Introduction: Primary hyperparathyroidism (PHPT) is rare and usually symptomatic in children. There is no approved medication to lower serum calcium levels in this patient group. Denosumab is used in adult patients with osteoporosis and hyperparathyroidism. To our knowledge, only 1 case of denosumab treatment in a child with severe PHPT has been reported to date. Case Presentation: A 16-year-old female was referred to our clinic with symptoms including pathologic fractures, nausea, emesis, and progressive weight loss. At admission, her serum total calcium was 4.17 mmol/L (reference range 2.15–2.55), parathyroid hormone 2,151 pg/mL (15–65), and phosphate 1.07 mmol/L (1.45–1.78). Due to potentially life-threatening hypercalcemia, denosumab 60 mg subcutaneously was administered after obtaining informed consent. Serum calcium levels were reduced within 12 h of injection and the patient’s condition rapidly improved, which allowed genetic testing to be done prior to surgery. A heterozygous mutation in the CDC73 gene was revealed, and a parathyroidectomy was performed on day 22 after denosumab administration. Morphological examination revealed solitary parathyroid adenoma. After surgery, hypocalcemia developed requiring high doses of alfacalcidol and calcium supplements. Conclusion: Our case supports the previous observations in adults that denosumab can be safely and effectively used as a preoperative treatment in patients with PHPT and severe hypercalcemia and shows that it may be used in pediatric patients.

1.
Alagaratnam
S
,
Kurzawinski
TR
.
Aetiology, diagnosis and surgical treatment of primary hyperparathyroidism in children: new trends
.
Horm Res Paediatr
.
2015
;
83
(
6
):
365
75
.
2.
Roizen
J
,
Levine
MA
.
Primary hyperparathyroidism in children and adolescents
.
J Chin Med Assoc
.
2012 Sep
;
75
(
9
):
425
34
.
3.
Iacobone
M
,
Carnaille
B
,
Palazzo
FF
,
Vriens
M
.
Hereditary hyperparathyroidism: a consensus report of the European Society of Endocrine Surgeons (ESES)
.
Langenbecks Arch Surg
.
2015 Dec
;
400
(
8
):
867
86
.
4.
Lewiecki
EM
.
New and emerging concepts in the use of denosumab for the treatment of osteoporosis
.
Ther Adv Musculoskelet Dis
.
2018
;
10
(
11
):
209
23
.
5.
Pugliese
F
,
de Martino
D
,
Scillitani
A
,
Carnevalle
V
.
Denosumab as a bridge to surgery in patients with primary hyperparathyroidism, severe hypercalcemia and renal impairment
.
Curr Trends Endocrinol
.
2016
;
8
:
41
4
.
6.
Rajan
R
,
Cherian
KE
,
Kapoor
N
,
Paul
TV
.
Denosumab as a bridge to surgery in a patient with severe hypercalcemia due to primary hyperparathyroidism in the setting of renal dysfunction
.
Indian J Endocrinol Metab
.
2019 Mar-Apr
;
23
(
2
):
269
70
.
7.
Vellanki
P
,
Lange
K
,
Elaraj
D
,
Kopp
PA
,
El Muayed
M
.
Denosumab for management of parathyroid carcinoma-mediated hypercalcemia
.
J Clin Endocrinol Metab
.
2014 Feb
;
99
(
2
):
387
90
.
8.
Fountas
A
,
Andrikoula
M
,
Giotaki
Z
,
Limniati
C
,
Tsakiridou
E
,
Tigas
S
, et al
The emerging role of denosumab in the long-term management of parathyroid carcinoma-related refractory hypercalcemia
.
Endocr Pract
.
2015 May
;
21
(
5
):
468
73
.
9.
Karuppiah
D
,
Thanabalasingham
G
,
Shine
B
,
Wang
LM
,
Sadler
GP
,
Karavitaki
N
, et al
Refractory hypercalcaemia secondary to parathyroid carcinoma: response to high-dose denosumab
.
Eur J Endocrinol
.
2014 Jul
;
171
(
1
):
K1
5
.
10.
Eller-Vainicher
C
,
Palmieri
S
,
Cairoli
E
,
Goggi
G
,
Scillitani
A
,
Arosio
M
, et al
Protective effect of denosumab on bone in older women with primary hyperparathyroidism
.
J Am Geriatr Soc
.
2018 Mar
;
66
(
3
):
518
24
.
11.
Semler
O
,
Netzer
C
,
Hoyer-Kuhn
H
,
Becker
J
,
Eysel
P
,
Schoenau
E
.
First use of the RANKL antibody denosumab in osteogenesis imperfecta type VI
.
J Musculoskelet Neuronal Interact
.
2012 Sep
;
12
(
3
):
183
8
.
12.
Hoyer-Kuhn
H
,
Franklin
J
,
Allo
G
,
Kron
M
,
Netzer
C
,
Eysel
P
, et al
Safety and efficacy of denosumab in children with osteogenesis imperfect: a first prospective trial
.
J Musculoskelet Neuronal Interact
.
2016 Mar
;
16
(
1
):
24
32
.
13.
Trejo
P
,
Rauch
F
,
Ward
L
.
Hypercalcemia and hypercalciuria during denosumab treatment in children with osteogenesis imperfecta type VI
.
J Musculoskelet Neuronal Interact
.
2018 Mar 1
;
18
(
1
):
76
80
.
14.
Boyce
AM
,
Chong
WH
,
Yao
J
,
Gafni
RI
,
Kelly
MH
,
Chamberlain
CE
, et al
Denosumab treatment for fibrous dysplasia
.
J Bone Miner Res
.
2012 Jul
;
27
(
7
):
1462
70
.
15.
Lange
T
,
Stehling
C
,
Fröhlich
B
,
Klingenhöfer
M
,
Kunkel
P
,
Schneppenheim
R
, et al
Denosumab: a potential new and innovative treatment option for aneurysmal bone cysts
.
Eur Spine J
.
2013 Jun
;
22
(
6
):
1417
22
.
16.
Dürr
HR
,
Grahneis
F
,
Baur-Melnyk
A
,
Knösel
T
,
Birkenmaier
C
,
Jansson
V
, et al
Aneurysmal bone cyst: results of an off label treatment with denosumab
.
BMC Musculoskelet Disord
.
2019 Oct 20
;
20
(
1
):
456
.
17.
Raux
S
,
Bouhamama
A
,
Gaspar
N
,
Brugières
L
,
Entz-Werlé
N
,
Mallet
C
, et al
Denosumab for treating aneurysmal bone cysts in children
.
Orthop Traumatol Surg Res
.
2019 Oct
;
105
(
6
):
1181
5
.
18.
Upfill-Brown
A
,
Bukata
S
,
Bernthal
NM
,
Felsenfeld
AL
,
Nelson
SD
,
Singh
A
, et al
Use of denosumab in children with osteoclast bone dysplasias: report of three cases
.
JBMR Plus
.
2019 Aug 22
;
3
(
10
):
e10210
.
19.
Karras
NA
,
Polgreen
LE
,
Ogilvie
C
,
Manivel
JC
,
Skubitz
KM
,
Lipsitz
E
.
Denosumab treatment of metastatic giant-cell tumor of bone in a 10-year-old girl
.
J Clin Oncol
.
2013 Apr 20
;
31
(
12
):
e200
2
.
20.
Grasemann
C
,
Schündeln
MM
,
Hövel
M
,
Schweiger
B
,
Bergmann
C
,
Herrmann
R
, et al
Effects of RANK-ligand antibody (denosumab) treatment on bone turnover markers in a girl with juvenile Paget’s disease
.
J Clin Endocrinol Metab
.
2013 Aug
;
98
(
8
):
3121
6
.
21.
Kumaki
D
,
Nakamura
Y
,
Sakai
N
,
Kosho
T
,
Nakamura
A
,
Hirabayashi
S
, et al
Efficacy of denosumab for glucocorticoid-induced osteoporosis in an adolescent patient with Duchenne muscular dystrophy: a case report
.
JBJS Case Connect
.
2018 Apr–Jun
;
8
(
2
):
e22
.
22.
Vázquez
MA
,
Pérez-Temprano
R
,
Montoya
MJ
,
Giner
M
,
Carpio
J
,
Pérez-Cano
R
.
Response to denosumab treatment for 2 years in an adolescent with osteoradionecrosis
.
J Bone Miner Res
.
2015 Oct
;
30
(
10
):
1790
6
.
23.
Kugushev
AY
,
Lopatin
AV
,
Yasonov
SA
.
Probl sotsialnoi gig zdravookhranenniiai istor med. [unique experience of cherubism targeted therapy]
.
Probl Sotsialnoi Gig Zdravookhranenniiai Istor Med
.
2019 Aug
;
27
(
Special Issue
):
608
22
.
24.
Shroff
R
,
Beringer
O
,
Rao
K
,
Hofbauer
LC
,
Schulz
A
.
Denosumab for post-transplantation hypercalcemia in osteopetrosis
.
N Engl J Med
.
2012 Nov 1
;
367
(
18
):
1766
7
.
25.
Giri
D
,
Ramakrishnan
R
,
Hayden
J
,
Brook
L
,
Das
U
,
Mughal
MZ
, et al
Denosumab therapy for refractory hypercalcemia secondary to squamous cell carcinoma of skin in epidermolysis bullosa
.
World J Oncol
.
2015 Apr
;
6
(
2
):
345
8
.
26.
Lenherr-Taube
N
,
Lam
CK
,
Vali
R
,
Shammas
A
,
Campisi
P
,
Zawawi
F
, et al
Severe primary hyperparathyroidism caused by parathyroid carcinoma in a 13-year-old child; novel findings from HRpQCT
.
JBMR Plus
.
2020 Mar
;
4
(
3
):
e10324
.
27.
Wang
K
,
Li
M
,
Hakonarson
H
.
ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data
.
Nucleic Acids Res
.
2010
;
38
(
16
):
e164
.
28.
den Dunnen
JT
,
Dalgleish
R
,
Maglott
DR
,
Hart
RK
,
Greenblatt
MS
,
McGowan-Jordan
J
, et al
HGVS recommendations for the description of sequence variants: 2016 update
.
Hum Mutat
.
2016
;
37
(
6
):
564
9
.
29.
Haven
CJ
,
van Puijenbroek
M
,
Tan
MH
,
Teh
BT
,
Fleuren
GJ
,
van Wezel
T
, et al
Identification of MEN1 and HRPT2 somatic mutations in paraffin-embedded (sporadic) parathyroid carcinomas
.
Clin Endocrinol
.
2007
;
67
(
3
):
370
6
.
30.
Hosking
DJ
,
Cowley
A
,
Bucknall
CA
.
Rehydration in the treatment of severe hypercalcaemia
.
Q J Med
.
1981
;
50
(
200
):
473
81
.
31.
Singer
FR
,
Ritch
PS
,
Lad
TE
,
Ringenberg
QS
,
Schiller
JH
,
Recker
RR
, et al
Treatment of hypercalcemia of malignancy with intravenous etidronate. A controlled, multicenter study. The hypercalcemia study group
.
Arch Intern Med
.
1991
;
151
(
3
):
471
6
.
32.
Silva
BC
,
Bilezikian
JP
.
Parathyroid hormone: anabolic and catabolic actions on the skeleton
.
Curr Opin Pharmacol
.
2015 Jun
;
22
:
41
50
.
33.
Kir
S
,
Komaba
H
,
Garcia
AP
,
Economopoulos
KP
,
Liu
W
,
Lanske
B
, et al
PTH/PTHrP receptor mediates cachexia in models of kidney failure and cancer
.
Cell Metab
.
2016 Feb 9
;
23
(
2
):
315
23
.
34.
Bonnet
N
,
Bourgoin
L
,
Biver
E
,
Douni
E
,
Ferrari
S
.
RANKL inhibition improves muscle strength and insulin sensitivity and restores bone mass
.
J Clin Invest
.
2019 May 23
;
129
(
8
):
3214
23
.
35.
Hamoudi
D
,
Marcadet
L
,
Piette Boulanger
A
,
Yagita
H
,
Bouredji
Z
,
Argaw
A
, et al
An anti-RANKL treatment reduces muscle inflammation and dysfunction and strengthens bone in dystrophic mice
.
Hum Mol Genet
.
2019 Sep 15
;
28
(
18
):
3101
12
.
36.
Chotiyarnwong
P
,
McCloskey
E
,
Eastell
R
,
McClung
MR
,
Gielen
E
,
Gostage
J
, et al
Pooled analysis of fall incidence from placebo-controlled trials of denosumab
.
J Bone Miner Res
.
2020 Jun
;
35
(
6
):
1014
21
.
37.
Witteveen
JE
,
van Thiel
S
,
Romijn
JA
,
Hamdy
NA
.
Hungry bone syndrome: still a challenge in the post-operative management of primary hyperparathyroidism: a systematic review of the literature
.
Eur J Endocrinol
.
2013 Feb 20
;
168
(
3
):
R45
53
.
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.