Introduction
Femoral intertrochanteric fracture mostly occurs in
the elderly aged >60 years, who usually have confounding factors
including osteoporosis or other internal medical conditions.
Conservative treatment used in clinical practice easily results in
serious complications, including bedsore, urinary system infection,
pulmonary infection and joint contracture due to long-term bed
rest. The associated mortality rate is up to 34.6% (1). Surgical fixation is the first-line
strategy for the treatment of femoral intertrochanteric fracture,
as it significantly reduces the duration of bed rest, is conducive
to early functional exercise and effective in avoiding
complications (2,3). Methods commonly used for clinical
fixation include proximal femoral nail antirotation (PFNA), PFN and
dynamic hip screw (DHS) (4). PFNA is
advantageous as it utilizes a small incision and produces less
bleeding. However, the operation for PFNA is more difficult to
perform and more expensive than DHS (4). DHS is an easy procedure that can
increase pressure by sliding; however, surgical exposure is large
and the incidence of coxa varus is high following surgery (4). Transforming growth factor β2 (TGF-β2)
is one of the most abundant cytokines in bone tissues. It has been
demonstrated that TGF-β2 may be expressed in all stages of fracture
healing, promoting the internal and cartilaginous osteogenesis
during the healing process (5). In
the present study, changes in TGF-β2 expression were detected after
treatment of femoral intertrochanteric fracture with DHS and PFNA
fixation. The curative effects and complications of DHS and PFNA
fixation were compared to explore effects of two treatment methods
on the healing of femoral intertrochanteric fracture, providing a
practical basis for the choice of surgical method in clinical
practice.
Patients and methods
Clinical data
A total of 100 elderly patients with femoral
intertrochanteric fracture (45 males and 55 females; age, 65–91
years) admitted to and treated at the Orthopedics Department of the
Affiliated Hospital of Yangzhou University (Jiangsu, China) from
January 2016 to January 2017 were included in the present study.
All patients were diagnosed via pelvic anteroposterior X-ray
examination, as well as anteroposterior and lateral X-ray
examination of the affected hip. The inclusion criteria were as
follows: Age, ≥65 years; femoral neck bone density determination
T-score (bone density score) <-2.5 standard deviations (4); and primary femoral intertrochanteric
fracture. The exclusion criteria were as follows: Cortical
pulverization, femoral head necrosis, Evans type II fracture or
other serious complications detected in imaging eaminations, or
surgical contraindications. These elderly patients were randomly
divided into two groups that received DHS and PFNA treatment,
respectively. Differences in age, gender and severity of the
disease were not statistically significant between the two groups.
The present study was approved by the ethics committee of the
Affiliated Hospital of Yangzhou University (Yangzhou, China).
Written informed consent was obtained from the patients and/or
their guardians.
Grouping and treatment
The two groups were treated with DHS and PFNA
surgical therapy, respectively. Pre-operative examinations were
performed and antibiotics were routinely administered to prevent
infection prior to the operation. After the operation, preventive
anti-inflammatory therapy was performed, subcutaneous injection of
low-molecular-weight heparin calcium was given to prevent venous
thrombosis, and anti-osteoporosis drugs were administered. Drainage
tubes were removed within 24–36 h based on the individual
circumstances. On the day after the operation, lower limb muscle
contraction exercise was commenced depending on the condition of
each patient, and subsequently, joint function exercise was
performed gradually. At 1, 4, 8 and 12 weeks after the operation,
the time of weight-bearing ambulation was determined according to
the results of X-ray examinations (Multix Select DR; Siemens,
Erlangen, Germany). Patients were followed up for 3 months after
discharge and had re-examinations on the affected limb joints via
X-ray every month.
Observation indexes
The following operation-associated conditions of
patients were observed: Operation time, intra-operative bleeding
volume, post-operative weight-bearing time and length of hospital
stay. The post-operative callusing time and swelling reduction time
of patients were noted. Blood sampling was performed at 1, 7, 15
and 30 days after the operation for TGF-β2 determination. Fasting
venous blood (3 ml) was collected early in the morning, centrifuged
for serum separation after standing for 0.5 h (Microfuge 16;
Beckman Coulter, Brea, CA, USA) and then stored at −70°C. TGF- β2
levels were determined using an ELISA kit (cat. no. 1217; Shanghai
Yubo Biotechnology Co., Ltd., Shanghai, China;). A microplate
reader (Synergy H1; BioTek, Winoosky, VT, USA) was adopted to
measure the TGF-β2 content.
The post-operative hip function Harris score was
used as the scoring standard for efficacy (6). The efficacy score was evaluated as
follows: ≥90 points, excellent; 80–89 points, good; 70–89 points,
fair; ≤70 points, poor. Post-operative complications were compared
between the two groups.
Statistical analysis
SPSS version 19.0 (IBM Corp., Armonk, NY, USA) was
used for data processing. Values are expressed as the mean ±
standard deviation. The Student's t-test was applied for comparison
between two groups. The χ2 test was employed for
comparison among enumeration data. P<0.05 was considered to
indicate a statistically significant difference.
Results
Comparison of general clinical
characteristics
Between the DHS and the PFNA group, no statistically
significant differences in age, amount of hemoglobin prior to the
operation, gender distribution, fracture type and complications
were observed (P>0.05; Table
I).
 | Table I.Comparison of general clinical data
between the DHS group and the PFNA group. |
Table I.
Comparison of general clinical data
between the DHS group and the PFNA group.
|
|
|
|
| Evans type (n) |
|
|---|
|
|
|
|
|
|
|
|---|
| Group | N | Age (years) | Males/females
(n) | Ia | Ib | Ic | Id | Complications n
(%) |
|---|
| DHS | 50 | 70.3±6.2 | 22/28 | 15 | 14 | 16 | 5 | 29 (58) |
| PFNA | 50 | 68.2±7.4 | 23/27 | 13 | 16 | 14 | 7 | 33 (66) |
|
χ2/t |
| 1.283 | 0.506 | 0.051 | 0.077 |
| P-value |
| 0.315 | 0.477 | 1.256 | 0.943 |
Comparison of peri-operative
parameters between the DHS and PFNA groups
Compared with those in the DHS group, the operation
time and bleeding volume were reduced, and the length of hospital
stay and post-operative weight-bearing time were shortened in the
PFNA group (P<0.05 or P<0.01; Table II).
| Table II.Comparison of operative details
between the DHS group and the PFNA group. |
Table II.
Comparison of operative details
between the DHS group and the PFNA group.
| Group | N | Operation time
(min) | Length of hospital
stay (days) | Intra-operative
bleeding volume (ml) | Post-operative
weight-bearing time (days) |
|---|
| DHS | 50 | 112.21±22.42 | 24.54±4.98 | 290.8±88.1 | 12.32±3.47 |
| PFNA | 50 |
78.45±24.38 | 20.22±4.12 | 163.3±78.3 |
9.21±3.02 |
| t |
| 5.484 | 3.015 | 0.513 | 2.318 |
| P-value |
| 0.002 | 0.006 | 0.041 | 0.016 |
Callusing time and swelling reduction
time in DHS and PFNA group
Comparison of the recovery process in the two groups
of patients indicated that the callusing time and swelling
reduction time in the PFNA vs. the DHS group were 31.5±3.1 vs.
43.3±3.5 days and 8.3±4.9 vs. 13.6±5.0 days, respectively, and
differences were statistically significant (P<0.05), indicating
that the PFNA group had a faster post-operative fracture healing
process (Table III).
| Table III.Callusing time and swelling reduction
time in the DHS group and the PFNA group. |
Table III.
Callusing time and swelling reduction
time in the DHS group and the PFNA group.
| Group | N | Callusing time
(days) | Swelling reduction
time (days) |
|---|
| DHS | 50 | 43.3±3.5 | 13.6±5.0 |
| PFNA | 50 | 31.5±3.1a | 8.3±4.9a |
Comparison of TGF-β2 expression
between the DHS and PFNA groups
The results of the dynamic TGF-β2 detection revealed
that after the operative treatment, the TGF-β2 content at 7 days
was increased compared with that at 1 day, reached the peak at 15
days and had declined again at 30 days with the gradual healing of
the fracture. The content of TGF-β2 at 1, 7, 15 and 30 days in the
PFNA group was obviously higher than that at the identical
time-points in the DHS group, and differences were statistically
significant (Table IV).
| Table IV.Comparison of post-surgical TGF-β2
expression between DHS group and PFNA group. |
Table IV.
Comparison of post-surgical TGF-β2
expression between DHS group and PFNA group.
|
|
| TGF-β2 (µg/l) |
|---|
|
|
|
|
|---|
| Group | N | 1 day | 7 days | 15 days | 30 days |
|---|
| DHS | 50 | 217.4±25.6 | 356.3±35.8 | 408.7±35.6 | 201.5±28.8 |
| PFNA | 50 | 238.7±33.3 | 390.4±40.6 | 458.3±44.5 | 223.4±31.5 |
| t |
| 3.858 | 4.720 | 3.899 | 1.357 |
| P-value |
| 0.006 | 0.003 | 0.007 | 0.031 |
Comparison of hip function scores
between the DHS and PFNA groups
Comparison of hip function scores at 3 months after
the operation indicated that in the DHS fixation group, the
efficacy was rated as excellent in 38 patients, good in 6 patients,
fair in 3 patients and poor in another 3 patients, with a rate of
excellent and good efficacy of 74.0%. In the PFNA fixation group,
the efficacy was rated as excellent in 45 cases, good in 2, fair in
2 and poor in 1 patient, with a rate of excellent and good efficacy
of 90.0%. Statistical analysis indicated that the rate of excellent
and good efficacy in the PFNA group was significantly higher than
that in the DHS fixation group (P<0.05; Table V).
| Table V.Comparison of hip function scores
between the DHS group and the PFNA group. |
Table V.
Comparison of hip function scores
between the DHS group and the PFNA group.
|
|
| Cases with hip
function score (n) |
|
|---|
|
|
|
|
|
|---|
| Group | N | Excellent | Good | Fair | Poor | Excellent and good
rate, n (%) |
|---|
| DHS | 50 | 38 | 6 | 3 | 3 | 37 (74.0) |
| PFNA | 50 | 45 | 2 | 2 | 1 | 45 (90.0) |
| χ2 |
|
|
|
|
| 2.76 |
| P-value |
|
|
|
|
| <0.05 |
Comparison of common complications
between DHS and PFNA groups
In the DHS fixation group, complications occurred in
8 patients (incidence rate, 16%), including hip varus in 2
patients, femoral shaft fracture in 2 patients, cutout of femoral
head in 1 patient, fracture site infection in 1 patient and
internal fixation breakage in 2 patients. In the PFNA fixation
group, 3 patients had complications (incidence rate, 6%), of which
1 patient had hip varus, 1 patient had fracture site infection and
1 patient had internal fixation breakage. In comparison with the
DHS group, the PFNA group had obviously fewer complications
(P<0.05; Table VI).
| Table VI.Comparison of common complications
between the DHS group and the PFNA group (n). |
Table VI.
Comparison of common complications
between the DHS group and the PFNA group (n).
| Group | Hip varus n
[rate(%)] | Femoral shaft
fracture n [rate(%)] | Cutout of femoral
head n [rate(%)] | Fracture site
infection n [rate(%)] | Internal fixation
breakage n [rate(%)] | Total incidence
rate (%) |
|---|
| DHS (n=50) | 2 (4) | 2 (4) | 1 (2) | 1 (2) | 2 (4) | 16 |
| PFNA (n=50) | 1 (2) | 0 (0) | 0 (0) | 1 (2) | 1 (2) | 6 |
| χ2 |
|
|
|
|
|
3.98 |
| P-value |
|
|
|
|
| <0.05 |
Discussion
Elderly patients with osteoporotic femoral
intertrochanteric fracture should be treated with surgical therapy
as soon as possible to restore fracture sites and recover hip
motions at the early stage if the patient's constitution allows for
surgical therapy. Reduction and internal fixation is routinely
adopted for treatment, as the femoral intertrochanteric fracture
site is cancellous bone, where blood supply is good. The most
commonly used surgical methods are DHS and PFNA fixation.
DHS has the function of a tension band and achieves
an ideal fixation effect through two types of pressure, i.e.,
static pressure and dynamic pressure (7). During internal fixation of DHS, hip
screws anchor less sclerotin and have a poor antirotation effect,
resulting in prolonged operation time and increased intra-operative
bleeding volume. Poor osteoarticular blood supply affects late
recovery, which is likely to delay the healing process (8,9).
Therefore, DHS fixation is not applicable in patients with severe
osteoporosis or comminuted fracture in the lateral cortical bone of
the femoral trochanter (10).
Developed and designed on the basis of a PFN, PFNA is a novel
intramedullary fixation system with an antirotation effect combined
with a strong bearing (11). A
series of biomechanical experiments (12–15) have
confirmed that PFNA, due to its uniquely designed screw blade, has
a high clinical application value because of the following points:
i) It increases the contact area with the femoral bone and enhances
the anchoring force of the blade. The blade is ‘hammered’ into the
cancellous bone and may be automatically locked, which does not
cause any loosening of the screw and avoids femoral shaft fracture
caused by excessive local stress; ii) it has a good anti-cutout
ability, anti-rotation and pressure effects, and biomechanics
features in comparison with the PFN screw, which is conducive to
applying close reduction and performing early rehabilitation
exercise; iii) it has a precise positioning device, which requires
opening of the lateral cortex only (without the requirement to
remove the sclerotin), and thus, the integrity of the femoral
trochanteric lateral cortex is retained. Due to all of these
advantages, PFNA is widely used in patients with unstable
comminuted intertrochanteric fracture or in frail osteoporosis
patients (12).
Growth factors have important roles in the fracture
healing process (16). TGF-β2, an
important growth factor, regulates the proliferation and
differentiation of various cell types, including mesenchymal cells,
osteoblasts, osteoclasts and chondrocytes, in the skeleton,
increases the extracellular bone matrix, regulates the formation of
bone and cartilage, promotes callus calcification and enhances bone
repair. In different stages of fracture healing, the expression
levels of TGF-β2 are altered due to the impact of factors including
the status of cell differentiation and growth conditions. It has
been proved that TGF-β2 stimulates collagen synthesis and is a
strong chemokine. It stimulates mesenchymal cells to differentiate
into chondrocytes during fracture healing. The net effect of this
is to increase extracellular matrix and exert an important role in
regulating bone and cartilage formation. At the same time, TGF-β2
also promotes bone repair by stimulating the proliferation of
osteoblasts and calcification of the callus. During the remodeling
of the callus, the locally released TGF-β2 coordinates the process
of bone absorption and bone formation. TGF expression is
dynamically expressed at different times of fracture healing. The
expression levels of TGF gene are different at various stages of
fracture healing, and are an important indicator in the evaluation
of fracture prognosis; according to a previous study, the mRNA
expression of TGF-β2 reached a peak at 13 days after fracture
(17).
The present study compared the peri-operative
situation between patients receiving DHS and PFNA, indicating that
operation time, length of hospital stay and intra-operative
bleeding volume in the DHS group were greater than those in the
PFNA group, and that the time to post-operative weight bearing was
relatively long. Comparison of the recovery process between the two
groups revealed that the callusing time and swelling reduction time
in the PFNA vs. DHS group were 31.5±3.1 vs. 43.3±3.5 days and
8.3±4.9 vs. 13.6±5.0 days, respectively, and differences were
statistically significant (P<0.05), indicating that the PFNA
group had a faster post-operative fracture healing process. The
results of the dynamic TGF-β2 detection indicated that 7 days
post-surgery, TGF-β2 was increased compared with that at 1 day and
reached a peak at 15 days, which is consistent with the results of
a previous study (17). With the
gradual healing of the fracture, the TGF-β2 content had declined
again at 30 days. The content of TGF-β2 at 1, 7, 15 and 30 days in
the PFNA group was obviously higher than that at the identical
time-points in the DHS group, indicating that PFNA stimulates the
secretion of TGF-β2 more than DHS and promotes the healing of the
fracture. The possible reason is that PFNA internal fixation only
requires a small incision and causes less trauma, with no need to
perform open reduction and suturing, and has the nailing point at
the tip of femoral trochanter. Therefore, it only causes mild
damage to soft tissues of the fracture site, and at the same time,
it only has a small impact on the femoral head, thereby promoting
and increasing the secretion of TGF-β2 in the body.
Hip function scores were compared at 3 months after
the operation and the results indicated that in the DHS fixation
group, the efficacy was rated as excellent in 38 patients, good in
6 patients, fair in 3 patients and poor in another 3 patients, with
a rate of excellent and good efficacy of 74.0%. In the PFNA
fixation group, the efficacy was rated as excellent in 45 cases,
good in 2, fair in 2 and poor in 1 patient, with a rate of
excellent and good efficacy of 90.0%. Statistical analysis revealed
that the rate of excellent and good efficacy in the DHS fixation
group was lower than that in the PFNA group (P<0.05). In the DHS
fixation group, complications occurred in 8 cases (incidence rate,
16%), including 2 cases of hip varus, 2 cases of femoral shaft
fracture, 1 case of cutout of the femoral head, 1 case of fracture
site infection and 2 cases of internal fixation breakage; in the
PFNA fixation group, complications were observed in 3 cases
(incidence rate, 6%), including 1 case of hip varus, 1 case of
fracture site infection and 1 case of internal fixation breakage.
In comparison with the DHS group, the PFNA group had obviously
fewer complications (P<0.05). DHS surgery requires a relatively
large incision and internal fixation is unstable. PFNA surgery only
requires a small incision and the operation is relatively simple,
without any peeling of deep soft tissue and periosteal reduction of
the fracture site, and therefore, it has less impact on the local
blood supply of the fracture, so that the blood supply of the
fracture block is retained the most. Therefore, PFNA has a shorter
operation time and lower bleeding volume, as well as a shortened
fracture healing time in comparison with those in the DHS group
(18).
In conclusion, PFNA fixation treatment, with its
shorter operation time, lower intraoperative bleeding volume, less
trauma, relatively faster fracture healing process, fewer
complications and better curative effect, is more suitable for
osteoporotic intertrochanteric fracture in elderly patients. As to
the treatment of femoral intertrochanteric fracture, PFNA fixation
is better than DHS fixation, which may be due to its high level of
TGF-β2 expression in comparison with that in the DHS group. The
specific underlying mechanisms remains to be elucidated in further
studies.
Acknowledgements
Not applicable.
Funding
This study was supported by the Research Project of
the Jiangsu Health and Family Planning Commission (grant no.
H201662).
Availability of data and materials
All data generated or analyzed during this study are
included in this published article.
Authors' contributions
RX designed the present study; JR and YJ collected
the data, FJ and DS analysed the data; JL and ZW interpreted the
data; RX and DS prepared the manuscript. All authors read and
approved the final manuscript.
Ethical approval and consent to
participate
The present study was approved by the Ethics
Committee of The Affiliated Hospital of Yangzhou University. Signed
written informed consents were obtained from the patients and/or
guardians.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
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