Analysis of Nanohydroxyapatite/Polyamide-66 Cage, Titanium Mesh, and Iliac Crest in Spinal Reconstruction of the Patients with Thoracic and Lumbar Tuberculosis
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.360908
Source of Support: None, Conflict of Interest: None
Keywords: Bone Graft Material, nanohydroxyapatite/polyamide-66 cage, posterior debridement, thoracolumbar tuberculosis, titanium mesh cage
Tuberculosis (TB), a common infectious disease in developing countries, also shows a gradually increasing trend in developed countries because of the presence of human immunodeficiency virus (HIV) infection and drug resistance, which also pose new challenges in developed nations., Spinal TB (STB) is a tissue-destroying disease that destroys the intervertebral discs and adjacent vertebral bodies. It accounts for approximately 50% of osteoarticular tuberculosis., STB might lead to devastating outcomes including kyphosis, compression of the spinal cord, and the formation of cold abscesses., Anti-TB chemotherapy remains the mainstream of treatment. However, patients with STB often have severe nerve impairment, spinal instability, and kyphosis. Therefore, surgical management is paramount for radical debridement, decompression of neural elements, correction of deformity, reconstruction of the anterior column, and stable fusion., Currently, anti-TB chemotherapy combined with radical surgical procedure is used by most medical institutions, which is recognized as the optimal treatment option.,, Thorough resection of the lesions can control the progression of the disease, promote bone fusion of intervertebral graft, and reduce the likelihood of recurrence of STB. However, thorough resection of the lesions will lead to vertebral defect and destroy the pedicles and tissues. So, proper bone grafts are necessary to repair the vertebral defect and reconstruct stability. Although great advances have been made in surgical techniques and bone graft materials, many implant-related complications such as chronic pain of donor site, nonunion, displacement of the bone graft materials, and cage subsidence have been frequently reported.,, To address these issues, various bone graft materials such as autogenous ribs, autogenous iliac crest, allograft, titanium mesh cages, and other grafting materials have been developed. However, the choice of bone graft materials in an infected area remains a matter of debate. At present, the most commonly used bone graft material in STB surgery is titanium mesh cage (TMC), which has been widely used for decades due to its excellent biomechanical properties and biocompatibility., However, stress shielding, high incidence of cage subsidence, lack of tissue adherence, and postoperative radiographic interference obstruct TMC from becoming an ideal reconstruction bone graft material. At the same time, the use of autogenous bone grafts from the iliac crest has long been considered as another alternative method. The tricortical iliac crest graft could achieve satisfactory osseous fusion due to the osteoinductive and osteogenetic properties; however, concerns over chronic donor site pain or infection pose big challenges., In recent years, nanohydroxyapatite (n-HA)/polyamide-66 (PA66) cage (n-HA/PA66 cage), a novel biomimetic nonmetal cage device, has shown competitive clinical efficacy in many medical centers.,, It provides more choices for posterior reconstruction to ensure satisfactory osseous fusion and reduce the complications, compared with traditional bone graft material. The chemical composition of the n-HA/PA66 cage is similar to the natural bone, which is made by covalent miscibility of n-HA and PA66.,, This cage has the advantage of preventing subsidence and migration by decreasing the cutting action and increasing friction between the vertebra and cage edges because of its characteristic design of several shallow recesses. However, detailed comparisons of the n-HA/PA66 cage with other bone graft materials have not been reported. The difference in clinical efficacy among n-HA/PA66 cage bone graft, iliac bone graft, and TMC bone graft combined with internal fixation after debridement remains unclear. In this study, we aimed to evaluate the clinical efficacy of n-HA/PA66 cage bone graft, iliac bone graft, and TMC bone graft in the treatment of thoracic and lumbar TB.
The inclusion criteria included single-segment or two-segment thoracic and thoracolumbar TB confirmed by postoperative histopathologic examination, one-stage posterior debridement, internal fixation, and reconstruction using TMCs, autogenous iliac crest, or n-HA/PA66 cages. The follow-up time was more than 6 months. The exclusion criteria included active pulmonary TB, malignant tumor, and discontinuous multisegment STB. Between January 2013 and December 2018, 57 patients with thoracic and lumbar TB were treated by interbody bone graft combined with one-stage posterior internal fixation after debridement. Of those, most patients had typical symptoms of STB, including night fever, loss of weight and back pain. The T-SPOT TB test was used to screen the presence of TB. X-ray, computed tomography (CT), and magnetic resonance imaging (MRI) of the thoracic or lumbar spine were performed on all the patients to evaluate the destruction degree of the vertebral body, the degree of intervertebral space narrowing, and spinal cord compression. The American Spinal Injury Association (ASIA) neurological classification was routinely used to evaluate the degree of neurological dysfunction, and the visual analog scale (VAS) was used to evaluate the degree of pain before and after surgery. Preoperative and postoperative Cobb angle was measured on lateral X-ray to evaluate the degree of kyphosis correction. X-ray and CT images in the follow-up time were used to observe the degree of bony fusion.
Before surgery, all patients were prescribed anti-TB chemotherapy of isoniazid (INH; 5 mg/kg), rifampicin (10 mg/kg), pyrazinamide (25 mg/kg), and ethambutol (15 mg/kg) for at least 2 weeks, until the erythrocyte sedimentation rate (ESR) decreased below 40 mm/h, the related symptoms of TB were relieved progressively, and other conditions were suitable for surgery. If there was no significant decrease in the ESR or the symptoms of TB poisoning were not improved, levofloxacin injection (intravenous drip, 400 mg/d) was added to reinforce the effect of drug therapy. For those patients who had a neurological worsening in a very short time, surgery was performed as soon as possible to achieve early spinal cord decompression. In this case, conservative therapy with a duration of no more than 1 week was administered to stabilize the general condition and control the infection as much as possible before surgery.
All patients were in the prone position after administration of general endotracheal anesthesia, and a C-arm X-ray was used to confirm the lesion segment. Subperiosteal detachment of the bilateral paraspinal muscles was performed through a posterior midline approach. The spinous process, lamina, transverse processes, and facet joints of the lesion segment and the upper and lower adjacent healthy vertebrae were exposed. Then, pedicle screws were inserted, respectively, at pedicles of the healthy vertebra adjacent to the lesion segment. After the placement of pedicle screws was confirmed by C-arm fluoroscopy, a temporary pre-bent rod referring to the physiological kyphotic angle was installed to avoid spinal cord injury induced by the instability of the spine during decompression and focal debridement. After the extent of vertebral destruction was determined, the posterior structures were removed to achieve complete decompression, and vertebrectomy, including removal of the intervertebral disks, was performed using a combination of a bone chisel and curette rongeur. To clear the surrounding abscess, the caseous tissue and the sequestrum were carefully removed. Moreover, various sizes of curettes were used to achieve full debridement. After decompression, a bone block with a three-sided cortex is cut from the iliac bone, trimmed appropriately, and then implanted into the bone defect area. Alternatively, uncontaminated autologous bone particles collected during surgery are filled into an appropriate titanium mesh cage or n-HA/PA66 cage. The cage is then implanted into the bone defect area. Subsequently, deformity correction and stabilization were ascertained by installing permanent rods. one or two g streptomycin were placed in the intervertebral area during the operation.
After surgery, temperature, pulse, respiratory rate, and blood pressure were closely monitored and nutritional support and anti-infective treatment were routinely provided. Mobility and sensation of the lower limbs were closely observed. Incision drainage catheter was removed when the drainage volume was less than 30 mL/d. X-ray and CT examination were checked after extubation. Patients were allowed to get out of bed with an appropriate thoracolumbar brace at 2 weeks postoperatively and the brace was applied for at least 3 months postoperatively. After surgery, all patients were asked to continue the same anti-TB drugs that they were taking preoperatively for at least 12 months. Some laboratory examinations including ESR, C-reactive protein (CRP), and hepatic and renal functions were recorded every 3 months to evaluate the efficacy and side effects of the chemotherapeutics. X-ray, CT, and MRI (if necessary) were performed during 3, 6, and 12 months of follow-up.
Operative time, operative blood loss, postoperative hospital stay, VAS score, ESR, CRP, and ASIA grade were recorded. Cobb angle (formed by the upper endplate of the upper vertebral body and the lower endplate of the lower vertebral body), the height of the fusion stage (the distance between the upper endplate of the upper vertebral body and the lower endplate of the lower vertebral body), and cage subsidence (the difference between the height of the fusion segment at the last follow up and the height of the fusion segment immediately after surgery) were evaluated during the follow up.
Bone graft fusion time: according to Three-dimensional CT results during the follow-up, the criterion of bone graft fusion reported by Brantigan et al. was used to evaluate whether bone fusion has been achieved. Grade D and Grade E are defined as bone graft fusion in this study.
Statistical Package for the Social Sciences (SPSS) 22.0 software (SPSS, Inc., Chicago, IL, USA) was used for statistical analysis. Quantitative data were expressed as mean ± standard deviation. Analysis of variance (ANOVA) and matched t-test were used for intergroup and intragroup comparisons of quantitative data, respectively. Intergroup comparison of disordered qualitative data (e.g., sex, abscess or not) was performed by Chi-square test. Wilcoxon rank-sum test and Mann–Whitney U test were used for intragroup and intergroup comparisons of ordered qualitative data (e.g., ASIA grade), respectively. P < 0.05 was considered to be significant.
There were no significant differences in demographic characteristics among the three groups
Fifty-seven patients eligible for inclusion in this study included 13 cases in the iliac bone graft group, 26 cases in the TMC group, and 18 cases in the n-HA/PA66 cage group. No statistically significant differences were found in age (P = 0.857), gender (P = 0.319), and paravertebral abscess (P = 0.376) among the three groups. Comparisons of preoperative demographics among the three groups of patients are shown in [Table 1].
VAS score, ESR, and CRP in each group were significantly improved compared with the values before operation
VAS score, ESR, and CRP were noticeably improved at the time of the last follow-up test compared with the preoperative levels in each group (P < 0.05), but there were no significant differences among the three groups (P = 0.058) [Figure 1]. There were no significant differences in operation time (P = 0.138), surgical blood loss (P = 0.378), and hospitalization stay (P = 0.589) among the three bone graft methods. Comparisons of clinical outcomes among the three groups are shown in [Table 2].
The Cobb angle in each group was significantly improved compared with the value before operation
The Cobb angle was significantly corrected in all three groups during the last follow up, compared with the preoperative values. But no significant differences were found among preoperative, postoperative, and last follow-up Cobb angles among the three groups. Comparisons of preoperative imaging outcomes among the three groups are shown in [Table 3].
The n-HA/PA66 cage had a faster bone graft fusion time and lower cage subsidence
It is worth noting that the bone graft fusion time of the n-HA/PA66 cage group (4.7 ± 1.8 months) was shorter than the iliac bone graft group (6.3 ± 3.0 months) and the TMC group (6.8 ± 2.6 months) (P < 0.05), and the cage subsidence of the n-HA/PA66 cage group (0.5 ± 0.2 mm) was lower than the iliac bone graft group (1.3 ± 0.3 mm) and the TMC group (1.2 ± 0.5 mm) (P = 0.013) [Figure 2]. Comparisons of the preoperative imaging outcomes among the three groups are shown in [Table 3].
Neurological function achieved great improvement among the three groups
In the iliac bone graft group, the preoperative ASIA grade changed from grade B to grade D in one case, from grade C to grade E in one case, and from grade D to grade E in one case. In the TMC group, ASIA grade changed from grade C to grade D in one case, from grade C to grade E in two cases, and from grade D to grade E in six cases. In the n-HA/PA66 cage group, ASIA grade changed from grade B to grade D in one case, from grade C to grade D in two cases, and from grade D to grade E in four cases. Patients with ASIA of grade B/C improved with one or two grades at the end of follow-up.
There was no difference in complications among the three groups
In the iliac bone graft group, eight cases had complications including five cases of donor-site pain, one case of superficial wound infection, and two cases of pulmonary infection. In the TMC group, seven cases had complications including one case of liver function damage, one case of superficial wound infection, four cases of pulmonary infection, and one case of urinary tract infection. There were five cases of postoperative complications in the n-HA/PA66 group, including one case of liver function damage, two cases of pulmonary infection, and two cases of superficial wound infection. Chi-square test showed that no significant difference was found in postoperative complications among the three groups. Neurologic deterioration and implant loosening were not observed during the follow-up period. All the complications recovered after active treatment. Changes in ASIA classification preoperatively and at the last follow-up are shown in [Table 4].
Typical cases are presented in [Figure 3], [Figure 4], [Figure 5].
Treatment of TB should follow the principles of early, appropriate, regular, combined, and whole course. Effective anti-TB chemotherapy is the only guaranteed mainstay treatment, whereas surgical treatment is reserved for the patients who have severe nerve impairment, spinal instability,, and progressive kyphosis. Complete removal of lesions is the key to surgical treatment of thoracic and lumbar TB. However, bone defects left by the complete removal of lesions need to be repaired by bone grafting in order to reconstruct the biomechanical line of the spine and achieve early bone fusion. STB often destroys the spinal anterior column and the middle column, and thereby results in instability. Reconstruction of spinal stability is beneficial to alleviate symptoms and to avoid recurrence of TB. According to the three-columns theory of Denis, it is important to integrate the anterior column and the middle column for the reconstruction of spinal stability. At present, the primary methods of reconstruction include the iliac crest, TMC, and new bone graft materials such as the n-HA/PA66 cage. The autogenous iliac crest has long been considered the gold standard for bone graft with good osteoconduction, bone formability, and osteoinductive activity. When tricortical autogenous iliac bone struts are used for grafting, the size and shape of the strut are difficult to estimate before it is removed from the iliac crest and it is also influenced by the experience of the surgeon. Therefore, it has a relatively small weight-bearing contact area and it is mechanically weak, and osteoporosis of the vertebrae and bone graft may lead to discrete loss of height from a fused motion segment. In addition, it has been reported in some literature that the iliac bone strut has some disadvantages such as insufficient strength to maintain axial distension, local microfractures, donor-site morbidities, inadequate bone grafting, and insufficient absorption. The TMC is a representative metal cage device that has been widely used since it was first introduced about 40 years ago. The previous results of using TMC were favorable. The size of TMC is designed by the bone defect, which can maximize the filling defect, and the cross section of TMC can provide the contact area with bone surfaces. Although the high rate of TMC fusion was encouraging, the same high rate of cage subsidence reported by many authors could not be ignored.,,,, The hollow cylindrical n-HA/PA66 cage is a novel biomimetic non-metallic cage device combining the strength properties of hydroxyapatite (HA) with the elasticity properties of PA66, which is close to the inherent attributes of human bone. The toughness and strength of n-HA/PA66 materials depend mainly on the homogeneous distribution of n-HA granules in the PA66 matrix. The n-HA/PA66 cage has an appropriate elastic modulus dispersing the stress distribution of the contact surface. Each n-HA/PA66 cage has wide rims, nearly 3 mm, with several shallow recesses designed to prevent subsidence and migration by decreasing the cutting action and increasing the friction between the cage edges with vertebral endplates. The n-HA/PA66 cage had been widely used as a bionic non-metallic bone implant material in STB surgery during the past decades. In this study, no significant difference was found in operative time and blood loss among the three groups. At the last follow-up, VAS score, ESR, CRP, and neurological function were all significantly improved in the three groups due to the effective anti TB chemotherapy and decompression of the spinal canal. A study by Ou et al. on the use of the n-HA/PA66 cage in thoracolumbar surgery reported a fusion rate of 100%, with nearly no loss of height correction in 42 patients with an average 13-month follow-up. The follow-up time of these 42 patients was not long, and pseudarthrosis or larger loss of correction may occur in the future. In a study by Yang et al., the authors reported a bony fusion rate of over 90% in using n-HA/PA66 cage. Zhao et al. showed an over 90% bony fusion rate and a less than 3% cage subsidence rate in their 35 patients who had an n-HA/PA66 cage fusion. All these studies indicate that the n-HA/PA66 cage is a promising device in STB surgery. In our study, we discovered that bony fusion occurred sooner in patients with n-HA/PA66 cage than with TMC and tricortical autogenous iliac bone. According to Greer, the bone will grow in response to applied stress and will be reabsorbed when lacking mechanical stimulus. The Young's moduli of the TMC and autogenous iliac bone were markedly higher than that of the bone graft inside the cage, whereas the Young's modulus of the n HA/PA66 cage was much lower than that of bone graft. Theoretically, the n-HA/PA66 cage can enable interaction of Ca2+ and PO43− between the cage and surrounding tissue and form a crystal layer on the cage surface. This layer will become a bone bridge assisting in the growth of bone graft. The n-HA/PA66 cage has wider edges, which increase the load-bearing area between the cage and endplate to achieve mechanical stability, ensuring sufficient and uniform compressive stress that facilitates bone fusion. The design of dentation located in the upper and lower end faces helps effectively fix the strut in the initial position with posterior internal fixation, which greatly reduces displacement of the cage. There are many small holes on the surface of the cylinder, which is conducive to the crawling and growing of the capillaries, to facilitate bone fusion.
Local pain, neurovascular injury, local hematoma, infection, and abnormal gait at the iliac donor site pose significant challenges to postoperative outcomes and patient satisfaction. Our study, we found no differences in Cobb angle correction among the three groups. The reason is that the posterior internal fixation system plays an important role in Cobb angle correction, instead of the support of the anterior column. Moreover, the degree of osteoporosis and improper management of endplate during surgery cannot be eliminated, which can influence the correction of Cobb angle. The collapse and displacement of the iliac bone or the subsidence of the cage may also cause Cobb angle loss.,,, All three reconstruction ways require careful handling of the bone graft bed but at the cost of potentially creating bone defects, which may affect the spine's stability and result in limited Cobb angle correction., The difference in the length of the posterior fixation segment may also affect local stability and Cobb angle correction., It is extremely difficult to achieve subchondral resection during surgery. Once the bony endplate is destroyed, the Cobb angle loss is prone to happen.
We consider that the three reconstruction methods in the surgery of thoracic and lumbar TB are safe and effective. Great advantages such as lower cage subsidence, higher rate of bone fusion, and fewer complications were observed in our study using n-HA/PA66 cage as the bone graft strut. However, this study has some limitations. Firstly, this study is a retrospective study. Secondly, our sample size for this study is small. Thirdly, we lack data on long-term follow-up. In conclusion, these three reconstruction methods, including iliac bone graft, titanium mesh bone graft, and n-HA/PA66 cage bone graft, can obtain satisfactory clinical results in restoring the ability of the spine and alleviating pain via one-stage posterior debridement, bone graft, and internal fixation, but n-HA/PA66 cage bone graft material can result in lower cage subsidence and a faster time of bone graft fusion.
List of abbreviations
VAS = visual analog scale; ESR = erythrocyte sedimentation rate; CRP = C-reactive protein; ASIA = American Spinal Injury Association; n-HA/PA66 cage = nanohydroxyapatite/polyamide-66 cage; TB = tuberculosis; STB = spinal tuberculosis; TMC = titanium mesh cage; CT = computed tomography; MRI = magnetic resonance imaging.
Ethics approval and consent to participate
The study was approved by the Institutional Review Board of the Second Affiliated Hospital of Chongqing Medical University. Informed consent was obtained from all the participants.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3], [Table 4]