Percutaneous kyphoplasty for osteoporotic vertebral compression fractures improves spino-pelvic alignment and global sagittal balance maximally in the thoracolumbar region.

BACKGROUND: Osteoporotic vertebral compression fractures (OVCFs) often cause local kyphosis. Percutaneous kyphoplasty (PKP) is a common method for the treatment of local kyphosis. However, the influence of kyphoplasty on spino-pelvic alignment and global sagittal balance when performed at specific treatment sites in the spine remains unclear. The purpose of the study is to investigate the influence of different fracture sites and PKP treatment on the spino-pelvic alignment and global sagittal balance in patients with OVCFs.
METHODS: 90 patients with OVCF who underwent PKP were included in the retrospective study. According to the site of the fractured vertebrae, all the cases were divided into 3 groups: Main thoracic (MT) group (T1 to T9), Thoracolumbar (TL) group (T10 to L2) and Lumbar (LU) group (L3 to L5). 26 healthy elderly volunteers (aged over 59) were enrolled as the control group. Sagittal spino-pelvic parameters were measured on the full-spine radiographs preoperatively and postoperatively. Information of sagittal spino-pelvic parameters and global sagittal balance was gathered.
RESULTS: Compared with the Control group, TL group showed significant differences in almost all parameters, except pelvic incidence (PI) and lumbar lordosis (LL). While only local sagittal parameters (Thoracic kyphosis (TK), Thoracolumbar kyphosis (TLK), LL) were significantly different in MT group. There was no significant difference in almost all of the parameters except for PT and TPA in LU group. Correspondingly, the sagittal parameters of TL group improved best after PKP, except for thoracic kyphosis (TK) and sagittal vertical axis (SVA). In MT group, only TLK was significantly decreased, while in LU group, only local kyphosis Cobb angle and SSA were improved.
CONCLUSIONS: OVCF mainly occurs in the thoracolumbar region. Compared with MT group and LU group, OVCF occurred in the thoracolumbar region had greater influence on the spino-pelvic alignment and global sagittal balance. When PKP was performed, the improvement of sagittal balance parameters of TL group was the best in the three groups.

Introduction

Sagittal balance is a state in which an individual maintains a stable standing position with minimal muscle effort [1]. This state is essential for maintaining normal spinal biomechanics. Several spinal diseases can cause sagittal imbalance, such as spinal deformities, spinal degenerative diseases etc.[2-4] Most researchers are more concerned with sagittal imbalances caused by spinal deformity and degeneration, while sagittal imbalance caused by OVCFs has received less attention [2].

Zhang YL et al confirmed that OVCFs can change the local sagittal alignment of the spine and multiple vertebral compression fractures can even lead to sagittal imbalance [2, 5]. Among patients with OVCFs, the incidence of thoracolumbar vertebral fracture is the most common due to the special anatomical structure and biomechanical characteristics of the thoracolumbar spine itself [6, 7]. Whether there is a difference in the effect of thoracolumbar fracture site on sagittal balance has not yet been studied. Moreover, differences in sagittal balance improvement after PKP procedure in different fracture sites have not been reported.

Our study retrospectively analyzed the sagittal balance parameters of 90 patients with OVCFs treated with PKP and selected 26 healthy elderly volunteers as the control group. We tried to analyze the differences in sagittal balance parameters after a vertebral fracture at different sites and to analyze the differences in sagittal balance improvement after PKP at different fracture sites.

Materials and methods

A total of 90 patients with OVCFs receiving PKP treatment between January 2013 and July 2018 in Shandong Provincial Hospital affiliated to Shandong University were enrolled. Three senior spine surgeons from the same surgical group operated on all patients. The patient-related data and imaging materials were obtained from the electronic medical record management system of Shandong Provincial Hospital affiliated to Shandong University. The study has been approved by the Ethics Committee of Shandong Provincial Hospital affiliated to Shandong University.

Inclusion criteria [2, 8]

(1).The vertebral compression ratio of the injured vertebrae was less than 80%; (2).Osteoporosis was confirmed via bone mineral density in elderly patients; (3).All fractured vertebrae showed a high signal intensity on short T1 inversion recovery(STIR) magnetic resonance (MR) images and a low signal intensity on T1-weighted MR images; (4).The imaging data were complete, including the preoperative and postoperative follow-up standing X-ray films of the whole spine with pelvis and femoral heads, and three-dimensional CT and MRI of the thoracolumbar spine.

Exclusion criteria [2, 8]

(1).Patients with lumbar disc herniation, spondylolisthesis, scoliosis, spinal osteoarthritis, ankylosing spondylitis, spinal tumors and spinal tuberculosis; (2).Patients with a history of spinal surgery; (3).Patients with hip and knee joint limitations (a history of hip and knee joint diseases, or abnormal hip and knee joint mobility in the medical records); (4).Patients with spinal cord compression with clinical manifestations of spinal cord and cauda equina nerve injury; (5).Patients with pathogenic fracture caused by a tumor or incomplete posterior wall of the vertebral body; (6).Patients who could not stand upright independently or who did not obtain a standing X-ray film.

After enrollment, the medical history of each patient was reviewed. The number of spinal vertebral fractures and the locations of the fractures were recorded. The demographic data and radiographic findings including plain radiography, computerized tomography, and MR imaging were recorded. The visual analogue scale (VAS) was assessed preoperatively and postoperatively. Full-length radiographs were analyzed for spino-pelvic sagittal parameters.

The sagittal balance of the patient was analyzed by standing radiographs of the whole spine, including the pelvis and the femoral heads[9-17] The fingers of the patient were resting on the clavicles, a position described as reproducible and reliable[17-19].

The sagittal parameters are greatly affected by the standing posture. Based on the numerous studies published by scholars, we chose the following positions for photography [20-23].

A natural standing lateral position.

Eyes were looking straight ahead.

The sagittal plane of the torso was perpendicular to the tube.

The hip and knee joints were as straight as possible, and the feet were spaced shoulder width apart.

The elbows were in flexion, wrists were in flexion, hands were clenched, and the fingers were resting on the clavicles.

Radiographic analysis[24]

The standing lateral radiographs were obtained preoperatively and within 2–3 days postoperatively. The main radiological parameters for measuring the sagittal alignment were as follows: PI, pelvic tilt (PT), sacral slope (SS), local kyphosis Cobb angle, TK, TLK, LL, PI-LL, SVA, spino-sacral angle (SSA), and T1 pelvic angle (TPA). The data of these measured parameters were recorded by two investigators using Surgimap software (version: 2.2.14.1, Nemaris, Inc., New York, NY, USA).

The spino-pelvic sagittal parameters are described in Figs 1–6[20, 24–27].

Fig 1

Radiographic measurements of SSA.

The angle between the upper endplate of the S1 and the line connecting the midpoint of the C7 to the midpoint of the upper endplate of the S1.

Fig 6

Radiographic measurements of spinal sagittal parameters (TLK, local kyphosis Cobb angle).

Local kyphosis Cobb angle: the angle formed by the upper endplate of the vertebra above the fractured vertebra and the lower endplate of the vertebra below the fractured vertebra.

Radiographic measurements of TPA.

The angle between the midpoint of the upper endplate of T1 and S1 to the midpoint of the femoral head.

According to the site of the fractured vertebrae, all patients were divided into 3 groups: the MT group (the fractured vertebrae were located between T1 and T9), TL group (the fractured vertebrae were located between T10 and L2) and LU group (the fractured vertebrae were located between L3 and L5). The improvement in the spino-pelvic sagittal parameters before and after the operation was calculated, and the differences in the sagittal parameters among the groups were compared.

Furthermore, all parameters were compared with those of 26 healthy elderly volunteers. Their ages range from 59 to 79 years. The control group consisted of healthy elderly volunteers of a similar age who underwent physical examinations at the authors’ hospital and did not have obvious back pain or a history of osteoporotic fracture of the spine.

Statistical analysis

All statistical analyses were conducted using the IBM Statistics Package for Social Sciences (IBM SPSS Statistics 24, SPSS Inc., Chicago, IL, USA). The normality of the data was evaluated using the Shapiro–Wilk test. Data were expressed as the means ± standard deviations. For non-normally distributed variables, we used medians and interquartile ranges. The independent sample t test was used to compare the data between two groups. If the data did not meet a normal distribution, the comparison was performed using the Mann-Whitney U test. The nonparametric test (K-W test) was used to compare the data among multiple groups. The mean values and standard deviations of the preoperative and postoperative radiological parameters were determined, and changes were evaluated using a paired-sample t test. If the changes did not meet the normal distribution, the comparison was performed using Wilcoxon Signed Ranks test. All statistical tests were two tailed, and a p-value <0.05 was considered statistically significant. The correlations between parameters were analyzed by Pearson correlation analysis. Moreover, the power of the study was estimated using a post-hoc analysis with G*Power software (version 3.1.9.4, Franz Faul, Universität Kiel, Germany).

Results

Patient data

Ninety patients met the inclusion criteria. They were 70 females and 20 males with a mean age of 69.3±8.1years. The total number of fractured vertebrae was 124. There was no significant differences in age (p = 0.654) and VAS score (p = 0.840 preoperatively; p = 0.352 postoperatively) among the three groups. The VAS scores were significantly decreased after the operation (p < 0.05). Demographic characteristics of the three groups are summarized in Table 1.

Table 1

Comparison of demographic characteristics of the three groups stratified according to the site of OVCFs.

	MT group	TL group	LU group	P-value
Number of patients	9	71	10	-
Female/male	6/3	57/14	7/3	-
Age(year-old)	69.6±8.1	68.8±8.1	72.1±8.7	.654
Pre-VAS	7.7±1.0	7.4±0.7	7.4±0.5	.840
Post-VAS	2.2±0.4	2.5±0.6	2.6±0.7	.352

Preoperative radiological measures

Almost all of the preoperative parameters of the TL group were significantly different from those of the healthy volunteers, except for the PI and LL. The TK, TLK, PT, SVA, and TPA were all significantly larger and the SS and SSA were significantly smaller than those of the volunteers. Compared with that of the controls, the TK, TLK and LL of the MT group were significantly larger. There was no significant difference in pelvic parameters or global sagittal parameters between the MT group and the volunteers. Significant differences were observed between the LU group and the volunteers in terms of the PT and TPA. The other parameters had no distinctive difference. Demographic characteristics and sagittal parameters of the controls and all patients prior to the operation are reported in Table 2.

Table 2

Demographics data and pre-operative spinal and pelvic sagittal parameters of healthy volunteers and OVCF patients.

	Group					P value
	Healthy volunteers	OVCF patients	MT group	TL group	LU group	Control vs overall	Control vs MT	Control vs TL	Control vs LU
Number of patients	26	90	9	71	10	-	-	-	-
Female/male	13/13	70/20	6/3	57/14	7/3	-	-	-	-
Age(year-old)	67.9±6.2	69.3±8.1	69.6±8.1	68.8±8.1	72.1±8.7	.425	0.525	.590	.112
TK	22.6±9.1	37.8±15.8	40.7±9.6	38.7±16.9	28.4±7.8	.000	.000	.000	.086
TLK	4.9(0.9,11.4)	27.3(16.4,40)	22.9±9.2	33.3±18.4	12.5±11.1	.000*	.000*	.000*	.177*
LL	-48.1±9.0	-48.4(-56.3,-37.4)	-57.4±5.7	-46.5±14.9	-47.7±13.4	0.934*	.007	.599	.917
PT	17.2±7.0	24.0±8.7	16.7±6.4	24.8±8.9	24.6±6.6	.000	.850	.000	.007
SS	34.3±6.4	30.0±8.9	35.0±7.0	28.9±9.0	33.7±7.0	.023	.785	.006	.804
PI	51.6±6.4	52.2(47.7,61.3)	52.9±7.6	52.0(47.1,61.2)	58.3±11.6	0.408*	.623	.552*	.112
PI minus LL	3.5±8.7	9.3±14.2	-4.5±8.2	7.1±13.6	10.6±7.9	.014	.022	.213	.032
SVA	-2.0±18.5	14.5(-4.8,38.2)	11.5±21.7	20.7±36.9	18.9±44.5	.003*	.082	.000	.182
SSA	126.3±6.3	119.2±9.6	124.3±6.5	118.0±9.6	123.8±10.5	.001	.435	.000	.399
TPA	11.7±5.8	18.7(12.8,22.6)	11.1(9.0,14.3)	19.6±8.4	19.6±5.1	.000*	0.985*	.000	.001

*p-value derived using Mann-Whitney U test for nonparametric unpaired data

Postoperative radiological measures

The VAS score of all patients decreased from 7.4±0.7 preoperatively to 2.5±0.6 postoperatively, and the pain was significantly relieved (p < 0.01). The results of the comparison between the preoperative and postoperative conditions are shown in Table 3. In the total patient group, significant increases in LL, SS and SSA were observed (p < 0.05). And there was also a significant decrease in PT, PI minus LL, TLK, local kyphosis Cobb angle, and TPA (p < 0.05).

Table 3

Comparison of spinal and pelvic parameters of patients with OVCF between pre- and post-treatment.

Region	Parameters	Overall patient(90)			MT group(9)			TL group(71)			LU group (10)
		Pre-operative	Post-operative	P value	Pre-operative	Post-operative	P value	Pre-operative	Post-operative	P value	Pre-operative	Post-operative	P value
Thoracolumbar	local kyphosis Cobb angle	24±16.1	17.7(9.3,28.5)	.000*	25.1±14.2	22.0±12.95	.094	23.3±15.6	18.3±13.6	.000	27.5±21.8	30.96±21.6	.047
	TK	37.8±15.8	36.7±14.3	.066	40.7±9.6	36.5±11.2	.068	38.7±16.9	37.9±15.1	.207	28.4±7.8	28.2±5.9	.892
	TLK	27.3(16.4,40.0)	23.4(16.2,35.2)	.000*	22.9±9.2	19.0±9.6	.040	33.3±18.4	29.3±16.3	.000	12.5±11.1	11.9±10.8	.631
	LL	-48.4(-56.3,-37.4)	-50.2±12.9	.001*	-57.4±5.7	-55.8±6.5	.255	-46.5±14.9	-49.5±13.4	.000	-47.7±13.4	-49.99±13.2	.079
Pelvic	PT	23.97±8.7	22.1±7.7	.001	16.7±6.4	15.5±7.7	.396	24.8±8.9	22.7±7.4	.001	24.6±6.6	23.9±7.8	.484
	SS	30.0±8.9	31.7±8.5	.003	35.0±7.0	37.2±6.0	.170	28.9±9.0	30.6±8.5	.008	33.7±7.0	34.2±8.4	.642
	PI	52.2(47.7,61.3)	53.9±10.3	.106*	52.9±7.6	52.7±7.8	.451	52.0(47.1,61.2)	53.4±10.3	.171*	58.3±11.6	58.1±11.6	.589
	PI-LL	6.29±13.1	3.7±10.9	.000	-4.5±8.2	-3.1±10.1	.281	7.1±13.6	3.9±11.1	.000	10.6±7.9	8.2±8.3	.040
Global	SVA	14.5(-4.8,38.2)	5.8(-17.6,38.8)	.128*	11.5±21.7	17.2±38.8	.493	20.7±36.9	13.4±43.9	.094	18.9±44.5	-0.5(-17.6,26.2)	.285*
	SSA	119.3±9.6	121.7±9.5	.000	124.3±6.5	129.2(123.9,129.8)	.173*	118.0±9.6	120.5±9.5	.000	123.8±10.5	126.2±9.7	.043
	TPA	18.7(12.8,22.6)	16.7±7.1	.000*	11.1(9.0,14.3)	11.8±6.0	.483*	19.6±8.4	17.1±7.2	.000	19.6±5.19	18.2±5.8	.080

*p-value derived using Wilcoxon signed rank test for nonparametric paired data

In the TL group, the PT decreased from 24.8±8.9 to 22.7±7.4 and the SS increased from 28.9±9.0 to 30.6±8.5 after the operation (p < 0.01). The TLK and local kyphosis Cobb angle decreased from 33.3±18.4 and 23.3±15.6 to 29.3±16.3 and 18.3±13.6, respectively. The LL increased from -46.5±14.9 to -49.5±13.4, and there were significant differences in all local sagittal parameters except for the TK. Among the global sagittal parameters, the SSA increased from 118.0±9.6 to 120.5±9.5 and the TPA decreased from 19.6±8.4 to 17.1±7.2 after PKP (p < 0.001). Although the SVA decreased from 20.7±36.9 to 13.4±43.9 postoperatively, the difference was not significant (p = 0.094).

In the MT group, only TLK decreased from 22.9±9.2 to 19±9.6 after PKP. Other parameters were not statistically different after surgery.

In the LU group, the local kyphosis Cobb angle (p = 0.047) and SSA (p = 0.043) increased significantly after surgery. The PI minus LL was significantly reduced after surgery (p = 0.04).

The correlations between the spinal and pelvic parameters in OVCFs preoperatively are shown in Table 4.There was a moderate correlation among the SVA, SSA and TPA (p<0.01). The TPA was positively correlated with the PT (r = 0.862) and PI-LL (r = 0.672, and the SSA was positively correlated with the SS (r = 0.801) and negatively correlated with the LL (r = -0.672) (p<0.01). Based on these results, the SSA is affected by the parameters of the pelvis and spine. The TPA is mainly affected by the pelvic parameters. There was no significant correlation between the SVA and most of the spinal and pelvic parameters.

Table 4

The correlation between the preoperative spinal and pelvic parameters in OVCFs.

	SSA	TPA	Cobb	TK	TLK	LL	PT	SS	PI	PI-LL
SVA	-0.482*	0.471*	-0.057	-0.056	0.086	0.388*	0.006	0.021	0.012	0.434*
SSA		-0.411*	-0.142	-0.183	-0.548*	-0.672*	-0.285*	0.801*	0.484*	-0.359*
TPA			0.171	0.116	0.221	0.229	0.862*	-0210	0.542*	0.672*
Cobb				0.441*	0.479*	-0.147	0.315*	-0.198	0.067	-0.110
TK					0.678*	-0.542*	0.227	-0.215	0	-0.594*
TLK						0.052	0.283*	-0.550*	-0.257	-0.143
LL							0.075	-0.592*	-0.471*	0.728*
PT								-0.334*	0.543*	0.503*
SS									0.599*	-0.182
PI										0.261

*Correlation is significant at the 0.01 level (2-tailed)

Power analysis

With effect size of 0.8 and 0.05 level of statistical significance, the TL group (n = 71) achieved a power of 0.99. Thus, the TL group was sufficiently powered to detect the effect of PKP on sagittal balance in patients with OVCF. However, power in the non-TL groups ranged from 0.55 to 0.65. Based on these findings, there is insufficient data to investigate the parameters in the non-TL groups. Thus, additional studies with proper large-scale cohorts are still warranted.

Discussion

Global sagittal balance is an optimal state of equilibrium, during which the standing position is maintained with a horizontally balanced posture, minimal energy expenditure, and minimal ligament discomfort [4, 28]. The most important aspects of sagittal balance are to achieve harmony between the sagittal parameters of the spine and the pelvis and to maintain the axis of gravity at its natural location with minimal energy consumption [28-32].

When the local sagittal alignment of the spine is abnormal, the body will initiate multiple compensatory mechanisms to maintain global balance. Compensatory mechanisms have been found in the pelvis, spine and lower extremities[33]. When a spinal disease affects the spinal compensations, the main manifestations of the compensatory process are a pelvic posterior rotation and knee flexion compensation [34].

When the deformity gradually worsens beyond the compensatory capacity of the pelvis, spine and lower limbs and the body cannot maintain balance by increasing muscle strength, there will be a failure to achieve a horizontal gaze and to maintain alignment of the gravity line, resulting in a sagittal imbalance.

In clinical practice, many metric and angular parameters of the full-length lateral radiograph of the spine have been used to assess the sagittal balance. Global sagittal balance is typically determined by measuring the SVA [4, 35].

With the increasing use of the SVA in clinical research, a shortcoming has gradually emerged. The limitation of the SVA is that it is influenced by the patient’s position and pelvic rotation [36]. For instance, when a large thoracolumbar kyphosis occurs, the spine could maintain balance through muscle adjustments and the SVA could achieve normal values, but the patient's pain symptoms would be more obvious. Therefore, the SVA does not truly reflect the structure of the spine and the severity of the patient's symptoms. In addition, the SVA is a linear parameter that must be calibrated proportionally due to the influence of the X-ray projection distance, and the deviation is relatively large.

To avoid these drawbacks, we and other researchers propose to use angular parameters such as the SSA and TPA[20, 33].

Roussouly et al [20] proposed the concept of the SSA. In a normal population, the mean value of this angle is 135 ± 8 [20, 33]. The SSA has been used not only to assess the global sagittal alignment of the spine above the pelvis but also to reflect the size of the entire kyphosis. The SSA value decreases when kyphosis is present in the spine.

Protopsaltis et al [27] proposed a new parameter reflecting sagittal balance: the TPA. The TPA integrates global and local spino-pelvic sagittal balance information and reflects the compensatory mechanism of the spine and pelvis. Similar to the SSA, the TPA is also an angular parameter. These parameters do not need to be calibrated proportionally on imaging data, and their errors are smaller than those of metric parameters such as the SVA.

Our study found that the SSA and TPA displayed greater correlations with the sagittal parameters of the spine and pelvis than the SVA. Our results showed that the TPA was positively correlated with the PT and PI-LL, and the SSA was positively correlated with the SS and negatively correlated with the LL. These results suggest that the SSA and TPA are affected by the parameters of the pelvis and spine. There was no significant correlation between the SVA and most of the spino-pelvic sagittal parameters. Therefore, the clinical reference values of these two parameters are better than that of the SVA.

A spinal sagittal imbalance can be caused by many spinal diseases, such as spinal deformity and spinal degeneration. In recent years, some scholars have begun to pay attention to the sagittal imbalances caused by osteoporotic vertebral compression fractures.

Sutipornpalangkul et al[37] confirmed that patients with OVCFs had anterior wedge deformities, leading to the progression of kyphotic deformity and an anterior shift in the center of gravity, and ultimately causing a spinal sagittal imbalance.

Le Huec JC et al [38] reported that patients with OVCFs showed a worse global sagittal alignment and decreased quality of life. The number and severity of vertebral compression fractures had a negative influence on global sagittal balance.

In our study, we confirmed that after fracture, especially thoracolumbar fracture, the kyphosis deformity worsened, the C7 plumb line shifted forward, and the sagittal balance was mainly compensated by pelvic retroversion. Some patients with severe fractures could not be corrected by compensation, resulting in a sagittal imbalance. These patients showed more obvious symptoms than simple low back pain caused by vertebral fractures. The most common symptoms were the tendency to tilt forward when standing or walking and the failure to walk on his/her own without support from the front of the body.

Kyphoplasty is a minimally invasive treatment for OVCFs. In this case, whether the classic surgical method of OVCF, PKP, can be used to restore the global sagittal balance is still controversial [39-43].

Some scholars have confirmed that PKP not only alleviates the pain caused by a fracture but also improves the sagittal balance by restoring the anterior height of the vertebral body and improving the local kyphosis deformity [8, 37].

However, few detailed studies have investigated the effects of kyphoplasty on total spinal alignment or global sagittal balance [8].

Kanayama et al[39] analyzed 56 patients with OVCF who underwent PKP. After 32 months of follow-up, the research group found that PKP contributed to immediate pain relief but did not improve the global sagittal alignment after OVCF. The researchers concluded that PKP should be solely used to address pain or the nonunion of an OVCF and could not be expected to restore the global sagittal alignment.

Sutipornpalangkul et al[37] analyzed 17 patients with OVCF who underwent PKP and concluded that, kyphoplasty did not play a role in improving the overall alignment of the spine for the treatment of OVCF. However, kyphoplasty did demonstrate regional improvement of the OVCF. The researchers supposed that a multiple-level kyphoplasty might improve overall sagittal balance. The main reason may be the cumulative improvements in the degrees of correction of the kyphotic angle.

However, Yokoyama et al [8] analyzed 21 patients with OVCF treated with PKP and showed that PKP not only alleviated the pain associated with fractures but also significantly improved sagittal imbalance.

In our study, we found that patients with OVCFs had a reduction in kyphosis after PKP and that the pelvic posterior retroversion was significantly restored after surgery. Some patients with sagittal imbalance regained sagittal balance or at least achieved a compensatory balance. According to the analysis of our data, PKP could improve the sagittal balance parameters, including the overall balance parameters. Osteoporotic compression fractures of the thoracolumbar segment achieved the best improvement among the three fracture groups.

We found that although fractures of the thoracolumbar segment had the largest incidence and were associated with the most severe kyphosis, the improvement of the thoracolumbar segment after PKP was the greatest. This improvement may be mainly attributed to the anatomical and biomechanical characteristics of the thoracolumbar segment. The thoracolumbar spine section generally extends from T10 to L2, which includes the junction of the thoracic and lumbar segments. This section carries a large spinal load and is extremely susceptible to damage, and a certain degree of kyphosis deformity occurs upon injury.

The compressive stress that occurs during an injury is likely to cause the collapse of an anterior vertebral fracture. The superior endplate is often involved in an osteoporotic vertebral fracture due to the unique structure and different distribution of trabecular bone across the vertebral body [7, 44, 45]. After the PKP treatment, the stability of the anterior and middle columns of the thoracolumbar segments improved significantly, and the anterior support function recovered partially. The reverse injury mechanism gradually corrected a part of the sagittal imbalance. Another potential explanation for the improvement in sagittal imbalance after thoracolumbar fracture is the large amount of sagittal loss after the thoracolumbar fracture.

Osteoporotic vertebral compression fractures mainly occurred in the thoracolumbar region (T10-L2) in several previous studies[46-49]. Liu T et al studied 77 patients with single-segment OVCF, of which 77.9% occurred in the thoracolumbar region[50]. Kong LD et al studied 53 patients with OVCF and 75.5% of fractures occurred in the thoracolumbar region [51]. In our study, this probability was 78.9%. Therefore, the number of patients in non-TL group was relatively small. And some of these patients also had fractures in the thoracolumbar region at the same time. In order to avoid confounding factors in the statistical analysis, we excluded patients with fractures in two or more different regions. Therefore, the number of patients in non-TL group was even smaller, which may have resulted in a higher statistical bias. Thus, additional studies with high-quality and large-scale are still warranted.

Conclusion

PKP is an effective treatment for osteoporotic thoracolumbar vertebral compression fractures. When OVCFs occurred in the thoracolumbar region (T10-L2), PKP can not only relieves the low back pain caused by fractures but also corrects the pelvic posterior rotation that occurs during sagittal compensatory balance within 2–3 days. PKP can significantly improves the angular parameters (TPA and SSA) caused by vertebral fractures and improves the overall sagittal alignment.

Osteoporotic vertebral compression fractures mainly occur in the thoracolumbar region, affecting the spino-pelvic alignment and global sagittal balance to a greater extent than in the MT region and LU region. On the other hand, among the three groups, the improvement of sagittal balance parameters was greatest in patients with a fracture in the thoracolumbar region.

Drawbacks of this study

1. Due to the incidence rate, the numbers of fracture cases in the upper thoracic vertebrae and lower lumbar vertebrae were small, which may have caused statistical errors and lack of persuasiveness.

2. Because most of the patients were elderly, their activity was limited, and their self-care ability was poor. When the whole spine was taken into account, the most satisfactory standing posture was not always able to be achieved, resulting in some errors.

3. All patients were from the same surgical group, and the surgical procedures were basically the same, but there were inevitable surgical differences among the three surgeons.

Demographics data and spino-pelvic sagittal parameters of OVCF patients.

(XLSX)

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Demographics data and spino-pelvic sagittal parameters of healthy volunteers.

(XLSX)

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The STROBE statement—Checklist.

(DOCX)

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20 Sep 2019

PONE-D-19-23099

The influences of the site of osteoporotic vertebral compression fracture and percutaneous kyphoplasty treatment on spino-pelvic alignment and global sagittal balance

PLOS ONE

Dear Mr. Sun,

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The study was well received by the reviewers. Some salient points that came up in this initial review include concerns about patient selection in the study cohort that may produce some bias; the lordosis measurements need to be confirmed as well, and finally, the reviewer panel also urges to look carefully into the statistics to draw the correct conclusions.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #2: Yes

Reviewer #3: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: My review for PLOS One article:

The influences of the site of osteoporotic vertebral compression fracture and percutaneous kyphoplasty treatment on spino-pelvic alignment and global sagittal balance

Mon Sep 16

20,000 characters max

Some although not all correctable English language errors are included below.

Full Title: Consider re-stating as a hypothesis, something like: Percutaneous Kyphoplasty for Osteoporotic Vertrebral Compression Fractures Improves Spino-Pelvic and Sagittal Alignment Maximally in the Thoracolumbar Region.

For the 3 groups of vertebral compression fracture regions, MT, TL, and LU, please mention the words represented by these abbreviations (or rename them to something more intuitive?)

The authors refer to ‘PKP’ as a surgery, whereas I would use the word ‘procedure’ to describe it. This may be confirmed with subspecialists performing the procedure, interventional radiologists in my experience.

‘Eldery patients’: Can you include the age range?

Additional specific suggested edits/ideas listed below:

Line #

25 The sentence including ‘it’s still blank on’ is unclear

29 Change ‘OCVF underwent’ to ‘OCVF who underwent’

31 Please explain here meaning of the 3 group abbreviations MT, TL, LU

33 Radiographs, not radiographies

44 ‘When performed’ not ‘while available

72 ‘with’ Shandong University

75 Mention why only compression fractures of less than 80% an inclusion criteria.

80 begin this line with ‘and’

127 use ‘before and after’ instead of ‘from before to after’

159 ‘increased significantly’ associated with what? Please specify. This is in the pre-operative section so I assume not due to treatment.

305 Using ‘from T10 – L2’ is convention in USA or write it out fully in English.

310 Briefly clarify where the ‘rib support is lost’—I assume from T12 to L1, or lumber compared to thoracic regions.

325 How do we know that ‘support strengthened’ after PKP? It makes sense that the additional improvements in pain and strength improving can be objectively measured, but unsure what is meant by ‘support strengthened’.

Reviewer #2: The authors of the study pose a relevant question that has not been answered sufficiently in the literature. The study is generally well performed with appropriate methods. The paper titled “The influences of the site of osteoporotic vertebral compression fracture and percutaneous kyphoplasty treatment on spino-pelvic alignment and global sagittal

balance” is generally well written, however, there are some minor issues to address:

-Please provide list of abbrevations

Introduction:

-Line 43-45 (Conclusion): Language issue – please revise

Materials + Methods:

-Line 79: .. the whole spine with pelvis and femoral heads…

Results:

-Line 157: please provide possible explanation why LL is not different in healthy volunteer group vs. LU group. In conclusions, you describe “…improve the local kyphosis caused by fractures…”. Your data of lumbar lordosis does not support that assumption. Please provide additional explanation or change conclusion.

-Please provide a numerical definition of what you consider as strong vs. moderate vs. weak statistical correlation

-Table 4: I am not sure what you mean by significant correlation: e.g. a correlation of SSA vs. PT of -0.285 does not seem significant to me. please clarify.

Discussion:

Line 209: “The experience…” Language – please revise

Line 238: we and others propose

Line 251-253: a correlation of TPA and PI of 0.542 will usually be considered as weak. Same applies for SSA and PI when r=0.484 and LL and TLK.

Line 290: suppose – Language- please revise

Line 308-319: this does not seem relevant to the study. consider removal.

Line 320-322: this does not seem relevant to the study. consider removal.

Line 327-329: unclear language – please revise

Conclusion

Line 335: “PKP can significantly improve the angular parameters (TPA, SSA) caused by vertebral fractures and improve the overall sagittal alignment.” Did you find any correlation of improved TPA and/or SSA to improved VAS?

Reviewer #3: First of all congratulations to the authors for this excellent work. I think that you have worked hard and the ammount of data that you have is so good.

Prior to the publication, I would need to know some details of the work:

- kyphoplasty has shown to reduce the pain related with the osteoporotic vertebral fracture faster than the conservative treatment, but it has not shown clearly to reduce the disbalance. Your work is based on "the influence of the site of osteoporotic fracture AND percutaneous kyphoplasty", and you finish your discussion with the phrase "PKP is an effective treatment for osteoporotic thoracolumbar vertebral compression fractures". And then you follow: "... also improve the local kyphosis caused by fractures and correct the pelvic posterior rotation that occurs during sagittal compensatory balance". In my opinion, you don't have evidence enough to say that, for this reason: you have not compared the balance of people with a vertebral fracture treated with conservative management vs PKP treatment. You can define what deformity do you expect after a fracture treated with PKP but you can't say that improves the kyphosis.

It's clear that the kyphoplasty improves the heigh of the vertebral body, but It has been related with adjacent vertebra fractures, wich could produce kyphosis too. That's why you must compare the kyphosis after the conservative treatment to say that PKP improves the kyphosis, or, at least, to define what do you mean with "local kyphosis", and mentioning that it can produce an hiper-kyphosis in other segments.

- When were the post-op X-ray taken? That's probably the most important factor of the study. PKP has shown to heel the fractures and to reduce the pain faster than conservative treatment, and obviously, when the patient has pain, he tries to compensate the spine balance, what could produce an hiper-kyphosis that would disappear after the consertative management when the pain is not so strong. You must compare the effect of the PKP in the spine balance in a chronic timeline, cause the spine balance is important to evaluate the chronic back pain, not the acute back pain. In other words, when we have neck pain after a car accident, we can modify the cervical lordosis, but it's not a surgical indication to correct it, cause when the pain will dissappear, the lordosis will come again to its normal position.

- Why did you select just patients on wich the injured vertebrae compression was less than 80%? How could you explain the ammount of kyphosis produced before surgery only with a maxium of 20% compression? Could the pain be an explanation for that?

- How did you define the parametric statistics for the comparisons? On which values the normality test was applied? It's difficult to get a Normal distribution in the MT and LU group just with 9 and 10 patients respectively.

- You must be careful when you say "there was no significant difference in... when p value is higher than 0,05. As you probably know, when the p value is higher than the a value, you cannot establish that there are no differences: you can say that in your data you don't have found them, but with the n value of the MT and the LU group, you could be producing a Type II error.

- Finally, this is a retrospective study on which you assume as exclusion criteria patients with "hip and knee joint limitations". How did you verify that the population of your study didn't have symptoms or limitations due to hip or knee osteoarthritis

Finally, I would like to verify the statistics and data personally.

Thanks for all these clarifications.

**********

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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29 Oct 2019

Reviewer's Responses to Questions：

1. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

Response: We appreciate the reviewer’s comments. We asked professional statisticians to conduct a statistical analysis of our data again, and made corresponding changes to our conclusions.

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #2: Yes

Reviewer #3: Yes

Response: Thanks to the reviewers for their affirmation of our statistical methods. All of our data statistics programs are consulted by statistical professionals, and it is believed that the statistical methods applied should be appropriate and rigorous.

3. Have the authors made all data underlying the findings in their manuscript fully available?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

Response: Thanks for the two reviewers. All the data involved in our manuscript has been uploaded as an attachment during the submission. Please see the attached S1 Table and S2 Table.

4. Is the manuscript presented in an intelligible fashion and written in standard English?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Response: Thanks for the reviewer's recognition of our manuscript language.

5. Review Comments to the Author

Responses to Reviewer #1

We would like to extend a special thank you for your helpful comments and constructive criticism.

1) Comment：Full Title: Consider re-stating as a hypothesis, something like: Percutaneous Kyphoplasty for Osteoporotic Vertebral Compression Fractures Improves Spino-Pelvic and Sagittal Alignment Maximally in the Thoracolumbar Region.

Response: Thanks for your valuable advice. We have made the correction according to the Reviewer’s comments.

2) Comment：For the 3 groups of vertebral compression fracture regions, MT, TL, and LU, please mention the words represented by these abbreviations (or rename them to something more intuitive?)

Response: We are very sorry to have missed the full name of MT, TL, and LU. In our manuscript, MT, TL, and LU are short for Main Thoracic, Thoracolumbar, and Lumbar, respectively. According to the reviewer's suggestion, we added the full name and the corresponding abbreviation of three groups in the manuscript.

3) Comment：The authors refer to ‘PKP’ as a surgery, whereas I would use the word ‘procedure’ to describe it. This may be confirmed with subspecialists performing the procedure, interventional radiologists in my experience.

Response: Thanks for the kind advices. In our hospital, PKP is performed by spinal surgeons in the operating room, so we are used to calling it "surgery." Considering the Reviewer’s warm suggestion, we agree to use ' procedure ' to describe it in the manuscript.

4) Comment：‘Elderly patients’: Can you include the age range?

Response: We appreciate the reviewer’s comments. In the manuscript, we were too vague about ‘Elderly patients’. In our study, the control group was no younger than 59 years old and we have modified it accordingly.

5) Comment：Additional specific suggested edits/ideas listed below:

Line #

25 The sentence including ‘it’s still blank on’ is unclear

29 Change ‘OCVF underwent’ to ‘OCVF who underwent’

31 Please explain here meaning of the 3 group abbreviations MT, TL, LU

33 Radiographs, not radiographies

44 ‘When performed’ not ‘while available

80 begin this line with ‘and’

127 use ‘before and after’ instead of ‘from before to after’

305 Using ‘from T10 – L2’ is convention in USA or write it out fully in English.

Response: We are very sorry for the mistakes. In response to the above language expressions, we have made corresponding modifications according to the comments of reviewers. Thank you!

6) Comment：Line 72 ‘with’ Shandong University

Response: Thanks for your valuable advice. As Shandong provincial hospital affiliated to Shandong University is the official name of our hospital, so it's the best way to use the official name to represent my institution. Many thanks!

7) Comment：Line 75 Mention why only compression fractures of less than 80% an inclusion criteria.

Response: Thanks for your reminding. The vertebral compression ratio of less than 80% is one of the surgical indications that most orthopedic surgeons in our country have for patients with osteoporotic vertebral compression fractures [1]. We believe that if the compression ratio of the vertebral body is greater than 80%, the difficulty of PKP puncture is significantly increased, and cement leakage in percutaneous kyphoplasty is more likely to occur.

[1] Yin P, Ma YZ, Ma X, Chen BH, Hong Y, Liu BG, et al. Guidelines for the treatment of osteoporosis vertebral compression fractures[ J].Chinese Journal of Osteoporosis, 2015, 21(06): 643-648.

8) Comment：Line 159 ‘increased significantly’ associated with what? Please specify. This is in the pre-operative section so I assume not due to treatment.

Response: We are very sorry for the mistakes. Our original intention was that the TK, TLK, and LL were significantly larger in the MT group compared with the control group, and the expression in the manuscript was inaccurate. We have made correction according to the Reviewer’s comments. Thank you!

9) Comment：Line 310 Briefly clarify where the ‘rib support is lost’—I assume from T12 to L1, or lumber compared to thoracic regions.

Response: Thanks for your valuable advice. We believe that from the thoracic spine to the lumbar spine, the fixation of the ribs gradually diminishes until it disappears. Because another reviewer believes that lines 308-322 do not seem relevant to the study, so we corrected the description.

10) Comment：Line 325 How do we know that ‘support strengthened’ after PKP? It makes sense that the additional improvements in pain and strength improving can be objectively measured, but unsure what is meant by ‘support strengthened’.

Response: Special thanks to you for your good comments. ‘support strengthened’ after PKP has no literature support yet, we have corrected the description.

Responses to Reviewer #2

We would like to extend a special thank you for your helpful comments and constructive criticism.

1) Comment：Please provide list of abbreviations.

Response: Thanks for your valuable advice. We have added a list of abbreviations and noted them in the manuscript.

2) Comment：Introduction: Line 43-45 (Conclusion): Language issue – please revise

Materials + Methods: Line 79: …the whole spine with pelvis and femoral heads…

Response: Considering the Reviewer’s suggestion, we have made corresponding modifications. Please review again, Thank you!

3) Comment：Results: Line 157: please provide possible explanation why LL is not different in healthy volunteer group vs. LU group. In conclusions, you describe “…improve the local kyphosis caused by fractures…”. Your data of lumbar lordosis does not support that assumption. Please provide additional explanation or change conclusion.

Response: Thanks for your valuable advice. Our statistics do show no significant difference in LL between LU group and control group. We re-read the full-length X-ray of the spine of all patients in the LU group. We found that all 10 patients in the LU group were just mild compression fractures or biconcave compression fractures. There was no obvious wedge deformation in the anterior and posterior columns of the injured vertebral body, so the LL did not change much. It may explain why there is no difference in LL between the LU group and control group. Of course, this situation is mainly related to the low incidence of OVCF in the lower lumbar vertebrae in clinical practice, and thus the number of patients enrolled in the group is relatively small. Inevitably there will be some statistical errors, causing data bias.

The conclusion of "... improve the local kyphosis by products ..." cannot be directly derived from this data. We analyzed the data and found that PKP did not improve the kyphosis of the MT and LU groups, but significantly improved the kyphosis of the TL group. These data can be obtained from the comparison of TLK, LL, and local kyphosis Cobb angle data before and after PKP in TL group. Therefore, we have made relevant amendments to the conclusions in order to be more objective and fair. Thank you for your reminder.

4) Comment：Please provide a numerical definition of what you consider as strong vs. moderate vs. weak statistical correlation

-Table 4: I am not sure what you mean by significant correlation: e.g. a correlation of SSA vs. PT of -0.285 does not seem significant to me. please clarify.

Line 251-253: a correlation of TPA and PI of 0.542 will usually be considered as weak. Same applies for SSA and PI when r=0.484 and LL and TLK.

Response: We appreciate the reviewer’s comments. The strength of the correlation was determined using the following guide for the absolute value: 0.00–0.19 “very weak,” 0.20–0.39 “weak,” 0.40–0.59 “moderate,” 0.60–0.79 “strong,” ,0.8-1.0 “very strong,”. We have re-written this part according to the Reviewer’s suggestion. Thanks a lot.

5) Comment：Discussion:

Line 209: “The experience…” Language – please revise

Line 238: we and others propose

Line 290: suppose – Language- please revise

Line 308-319: this does not seem relevant to the study. consider removal.

Line 320-322: this does not seem relevant to the study. consider removal.

Line 327-329: unclear language – please revise

Response: Thank you for your valuable comments. We have made the corresponding changes according to the Reviewer’s comments.

6) Comment：Conclusion

Line 335: “PKP can significantly improve the angular parameters (TPA, SSA) caused by vertebral fractures and improve the overall sagittal alignment.” Did you find any correlation of improved TPA and/or SSA to improved VAS?

Response: Thank you for your great comments. We have also done relevant statistical analysis in the early stage. After statistical analysis, it was found that there was no strong statistical correlation between improved TPA or SSA and improved VAS. Therefore, this aspect was not mentioned in our manuscript. We supposed that VAS, as subjective data, was greatly influenced by the patients themselves, and the individual differences are relatively large, which may affect the accuracy of statistics.

Reviewer #3:

We would like to extend a special thank you for your helpful comments and constructive criticism.

1) Comment：kyphoplasty has shown to reduce the pain related with the osteoporotic vertebral fracture faster than the conservative treatment, but it has not shown clearly to reduce the disbalance. Your work is based on "the influence of the site of osteoporotic fracture AND percutaneous kyphoplasty", and you finish your discussion with the phrase "PKP is an effective treatment for osteoporotic thoracolumbar vertebral compression fractures". And then you follow: "... also improve the local kyphosis caused by fractures and correct the pelvic posterior rotation that occurs during sagittal compensatory balance". In my opinion, you don't have evidence enough to say that, for this reason: you have not compared the balance of people with a vertebral fracture treated with conservative management vs PKP treatment. You can define what deformity do you expect after a fracture treated with PKP but you can't say that improves the kyphosis.

It's clear that the kyphoplasty improves the height of the vertebral body, but It has been related with adjacent vertebra fractures, which could produce kyphosis too. That's why you must compare the kyphosis after the conservative treatment to say that PKP improves the kyphosis, or, at least, to define what do you mean with "local kyphosis", and mentioning that it can produce an hiper-kyphosis in other segments.

Response: Thanks for your reminding. We have re-written this part according to the Reviewer’s suggestion.

PKP has been reported to improve the imbalance caused by OVCF (YOKOYAMA K, et al. 2015), but it is still on controversy. In clinical practice, we encountered some patients with sagittal imbalance caused by OVCF. The sagittal balance was greatly improved within 2-3 days after PKP, these findings raise concern. We retrospectively studied that PKP could indeed correct mild to moderate sagittal imbalance early, especially in patients with fractures of the thoracolumbar region. It is the purpose to do the study.

The improvement in the sagittal imbalance involved in our study occurred within 2-3 days after PKP, and we all knew that the conservative treatment group did not change significantly within 2-3 days. Therefore, we did not choose a conservative treatment group as a comparison. Because no other interventions were taken during this period, we believed that PKP was helpful in improving the sagittal imbalance. We analyzed the data and found that PKP did not improve the kyphosis of the MT and LU groups, but significantly improved the kyphosis of the TL group. These data could be obtained from the comparison of TLK, LL, and local kyphosis Cobb angle data before and after PKP in TL group. Therefore, we have made relevant amendments to the conclusions in order to be more objective and fair. Long-term follow-up of these patients is still ongoing, and we will add a conservative treatment group for long-term follow-up. Thank you for your suggestion.

Of course, we must admit that PKP has no effect on the improvement of severe kyphosis or severe sagittal imbalance. These need to be corrected by osteotomy and are not suitable for PKP treatment. Therefore, we need to explain that the local kyphosis involved in the study is mostly mild to moderate thoracolumbar kyphosis.

2) Comment: When were the post-op X-ray taken? That's probably the most important factor of the study. PKP has shown to heel the fractures and to reduce the pain faster than conservative treatment, and obviously, when the patient has pain, he tries to compensate the spine balance, what could produce an hiper-kyphosis that would disappear after the conservative management when the pain is not so strong. You must compare the effect of the PKP in the spine balance in a chronic timeline, cause the spine balance is important to evaluate the chronic back pain, not the acute back pain. In other words, when we have neck pain after a car accident, we can modify the cervical lordosis, but it's not a surgical indication to correct it, cause when the pain will disappear, the lordosis will come again to its normal position.

Response: We appreciate the reviewer’s comments.Our postoperative radiographs were taken 2-3 days after PKP treatment. What we wanted to confirm was that PKP could significantly improve the sagittal imbalance earlier. It was an extra finding when we used PKP to treat OVCF to relieve pain and improve quality of life.

At the same time, we play correlation statistics on the improvement of VAS and the improvement of sagittal parameters such as SSA and TPA. It had been confirmed that there was no strong correlation between them. It also indicated that the improvement of the patient's sagittal imbalance was not caused solely by pain relief. We suspected that it might be related to factors such as back muscles. We were currently conducting a prospective study and the results will be reported later.

3) Comment: Why did you select just patients on which the injured vertebrae compression was less than 80%? How could you explain the amount of kyphosis produced before surgery only with a maximum of 20% compression? Could the pain be an explanation for that?

Response: Thanks for your valuable advice. The reason why the selected cases in our study are less than 80% of the vertebral compression is that PKP is not recommended for OVCF patients with more than 80% injured vertebrae compression in our country. If the degree of compression of the injured vertebra is greater than 80%, cement leakage is more likely to occur, and intraoperative puncture is difficult.

The kyphosis is not only caused by the wedge deformation of the vertebral body, but also by other factors. We speculate that imbalance of muscle strength is one of the causes of kyphosis when the compression of the injured vertebra is less than 20%. Our hypothesis is that after fracture, the muscle activity in the back of the spine is abnormal, the muscle strength is decreased, the muscle strength in front of and behind the spine is unbalanced, and the kyphosis is aggravated. Severe cases further cause sagittal imbalance. Of course, pain after a vertebral fracture may also be an important cause.

4) Comment: How did you define the parametric statistics for the comparisons? On which values the normality test was applied? It's difficult to get a Normal distribution in the MT and LU group just with 9 and 10 patients respectively.

You must be careful when you say "there was no significant difference in... when p value is higher than 0,05. As you probably know, when the p value is higher than the a value, you cannot establish that there are no differences: you can say that in your data you don't have found them, but with the n value of the MT and the LU group, you could be producing a Type II error.

Response:

Prerequisites for using parameter statistics: 1. The data satisfies the normality; 2. The variances between the groups of data are equal (satisfying the homogeneity of the variance). We use the Shapiro-Wilk normality test, and when the p-value of the test result is greater than 0.05, the data is considered to satisfy the normality.

The incidence of OVCF in the upper thoracic and lower lumbar was relatively low. In addition, we also needed the patients to meet the inclusion and exclusion criteria, as well as underwent preoperative and postoperative full-length radiographs. Therefore, the number of cases which satisfied the condition was indeed small, which inevitably caused a certain statistical error. This is also the limitations of our research.

From the statistical analysis, we were fortunate to find that most of the parameters of the MT group and the LU group met a normal distribution. For data that did not conform to the normal distribution, we used nonparametric statistics.

5) Comment: Finally, this is a retrospective study on which you assume as exclusion criteria patients with "hip and knee joint limitations". How did you verify that the population of your study didn't have symptoms or limitations due to hip or knee osteoarthritis?

Response: Our treatment group patients were all inpatients, and their hospital records detailed whether the patients had a history of hip and knee disease. And the patient's range of motion of hip and knee can be seen in the physical examination of the medical record.

6) Comment: Finally, I would like to verify the statistics and data personally.

Response: We are very pleased that you can help us verify the statistics and data. The original data of our research has been uploaded to the attachment during the submission. Please review attachment S1 Table and S2 Table. Thank you!

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

4 Dec 2019

PONE-D-19-23099R1

Percutaneous Kyphoplasty for Osteoporotic Vertebral Compression Fractures Improves Spino-Pelvic Alignment and Global Sagittal Balance Maximally in the Thoracolumbar Region

PLOS ONE

Dear Mr. Sun,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

The manuscript has seen important improvements since the first review, but on this occasion the reviewer panel found minor grammar and writing issues that need to be addressed, preferably with the aid of a native English speaker, so that the message is appropriately transmitted to the readership of the Journal. Please follow the reviewers' recommendations when making these corrections.

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We look forward to receiving your revised manuscript.

Kind regards,

Alejandro A. Espinoza Orías, PhD

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #4: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #4: Partly

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #4: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #4: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #4: No

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Thank you for your work on this submission. I'm not able to perform statistical analysis which I leave to you and the other reviewer(s).

Reviewer #4: General comments: While the overall message is able to be conveyed, much of the wording is confusing and frequently grammatically incorrect. I encountered numerous errors in structure and grammar throughout the paper some of which have been highlighted in the specific comments section; however, there are many more throughout. Suggest review by another editor or thorough reworking to refine the syntax.

Was there a power analysis? Should include this in the statistical analysis section, especially given the small numbers for the non-TL groups, which may make the findings for these groups irrelevant. While this is addressed briefly in the drawbacks section, it should also be addressed in the discussion section and backed up by literature where applicable.

Lines 217 to 270 reads like a review of sagittal parameters and, while helpful, detracts from the overall findings of the study and is – to some degree – extraneous. If the purpose of the study is to describe an improvement in sagittal balance after PKP, then the discussion section should be focused on discussing these findings with appropriate references to support these findings (which the authors do in the latter half of the discussion section.) The discussion section needs to be trimmed down and focused on the relevant results.

Specific Comments

Line 25: Reword this sentence – would not use contractions in a scientific paper. i.e. “However, the influence of kyphoplasty on spino-pelvic aligment and global sagittal balance when performed at specific treatment sites in the spine remains unclear.”

Line 37: Remove “of;” Sentence beginning

Line 46: improvement of what in the TL group? Needs to be reworded.

Line 69: Needs references to back up this claim, possibly naming specific examples.

Line 72: Please combine with another paragraph – this sentence should not stand alone as its own paragraph.

Line 76: Sentence beginning “Whether the effect…” is confusingly worded.

Line 101: Be specific regarding “hip and knee joint limitations.” I see that you addressed this in the previous reviewer comments, but it bears explaining in the text. Otherwise it remains confusing and vague.

Line 224: Difficult to understand this sentence as written.

Line 238: Please provide a reference for this paragraph

Line 327: The sentence “After PKP, back pain…” is conjecture. The study did not measure back muscle strength and cannot claim improvement in strength as a reason for improvement in sagittal balance.

**********

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Reviewer #1: No

Reviewer #4: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files to be viewed.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org. Please note that Supporting Information files do not need this step.

28 Dec 2019

Reviewer's Responses to Questions：

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #4: (No Response)

Response: Thanks for the reviewer's affirmation of our revised manuscript. We revised the manuscript again according to the reviewer's comments, and strived to meet PLOS ONE’s publication criteria.

2. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #1: Yes

Reviewer #4: Partly

Response: We appreciate the reviewer’s comments. We asked professional statisticians to perform a statistical analysis of our data again, and added power analysis at the recommendation of reviewers.

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #4: Yes

Response: Thanks to the reviewers for their affirmation of our statistical methods. All of our data statistics programs are consulted by statistical professionals, and it is believed that the statistical methods applied should be appropriate and rigorous.

4. Have the authors made all data underlying the findings in their manuscript fully available?

Reviewer #1: Yes

Reviewer #4: Yes

Response: Thanks for the two reviewers. All the data involved in our manuscript has been uploaded as an attachment during the submission.

5. Is the manuscript presented in an intelligible fashion and written in standard English?

Reviewer #1: Yes

Reviewer #4: No

Response: We invited native English speaking professionals to proofread our manuscript and revised the grammar and writing issues in the manuscript again. Please review it again and give us your valuable comments. Thank you!

6. Review Comments to the Author

Reviewer #1: Thank you for your work on this submission. I'm not able to perform statistical analysis which I leave to you and the other reviewer(s).

Responses to Reviewer #1

We would like to extend a special thank you for your helpful comments and recognition of our revised manuscript.

Responses to Reviewer #4:

We would like to extend a special thank you for your helpful comments and constructive criticism.

1) Comment：General comments: While the overall message is able to be conveyed, much of the wording is confusing and frequently grammatically incorrect. I encountered numerous errors in structure and grammar throughout the paper some of which have been highlighted in the specific comments section; however, there are many more throughout. Suggest review by another editor or thorough reworking to refine the syntax.

Response: Thanks for your valuable advice. We are very sorry for the many grammar and writing problems in the manuscript. We consulted native English speaking professionals to review our manuscript and made corresponding modifications to the grammar and writing issues in the text. Please review it again and give us your valuable comments. Thank you!

2) Comment：Was there a power analysis? Should include this in the statistical analysis section, especially given the small numbers for the non-TL groups, which may make the findings for these groups irrelevant. While this is addressed briefly in the drawbacks section, it should also be addressed in the discussion section and backed up by literature where applicable.

Response: We appreciate the reviewer’s comments. We have supplemented power analysis in the statistical analysis section (Line221-227) and discussed the results of power analysis in the discussion section (Line331-340). The power of the study was estimated using a post-hoc analysis with G*Power software (version 3.1.9.4, Franz Faul, Universität Kiel, Germany).With effect size of 0.8 and 0.05 level of statistical significance, the actual power of TL group was calculated to be 0.99. However, the powers of non-TL groups were ranged from 0.55 to 0.65. The reason is that osteoporotic vertebral compression fractures mainly occurred in the thoracolumbar region (T10-L2). Therefore, the number of patients in non-TL group was relatively small. And some of these patients also had fractures in the thoracolumbar region at the same time. In order to avoid confounding factors in the statistical analysis, we excluded patients with fractures in two or more different regions. Therefore, the number of patients in non-TL group was even smaller, which may have resulted in a higher statistical bias.

3) Comment：Lines 217 to 270 reads like a review of sagittal parameters and, while helpful, detracts from the overall findings of the study and is – to some degree – extraneous. If the purpose of the study is to describe an improvement in sagittal balance after PKP, then the discussion section should be focused on discussing these findings with appropriate references to support these findings (which the authors do in the latter half of the discussion section.) The discussion section needs to be trimmed down and focused on the relevant results.

Response: Thank you for your valuable comments. According to your advice, we have reduced some parts of the discussion.

In most cases, global sagittal balance is usually determined by measuring the SVA. Lines 243 to 271 explained why we chose SSA, TPA instead of SVA as the main parameters. We consider that this part should be kept in the manuscript. Thank you!

4) Comment：Specific Comments

Line 25: Reword this sentence – would not use contractions in a scientific paper. i.e. “However, the influence of kyphoplasty on spino-pelvic aligment and global sagittal balance when performed at specific treatment sites in the spine remains unclear.”

Line 37: Remove “of;” Sentence beginning

Line 72: Please combine with another paragraph – this sentence should not stand alone as its own paragraph.

Response: We are very sorry for these mistakes. We have made corresponding modifications according to the reviewer’s comments. Thank you!

5) Comment：

Line 46: improvement of what in the TL group? Needs to be reworded.

Response: Thank you for your suggestion. We have changed to “When PKP was performed, the improvement of sagittal balance parameters of TL group was the best in the three groups.”

6) Comment：

Line 69: Needs references to back up this claim, possibly naming specific examples.

Response: Thank you for your valuable advice. We have added the corresponding references to the manuscript, and taken spinal deformities as an example.

7) Comment：

Line 76: Sentence beginning “Whether the effect…” is confusingly worded.

Response: Thank you for your valuable comments. We have changed to “Whether there is a difference in the effect of thoracolumbar fracture site on sagittal balance has not yet been studied.”

8) Comment：

Line 101: Be specific regarding “hip and knee joint limitations.” I see that you addressed this in the previous reviewer comments, but it bears explaining in the text. Otherwise it remains confusing and vague.

Response: Thank you for your valuable comments. We have added an explanatory note to the manuscript to prevent readers from having the same doubts as you. We have changed to “Patients with hip and knee joint limitations (a history of hip and knee joint diseases, or abnormal hip and knee joint mobility in the medical records).”

9) Comment：

Line 224: Difficult to understand this sentence as written.

Line 238: Please provide a reference for this paragraph

Response: Considering that most of the first half of the discussion section is a review of sagittal parameters, we have deleted some paragraphs according to the reviewer’s comments. Line 224 and Line 238 have been removed already.

10) Comment：

Line 327: The sentence “After PKP, back pain…” is conjecture. The study did not measure back muscle strength and cannot claim improvement in strength as a reason for improvement in sagittal balance.

Response: Thank you for your valuable comments. At present, the influence of back muscle strength on sagittal balance is only our conjecture, which is not suitable for the discussion section. We have deleted it from the manuscript.

Special thanks to you for your good comments.

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

8 Jan 2020

PONE-D-19-23099R2

Percutaneous Kyphoplasty for Osteoporotic Vertebral Compression Fractures Improves Spino-Pelvic Alignment and Global Sagittal Balance Maximally in the Thoracolumbar Region

PLOS ONE

Dear Mr. Sun,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

The authors have responded well by addressing all the reviewers' comments. However, I regret having to return the manuscript for one very minor correction. This is because no edits can be performed after acceptance.

The new paragraph on power analysis needs some improvement. It currently says:

"With effect size of 0.8 and 0.05 level of statistical significance, the actual power of TL group was calculated to be 0.99. Thus, our sample size of 71 patients was adequate, and the TL group was sufficiently powered to detect the effect of PKP on sagittal balance in patients with OVCF.

However, the powers of non-TL groups were ranged from 0.55 to 0.65. Based on these findings, the evidence is insufficient to investigate the parameters in non TL groups. Thus, additional studies with high-quality and large-scale are still warranted. "

It should say:

"With effect size of 0.8 and 0.05 level of statistical significance, the TL group (n=71) achieved a power of 0.99. Thus, the TL group was sufficiently powered to detect the effect of PKP on sagittal balance in patients with OVCF. However, power in the non-TL groups ranged from 0.55 to 0.65. Based on these findings, there is insufficient data to investigate the parameters in the non-TL groups. Thus, additional studies with proper large-scale cohorts are still warranted."

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Academic Editor

PLOS ONE

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files to be viewed.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org. Please note that Supporting Information files do not need this step.

11 Jan 2020

Comment：

The new paragraph on power analysis needs some improvement. It currently says:

"With effect size of 0.8 and 0.05 level of statistical significance, the actual power of TL group was calculated to be 0.99. Thus, our sample size of 71 patients was adequate, and the TL group was sufficiently powered to detect the effect of PKP on sagittal balance in patients with OVCF.

However, the powers of non-TL groups were ranged from 0.55 to 0.65. Based on these findings, the evidence is insufficient to investigate the parameters in non TL groups. Thus, additional studies with high-quality and large-scale are still warranted. "

It should say:

"With effect size of 0.8 and 0.05 level of statistical significance, the TL group (n=71) achieved a power of 0.99. Thus, the TL group was sufficiently powered to detect the effect of PKP on sagittal balance in patients with OVCF. However, power in the non-TL groups ranged from 0.55 to 0.65. Based on these findings, there is insufficient data to investigate the parameters in the non-TL groups. Thus, additional studies with proper large-scale cohorts are still warranted."

Response: We would like to extend a special thank you for your helpful comments and constructive criticism. According to your advice, we have made corresponding modifications in the manuscript. Thank you!

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

14 Jan 2020

Percutaneous kyphoplasty for osteoporotic vertebral compression fractures improves spino-pelvic alignment and global sagittal balance maximally in the thoracolumbar region

PONE-D-19-23099R3

Dear Dr. Sun,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

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With kind regards,

Alejandro A. Espinoza Orías, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

23 Jan 2020

PONE-D-19-23099R3

Percutaneous kyphoplasty for osteoporotic vertebral compression fractures improves spino-pelvic alignment and global sagittal balance maximally in the thoracolumbar region

Dear Dr. Sun:

I am pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

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on behalf of

Dr. Alejandro A. Espinoza Orías

Academic Editor

PLOS ONE