Introduction: Muscle and bone metabolism are both important for the healing of fractures and the regeneration of injured muscle tissue. The aim of this investigation was to evaluate myostatin and other regulating factors in patients with hip fractures who underwent hemi-arthroplasty. Methods: Serum levels of myostatin (MSTN), follistatin (FSTN), dickkopf-1 (Dkk1), and periostin (PSTN) as well as markers of bone turnover were evaluated in patients with hip fractures before surgery and twice in the 2 weeks after surgery. These parameters were also evaluated in age- and gender-matched subjects without major musculoskeletal injury. Results: MSTN was transiently reduced; its opponent FSTN was transiently increased. Dkk1, the negative regulator of bone mass, and PSTN, a marker of subperiosteal bone formation, increased after surgery. With regard to markers of bone turnover, resorption was elevated during the entire period of observation whereas the early bone formation marker N-terminal propeptide of type I collagen was elevated 12 days after surgery. Conclusions: Unexpectedly, MSTN, a negative regulator of muscle growth, was reduced after surgery compared with before surgery. As musculoskeletal markers are altered during bone healing, they do not reflect general bone metabolism after fracture or joint arthroplasty. This is important because many elderly patients receive treatment for osteoporosis.

1.
Cooper
C
,
Cole
ZA
,
Holroyd
CR
,
Earl
SC
,
Harvey
NC
,
Dennison
EM
, et al.;
IOF CSA Working Group on Fracture Epidemiology
.
Secular trends in the incidence of hip and other osteoporotic fractures
.
Osteoporos Int
.
2011
May
;
22
(
5
):
1277
88
.
[PubMed]
0937-941X
2.
Cooper
C
,
Campion
G
,
Melton
LJ
 3rd
.
Hip fractures in the elderly: a world-wide projection
.
Osteoporos Int
.
1992
Nov
;
2
(
6
):
285
9
.
[PubMed]
0937-941X
3.
Kawao
N
,
Kaji
H
.
Interactions between muscle tissues and bone metabolism
.
J Cell Biochem
.
2015
May
;
116
(
5
):
687
95
.
[PubMed]
0730-2312
4.
Bonewald
L
.
Use it or lose it to age: A review of bone and muscle communication
.
Bone
.
2019
Mar
;
120
:
212
8
.
[PubMed]
8756-3282
5.
Liu
R
,
Schindeler
A
,
Little
DG
.
The potential role of muscle in bone repair
.
J Musculoskelet Neuronal Interact
.
2010
Mar
;
10
(
1
):
71
6
.
[PubMed]
1108-7161
6.
Cho
TJ
,
Gerstenfeld
LC
,
Einhorn
TA
.
Differential temporal expression of members of the transforming growth factor beta superfamily during murine fracture healing
.
J Bone Miner Res
.
2002
Mar
;
17
(
3
):
513
20
.
[PubMed]
0884-0431
7.
Kellum
E
,
Starr
H
,
Arounleut
P
,
Immel
D
,
Fulzele
S
,
Wenger
K
, et al.
Myostatin (GDF-8) deficiency increases fracture callus size, Sox-5 expression, and callus bone volume
.
Bone
.
2009
Jan
;
44
(
1
):
17
23
.
[PubMed]
8756-3282
8.
Hamrick
MW
,
Arounleut
P
,
Kellum
E
,
Cain
M
,
Immel
D
,
Liang
LF
.
Recombinant myostatin (GDF-8) propeptide enhances the repair and regeneration of both muscle and bone in a model of deep penetrant musculoskeletal injury
.
J Trauma
.
2010
Sep
;
69
(
3
):
579
83
.
[PubMed]
0022-5282
9.
Elkasrawy
M
,
Fulzele
S
,
Bowser
M
,
Wenger
K
,
Hamrick
M
.
Myostatin (GDF-8) inhibits chondrogenesis and chondrocyte proliferation in vitro by suppressing Sox-9 expression
.
Growth Factors
.
2011
Dec
;
29
(
6
):
253
62
.
[PubMed]
0897-7194
10.
Elkasrawy
M
,
Immel
D
,
Wen
X
,
Liu
X
,
Liang
LF
,
Hamrick
MW
.
Immunolocalization of myostatin (GDF-8) following musculoskeletal injury and the effects of exogenous myostatin on muscle and bone healing
.
J Histochem Cytochem
.
2012
Jan
;
60
(
1
):
22
30
.
[PubMed]
0022-1554
11.
Reardon
KA
,
Davis
J
,
Kapsa
RM
,
Choong
P
,
Byrne
E
.
Myostatin, insulin-like growth factor-1, and leukemia inhibitory factor mRNAs are upregulated in chronic human disuse muscle atrophy
.
Muscle Nerve
.
2001
Jul
;
24
(
7
):
893
9
.
[PubMed]
0148-639X
12.
Zhu
X
,
Topouzis
S
,
Liang
LF
,
Stotish
RL
.
Myostatin signaling through Smad2, Smad3 and Smad4 is regulated by the inhibitory Smad7 by a negative feedback mechanism
.
Cytokine
.
2004
Jun
;
26
(
6
):
262
72
.
[PubMed]
1043-4666
13.
Lee
SJ
,
McPherron
AC
.
Regulation of myostatin activity and muscle growth
.
Proc Natl Acad Sci USA
.
2001
Jul
;
98
(
16
):
9306
11
.
[PubMed]
0027-8424
14.
Dovjak
P
,
Dorfer
S
,
Föger-Samwald
U
,
Kudlacek
S
,
Marculescu
R
,
Pietschmann
P
.
Serum levels of sclerostin and dickkopf-1: effects of age, gender and fracture status
.
Gerontology
.
2014
;
60
(
6
):
493
501
.
[PubMed]
0304-324X
15.
Wanby
P
,
Nobin
R
,
Von
SP
,
Brudin
L
,
Carlsson
M
.
Serum levels of the bone turnover markers dickkopf-1, sclerostin, osteoprotegerin, osteopontin, osteocalcin and 25-hydroxyvitamin D in Swedish geriatric patients aged 75 years or older with a fresh hip fracture and in healthy controls
.
J Endocrinol Invest
.
2016
Aug
;
39
(
8
):
855
63
.
[PubMed]
0391-4097
16.
Hara
M
,
Yokota
K
,
Saito
T
,
Kobayakawa
K
,
Kijima
K
,
Yoshizaki
S
, et al.
Periostin Promotes Fibroblast Migration and Inhibits Muscle Repair After Skeletal Muscle Injury
.
J Bone Joint Surg Am
.
2018
Aug
;
100
(
16
):
e108
.
[PubMed]
0021-9355
17.
van Varsseveld
NC
,
Sohl
E
,
Drent
ML
,
Lips
P
.
Gender-specific associations of serum insulin-like growth factor-1 with bone health and fractures in older persons
.
J Clin Endocrinol Metab
.
2015
Nov
;
100
(
11
):
4272
81
.
[PubMed]
0021-972X
18.
Lau
KW
,
Rundle
CH
,
Zhou
XD
,
Baylink
DJ
,
Sheng
MH
.
Conditional deletion of IGF-I in osteocytes unexpectedly accelerates bony union of the fracture gap in mice
.
Bone
.
2016
Nov
;
92
:
18
28
.
[PubMed]
8756-3282
19.
Chisalita
SI
,
Chong
LT
,
Wajda
M
,
Adolfsson
L
,
Woisetschläger
M
,
Spångeus
A
.
Association of Insulin-like growth factor -1, bone mass and inflammation to low-energy distal radius fractures and fracture healing in elderly women attending emergency care
.
Orthop Surg
.
2017
Nov
;
9
(
4
):
380
5
.
[PubMed]
1757-7853
20.
Garden
RS
. Stability and union in subcapital fractures of the femur. J Bone Joint Surg.
1964
; 46 B: 630-47.
21.
Bertin
KC
,
Röttinger
H
.
Anterolateral mini-incision hip replacement surgery: a modified Watson-Jones approach
.
Clin Orthop Relat Res
.
2004
Dec
;(
429
):
248
55
.
[PubMed]
0009-921X
22.
Quan
H
,
Sundararajan
V
,
Halfon
P
,
Fong
A
,
Burnand
B
,
Luthi
JC
, et al.
Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data
.
Med Care
.
2005
Nov
;
43
(
11
):
1130
9
.
[PubMed]
0025-7079
23.
Knuf
KM
,
Maani
CV
,
Cummings
AK
.
Clinical agreement in the American Society of Anesthesiologists physical status classification.
Perioper Med (Lond).
2018
; 7: 14. doi: . eCollection 2018.
24.
Roh
YH
,
Hong
SW
,
Chung
SW
,
Lee
YS
.
Altered gene and protein expressions of vitamin D receptor in skeletal muscle in sarcopenic patients who sustained distal radius fractures
.
J Bone Miner Metab
.
2019
Sep
;
37
(
5
):
920
7
.
[PubMed]
0914-8779
25.
Delfino
GB
,
Peviani
SM
,
Durigan
JL
,
Russo
TL
,
Baptista
IL
,
Ferretti
M
, et al.
Quadriceps muscle atrophy after anterior cruciate ligament transection involves increased mRNA levels of atrogin-1, muscle ring finger 1, and myostatin
.
Am J Phys Med Rehabil
.
2013
May
;
92
(
5
):
411
9
.
[PubMed]
0894-9115
26.
Silva
JM
,
Alabarse
PV
,
Teixeira
VO
,
Freitas
EC
,
de Oliveira
FH
,
Chakr
RM
, et al.
Muscle wasting in osteoarthritis model induced by anterior cruciate ligament transection
.
PLoS One
.
2018
Apr
;
13
(
4
):
e0196682
.
[PubMed]
1932-6203
27.
Inoue
S
,
Nomura
S
,
Hosoi
T
,
Ouchi
Y
,
Orimo
H
,
Muramatsu
M
.
Localization of follistatin, an activin-binding protein, in bone tissues
.
Calcif Tissue Int
.
1994
Nov
;
55
(
5
):
395
7
.
[PubMed]
0171-967X
28.
Nagamine
T
,
Imamura
T
,
Ishidou
Y
,
Kato
M
,
Murata
F
,
ten Dijke
P
, et al.
Immunohistochemical detection of activin A, follistatin, and activin receptors during fracture healing in the rat
.
J Orthop Res
.
1998
May
;
16
(
3
):
314
21
.
[PubMed]
0736-0266
29.
Benabdallah
BF
,
Bouchentouf
M
,
Rousseau
J
,
Tremblay
JP
.
Overexpression of follistatin in human myoblasts increases their proliferation and differentiation, and improves the graft success in SCID mice
.
Cell Transplant
.
2009
;
18
(
7
):
709
18
.
[PubMed]
0963-6897
30.
Zhu
J
,
Li
Y
,
Lu
A
,
Gharaibeh
B
,
Ma
J
,
Kobayashi
T
, et al.
Follistatin improves skeletal muscle healing after injury and disease through an interaction with muscle regeneration, angiogenesis, and fibrosis
.
Am J Pathol
.
2011
Aug
;
179
(
2
):
915
30
.
[PubMed]
0002-9440
31.
Yaden
BC
,
Croy
JE
,
Wang
Y
,
Wilson
JM
,
Datta-Mannan
A
,
Shetler
P
, et al.
Follistatin: a novel therapeutic for the improvement of muscle regeneration
.
J Pharmacol Exp Ther
.
2014
May
;
349
(
2
):
355
71
.
[PubMed]
0022-3565
32.
Kruck
B
,
Zimmermann
EA
,
Damerow
S
,
Figge
C
,
Julien
C
,
Wulsten
D
, et al.
Sclerostin neutralizing antibody treatment enhances bone formation but does not rescue mechanically induced delayed healing
.
J Bone Miner Res
.
2018
Sep
;
33
(
9
):
1686
97
.
[PubMed]
0884-0431
33.
Sarahrudi
K
,
Thomas
A
,
Albrecht
C
,
Aharinejad
S
.
Strongly enhanced levels of sclerostin during human fracture healing
.
J Orthop Res
.
2012
Oct
;
30
(
10
):
1549
55
.
[PubMed]
0736-0266
34.
Garnero
P
.
New developments in biological markers of bone metabolism in osteoporosis
.
Bone
.
2014
Sep
;
66
:
46
55
.
[PubMed]
8756-3282
35.
Duchamp de Lageneste
O
,
Julien
A
,
Abou-Khalil
R
,
Frangi
G
,
Carvalho
C
,
Cagnard
N
, et al.
Periosteum contains skeletal stem cells with high bone regenerative potential controlled by Periostin
.
Nat Commun
.
2018
Feb
;
9
(
1
):
773
.
[PubMed]
2041-1723
36.
Nakazawa
T
,
Nakajima
A
,
Seki
N
,
Okawa
A
,
Kato
M
,
Moriya
H
, et al.
Gene expression of periostin in the early stage of fracture healing detected by cDNA microarray analysis
.
J Orthop Res
.
2004
May
;
22
(
3
):
520
5
.
[PubMed]
0736-0266
37.
Yan
J
,
Liu
HJ
,
Li
H
,
Chen
L
,
Bian
YQ
,
Zhao
B
, et al.
Circulating periostin levels increase in association with bone density loss and healing progression during the early phase of hip fracture in Chinese older women
.
Osteoporos Int
.
2017
Aug
;
28
(
8
):
2335
41
.
[PubMed]
0937-941X
38.
Saribal
D
,
Hocaoglu-Emre
FS
,
Erdogan
S
,
Bahtiyar
N
,
Caglar Okur
S
,
Mert
M
.
Inflammatory cytokines IL-6 and TNF-α in patients with hip fracture
.
Osteoporos Int
.
2019
May
;
30
(
5
):
1025
31
.
[PubMed]
0937-941X
39.
Pesic
G
,
Jeremic
J
,
Nikolic
T
,
Zivkovic
V
,
Srejovic
I
,
Vranic
A
, et al.
Interleukin-6 as possible early marker of stress response after femoral fracture
.
Mol Cell Biochem
.
2017
Jun
;
430
(
1-2
):
191
9
.
[PubMed]
0300-8177
40.
Veitch
SW
,
Findlay
SC
,
Hamer
AJ
,
Blumsohn
A
,
Eastell
R
,
Ingle
BM
.
Changes in bone mass and bone turnover following tibial shaft fracture
.
Osteoporos Int
.
2006
;
17
(
3
):
364
72
.
[PubMed]
0937-941X
41.
Kanis
JA
,
Cooper
C
,
Rizzoli
R
,
Reginster
JY
;
Scientific Advisory Board of the European Society for Clinical and Economic Aspects of Osteoporosis (ESCEO) and the Committees of Scientific Advisors and National Societies of the International Osteoporosis Foundation (IOF)
.
European guidance for the diagnosis and management of osteoporosis in postmenopausal women
.
Osteoporos Int
.
2019
Jan
;
30
(
1
):
3
44
.
[PubMed]
0937-941X
42.
Zhou
W
,
Liu
Y
,
Guo
X
,
Yang
H
,
Xu
Y
,
Geng
D
.
Effects of zoledronic acid on bone mineral density around prostheses and bone metabolism markers after primary total hip arthroplasty in females with postmenopausal osteoporosis
.
Osteoporos Int
.
2019
Aug
;
30
(
8
):
1581
9
.
[PubMed]
0937-941X
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.