Shalet
SM
,
Williams
GR
.
Thyroid hormones regulate hypertrophic chondrocyte differentiation and expression of parathyroid hormone-related peptide and its receptor during endochondral bone formation
.
J Bone Miner Res
.
2000
;
15
(
12
):
2431
42
.
9.
Mazziotti
G
,
Giustina
A
.
Glucocorticoids and the regulation of growth hormone secretion
.
Nat Rev Endocrinol
.
2013
;
9
(
5
):
265
76
. .
10.
Allen
DB
,
Julius
JR
,
Breen
TJ
,
Attie
KM
.
Treatment of glucocorticoid-induced growth suppression with growth hormone. National Cooperative Growth Study
.
J Clin Endocrinol Metab
.
1998
;
83
(
8
):
2824
9
.
11.
Lui
JC
,
Baron
J
.
Effects of glucocorticoids on the growth plate
.
Endocr Dev
.
2011
;
20
:
187
93
. .
12.
Marino
R
,
Hegde
A
,
Barnes
KM
,
Schrier
L
,
Emons
JA
,
Nilsson
O
,
Catch-up growth after hypothyroidism is caused by delayed growth plate senescence
.
Endocrinology
.
2008
;
149
(
4
):
1820
8
.
13.
Shalitin
S
,
Kiess
W
.
Putative effects of obesity on linear growth and puberty
.
Horm Res Paediatr
.
2017
;
88
(
1
):
101
10
. .
14.
Nakajima
R
,
Inada
H
,
Koike
T
,
Yamano
T
.
Effects of leptin to cultured growth plate chondrocytes
.
Horm Res
.
2003
;
60
(
2
):
91
8
.
15.
Masarwi
M
,
Shamir
R
,
Phillip
M
,
Gat-Yablonski
G
.
Leptin stimulates aromatase in the growth plate: limiting catch-up growth efficiency
.
J Endocrinol
.
2018
;
237
(
3
):
229
42
.
16.
Reinehr
T
,
Roth
CL
.
Is there a causal relationship between obesity and puberty?
Lancet Child Adolesc Health
.
2019
;
3
(
1
):
44
54
. .
17.
Karimian
E
,
Chagin
AS
,
Sävendahl
L
.
Genetic regulation of the growth plate
.
Front Endocrinol
.
2012
;
2
:
113
. .
18.
Collett-Solberg
PF
,
Jorge
AAL
,
Boguszewski
MCS
,
Miller
BS
,
Choong
CSY
,
Cohen
P
,
Growth hormone therapy in children; research and practice: a review
.
Growth Horm IGF Res
.
2019
;
44
:
20
32
.
19.
Stephure
DK
.
Impact of growth hormone supplementation on adult height in Turner syndrome: results of the Canadian randomized controlled trial
.
J Clin Endocrinol Metab
.
2005
;
90
(
6
):
3360
6
. .
20.
van Pareren
YK
,
de Muinck Keizer-Schrama
SMPF
,
Stijnen
T
,
Sas
TCS
,
Jansen
M
,
Otten
BJ
,
Final height in girls with turner syndrome after long-term growth hormone treatment in three dosages and low dose estrogens
.
J Clin Endocrinol Metab
.
2003
;
88
(
3
):
1119
25
.
21.
Gravholt
CH
,
Andersen
NH
,
Conway
GS
,
Dekkers
OM
,
Geffner
ME
,
Klein
KO
,
Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting
.
Eur J Endocrinol
.
2017
;
177
(
3
):
G1
g70
.
22.
Murphy
N
,
Knuppel
A
,
Papadimitriou
N
,
Martin
RM
,
Tsilidis
KK
,
Smith-Byrne
K
,
Insulin-like growth factor-1, insulin-like growth factor-binding protein-3, and breast cancer risk: observational and Mendelian randomization analyses with ∼430 000 women
.
Ann Oncol
.
2020
;
31
(
5
):
641
9
.
23.
Larsson
SC
,
Carter
P
,
Vithayathil
M
,
Kar
S
,
Mason
AM
,
Burgess
S
.
Insulin-like growth factor-1 and site-specific cancers: a Mendelian randomization study
.
Cancer Med
.
2020
;
9
(
18
):
6836
42
.
24.
de Andre Cardoso-Demartini
A
,
Malaquias
AC
,
da Silva Boguszewski
MC
.
Growth hormone treatment for short children born small for gestational age
.
Pediatr Endocrinol Rev
.
2018
;
16
(
Suppl 1
):
105
12
. .
25.
Smeets
CC
,
Zandwijken
GRJ
,
Renes
JS
,
Hokken-Koelega
ACS
.
Long-term results of GH treatment in silver-russell syndrome (SRS): do they benefit the same as non-SRS short-SGA?
J Clin Endocrinol Metab
.
2016
;
101
(
5
):
2105
12
.
26.
Quigley
CA
.
Growth hormone treatment of non-growth hormone-deficient growth disorders
.
Endocrinol Metab Clin North Am
.
2007
;
36
(
1
):
131
86
. .
27.
van Gool
SA
,
Kamp
GA
,
Visser-van Balen
H
,
Mul
D
,
Waelkens
JJJ
,
Jansen
M
,
Final height outcome after three years of growth hormone and gonadotropin-releasing hormone agonist treatment in short adolescents with relatively early puberty
.
J Clin Endocrinol Metab
.
2007
;
92
(
4
):
1402
8
.
28.
Ranke
MB
,
Lindberg
A
,
Carlsson
M
,
Camacho-Hübner
C
,
Rooman
R
.
Treatment with growth hormone in noonan syndrome observed during 25 years of KIGS: near adult height and outcome prediction
.
Horm Res Paediatr
.
2019
;
91
(
1
):
46
55
.
29.
Gahunia
HK
,
Babyn
PS
,
Kirsch
S
,
Mendoza-Londono
R
.
Imaging of SHOX-associated anomalies
.
Semin Musculoskelet Radiol
.
2009
;
13
(
3
):
236
54
.
30.
Shima
H
,
Tanaka
T
,
Kamimaki
T
,
Dateki
S
,
Muroya
K
,
Horikawa
R
,
Systematic molecular analyses of SHOX in Japanese patients with idiopathic short stature and Leri-Weill dyschondrosteosis
.
J Hum Genet
.
2016
;
61
(
7
):
585
91
.
31.
Wolters
B
,
Lass
N
,
Wunsch
R
,
Böckmann
B
,
Austrup
F
,
Reinehr
T
.
Short stature before puberty: which children should be screened for SHOX deficiency?
Horm Res Paediatr
.
2013
;
80
(
4
):
273
80
.
32.
Blum
WF
,
Ross
JL
,
Zimmermann
AG
,
Quigley
CA
,
Child
CJ
,
Kalifa
G
,
GH treatment to final height produces similar height gains in patients with SHOX deficiency and Turner syndrome: results of a multicenter trial
.
J Clin Endocrinol Metab
.
2013
;
98
(
8
):
E1383
92
.
33.
Leschek
EW
,
Rose
SR
,
Yanovski
JK
,
Troendle
JF
,
Quigley
CA
,
Chipman
JJ
,
Effect of growth hormone treatment on adult height in peripubertal children with idiopathic short stature: a randomized, double-blind, placebo-controlled trial
.
J Clin Endocrinol Metab
.
2004
;
89
(
7
):
3140
8
.
34.
Scalco
RC
,
Melo
SSJ
,
Pugliese-Pires
PN
,
Funari
MFA
,
Nishi
MY
,
Arnhold
IJP
,
Effectiveness of the combined recombinant human growth hormone and gonadotropin-releasing hormone analog therapy in pubertal patients with short stature due to SHOX deficiency
.
J Clin Endocrinol Metab
.
2010
;
95
(
1
):
328
32
.
35.
Carrel
AL
,
Myers
SE
,
Whitman
BY
,
Allen
DB
.
Benefits of long-term GH therapy in Prader-Willi syndrome: a 4-year study
.
J Clin Endocrinol Metab
.
2002
;
87
(
4
):
1581
5
.
36.
Daughaday
WH
.
Growth hormone axis overview – somatomedin hypothesis
.
Pediatr Nephrol
.
2000
;
14
(
7
):
537
40
. .
37.
Phillips
LS
,
Herington
AC
,
Daughaday
WH
.
Steroid hormone effects on sonatomedin. I. Somatomedin action in vitro
.
Endocrinology
.
1975
;
97
(
4
):
780
6
. .
38.
Salmon
WD
 Jr
,
Daughaday
WH
.
The importance of amino acids as dialyzable components of rat serum which promote sulfate uptake by cartilage from hypophysectomized rats in vitro
.
J Lab Clin Med
.
1958
;
51
(
2
):
107
73
.
39.
Rotwein
P
,
William
H
.
William H. Daughaday and the foundations of modern research into growth hormone and the insulin-like growth factors
.
Pediatr Endocrinol Rev
.
2013
;
10
(
3
):
280
3
.
40.
Green
H
,
Morikawa
M
,
Nixon
T
.
A dual effector theory of growth-hormone action
.
Differentiation
.
1985
;
29
(
3
):
195
8
. .
41.
Wang
J
,
Zhou
J
,
Cheng
CM
,
Kopchick
JJ
,
Bondy
CA
.
Evidence supporting dual, IGF-I-independent and IGF-I-dependent, roles for GH in promoting longitudinal bone growth
.
J Endocrinol
.
2004
;
180
(
2
):
247
55
.
42.
Wu
S
,
Yang
W
,
De Luca
F
.
Insulin-like growth factor-independent effects of growth hormone on growth plate chondrogenesis and longitudinal bone growth
.
Endocrinology
.
2015
;
156
(
7
):
2541
51
. .
43.
Backeljauw
P
.
Therapy with recombinant human IGF-1 for children with primary insulin-like growth factor-I deficiency
.
Growth Horm IGF Res
.
2020
;
51
:
22
6
. .
44.
Backeljauw
PF
,
Kuntze
J
,
Frane
J
,
Calikoglu
AS
,
Chernausek
SD
.
Adult and near-adult height in patients with severe insulin-like growth factor-I deficiency after long-term therapy with recombinant human insulin-like growth factor-I
.
Horm Res Paediatr
.
2013
;
80
(
1
):
47
56
.
45.
Lui
JC
,
Colbert
M
,
Cheung
CSF
,
Ad
M
,
Lee
A
,
Zhu
Z
,
Cartilage-targeted IGF-1 treatment to promote longitudinal bone growth
.
Mol Ther
.
2019
;
27
(
3
):
673
80
.
46.
Carel
JC
,
Eugster
EA
,
Rogol
A
,
Ghizzoni
L
,
Palmert
MR
;
ESPE-LWPES GnRH Analogs Consensus Conference Group
;
Consensus statement on the use of gonadotropin-releasing hormone analogs in children
.
Pediatrics
.
2009
;
123
(
4
):
e752
62
.
47.
Comite
F
,
Cassorla
F
,
Barnes
KM
,
Hench
KD
,
Dwyer
A
,
Skerda
MC
,
Luteinizing hormone releasing hormone analogue therapy for central precocious puberty. Long-term effect on somatic growth, bone maturation, and predicted height
.
JAMA
.
1986
;
255
(
19
):
2613
6
.
48.
Pescovitz
OH
,
Comite
F
,
Hench
K
,
Barnes
K
,
McNemar
A
,
Foster
C
,
The NIH experience with precocious puberty: diagnostic subgroups and response to short-term luteinizing hormone releasing hormone analogue therapy
.
J Pediatr
.
1986
;
108
(
1
):
47
54
.
49.
Bangalore Krishna
K
,
Fuqua
JS
,
Rogol
AD
,
Klein
KO
,
Popovic
J
,
Houk
CP
,
Use of gonadotropin-releasing hormone analogs in children: update by an international consortium
.
Horm Res Paediatr
.
2019
;
91
(
6
):
357
72
.
50.
Kaplowitz
PB
,
Backeljauw
PF
,
Allen
DB
.
Toward more targeted and cost-effective gonadotropin-releasing hormone analog treatment in girls with central precocious puberty
.
Horm Res Paediatr
.
2018
;
90
(
1
):
1
7
. .
51.
Bereket
A
.
A critical appraisal of the effect of gonadotropin-releasing hormon analog treatment on adult height of girls with central precocious puberty
.
J Clin Res Pediatr Endocrinol
.
2017
;
9
(
Suppl 2
):
33
48
. .
52.
Palmert
MR
,
Malin
HV
,
Boepple
PA
.
Unsustained or slowly progressive puberty in young girls: initial presentation and long-term follow-up of 20 untreated patients
.
J Clin Endocrinol Metab
.
1999
;
84
(
2
):
415
23
. .
53.
Pasquino
AM
,
Pucarelli
I
,
Accardo
F
,
Demiraj
V
,
Segni
M
,
Di Nardo
R
.
Long-term observation of 87 girls with idiopathic central precocious puberty treated with gonadotropin-releasing hormone analogs: impact on adult height, body mass index, bone mineral content, and reproductive function
.
J Clin Endocrinol Metab
.
2008
;
93
(
1
):
190
5
.
54.
Wilson
DM
,
McCauley
E
,
Brown
DR
,
Dudley
R
.
Oxandrolone therapy in constitutionally delayed growth and puberty. Bio-Technology General Corporation Cooperative Study Group
.
Pediatrics
.
1995
;
96
(
6
):
1095
100
.
55.
Schroor
EJ
,
van Weissenbruch
MM
,
Knibbe
P
,
Delemarre-van de Waal
HA
.
The effect of prolonged administration of an anabolic steroid (oxandrolone) on growth in boys with constitutionally delayed growth and puberty
.
Eur J Pediatr
.
1995
;
154
(
12
):
953
7
.
56.
Poyrazoğlu
S
,
Günöz
H
,
Darendeliler
F
,
Saka
N
,
Bundak
R
,
Baş
F
.
Constitutional delay of growth and puberty: from presentation to final height
.
J Pediatr Endocrinol Metab
.
2005
;
18
(
2
):
171
9
.
57.
Arrigo
T
,
Cisternino
M
,
De
FL
,
Saggese
G
,
Messina
MF
,
Pasquino
AM
,
Final height outcome in both untreated and testosterone-treated boys with constitutional delay of growth and puberty
.
J Pediatr Endocrinol Metab
.
1996
;
9
(
5
):
511
7
.
58.
Malhotra
A
,
Poon
E
,
Tse
WY
,
Pringle
PJ
,
Hindmarsh
PC
,
Brook
CG
.
The effects of oxandrolone on the growth hormone and gonadal axes in boys with constitutional delay of growth and puberty
.
Clin Endocrinol
.
1993
;
38
(
4
):
393
8
.
59.
Gault
EJ
,
Cole
TJ
,
Casey
S
,
Hindmarsh
PC
,
Betts
P
,
Dunger
DB
,
Effect of oxandrolone and timing of pubertal induction on final height in Turner syndrome: final analysis of the UK randomised placebo-controlled trial
.
Arch Dis Child
.
2021
;
106
(
1
):
74
6
.
60.
Allen
DB
,
Cuttler
L
.
Clinical practice. Short stature in childhood – challenges and choices
.
N Engl J Med
.
2013
;
368
(
13
):
1220
8
. .
61.
Cutler
GB
 Jr
.
The role of estrogen in bone growth and maturation during childhood and adolescence
.
J Steroid Biochem Mol Biol
.
1997
;
61
(
3–6
):
141
4
. .
62.
Ross
JL
,
Quigley
CA
,
Cao
D
,
Feuillan
P
,
Kowal
K
,
Chipman
JJ
,
Growth hormone plus childhood low-dose estrogen in Turner’s syndrome
.
N Engl J Med
.
2011
;
364
(
13
):
1230
42
.
63.
Bierich
JR
.
Estrogen treatment of girls with constitutional tall stature
.
Pediatrics
.
1978
;
62
(
6 Pt 2
):
1196
201
.
64.
Venn
A
,
Hosmer
T
,
Hosmer
D
,
Bruinsma
F
,
Jones
P
,
Lumley
J
,
Oestrogen treatment for tall stature in girls: estimating the effect on height and the error in height prediction
.
Clin Endocrinol
.
2008
;
68
(
6
):
926
9
.
65.
Hendriks
AE
,
Drop
SLS
,
Laven
JSE
,
Boot
AM
.
Fertility of tall girls treated with high-dose estrogen, a dose-response relationship
.
J Clin Endocrinol Metab
.
2012
;
97
(
9
):
3107
14
.
66.
Venn
A
,
Bruinsma
F
,
Werther
G
,
Pyett
P
,
Baird
D
,
Jones
P
,
Oestrogen treatment to reduce the adult height of tall girls: long-term effects on fertility
.
Lancet
.
2004
;
364
(
9444
):
1513
8
.
67.
Lee
JM
,
Howell
JD
.
Tall girls: the social shaping of a medical therapy
.
Arch Pediatr Adolesc Med
.
2006
;
160
(
10
):
1035
9
. .
68.
Pollock
AJ
,
Fost
N
,
Allen
DB
.
Growth attenuation therapy: practice and perspectives of paediatric endocrinologists
.
Arch Dis Child
.
2015
;
100
(
12
):
1185
. .
69.
Drop
SL
,
De Waal
WJ
,
De Muinck Keizer-Schrama
SM
.
Sex steroid treatment of constitutionally tall stature
.
Endocr Rev
.
1998
;
19
(
5
):
540
58
. .
70.
Gunther
DF
,
Diekema
DS
.
Attenuating growth in children with profound developmental disability: a new approach to an old dilemma
.
Arch Pediatr Adolesc Med
.
2006
;
160
(
10
):
1013
7
. .
71.
Wolthers
OD
,
Allen
DB
.
Inhaled corticosteroids, growth, and compliance
.
N Engl J Med
.
2002
;
347
(
15
):
1210
1
. .
72.
Allen
DB
,
Kappy
M
,
Diekema
D
,
Fost
N
.
Growth-attenuation therapy: principles for practice
.
Pediatrics
.
2009
;
123
(
6
):
1556
61
.
73.
Börjesson
AE
,
Windahl
SH
,
Karimian
E
,
Eriksson
EE
,
Lagerquist
MK
,
Engdahl
C
,
The role of estrogen receptor-α and its activation function-1 for growth plate closure in female mice
.
Am J Physiol Endocrinol Metab
.
2012
;
302
(
11
):
E1381
9
.
74.
Estrada
A
,
Boyce
AM
,
Brillante
BA
,
Guthrie
LC
,
Gafni
RI
,
Collins
MT
.
Long-term outcomes of letrozole treatment for precocious puberty in girls with McCune-Albright syndrome
.
Eur J Endocrinol
.
2016
;
175
(
5
):
477
83
.
75.
Lanes
R
,
González Briceño
LG
.
Alternatives in the treatment of short stature
.
Adv Pediatr
.
2017
;
64
(
1
):
111
31
. .
76.
Ramchand
SK
,
Cheung
Y-M
,
Yeo
B
,
Grossmann
M
.
The effects of adjuvant endocrine therapy on bone health in women with breast cancer
.
J Endocrinol
.
2019
;
241
(
3
):
R111
24
.
77.
Mauras
N
,
de Pijem
LG
,
Hsiang
HY
,
Desrosiers
P
,
Rapaport
R
,
David Schwartz
I
,
Anastrozole increases predicted adult height of short adolescent males treated with growth hormone: a randomized, placebo-controlled, multicenter trial for one to three years
.
J Clin Endocrinol Metab
.
2008
;
93
(
3
):
823
31
.
78.
Mauras
N
,
Ross
JL
,
Gagliardi
P
,
Yu
YM
,
Hossain
J
,
Permuy
J
,
Randomized trial of aromatase inhibitors, growth hormone, or combination in pubertal boys with idiopathic, short stature
.
J Clin Endocrinol Metab
.
2016
;
101
(
12
):
4984
93
.
79.
Hero
M
,
Tommiska
J
,
Vaaralahti
K
,
Laitinen
E-M
,
Sipilä
I
,
Puhakka
L
,
Circulating antimüllerian hormone levels in boys decline during early puberty and correlate with inhibin B
.
Fertil Steril
.
2012
;
97
(
5
):
1242
7
.
80.
Salehpour
S
,
Alipour
P
,
Razzaghy-Azar
M
,
Ardeshirpour
L
,
Shamshiri
A
,
Monfared
MF
,
A double-blind, placebo-controlled comparison of letrozole to oxandrolone effects upon growth and puberty of children with constitutional delay of puberty and idiopathic short stature
.
Horm Res Paediatr
.
2010
;
74
(
6
):
428
35
.
81.
Shams
K
,
Cameo
T
,
Fennoy
I
,
Hassoun
AA
,
Lerner
SE
,
Aranoff
GS
,
Outcome analysis of aromatase inhibitor therapy to increase adult height in males with predicted short adult stature and/or rapid pubertal progress: a retrospective chart review
.
J Pediatr Endocrinol Metab
.
2014
;
27
(
7–8
):
725
30
.
82.
Ferris
JA
,
Geffner
ME
.
Are aromatase inhibitors in boys with predicted short stature and/or rapidly advancing bone age effective and safe?
J Pediatr Endocrinol Metab
.
2017
;
30
(
3
):
311
7
. .
83.
Hero
M
,
Norjavaara
E
,
Dunkel
L
.
Inhibition of estrogen biosynthesis with a potent aromatase inhibitor increases predicted adult height in boys with idiopathic short stature: a randomized controlled trial
.
J Clin Endocrinol Metab
.
2005
;
90
(
12
):
6396
402
. .
84.
Mauras
N
,
Bell
J
,
Snow
BG
,
Winslow
KL
.
Sperm analysis in growth hormone-deficient adolescents previously treated with an aromatase inhibitor: comparison with normal controls
.
Fertil Steril
.
2005
;
84
(
1
):
239
42
.
85.
Shulman
DI
,
Francis
GL
,
Palmert
MR
,
Eugster
EA
;
Lawson Wilkins Pediatric Endocrine Society Drug and Therapeutics Committee
.
Use of aromatase inhibitors in children and adolescents with disorders of growth and adolescent development
.
Pediatrics
.
2008
;
121
(
4
):
e975
83
.
86.
Rosenfeld
RG
,
Bakker
B
.
Compliance and persistence in pediatric and adult patients receiving growth hormone therapy
.
Endocr Pract
.
2008
;
14
(
2
):
143
54
. .
87.
Farfel
A
,
Shalitin
S
,
Morag
N
,
Meyerovitch
J
.
Long-term adherence to growth hormone therapy in a large health maintenance organization cohort
.
Growth Horm IGF Res
.
2019
;
44
:
1
5
.
88.
Cutfield
WS
,
Derraik
JGB
,
Gunn
AJ
,
Reid
K
,
Delany
T
,
Robinson
E
,
Non-compliance with growth hormone treatment in children is common and impairs linear growth
.
PLoS One
.
2011
;
6
(
1
):
e16223
.
89.
Lass
N
,
Reinehr
T
.
Low treatment adherence in pubertal children treated with thyroxin or growth hormone
.
Horm Res Paediatr
.
2015
;
84
(
4
):
240
7
. .
90.
Kapoor
RR
,
Burke
SA
,
Sparrow
SE
,
Hughes
IA
,
Dunger
DB
,
Ong
KK
,
Monitoring of concordance in growth hormone therapy
.
Arch Dis Child
.
2008
;
93
(
2
):
147
8
.
91.
De Pedro
S
,
Murillo
M
,
Salinas
I
,
Granada
M-L
,
Martinez
M
,
Puig-Domingo
M
,
Variability in adherence to rhGH treatment: socioeconomic causes and effect on children’s growth
.
Growth Horm IGF Res
.
2016
;
26
:
32
5
.
92.
Miller
BS
,
Velazquez
E
,
Yuen
KCJ
.
Long-acting growth hormone preparations – current status and future considerations
.
J Clin Endocrinol Metab
.
2020
;
105
(
6
):
e2121
33
. .
93.
Lippe
B
,
Frasier
SD
,
Kaplan
SA
.
Use of growth hormone-gel
.
Arch Dis Child
.
1979
;
54
(
8
):
609
13
. .
94.
Khadilkar
V
,
Radjuk
KA
,
Bolshova
E
,
Khadgawat
R
,
El Kholy
M
,
Desai
M
,
24-Month use of once-weekly GH, LB03002, in prepubertal children with GH deficiency
.
J Clin Endocrinol Metab
.
2014
;
99
(
1
):
126
32
.
95.
Luo
X
,
Hou
L
,
Liang
L
,
Dong
G
,
Shen
S
,
Zhao
Z
,
Long-acting PEGylated recombinant human growth hormone (Jintrolong) for children with growth hormone deficiency: phase II and phase III multicenter, randomized studies
.
Eur J Endocrinol
.
2017
;
177
(
2
):
195
205
.
96.
Thornton
PS
,
Maniatis
AK
,
Aghajanova
E
,
Chertok
E
,
Vlachopapadopoulou
E
,
Lin
Z
,
Weekly lonapegsomatropin in treatment-naïve children with growth hormone deficiency: the phase 3 heiGHt trial
.
J Clin Endocrinol Metab
.
2021
;
106
(
11
):
3184
95
.
97.
Deal
CL
,
Pastrak
A
,
Silverman
LA
,
Rao Valluri
S
,
Wajnrajch
MP
,
Cara
JF
.
OR10-06 somatrogon growth hormone in the treatment of pediatric growth hormone deficiency: results of the pivotal pediatric phase 3 clinical trial
.
J Endocr Soc
.
2020
;
4
(
Suppl_1
):
OR10-06
.
98.
Sävendahl
L
,
Battelino
T
,
Brod
M
,
Højby Rasmussen
M
,
Horikawa
R
,
Vestergaard Juul
R
,
Once-weekly somapacitan vs daily GH in children with GH deficiency: results from a randomized phase 2 trial
.
J Clin Endocrinol Metab
.
2020
;
105
(
4
):
e1847
61
.
99.
Blum
WF
,
Bright
GM
,
Do
M-HT
,
McKew
JC
,
Chen
H
,
Thorner
MO
.
Corroboration of height velocity prediction markers for rhGH with an oral GH secretagogue treatment in children with GHD
.
J Endocr Soc
.
2021
;
5
(
6
):
bvab029
.
100.
Bright
GM
,
Do
M-HT
,
McKew
JC
,
Blum
WF
,
Thorner
MO
.
Development of a predictive enrichment marker for the oral GH secretagogue LUM-201 in pediatric growth hormone deficiency
.
J Endocr Soc
.
2021
;
5
(
6
):
bvab030
.
101.
Hirota
K
,
Furuya
M
,
Morozumi
N
,
Yoshikiyo
K
,
Yotsumoto
T
,
Jindo
T
,
Exogenous C-type natriuretic peptide restores normal growth and prevents early growth plate closure in its deficient rats
.
PLoS One
.
2018
;
13
(
9
):
e0204172
.
102.
Wang
SR
,
Amano
N
,
Docko
AJ
,
Funari
MFA
,
Quedas
EPS
,
Nishi
MY
,
Heterozygous mutations in natriuretic peptide receptor-B (NPR2) gene as a cause of short stature
.
Hum Mutat
.
2015
;
36
(
4
):
474
81
.
103.
Hisado-Oliva
A
,
Garre-Vázquez
AI
,
Santaolalla-Caballero
F
,
Belinchón
A
,
Barreda-Bonis
AC
,
Vasques
GA
,
Heterozygous NPR2 mutations cause disproportionate short stature, similar to Léri-Weill dyschondrosteosis
.
J Clin Endocrinol Metab
.
2015
;
100
(
8
):
E1133
42
.
104.
Wendt
DJ
,
Dvorak-Ewell
M
,
Bullens
S
,
Lorget
F
,
Bell
SM
,
Peng
J
,
Neutral endopeptidase-resistant C-type natriuretic peptide variant represents a new therapeutic approach for treatment of fibroblast growth factor receptor 3-related dwarfism
.
J Pharmacol Exp Ther
.
2015
;
353
(
1
):
132
49
.
105.
Savarirayan
R
,
Irving
M
,
Bacino
CA
,
Bostwick
B
,
Charrow
J
,
Cormier-Daire
V
,
C-type natriuretic peptide analogue therapy in children with achondroplasia
.
N Engl J Med
.
2019
;
381
(
1
):
25
35
.
106.
Savarirayan
R
,
Tofts
L
,
Irving
M
,
Wilcox
W
,
Bacino
CA
,
Hoover-Fong
J
,
Once-daily, subcutaneous vosoritide therapy in children with achondroplasia: a randomised, double-blind, phase 3, placebo-controlled, multicentre trial
.
Lancet
.
2020
;
396
(
10252
):
684
92
.
107.
Savarirayan
R
,
Tofts
L
,
Irving
M
,
Wilcox
WR
,
Bacino
CA
,
Hoover-Fong
J
,
Safe and persistent growth-promoting effects of vosoritide in children with achondroplasia: 2-year results from an open-label, phase 3 extension study
.
Genet Med
.
2021
;
23
:
2443
7
.
108.
Gonçalves
D
,
Rignol
G
,
Dellugat
P
,
Hartmann
G
,
Garcia
SS
,
Stavenhagen
J
,
In vitro and in vivo characterization of recifercept, a soluble fibroblast growth factor receptor 3, as treatment for achondroplasia
.
PLoS One
.
2020
;
15
(
12
):
e0244368
.
109.
Komla-Ebri
D
,
Dambroise
E
,
Kramer
I
,
Benoist-Lasselin
C
,
Kaci
N
,
Le Gall
C
,
Tyrosine kinase inhibitor NVP-BGJ398 functionally improves FGFR3-related dwarfism in mouse model
.
J Clin Invest
.
2016
;
126
(
5
):
1871
84
.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.