Introduction

Kyphoplasty has been shown to correct vertebral deformities, at least partially, and reduce pain in short term outcomes [1, 2, 3]. Previously, we reported that pain reduction and consequent improvement of physical function after kyphoplasty was sustained for 6 months in patients with primary osteoporosis and chronically painful vertebral compression fractures, compared with a conservatively treated group, in a prospective trial [4]. Prevalent vertebral fractures are one of the strongest predictors of subsequent vertebral fractures independently from bone density [5, 6, 7, 8]. We suggested that even partial restoration of vertebral body height by kyphoplasty positively affects spinal biomechanics and, thus, may reduce fracture incidence after kyphoplasty in the long-term. In order to assess the incidence of fracture and to evaluate the persistence of the previously reported beneficial clinical effects on pain reduction and back-pain-related doctor visits, here we extend our previous work by reporting the 12-month outcomes of our prospective controlled trial that compared 40 patients after kyphoplasty with 20 conservatively treated patients.

Methods

Patient selection—inclusion criteria

As previously reported, the X-rays, CT-scans and MR images of 211 consecutive patients of both genders, with primary osteoporosis, complaining of back pain were evaluated with regard to technical practicability of kyphoplasty by our interdisciplinary kyphoplasty team, which consisted of endocrinologists, orthopedic surgeons and radiologists [4]. Patients were suffering from chronic back pain, in spite of analgesic treatment, due to osteoporotic vertebral fractures older than 12 months. Kyphoplasty was considered to be indicated if the location of the most severe back pain, determined by triggering the processus spinosi, was identical to the location of a vertebral fracture.

Exclusion criteria

Kyphoplasty was not performed in cases of severe degenerative spine alterations (n=30), nerve compression by intervertebral disc prolapse (n=24), vertebra plana (n=24) or in the case of fractured posterior vertebral wall (n=12). Kyphoplasty was also not considered if the vertebral pedicles were not clearly discernable on X-rays or if the risk by general anesthesia was severely increased due to cardiovascular or pulmonary diseases or due to advanced liver and kidney disorders (n=18).

All patients eligible for kyphoplasty were offered hospitalization after assessment of risk factors. All hospitalized patients (n=60; Table 1) were informed in detail about kyphoplasty and its possible risks, including spinal cord injury. Forty-eight hours prior to kyphoplasty patients were asked to sign an informed consent form as required by the ethics committee of the University of Heidelberg, who approved the study. All patients were offered intensified conservative treatment, including optimized pain medication and physical training, as an alternative to kyphoplasty. Twenty individuals chose the conservative therapy the day before planned kyphoplasty (control group).

Table 1 Demographic and clinical characteristics (PP per patient)

Intervention and control

A total of 73 kyphoplasty procedures were performed on 40 patients (kyphoplasty group) with primary osteoporosis. Two balloon catheters were inserted into a fractured vertebral body. Inflation of the balloon creates a cavity within the fractured vertebral body and corrects vertebral deformity to some extent. After removal of the balloon catheter, bone cement was inserted into the pre-formed cavity, which stabilized the treated vertebral body. Patients were treated with polymethylmethacrylate (PMMA) cement [KyphX (Kyphon, USA) and Cemex (Tecres S.p.a., Verona, Italy)] or calcium phosphate cement [Calcibon (Biomet, Darmstadt, Germany)] [9]. Cement position was controlled postoperatively by CT. Forty-eight hours after kyphoplasty the patients were discharged.

All patients were examined postoperatively and at 6 months and 12 months. They all received a daily standard dose of an oral amino-bisphosphonate and 1,000 mg calcium and 1,000 IU vitamin D3. Additionally, regular physiotherapy and the required pain medication according to WHO criteria were prescribed. There were no statistically significant differences regarding baseline characteristics of patients and treated/planned vertebral levels between the kyphoplasty and control group at entry into the study (Table 1).

Outcomes

Radiomorphometric outcomes

Radiomorphometric measurements were performed by two independent examiners using standard radiological procedures [10, 11]. Midline vertebral body height of the fractured vertebrae (Fig. 1) was defined as the percentage of the intact posterior height of the fractured vertebrae or of the closest non-deformed vertebral body. Blind reading of the X-rays was not possible because the cement was clearly discernable. There was no difference between the treatment and the control group regarding midline vertebral body height at the start of the study (P=0.553) (Table 2).

Fig. 1
figure 1

Measurement of midline vertebral height on X-ray

New vertebral fractures

After 12 months the occurrence of new vertebral fractures of the thoracic and lumbar spine (1,022 vertebral bodies) was assessed. New fractures were assessed in previously unfractured and pre-fractured vertebrae and defined as a height reduction of at least 20% [12].

Pain and activity

Back pain was evaluated by a 11-question visual analogue scale (VAS) spine score [13] (where a score of 0 represents “maximum” pain and a score of 100 represents “no pain”). Patients’ mobility was evaluated by the 23-question physical function part of the European Vertebral Osteoporosis Study (EVOS) Group questionnaire [14], which has been validated for osteoporotic patients and has been demonstrated to have good reproducibility [15] (where a score of 0 represents “worst” impairment of mobility and a score of 100 represents “no physical impairment” of mobility).

Healthcare utilization

The number of doctors’ visits due to any complaint and due to back pain was quantified by telephone interviews with family physicians and face-to-face interviews of patients.

Adverse events

All adverse events, including cement leakages, were collected. Cement leaks were assessed by postoperative CT.

Statistical analyses

VAS and EVOS scores and midline vertebral body height in the kyphoplasty and control group were compared at baseline using an independent, two-sample, t-test. Analysis of covariance was used to compare between groups at 6 months and 12 months, adjusted for baseline outcome values. Pairwise t-tests were used to assess within-group differences postoperatively (kyphoplasty group) and after 6 months and 12 months. The association between clinical outcomes and radiomorphometric changes was assessed with Pearson’s correlation coefficient. Occurrence of new vertebral fractures in different groups was compared, with chi-square and Fisher’s exacts test. The Mann–Whitney U test and the Kruskal–Wallis test were used to compare total and back-pain-related doctors’ visits. Statistical significance was taken as a probability level of ≤0.05. SAS statistical software was used for all analyses.

Results

Radiomorphometric outcomes

Postoperatively, the midline vertebral body height was significantly increased in the kyphoplasty group compared with that at baseline (P<0.0001); this difference sustained at 6 months and 12 months (P<0.0001 for both) (Table 2). At 6 months and 12 months the midline vertebral body height was significantly greater in the kyphoplasty group than in controls (P<0.0001 for both) (Table 2). In the control group there was a progressive height loss of the fractured vertebral bodies originally planned for kyphoplasty (P<0.001). There was no evidence of a difference between the PMMA group and the calcium phosphate group regarding midline vertebral body height at any time point (Table 2).

Table 2 Radiomorphometric outcomes. Midline vertebral body height of the fractured vertebral bodies as a percentage of the intact posterior height of the fractured vertebrae or of the closest non-deformed vertebral body [n number of fractured vertebral bodies assessed, CaP calcium phosphate cement (Calcibon)]

New vertebral fractures

After 12 months seven new vertebral fractures were observed in seven patients (17.5%) of the kyphoplasty group and 11 new vertebral fractures in ten patients (50.0%) of the control group (P=0.008) (Table 3). Among the 84 adjacent vertebrae in the kyphoplasty group six new fractures occurred, compared with four new fractures in the 41 vertebrae adjacent to the initially planned vertebral bodies in the control group (P=0.728).

Table 3 New vertebral fractures during the 12 month follow-up

Pain and activity

There was no evidence of a difference between the kyphoplasty group and the control group regarding baseline VAS scores (P=0.123) (Table 4). Kyphoplasty treated patients exhibited a significant improvement in VAS score postoperatively, after 6 months and after 12 months (P=0.0002, P<0.0001 and P<0.0001, respectively). At 6 months and 12 months, VAS scores were improved in kyphoplasty treated patients compared with the controls (P=0.019, P=0.008, respectively) (Table 4). There was no significant change of VAS score during follow-up across controls. Of the 40 patients in the kyphoplasty group, 31 (77.5%) exhibited an improved VAS score after 12 months, whereas 11 of the 20 patients (55%) in the control group showed an improved VAS score; this difference was not statistically significant (P=0.099).

Table 4 Pain score (VAS). CaP calcium phosphate cement (Calcibon)

For EVOS baseline values no statistically significant difference between treatment and control group was detected (P=0.401) (Table 5). EVOS scores improved in the kyphoplasty group postoperatively and at 6 months and 12 months (P=0.003, P<0.0001 and P=0.0003, respectively) (Table 5). At 6-months follow-up the kyphoplasty group exhibited significantly improved EVOS scores compared with controls (P=0.027); however, this improvement failed to reach statistical significance at 12 months (P=0.105) (Table 5). After 12 months 30 of the 40 patients (75%) in the kyphoplasty group exhibited an improved EVOS score, whereas 11 of the 20 patients (55%) in the control group showed an improved EVOS score; this difference was not statistically significant (P=0.144).

Table 5 Mobility score (EVOS). CaP calcium-phosphate cement (Calcibon)

Among the patients of the kyphoplasty group there was no difference between the PMMA-cement-treated cohort and the calcium phosphate-cement-treated cohort in VAS or EVOS-scores at any study time point (Tables 4 and Table 5).

Relationship between radiographic and patient-oriented outcomes

To evaluate whether morphological changes corresponded to clinical parameters we investigated whether the change of vertebral height after kyphoplasty corresponded to an improved VAS or EVOS score postoperatively and 12 months after the procedure. There was no significant correlation between change in vertebral height directly after kyphoplasty and the change of the VAS score postoperatively and after 12 months (r=0.1, P=0.581 and r=−0.24, P=0.153, respectively). There was also no significant correlation between changes in vertebral height and EVOS score postoperatively and after 12 months (r=0.12, P=0.506 and r=-0.09, P=0.612, respectively).

Healthcare contacts

Patients in the kyphoplasty group required fewer back-pain-related doctors’ visits during the 12 months follow-up period than did the controls (5.3±0.7 vs 11.6±2.7 (mean ± SE), respectively; P=0.006).

Adverse events

No neurological, embolic or cardiovascular complications were observed in any patient of the study group during or following kyphoplasty. No device-related adverse events occurred. No cement dislocation was seen during the follow-up period. There were clinically asymptomatic cement leaks in 12 treated vertebral bodies (9.0%; five ventral leaks, seven lateral leaks, no posterior leaks), which is comparable to previous reports [1, 3, 16, 17, 18].

Discussion

Kyphoplasty is a treatment option for chronically painful, osteoporotic, vertebral compression fractures (concavity, biconcavity or wedge-shaped fracture), and several authors have reported pain relief after kyphoplasty in uncontrolled and retrospective observational cohort studies [1, 2, 3, 16, 17, 18, 19]. In a prospective controlled trial we established that, in patients with primary osteoporosis and painful vertebral fractures that were older than 12 months, a clinically important reduction of pain and gain of mobility can be accomplished by kyphoplasty, immediately after the procedure, which is maintained for several months [4].

Some reports suggest an increased incidence of fractures after kyphoplasty by demonstrating accelerated vertebral fracturing after kyphoplasty. This increased fracture incidence was demonstrated in one patient with lupus erythematosus after 19 years of glucocorticoid treatment [20]. In another retrospective evaluation 70% of the reported new fractures after kyphoplasty also occurred in glucocorticoid-treated patients [21]. Finally, Fribourg et al. report increased fracturing after kyphoplasty by retrospectively comparing fracture rates in high risk patients (due to multiple prevalent fractures) without medical treatment after kyphoplasty with effectively calcium and vitamin-D treated control patients from published clinical trials [22].

Therefore, 1 year after kyphoplasty, we re-assessed vertebral fractures in our ongoing controlled prospective study. Here, we extend our previous work [4] and demonstrate for the first time in a controlled fashion a maintained correction of lost vertebral height, a decreased incidence of fractures, sustained pain reduction and a further reduction in back-pain-related doctors’ visits 12 months after kyphoplasty in patients with primary osteoporosis compared with a conservatively treated control group.

Prevalent osteoporotic vertebral fractures per se are a strong predictor of subsequent fractures [5, 6] and lead to alterations of spinal biomechanics resulting in progressive spine deformity [23, 24], with an extended load on the anterior column of the osteoporotic spine [25]. This may be the main mechanism of the 35-times increased risk for subsequent fractures in the presence of more than three fractured vertebrae [5, 26]. In the control group of our trial a progressive decrease in height of the vertebrae originally planned for kyphoplasty occurred after 12 months, whereas, in the kyphoplasty group, we observed a significantly reduced number of new vertebral fractures during the 12-month follow-up period. The high incidence of fractures in the control group may have resulted from the coincidence of multiple prevalent fractures in patients with chronic pain and impaired physical function, also due to pain medication. Additionally, there was no evidence for a higher incidence of fractures among the adjacent vertebral bodies after cement implantation by kyphoplasty. Even minor corrections of the spinal morphology may positively affect stress distribution in the spinal biomechanics [27] and thus reduce subsequent incidence of fracture in patients with primary osteoporosis, in addition to standard medical treatment.

After kyphoplasty there was a trend towards a positive correlation between the initial height gain and the improvement of the pain score after 12 months, although this correlation failed to reach significance. The immediate clinical benefit of kyphoplasty in osteoporotic patients with chronically painful vertebral fractures does not appear to depend on a complete morphological correction of the fractured vertebrae [19]. Interestingly, comparable, immediate, pain reduction is reported after vertebroplasty, a technique which does not restore vertebral height [2, 28, 29, 30]; however, the only available controlled study investigating the clinical outcome after vertebroplasty did not show significant pain reduction 6 weeks after vertebroplasty anymore [29]. The role of vertebral height restoration in persistent pain reduction after kyphoplasty remains unclear. Future long-term studies may indicate that greater height restoration may have a greater beneficial effect on pain reduction and fracture incidence than minor corrections, because, in addition to prevention from progressive spine deformities by intravertebral stabilization, improved spinal morphology will reduce pathological overload of the anterior column of the spine and may thus reduce an imbalance of the muscular system, which may contribute to back pain [31, 32]. As a corollary, improved neuromuscular reflexes due to sustained pain reduction may contribute to a reduced risk of fracture.

Pain reduction and improved physical function may also have an impact on healthcare utilization. During the 12 months follow-up period after kyphoplasty back-pain-related doctors’ visits were significantly reduced compared with those of the control group. In addition, we found that after 12 months the difference in the activity levels between the kyphoplasty group and the control group was not significant any more, indicating that, after 12 months of conservative treatment, the control patients had a physical performance similar to that of patients immediately after kyphoplasty. Since physical inactivity is a major risk factor for progressive bone loss [33, 34], maintenance of bone mass may be more likely after kyphoplasty, due to reduced pain and consequent improved mobility. Ledlie and Renfro also showed that the ambulatory status improves right after kyphoplasty and that this effect was persistent for at least 12 months [17]. These observations may support possible long-term cost effectiveness of the treatment of osteoporotic fractures [35]. Further studies need to investigate, in greater detail, a possible impact of kyphoplasty on better self-support, less need for medical equipment, nursing and analgesic medication.

The principle limitations of this study are the lack of a formal power calculation and its non-randomized design. As patients were not randomly allocated to treatment groups, selection bias and confounding cannot be discounted. Nevertheless, no statistically significant differences in baseline characteristics between the two groups were observed. Furthermore, between-group comparisons were adjusted for baseline score. The possibility of differences between groups due to non-measured confounders cannot be completely discounted. Because of lack of data on the potential differences in outcome that might exist between groups, it was not possible to formally estimate sample size at the outset of this study. Failure to detect differences in outcomes between groups at some study time points may, therefore, reflect the lack of statistical power.

To our knowledge this is the first prospective controlled study that provides evidence that, in patients with primary osteoporosis suffering from chronically painful osteoporotic vertebral fractures, kyphoplasty is a safe method, which persistently reduces pain, stabilizes vertebral deformities and further decreases the incidence of vertebral fractures, in addition to the fracture prevention accomplished by current pharmacological treatment. However, randomized controlled trials are required to confirm the findings of this study, as previously stated.