中国组织工程研究 第 17 卷 第 39 期 2013–09–24 出版

Chinese Journal of Tissue Engineering Research September 24, 2013 Vol.17, No.39 www.CRTER.org

doi:10.3969/j.issn.2095-4344.2013.39.002 [http://www.crter.org]
Zeng YR, Jian LY, Feng WJ, Li J, Li FL, He S. Meloxicam versus indomethacin in the prevention of heterotopic ossification after total hip
arthroplasty, Zhongguo Zuzhi Gongcheng Yanjiu. 2013;17(39): 6867-6874.

Meloxicam versus indomethacin in the prevention of

heterotopic ossification after total hip arthroplasty☆
Zeng Yi-rong, Jian Lin-yang, Feng Wen-jun, Li Jie, Li Fei-long, He Sheng

Department of Orthopedics, the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou 510405,
Guangdong Province, China

Abstract
Zeng Yi-rong☆, M.D.,
BACKGROUND: In order to avoid heterotopic ossification after total hip arthroplasty, nonsteroidal
Professor, Department of
anti-inflammatory drugs are commonly used for prevention. Orthopedics, the First
OBJECTIVE: To compare the effect of meloxicam and indomethacin in the prevention of heterotopic ossification Affiliated Hospital of
Guangzhou University of
after total hip arthroplasty.
Traditional Chinese Medicine,
METHODS: Fifty-one patients who treated in the Department of Orthopedics, the First Affiliated Hospital of Guangzhou 510405,
Guangzhou University of Traditional Chinese Medicine from 2010 to 2011 were collected. Among the Guangdong Province, China

51 patients, nine patients were treated with bilateral total hip arthroplasty, and all the patients had total hip
Corresponding author:
arthroplasty with the posterior-lateral approach. The patients were divided into the control group and the Zeng Yi-rong, Department of
experimental group according to the drugs used after replacement, and the patients in the two groups were Orthopedics, the First
Affiliated Hospital of
administered with indomethacin sustained-release tablet 25 mg + omeprazole capsule 20 mg or meloxicam
Guangzhou University of
tablet 15 mg after replacement. Traditional Chinese Medicine,
RESULTS AND CONCLUSION: There were no significant differences in the incidence of heterotopic Guangzhou 510405,
Guangdong Province, China
ossification, pain, modified D’Aubigne and Postel scores after replacement between two groups (P > 0.05). But,
Zeng6612@139.com
the gastrointestinal adverse reactions of the experimental group were less than those of the control group. The
application of meloxicam only can effectively avoid the heterotopic ossification and release pain. Consequently, Received:2013-06-18
Accepted:2013-07-29
we recommend meloxicam as postoperative drug for the prevention of heterotopic ossification and pain
(201305067/YJ)
remission following total hip arthroplasty.

Subject headings: arthroplasty, replacement, hip; prosthesis implantation; anti-inflammatory agents,

non-steroidal; ossification, heterotopic

prevention and treatment. Many

INTRODUCTION
Heterotopic ossification has a definition that
non-calcification tissue has a tendency of
osteogenesis, and mature lamellar bone
occurs in the soft tissue around the articular.
It reported that the phenomenon of
heterotopic ossification companied by total
hip arthroplasty surgeries in 1972 at first,
which, to some severe extent, could largely
limit the range of motion of the hip[1]. So did
the efficacy of total hip arthroplasty surgeries.
With the widely development of total hip
arthroplasty surgeries, heterotopic
ossification around hip joint has attracted
more and more attention about its
research [2-4] , mainly centered on its etiology
and pathogenesis [5-8] , as well as its
documents at home and abroad have
reported the possible incidence of
heterotopic ossification ranged from 8%
to 90%[9-10] . Schmidt et al [11] discovered
an approximately incidence of 60% to
75% of heterotopic ossification without
taking any prevent measures.
To prevent heterotopic ossification, the
well-recognized treatments mainly include
the use of nonsteroidal antiinflammatory
drugs, bisphosphonates and local
radiation[12-16]. However, nonsteroidal
antiinflammatory drugs do great harm to
patients’ gastrointestinal tract, especially
for those who are over 65 years, so its
utilization is largely limited. Besides,
though nonsteroidal antiinflammatory

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 Zeng YR, et al. Meloxicam versus indomethacin in the prevention of heterotopic ossification after total hip arthroplasty
drugs can prevent the happening of heterotopic
ossification, it can also inhibit osteogenesis reaction[17],
which may affect the stablization of the uncemented
prosthesis. Moreover, it is rarely documented that
whether the use of nonsteroidal antiinflammatory drugs
can prevent heterotopic ossification after total hip
arthroplasty surgeries or not, because of lacking
long-term follow-up observation, as well as the reports
on the efficacy regarding the improvement of range of
motion of hip and prosthesis loosen. Therefore, our
study aimed at the clinical observations about
meloxicam tablet[18-21] , a kind of gastrointestinal
protective cyclooxygenase-(COX) 2 inhibitor drug, in
order to explore its efficacy in the prevention of
heterotopic ossification after total hip arthroplasty
surgeries, pain remission, safety, and the improvement
of range of motion of hip joint.
SUBJECTS AND METHODS
Design
A same period non-randomized controlled trials
Time and setting
The study was conducted in the Department of
Orthopedics, the First Affiliated Hospital of Guangzhou
University of Traditional Chinese Medicine from 2010 to
2011.
Subjects
We stated here that our study was compliance with
Helsinki Declaration and got the approval of the Ethics
Committee of the First Affiliated Hospital of Guangzhou
University of Chinese Medicine. Nearly 51 patients
(60 hips), who underwent total hop arthroplasty
surgeries with posterior and lateral approach in our
Department of Orthopedics from October 2010 to
October 2011, were recruited in our study. All the
patients were informed of relevant benefits and risks
though no written consent was not signed at that time.
Inclusion criterion: patients who underwent total hip
arthroplasty surgeries, whose ages ranged from 20 to
80 years.
Exclusion criterion: patients who had long-term
nonsteroidal antiinflammatory drugs usage history,
malignant tumor, forbidden usage of non-selective
nonsteroidal antiinflammatory drugs because of
relevant diseases (such as peptic ulcer, asthma and so
on), clear cardiovascular diseases (such as
hypertension, coronary diseases and so on), and
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history of mental illness.
Patients did not reveal apparently statistical difference
in the study and control group, no matter age, gender,
surgical approach, and operation time. So, it had
comparability between those two groups.
They were randomly divided into the control group
(n=23) and the experimental group (n=28).
Methods
Total hip arthroplasty
All the patients underwent the same posterior-lateral
approach with the same analgesia approach (mainly
continuity epidural analgesia, sometimes general
anesthesia). Besides, patients performed neither the
greater trochanter osteotomy, nor the proximal femur
osteotomy surgeries, and posterior joint capsule was
regularly sutured. They were all completed by the
same surgeon.
Drug intervention
After the surgeries, all patients used negative pressure
drainage tubes in case of formation of hematoma,
which were removed for 48 hours. Patients in the
control group were administered with indomethacin
sustained-released tablet 25 mg twice a day together
with omeprazole capsule (one kind of gastrointestinal
mucosa protectants, 20 mg once a day postoperatively
till 6 weeks, while patients in the experimental group
only took meloxicam tablet (15 mg once a day for
6 weeks). The application dose was based on the
medicine’s instructions. No other measures were taken
to avoid heterotopic ossification formation.
Visual analogue scale score
The visual analogue scale score was counted every
day till 1 week postoperatively.
Brooker classification
The patients were suggested to take anterior-posterior
X-ray films of double hips and lateral X-ray films of the
operated hip follow-up was conducted in 1, 4, 8, 12, 24
and 48 weeks postoperatively, which were used for
estimating the degree of heterotopic ossification with
standard Brooker[22-23] classification (1973). The
Brooker classification can be described as follows:
level 0: no ossification is found in periprosthesis tissue;
level Ⅰ: bone islands within soft tissues about the hip;
level Ⅱ: bone spurs in pelvis or proximal end of femur,
leaving at least 1 cm between the opposing hip
surfaces; level Ⅲ: bone spurs extended from the
pelvis or the proximal end of femur, which reduces the
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 Zeng YR, et al. Meloxicam versus indomethacin in the prevention of heterotopic ossification after total hip arthroplasty www.CRTER.org

space between the opposing surfaces less than 1 cm;
level Ⅳ: radiographic ankylosis of the hip.
D’Aubigne and Postel score
At the same time, improved D’Aubigne and Postel
score[24] were used to assess the hip function at 12, 24
and 36 weeks postoperatively in the follow-up process.
Main outcome measures
The efficacy of meloxicam tablet and indomethacin
sustained-release tablet in the prevention of
heterotopic ossification after total hip arthroplasty
surgeries was observed. Besides, visual analogue
scale score, hip function improvement, and adverse
reaction were also observed.
had ankylosing spondylitis involving double hips, nine
hips had osteoarthritis, and 12 patients had avascular
necrosis of the femoral head.
However, the study group consisted of 28 patients
(30 hips), 18 males and 10 females, whose ages
ranged from 31 years to 77 years, mean age
(52.17±11.58) years. And the follow-up time also
ranged from 3 months to 9 months, mean (5.6±2.0)
months.
The preoperative diagnosis contained 11 cases of hip
osteoarthritis, 16 cases of avascular necrosis of the
femoral head and one case of ankylosing spondylitis
involving double hips.

Statistical analysis Incidence of heterotopic ossification and visual

A chi-square test was applied to make a comparison
about the prevention of heterotopic ossification after
total hip arthroplasty. The side effects, and the
improvement of range of motion of the hip joint
between the study and control group was measured
with a SPSS 17.0 system for statistical analysis, which
P value less than 0.05 revealed a significant meaning.
Remained aspects valued with a T test.
RESULTS
Demographic data and clinical information of all
participants (Table 1)
analogue scale score variation in the total hip
arthroplasty patients treated with meloxicam and
indomethacin
With the respect to the incidence of heterotopic
ossification qualified with Brooker classfication, in the
control group, 18 cases in level 0, four cases in level Ⅰ,
no case in level Ⅱ, one case in level Ⅲ, and no case in
level Ⅳ, and the incidence of heterotopic ossification
reached 21.74%. While in the experimental group, the
25 cases in level 0, one case in level Ⅰ, one case in
level Ⅱ, one case in level Ⅲ, and no case in level Ⅳ,
and the incidence rate was 10.71% (Figure 1).

Table 1 Demographic data of the total hip arthroplasty patients

Control group Experimental group

Item
(n=23) (n=28)

Gender (male/female, n) 14/ 9 18/10

_ A: A 70-year-old male patient, B: A 45-year-old female patient,
Mean age (yr, x±s) 45.96±14.64 52.17±11.58
12 wk postoperatively, showed 4 wk postoperatively, showed a
Preoperative diagnosis (n)
a level Ⅲ of heterotopic level Ⅰ of heterotopic
Osteonecrosis of femoral head 11 12
ossification of the right hip ossification of the right hip
Hip osteoarthritis 10 12
Ankylosing spondylitis 1 1 There was no significant difference in the imaging findings of the patients
Femoral neck fracture 1 2 with heterotopic ossification after total hip arthroplasty with meloxicam
and indomethacin.
Patients did not reveal apparently statistical difference in age and
gender (P > 0.05) by t test. Figure 1 Imaging findings of visual analogue scale score of
heterotopic ossification patients after total hip
arthroplasty
In the control group, there were 23 patients (28 hips),
14 males and nine females, whose ages ranged from
26 years to 70 years, mean age (45.96±11.64) years. There was no statistical significance between the two
Besides, the follow-up time was ranged from 3 months groups (P=0.281 4, Table 2). As for pain remission
to 9 months, mean (5.5±1.8) months. Among those quantified with visual analogue scale score, it also
23 patients, one hip had synovial inflammation, one hip revealed no significance (P > 0.05, Table 3).

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 Zeng YR, et al. Meloxicam versus indomethacin in the prevention of heterotopic ossification after total hip arthroplasty www.CRTER.org

there were no excellent case, 18 good cases, 10 fair

Table 2 Incidence of heterotopic ossification in the control cases, and no poor case respectively. The excellent and
group and the experimental group good rate was 61% and 64% respectively (P > 0.05,
Tables 4 and 5). The main adverse reaction in the control
Brooker classification (n) Heterotopic
group was gastrointestinal disorder (37.84%), and one
Group Total ossification P
0 Ⅰ Ⅱ Ⅲ Ⅳ
(%) patient was not suggested to take the indomethacin
sustained- release tablet because of severe irritation
Control (n=23) reaction. However, one patient suffered rash disease
Male 11 2 0 1 0 3 21.74 0.281
apart from gastrointestinal disorder (17.85%). There was
Female 7 2 0 0 0 2
Experimental
no statistical significance (P > 0.05, Table 6).
(n=28)
Male 17 1 0 0 0 1 10.71 Table 5 Details of heterotopic ossification cases of the control
Female 8 1 0 1 0 2 group and the experimental group

There was no significant difference in incidence of heterotopic ossification

Postoperative heterotopic ossification
after total hip arthroplasty with meloxicam and indomethacin. Excellent and
Group cases (n)
god rate (%)
Excellent Good Fair Poor

Control 0 14 9 0 61.0
Table 3 Visual analogue scale score at 1 wk postoperatively of
Experimenta
the control group and the experimental group 0 18 10 0 64.3
l
D’Aubigne and Postel score was 18 points in all. Excellent=18 points;
Day
Control group Experimental group P good=15-17 points; fair=13-14 points; poor=equal to or less than
postoperatively
13 points.

1 1.698 7±0.719 9 1.714 2±0.658 6 0.936 4

2 1.941 3±0.859 1 1.964 2±0.744 4 0.919 2
3 1.752 8±0.766 9 1.857 1±0.705 2 0.615 6 Table 6 Incidence of adverse event of the control group and the
4 1.600 2±0.598 9 1.571 4±0.634 1 0.869 3
experimental group
5 1.314 3±0.495 1 1.357 1±0.558 7 0.775 8
6 1.123 9±0.482 9 1.178 6±0.547 9 0.710 5
Adverse event (n) Incidence of
7 1.024 4±0.246 6 1.071 4±0.465 7 0.664 8 Non-adverse
Group adverse event P
GIR RV DHW event (n)
(%)
There was no significant difference in visual analogue scale score at
different time points in the total hip arthroplasty patients treated with
Control 5 1 2 15 34.78 0.168 0
meloxicam and indomethacin.
Experimental 2 2 1 23 17.85

GIR: gastrointestinal reaction (including nausea and vomiting, indigestion,

Modified D’Aubigne and Postel score and adverse constipation, stomachache, gastric perforation); RV: rash and vesicle;
reaction of the total hip arthroplasty patients DHF: dizziness, headache, and fever.

treated with meloxicam and indomethacin (Table 4)
Table 4 Modified D’Aubigne and Postel score postoperatively
of the control group and the experimental group
There was no significant difference in the incidence of adverse event of
the total hip arthroplasty patients treated with meloxicam and
indomethacin.

Follow-up
Control group Experimental group P
DISCUSSION
time (wk)

12 14.130 4±0.868 8 14.178 5±0.772 3 0.854 5

Causes of heterotopic ossification
24 14.937 5±0.927 8 15.000 0±0.612 3 0.860 7 Heterotopic ossification may not be the common
36 15.333 3±0.816 4 15.666 6±0.816 5 0.202 2 complication after total hip arthroplasty, which new-born
bone appears outside the skeletal system in patients.
There was no significant difference in hip function of the total hip
Medium to severe heterotopic ossification would lead to
arthroplasty patients treated with meloxicam and indomethacin.
dysfunction of the hip, which would affect the quality of
life of the patients[25-26]. Additionally, heterotopic
Hip function was assessed with the modified D’Aubigne ossification shows differences from myositis ossificans,
and Postel score. In the control group, there were no which is discovered commonly companied with muscle
excellent case, 14 good cases, nine fair cases, and no damage along with trauma. The pathogenesis of
poor case postoperatively. In the experimental group, heterotopic ossification has not been recognized clearly
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 Zeng YR, et al. Meloxicam versus indomethacin in the prevention of heterotopic ossification after total hip arthroplasty
so far, but present acknowledged perspective originates
from mesenchymal stem cells in the tissues, which can
be activated toward to tissue differentiation by some
inducing factors, and new-born bone gradually appears.
Chalmers et al [27] had put forward three mandatory
conditions concerning formation of heterotopic
ossification in 1975. They included osteogenic precursor
cells, osteogenic inducer, and osteogenic organizational
environment. Moreover, they also highlighted the critical
role of local and systemic stimulator and inhibitor of
osteogenic played in the formation of heterotopic
ossification. In 1975, Urist et al had claimed that bone
morphogentic protein was the explicit inducer which
acted as a key factor in the progress of bone
morphogentic protein. Scharstuhl et al [28] had discovered
the critical function of transforming growth factor-β in the
formation of heterotopic ossification. And Chauveau
et al [29] had found that the amount of osteocalcin and
osteonectin in ectopic bone cells was much higher than
normal bone cells. So did the higher biological express of
mRNA of collagen type Ⅱ.
Risk factors of heterotopic ossification
In total hip arthroplasty patients, the formation of
heterotopic ossification has a plenty of risk factors. In
published documents, many researchers have
concluded that the high risk factors mainly consist of
males, hip osteoarthritis patients, osteophyte hyperplasia
of the femoral head and acetabulum, preoperative
trauma of the hip, AS, degenerative arthritis, contralateral
total hip arthroplasty surgery history, hypertrophic
osteoarthropathy, rheumatoid arthritis, diffuse idiopathic
skeletal hyperostosis, surgical incision, and nutrition
condition[30-35]. In some other literatures, it had been
reported that heterotopic ossification was closely
correlated with the usage of bone cement and the type of
prosthesis. But it had been proved wrong by recent
studies which discovered that the correlation between
them did not exist[36-37]. Consequently, it is necessary to
make clear the high risks resulting in heterotopic
ossification for effective protective management. Patients
with heterotopic ossification in our research were largely
those who suffered from hip osteoarthritis, or hip
surgeries history, which was accord with above results.
Mechanism of indomethacin treatment
In the management of heterotopic ossification after total
hip arthroplasty surgeries, many researches have
suggested that the usage of nonsteroidal
antiinflammatory drugs can be obviously effective in the
prevention of heterotopic ossification, especially
indomethacin sustained-release tablet. However, they
deemed that there was no statistical significance[38] about
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the efficacy between the selective COX-2 inhibiting drugs
and traditional nonsteroidal antiinflammatory drugs in the
management of heterotopic ossification[38-41].
Nonsteroidal antiinflammatory drugs can stop the
production of prostaglandin (osteogenesis inducer) by
inhibiting the activity of COX, which can block local
inflammation reaction that activates the bone
reconstruction and inhibits mesenchymal cells (a kind of
osteogenic precursor cells) from differentiating into
osteoblasts. After reviewing relevant literature, Fijn et al [42]
figured out that nonsteroidal antiinflammatory drugs can
decrease the incidence of heterotopic ossification after
total hip arthroplasty surgeries up to 50%, and
meanwhile apparently decreased the incidence of
heterotopic ossification with obvious clinical symptoms
that low to 0% to 2%. However, the side effects of
indomethacin sustained-release tablet can largely limit its
widely application, especially for those who are in old
age and have gastrointestinal diseases history. In
recently, some documents have reported that COX-2
inhibiting drugs can effectively reduce the
gastrointestinal side effects[43-44]. However, it is rarely
documented that whether COX-2 inhibiting drugs can
acquire pain remission and improve the range of motion
of the hip or not, as there lacking of long-term efficacy
observation. Consequently, our research aimed to select
meloxicam tablet, a gastrointestinal protection selective
COX-2 inhibiting drugs, as an observation contrast.
Reference to the statistical results, our conclusion is
accord to those domestic and overseas documents
reported, which said that meloxicam tablet can prevent
the formation of heterotopic ossification around the hip
joint following with total hip arthropasty surgeries
effectively and find no severe heterotopic ossification
case (level Ⅲ and Ⅳ). However, the conclusion reveals
no significant meaning compared with indomethacin
sustained-release tablet. With respect to pain remission,
improved range of motion of the hip joint, and the
incidence of side effects, both acquire positive efficacy
without significance (P > 0.05). The possible reasons for
no difference regarding range of motion of the hip
improvement showed in two groups may contribute to
short follow-up time postoperatively, and no intimate
correlation between Brooker classification and modified
D'Aubigne and Postel score. Additionally, discovering no
apparently decrease in side effects can account for two
reasons. Firstly, it was related to the dosage used.
Meloxicam tablet, a selective COX-2 inhibiting drug, can
produce efficacy largely dependent on the dosage[45].
When used in 7.5 mg once a day, it tends to inhibit the
production of COX-2 induced by kinds of damage factors.
Meanwhile, when taken it more than 15 mg a day, it can
inhibit the production of COX-1 at the same time, which
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 Zeng YR, et al. Meloxicam versus indomethacin in the prevention of heterotopic ossification after total hip arthroplasty
can increase the incidence of gastrointestinal diseases.
Secondly, it might own to the assistance of omeprazole
capsule in the control group. Nevertheless, Barthel
et al [46] have reported that the application of 7.5 mg and
15 mg of meloxicam tablet dose not reveal the significant
difference in the prevention of heterotopic ossification.
Small samples make it not absolutely persuasion
whether selective COX-2 inhibiting drugs can reduce
gastrointestinal adverse reaction or not. More large
samples, strictly designed, and long-term observation
studies are essentially needed.
Treatment effect of nonsteroidal antiinflammatory
drugs
Nonsteroidal antiinflammatory drugs can affect the
healing of fracture, so it may lead to prosthesis loosen for
inhibiting osteogenesis reaction surrounding prosthesis.
Persson et al [47] have investigated 96 total hip
arthroplasty patients who used Ibuprofen (1 to 2 weeks)
for analgesia and prevention of heterotopic ossification, a
higher revision rate was reported than the control group
(without any nonsteroidal antiinflammatory drugs), which
can be explained with the theory that nonsteroidal
antiinflammatory drugs can inhibit new-born bone
formation. However, all patients in our study took
nonsteroidal antiinflammatory drugs for 6 weeks
postoperatively, and they were suggested to abandon
crutches-assistance walking at one month after surgeries.
The last follow-up showed that no lucent line was seen
from postoperative X-rays and no hip symptoms were
found and checked, indicating that nonsteroidal
antiinflammatory drugs nearly had no effect on the
osteogenesis reaction. However, there is still controversial
on whether nonsteroidal antiinflammatory drugs can
prevent heterotopic ossification in none-surgical position of
our body or not as there lacks of long-term follow-up study.
Without resolving the problem, the usage of nonsteroidal
antiinflammatory drugs should be cautious for patients who
have underwent total hip arthroplasty surgeries without
high risks of heterotopic ossification formation.
Effect of surgical treatment
When surgical intervention in the management of
heterotopic ossification should be made? Many
researchers insisted that when the ossification focal
became mature (usually one year later), surgical
resection should be applied. And early surgical resection
usually acquired no good efficacy, because it was
susceptible to bleeding and recurrence. However, when
respecting it too late, if more than 2 years, it was hard to
obtain the excellent efficacy, which may account for
osteoporosis because of intra-articular stiffness, which
usually leads to long-term bed lay. When those patients
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underwent total hip arthroplasty surgeries, fracture may
happen as a normal-seen complication, even lead to
more widely heterotopic ossification occurrence.
Gibbons et al [48] deemed that the perfect operating
conditions were as follows. Firstly, at least 6 months
postoperatively, it is better when the surgery operated at
12 to 18 months postoperatively. Secondly, no local skin
temperature raising and red swelling around hip joint was
found. Thirdly, heterotopic ossification was in the stability
stage detected by X-ray, CT, MRI. Fourthly, the amount
of alkaline phosphatase, a kind of sign manifesting the
osteoblast activity, was at the normal reference range.
Finally, bone scan (which used for assessing bone
metabolic activity) result was normal, or at least next to
normal. Heterotopic ossification patients in our study
were diagnosed less than 8 weeks, and no increasing in
size, so we gave up surgery plan because it did not put
much harmful effect in the range of motion of the hip.
Experimental conclusion
We believe meloxicam tablet, a selective COX-2
inhibiting drugs, can decrease the incidence of
heterotopic ossification, achieve excellent pain remission,
as well as improve the hip function though the efficacy
and gastrointestinal safety between meloxicam tablet
and indomethacin sustained-release tablet are
comparable. Consequently, we recommend meloxicam
tablet as the postoperative drugs for the prevention of
heterotopic ossification and pain remission after total hip
arthroplasty surgeries because of its relative cheap price.
REFERENCES
[1] Riegler HF, Harris CM. Heterotopic bone formation after total
hip arthroplasty. Clin Orthop Relat Res. 1976;(117):209-216.
[2] Regis D, Sandri A, Sambugaro E. Incidence of heterotopic
ossification after surface and conventional total hip
arthroplasty: A comparative study using anterolateral
approach and indomethacin prophylaxis. Biomed Res Int.
2013;2013:293528.
[3] Pavlou G, Salhab M, Murugesan L, et al. Risk factors for
heterotopic ossification in primary total hip arthroplasty. Hip
Int. 2012;22(1):50-55.
[4] Cohn RM, Schwarzkopf R, Jaffe F. Heterotopic ossification
after total hip arthroplasty. Am J Orthop (Belle Mead NJ).
2011;40(11):E232-235.
[5] Kwapisz A, Kozłowski P, Szemraj J, et al. Correlations
between BMP-4 gene expression, heterotopic ossification
and function after uncemented total hip replacement. Ortop
Traumatol Rehabil. 2013;15(2):117-124.
[6] Fang Z, Sun T, Yadav SK. Research progress of bone
morphogenetic protein and liability of ossification of
posterior longitudinal ligament. Zhongguo Xiu Fu Chong
Jian Wai Ke Za Zhi. 2012;26(10):1255-1258.
P.O. Box 1200, Shenyang 110004 www.CRTER.org
 Zeng YR, et al. Meloxicam versus indomethacin in the prevention of heterotopic ossification after total hip arthroplasty
[7] Katagiri T. BMP signaling and bone formation. Clin Calcium.
2012;22(11):1677-1683.
[8] Medici D, Olsen BR. The role of endothelial-mesenchymal
transition in heterotopic ossification. J Bone Miner Res.
2012; 27(8):1619-1622.
[9] Pakos EE, Pitouli EJ, Tsekeris PG, et al. Prevention of
heterotopic ossification in high-risk patients with total hip
arthroplasty: the experience of a combined therapeutic
protocol. Int Orthop. 2006;30(2):79-83.
[10] Cella JP, Salvati EA, Sculco TP. Indomethacin for the
prevention of heterotopic ossification following total hip
arthroplasty. Effectiveness, contraindications, and adverse
effects. J Arthroplasty. 1988;3(3):229-234.
[11] Schmidt SA, Kjaersgaard-Andersen P, Pedersen NW, et al.
The use of indomethacin to prevent the formation of
heterotopic bone after total hip replacement. A randomized,
double-blind clinical trial. J Bone Joint Surg Am. 1988; 70(6):
834-838.
[12] Vasileiadis GI, Sioutis IC, Mavrogenis AF, et al. COX-2
inhibitors for the prevention of heterotopic ossification after
THA. Orthopedics. 2011;34(6):467.
[13] Hoff P, Rakow A, Gaber T, et al. Preoperative irradiation for
the prevention of heterotopic ossification induces local
inflammation in humans. Bone. 2013;55(1):93-101.
[14] Pakos EE, Tsekeris PG, Paschos NK, et al. The role of
radiation dose in a combined therapeutic protocol for the
prevention of heterotopic ossification after total hip
replacement. J BUON. 2010;15(1):74-78.
[15] Cipriano C, Pill SG, Rosenstock J, et al. Radiation therapy
for preventing recurrence of neurogenic heterotopic
ossification. Orthopedics. 2009;32(9).
[16] Fransen M, Neal B. Withdrawn: Non-steroidal
anti-inflammatory drugs for preventing heterotopic bone
formation after hip arthroplasty. Cochrane Database Syst
Rev. 2013;3:CD001160.
[17] Aspenberg P. Avoid cox inhibitors after skeletal surgery!
Acta Orthop Scand. 2002;73(5):489-490.
[18] Tsailas PG, Babis GC, Nikolopoulos K, et al. The
effectiveness of two COX-2 inhibitors in the prophylaxis
against heterotopic new bone formation: an experimental
study in rabbits. J Surg Res. 2009;151(1):108-114.
[19] van der Heide HJ, Spruit M, Slappendel R, et al.
Prophylaxis for heterotopic ossification after primary total
hip arthroplasty. A cohort study between indomethacin and
meloxicam. Acta Orthop Belg. 2004;70(3):240-246.
[20] Legenstein R, Bösch P, Ungersböck A. Indomethacin
versus meloxicam for prevention of heterotopic ossification
after total hip arthroplasty. Arch Orthop Trauma Surg. 2003;
123(2-3):91-94.
[21] Barthel T, Baumann B, Nöth U, et al. Prophylaxis of
heterotopic ossification after total hip arthroplasty: a
prospective randomized study comparing indomethacin
and meloxicam. Acta Orthop Scand. 2002;73(6):611-614.
[22] Dahners LE, Mullis BH. Effects of nonsteroidal
anti-inflammatory drugs on bone formation and
soft-tissue healing. J Am Acad Orthop Surg. 2004;12(3):
139-143.
ISSN 2095-4344 CN 21-1581/R CODEN: ZLKHAH
www.CRTER.org
[23] Brooker AF, Bowerman JW, Robinson RA, et al. Ectopic
ossification following total hip replacement. Incidence and a
method of classification. J Bone Joint Surg Am. 1973;55(8):
1629-1632.
[24] D'aubigne RM, Postel M. Functional results of hip
arthroplasty with acrylic prosthesis. J Bone Joint Surg Am.
1954;36-A(3):451-475.
[25] Kocic M, Lazovic M, Mitkovic M, et al. Clinical significance
of the heterotopic ossification after total hip arthroplasty.
Orthopedics. 2010;33(1):16.
[26] Pohl F, Seufert J, Tauscher A, et al. The influence of
heterotopic ossification on functional status of hip joint
following total hip arthroplasty. Strahlenther Onkol. 2005;
181(8):529-533.
[27] Chalmers J, Gray DH, Rush J. Observations on the
induction of bone in soft tissues. J Bone Joint Surg Br.
1975;57(1):36-45.
[28] Scharstuhl A, Glansbeek HL, van Beuningen HM, et al.
Inhibition of endogenous TGF-beta during experimental
osteoarthritis prevents osteophyte formation and impairs
cartilage repair. J Immunol. 2002;169(1):507-514.
[29] Chauveau C, Devedjian JC, Blary MC, et al. Gene
expression in human osteoblastic cells from normal and
heterotopic ossification. Exp Mol Pathol. 2004;76(1):37-43.
[30] Pavlou G, Salhab M, Murugesan L, et al. Risk factors for
heterotopic ossification in primary total hip arthroplasty. Hip
Int. 2012;22(1):50-55.
[31] Okano K, Aoyagi K, Osaki M, et al. Bone mineral density is
not related to heterotopic ossification after total hip
arthroplasty. Int Orthop. 2012;36(6):1163-1166.
[32] Schwarzkopf R, Cohn RM, Skoda EC, et al. The predictive
power of preoperative hip range of motion for the
development of heterotopic ossification. Orthopedics.
2011;34(3):169.
[33] Spinarelli A, Patella V, Petrera M, et al. Heterotopic
ossification after total hip arthroplasty: our experience.
Musculoskelet Surg. 2011;95(1):1-5.
[34] Metzner G, Lindner B, Neumann D, et al. Incidence of
anterior intertrochanteric ossifications after total hip
arthroplasty—a retrospective long-term follow-up study. Z
Orthop Unfall. 2010;148(2):174-179.
[35] Gordon A, Southam L, Loughlin J, et al. Variation in the
secreted frizzled-related protein-3 gene and risk of
osteolysis and heterotopic ossification after total hip
arthroplasty. J Orthop Res. 2007;25(12):1665-1670.
[36] Nayak KN, Mulliken B, Rorabeck CH, et al. Prevalence of
heterotopic ossification in cemented versus noncemented
total hip joint replacement in patients with osteoarthrosis: a
randomized clinical trial. Can J Surg. 1997;40(5):368-374.
[37] Huang WM, Yu XC, Fu ZH, et al. Comparison of incidence
of heterotopic ossification in combination versus biotype
total hip arthroplasty. Zhongguo Gu yu Guanjie Sunshang
Zazhi. 2011;26(10):875-877.
[38] Xue D, Zheng Q, Li H, et al. Selective COX-2 inhibitor
versus nonselective COX-1 and COX-2 inhibitor in the
prevention of heterotopic ossification after total hip
arthroplasty: A meta-analysis of randomised trials. Int
Orthop. 2011;35(1):3-8.
6873
 Zeng YR, et al. Meloxicam versus indomethacin in the prevention of heterotopic ossification after total hip arthroplasty www.CRTER.org

[39] Vavken P, Castellani L, Sculco TP. Prophylaxis of heterotopic
ossification of the hip: systematic review and meta-analysis.
Clin Orthop Relat Res. 2009;467(12):3283-3289.
[40] van der Heide HJ, Koorevaar RT, Schreurs BW, et al.
Indomethacin for 3 days is not effective as prophylaxis for
heterotopic ossification after primary total hip arthroplasty. J
Arthroplasty. 1999;14(7):796-799.
[41] Bremen-Kühne R, Stock D, Franke C. Indomethacin—
short-term therapy vs. single low dosage radiation for
prevention of periarticular ossifications after total hip
endoprosthesis. Z Orthop Ihre Grenzgeb. 1997;135(5):
422-429.
[42] Fijn R, Koorevaar RT, Brouwers JR. Prevention of
heterotopic ossification after total hip replacement with
NSAIDs. Pharm World Sci. 2003;25(4):138-145.
[43] Bombardier C, Laine L, Reicin A, et al. Comparison of
upper gastrointestinal toxicity of rofecoxib and naproxen in
patients with rheumatoid arthritis. VIGOR Study Group. N
Engl J Med. 2000;343(21):1520-1528.
[44] Romanò CL, Duci D, Romanò D, et al. Celecoxib versus
indomethacin in the prevention of heterotopic ossification
after total hip arthroplasty. J Arthroplasty. 2004;19(1):14-18.
[45] Pairet M, van Ryn J, Schierok H, et al. Differential inhibition
of cyclooxygenases-1 and -2 by meloxicam and its
4'-isomer. Inflamm Res. 1998;47(6):270-276.
[46] Barthel T, Baumann B, Nöth U, et al. Prophylaxis of
heterotopic ossification after total hip arthroplasty: a
prospective randomized study comparing indomethacin
and meloxicam. Acta Orthop Scand. 2002;73(6):611-614.
[47] Persson PE, Nilsson OS, Berggren AM. Do non-steroidal
anti-inflammatory drugs cause endoprosthetic loosening? A
10-year follow-up of a randomized trial on ibuprofen for
prevention of heterotopic ossification after hip arthroplasty.
Acta Orthop. 2005;76(6):735-740.
[48] Gibbons JJ, Lennon RL, Rose SH, et al. Axillary block of
the brachial plexus: "you can't get there from here...".
Anesthesiology. 1988;68(2):314-315.

美洛昔康与吲哚美辛防治全髋关节置换后异位骨化的比较☆

曾意荣，简林养，冯文俊，李 杰，李飞龙，何 生(广州中医药大学第一附属医院骨科，广东省广州市 510405)

曾意荣☆，男，1966 年生，江西省上饶 药进行预防治疗。 相关雇主或其他经济组织直接或间接的

市人，汉族，博士，教授，主要从事儿童、 目的：对比观察美洛昔康与吲哚美辛对全 经济或利益的赞助。
中青年股骨头缺血性坏死及人工髋膝关 髋关节置换后预防异位骨化药物的效果。 伦理要求 ：研究在中国临床试验注
节置换方面的研究。 方法：收集 2010 至 2011 年广州中医药大 册 中心 进行 注册 ，注 册编 码为
通讯作者：曾意荣，广州中医药大学第一 学第一附属医院骨科收治的 51 例患者，其 ChiCTR-OCH-12002364 。 研 究 经 过 广
附属医院骨科，广东省广州市 510405 中 9 例患者行双侧全髋关节置换，所有患 州中医药大学伦理委员会批准，并且获
者均由同一位医师采用后外侧入路进行关 得所有患者及家属的知情同意。
文章亮点： 节置换。根据患者置换后使用的药物不同， 学术术语 ：非类固醇类消炎药—是
1 对比发现全髋关节置换后患者异 分为对照组及实验组，分别在置换后口服吲 一类非类固醇激素类的能够消除疼痛、
位骨化发生率、疼痛、改良 D’Aubigne 和 哚美辛缓释片 25 mg/d+奥美拉唑肠溶胶囊 肿胀、四肢僵直及炎症的药物。
Postel 评分，发现美洛昔康与吲哚美辛的 20 mg/d 或美洛昔康片 15 mg/d。 作者声明 ：文章为原创作品，数据
效果没有明显差异。 结果与结论：单独使用美洛昔康和使用吲哚 准确，内容不涉及泄密，无一稿两投，
2 鉴于使用吲哚美辛的患者出现胃 美辛+奥美拉唑对关节置换患者异位骨化 无抄袭，无内容剽窃，无作者署名争议，
肠道不良反应的情况较多，作者建议预防 的发生率、疼痛、改良 D'Aubigne 和 Postel 无与他人课题以及专利技术的争执，内
全髋关节置换后异位骨化的形成，优先选 评分的差异均无显著性意义(P > 0.05)，但 容真实，文责自负。
择美洛昔康。 美洛昔康的胃肠道不良反应较少。因此，认
关键词： 为单独服用美洛昔康能够有效避免异位骨 中图分类号: R318 文献标识码: B

骨关节植入物；人工假体；异位骨化；全 化的发生及缓解疼痛，可以作为预防全髋关 文章编号: 2095-4344(2013)39-06867-08

髋关节置换；美洛昔康；吲哚美辛； 节置换后异位骨化及疼痛的推荐用药。
Brooker 分级；髋关节 曾意荣，简林养，冯文俊，李杰，李飞龙，
主题词：关节成形术，置换，髋；假体植 作者贡献 ：曾意荣进行实验设计、 何生. 美洛昔康与吲哚美辛防治全髋关节置
入；消炎药，非甾类；骨化，异位性 实验实施及文章审校，实验评估、资料 换后异位骨化的比较[J].中国组织工程研究，
收集及文章成文为简林养，论文修改及 2013，17(39):6867-6874.
摘要 翻译审校为冯文俊，李杰、李飞龙、何
(Edited by Chen X/Yang Y)
背景：为了避免全髋关节置换后发生异位 生进行相关文献的查阅及统计学分析。
骨化，常使用吲哚美辛等非类固醇类消炎 利益冲突 ：课题未涉及任何厂家及

6874 P.O. Box 1200, Shenyang 110004 www.CRTER.org