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Abstract

Objective

A systematic review and meta-analysis of randomized controlled trials (RCTs) studying the clinical benefit of chemotherapy with surgical intervention over chemotherapy alone for the treatment of spinal tuberculosis.

Methods

Relevant RCTs were identified by computerized database searches. Trial eligibility and methodological quality were assessed and data were extracted and analysed using odds ratios with 95% confidence intervals. The primary outcome measure was kyphosis angle.

Results

The literature search identified two RCTs conducted in the 1970s and 1980s and a Cochrane Database Systematic Review published in 2006. There were no significant between-group differences in kyphosis angle, bony fusion, bone loss or development of neurological deficit.

Conclusions

There is no obvious statistically significant clinical precedence to suggest that routine surgery will improve the prognosis of patients with spinal tuberculosis.

Keywords

Spinal tuberculosis Pott disease kyphosis bony fusion bone loss neurological deficit meta-analysis systematic review

Introduction

Spinal tuberculosis (TB) or Pott disease was first reported in 1779 and represents <1% of all TB cases.^1–3 Given the increasing prevalence of TB worldwide, spinal TB is a significant healthcare issue,⁴ with the incidence of neurological complications varying between 10% and 43%.¹

The standard management protocol for spinal TB is isoniazid, rifampicin and pyrazinamide chemotherapy for a minimum of 6 months.^5–7 In addition, debridement of diseased tissues is routinely performed via an anterolateral extrapleural approach,^8–11 transpleural anterior approach^8,12,13 or posterior spinal fusion.^14,15 Pre- and postsurgical debridement chemotherapy is commonly employed.¹⁶

A review article suggested that surgery in spinal TB is an incidental decision, with no established protocol for the decision-making process and few randomized controlled trials regarding indications for surgery.¹⁷ Surgical intervention decisions are based on: (i) patient age; (ii) presence of comorbidities; (iii) location of bony loss; (iv) relative position of the compressive lesion with regard to the dura, and density of the compressive lesion; (v) number of segments involved; (vi) kyphosis angle; and (vii) region of focal infection,^17,18 with the major contraindications being high cost and risk of postoperative complications.¹⁷ It is imperative to perform surgery only if the outcome will be more beneficial than treatment with chemotherapy alone. The objective of the current review of randomized controlled trials was to compare the outcome of chemotherapy alone or a combination of surgery and chemotherapy in patients with spinal TB.

Materials and methods

Data sources and searches

Computerized searches were performed to identify randomized controlled human trials listed in Ovid MEDLINE® (1970 – December 2012), Ovid EMBASE® (1974 – December 2012), SCOPUS (1996 – December 2012), Web of Science® databases including Science Citation Index Expanded™ (1996 – December 2012), Conference Proceedings Citation Index – Science^SM (1990 – December 2012), Database of Abstracts of Reviews of Effects (DARE) (Issue 3 of 4, July 2012), Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 3 of 4, July 2012) and ClinicalTrials.gov (up to December 2012). Both database-specific controlled vocabulary and general free text terms were used to maximize retrieval. MeSH terms used were: Pott disease; tuberculosis; spinal tuberculosis; tuberculous spondylitis; medical management; chemotherapy; surgery; surgical intervention; randomized controlled trial. Hand searching of key article reference lists was used to locate additional relevant articles.

Assessment of methodological quality

Eligibility assessment and data extraction were both performed independently in an unblended standardized manner by two independent reviewers (X.Z. and B.L.) according to Critical Appraisal Skills Programme (CASP) guidelines.¹⁹ The inclusion of all randomized participants in the final analysis was evaluated and at least 60% completeness of follow-up at each time point was fixed as the threshold. The physicians treating the patients were not blinded either during treatment or follow-up. Scars were visible on X-radiographs of patients included in the studies used in the meta-analysis.

Data extraction, synthesis and analysis

The results of all searches were combined and duplicate articles were removed. Inclusion criteria were: (i) ≥1 year follow-up after initiation of treatment regimen; (ii) confirmed diagnosis of active TB of the thoracic and/or lumbar spine, including the upper sacral vertebra S1; (iii) diagnosis based on X-radiographs showing loss of thin cortical outline and rarefaction of the affected vertebral bodies; (iv) intervention was chemotherapy alone or chemotherapy plus surgery.

Statistical analyses

The outcomes (kyphosis angle, bone loss, bony formation and neurological deficit) of the collected manuscripts were synthesized in piloted forms independently and in duplicate (X.Z. and B.L.) and formed the basis for meta-analysis, which was performed according to Cochrane Collaboration and the Quality of Reporting of Meta-analyses (QUORUM) guidelines.²⁰ Odds ratios (OR) were used to analyse all dichotomous outcome measures, and data were presented with 95% confidence intervals (CI). The risk of bias of each relevant article was assessed using the 12 criteria recommended by the Cochrane Back Review Group.¹⁹ Criteria were scored ‘yes’ (criterion met), ‘no’ (criterion not met) or ‘unsure’ (not enough information to make the decision). Articles that met six of the 12 criteria were considered to have a low risk of bias. Potential publication bias was tested using a funnel plot. Data were compared using χ²-test. Statistical analyses were performed using SPSS® version 18.0 (SPSS Inc., Chicago, IL, USA) for Windows®. P-values <0.05 were considered to be statistically significant.

Results

The literature search identified 35 potentially relevant articles, of which 28^16,21–47 were excluded (Table 1, Figure 1). In addition, a systematic review published in 2006 was identified,¹⁷ which analysed seven papers reporting on two randomized controlled trials (total n = 331) (Table 2).^48–54 Both trials were initiated by the British Medical Research Council (MRC) Working Party on Tuberculosis of the Spine, with one performed in cooperation with the Indian Council of Medical Research (ICMR). These trials formed the basis of the current analysis.

Figure 1.

Schematic diagram of literature search performed in the current systematic review and meta-analysis of the management of spinal tuberculosis.

Table 1.

Characteristics of studies excluded from a review of the medical management of spinal tuberculosis.

Study	Reason for exclusion
Bakhsh 2010²¹	Not randomized
Guo et al. 2010²²	Not randomized
Fu et al. 2009¹⁶	Not randomized
Park et al. 2007²³	Not randomized
Wang et al. 2007²⁴	Not randomized
Sai Kiran et al. 2007²⁵	Not randomized
Chadha et al. 2007²⁶	Not randomized
Kotil et al. 2007²⁷	Not randomized
Jain et al. 2004²⁸	Not randomized
Loembe 1994²⁹	Not randomized
MRC 1973³⁰	No surgical group
MRC 1973³¹	No surgical group
MRC 1974³²	All participants had surgery
MRC 1976³³	No surgical group
MRC 1978³⁴	All participants had surgery
MRC 1982³⁵	All participants had surgery
MRC 1985³⁶	No surgical group
MRC 1986³⁷	All participants had surgery
MRC 1993³⁸	No surgical group
MRC 1998³⁹	No randomization for conservative or surgical treatment; two locations, Korea (all chemotherapy without surgery) and Hong Kong (all chemotherapy plus surgery)
Rajasekaran et al. 1998⁴⁰	No surgical group
Rajeswari et al. 1997⁴¹	Not a randomized controlled trial, poor methodological quality, randomization method and concealment unclear
Seddon 1976⁴²	Description of several MRC studies, not a study itself
Upadhyay et al. 1993⁴³	All participants had surgery
Upadhyay et al. 1994⁴⁴	All participants had surgery
Upadhyay et al. 1994⁴⁵	All participants had surgery
Upadhyay et al. 1994⁴⁶	All participants had surgery
Upadhyay et al. 1996⁴⁷	All participants had surgery

ICMR, Indian Council of Medical Research; MRC, Medical Research Council.

Table 2.

Characteristics of studies included in a review of the medical management of spinal tuberculosis.

Study	n	Inclusion criteria	Exclusion criteria	Interventions	Outcomes
MRC 1974^48,49	130	(i) Clinical and radiographic evidence of tuberculosis of any vertebral body from the first thoracic to the first sacral, inclusive, that is excluding cervical and sacral disease (ii) Disease active clinically and/or radiographically (iii) Radiographically active disease: (a) loss of the thin cortical outline, and (b) rarefaction of the affected vertebral bodies) (iv) Availability for observation over a period of 3 years	(i) Paraplegia or paraparesis severe enough to prevent walking (ii) Active tuberculosis in a lower limb requiring bed rest (iii) Management complicated by pulmonary tuberculosis (iv) Previous antituberculosis chemotherapy for ≥12 months (v) Serious nontuberculous disease likely to prejudice the response to treatment or its assessment (vi) Contraindication to treatment methods	(i) Chemotherapy: (a) adults ≥45 kg: 1 g streptomycin sulphate/day intramuscular injection for 3 months, plus 300 mg isoniazid/day and 10 g para-aminosalicylate sodium/day for 18 months (b) children (<15 years old) and adults <45 kg: 20 mg/kg bodyweight streptomycin sulphate/day intramuscular injection for 3 months, plus 6 mg/kg bodyweight isoniazid/day (max 300 mg) and 0.2 mg/kg bodyweight para-aminosalicylate sodium/day (maximum 10 g) for 18 months Participants randomized to this regimen or the same regimen without the initial 3 months of streptomycin (ii) Chemotherapy plus surgery (removal of all necrotic and diseased tissue without reconstruction)	(i) Kyphosis angle (ii) Neurological deficit (iii) Bony fusion (iv) Absence of spinal tuberculosis (v) Death from any cause (vi) Regained activity level (vii) Change of allocated treatment
ICMR/MRC 1989^50–54	201			(i) Chemotherapy – isoniazid plus rifampicin (1 dose daily for 6 months) (ii) Chemotherapy plus surgery (debridement and stabilization with a bone graft [reconstruction])

ICMR, Indian Council of Medical Research; MRC, Medical Research Council.

The characteristics of the study participants are summarized in Table 3. The methods used to generate allocation sequences were unclear in both trials, but allocation concealment was adequate. Completeness of follow up in the MRC 1974 trial^48,49 was adequate after 3 and 5 years (72% and 62%, respectively). In the ICMR/MRC 1989 trial,^50–54 follow-up was adequate at 3, 5 and 10 years (83%, 82% and 78%, respectively). Analysis in the both trials was by intention to treat.

Table 3.

Characteristics of patients included in two randomized controlled trials comparing chemotherapy and chemotherapy plus surgery for treatment of spinal tuberculosis.

Characteristic	MRC 1974^48,49	ICMR/MRC 1989^50–54
n	130	201
n at follow up
3 years	94 (47 in each group)	168 (85 in surgical group and 83 in chemotherapy group)
5 years	80 (45 in surgical group and 35 in chemotherapy group)	5 years: 164 (82 in each group)
10 years	–	10 years: 156 (78 in each group)
Age^a
<15 years	16	63
≥15 years	78	105
Sex^a	52 male/42 female	Not given
Involved vertebrae
1–2	70	115
>2	24	53
Location of lesions	Thoracic 39 Thoracolumbar 10 Lumbar 45	Thoracic/thoracolumbar 84 Lumbar/lumbosacral 84
Mean kyphosis angle at entry
Surgical group	27°	29°
Chemotherapy group	24°	29°
Mean total bone loss at entry, U
Chemotherapy group	0.7	1.0
Surgical group	0.8	0.8
Incomplete paraplegia on entry^a	12	11

Data presented as n of patients or mean (SD not available).

Includes patients available at 3-year follow up.

ICMR, Indian Council of Medical Research; MRC, Medical Research Council.

Kyphosis angle was a primary outcome measure in both trials. The mean kyphosis angle was reported to be within the same range at 18 months and at 3, 5 and 10 years (Table 4), but it was not possible to assess statistical significance in the present analysis as standard deviations were not provided. Deterioration in kyphosis angle >10° at 5 years had an OR of 1.02 (95% CI 0.41, 2.55) and 1.17 (95% CI 0.41, 3.29) in the ICMR/MRC 1989 and MRC 1974 studies, respectively. In ICMR/MRC 1989 at 10 years follow-up, a baseline kyphosis angle of >30° deteriorated (increased) with a mean of 10–30°.^48–52 A subgroup effect was reported in the chemotherapy group of the ICMR 1989 trial, where patients aged <15 years (initial angle >30°) had a mean deterioration of 30° compared with patients aged >15 years (initial angle >30°) who deteriorated with a mean of 10° (P = 0.001).^51,53,54 There were no statistically significant between-group differences in the number of patients with >10° deterioration at 3 years (n = 78, 1 trial) or 5 years (n = 144, 2 trials).^50–54

Table 4.

Comparison of mean kyphosis angle in two randomized controlled trials comparing chemotherapy and chemotherapy plus surgery for treatment of spinal tuberculosis.

Parameter	MRC 1974^48,49		ICMR/MRC 1989^50–54
Parameter	Chemotherapy plus surgery	Chemotherapy alone	Chemotherapy plus surgery	Chemotherapy alone
Location of lesions	T1–S1	T1–S1	T1–L2	T1–L2
Kyphosis angle, °
entry	27	24	29	29
18 months	40	30	41	41
3 years	40	32	41	42
5 years	39	30	37	40
10 years	–	–	41	47
Increase in angle, °
18 months	13 (n = 40)	6 (n = 33)	12 (n = 34)	12 (n = 42)
3 years	13 (n = 40)	8 (n = 33)	12 (n = 34)	13 (n = 42)
5 years	12 (n = 34)	6 (n = 24)	8 (n = 34)	11 (n = 45)
10 years	–	–	12 (n = 28)	18 (n = 41)

Data presented as mean (SD not available).

ICMR, Indian Council of Medical Research; MRC, Medical Research Council.

Both trials reported on the neurological status of the participants. No participants who were free from neurological deficit on entry developed any deficit, and there were no statistically significant changes over time in the numbers of patients with neurological deficit (n = 23 at entry, n = 23 at 18 months, n = 23 at 3 years and 20 at 5 years).^48–54

There was no statistically significant difference between the intervention and control at 18 months (n = 261, two trials), 3 years (n = 262, two trials), 5 years (n = 244, two trials) and 10 years (n = 156, one trial).^48–54 There was no statistically significant difference between chemotherapy plus surgery and chemotherapy alone on the presence of bone loss at 18 months (n = 256, two trials), 3 years (n = 247, two trials), 5 years (n = 236, two trials), or 10 years (n = 156, one trial) (Table 5).^48–54 It was not possible to assess the statistical significance of data regarding bone loss due to the absence of standard deviations; however, the majority of bone loss (vertebral destruction) was present at the time of diagnosis with limited further destruction occurring during treatment and the subsequent follow-up period.^48–54

Table 5.

Comparison of bone loss (U) in MRC 1974^48,49 and ICMR/MRC 1989^50–54 randomized controlled trials comparing chemotherapy and chemotherapy plus surgery for treatment of spinal tuberculosis.

Trial	Intervention	Fraction loss: start	Deterioration, years
Trial	Intervention	Fraction loss: start	3	5	10	Total bone loss: 5 years
MRC 1974^48,49	Chemotherapy plus surgery	0.8	0.2	0.3	0.2	1.0
MRC 1974^48,49	Chemotherapy	0.7	0.1	0.1	0.0	0.7
ICMR/MRC 1989^50–54	Chemotherapy plus surgery	0.8	0.3	0.3	0.3	1.1
ICMR/MRC 1989^50–54	Chemotherapy	0.95	0.4	0.5	0.5	1.45

ICMR, Indian Council of Medical Research; MRC, Medical Research Council.

Publication bias within the studies were assessed both visually, using a funnel plot (Figure 2), as well as the 12 criteria recommended by the Cochrane Back Review Group¹⁹ (Figure 3). There was no evidence of publication bias on the funnel plot, and the number of criteria met was 9/12 in both studies. All of the studies included in the current meta-analyses were thus considered to have a negligible risk of bias. None of the included studies had an adequate description of withdrawals or drop outs (Figure 3).

Figure 2.

Funnel plot of studies included in the current meta-analysis of randomized controlled trials comparing chemotherapy and chemotherapy plus surgery for treatment of spinal tuberculosis. There was no evidence of publication bias.

Figure 3.

Overall quality of the evidence for each outcome in studies included in the current meta-analysis of randomized controlled trials comparing chemotherapy and chemotherapy plus surgery for treatment of spinal tuberculosis (MRC 1974^48,49 and ICMR/MRC 1989^50–54). Quality was assessed using an adapted GRADE approach, as recommended by the Cochrane Back Review Group.¹⁹ The quality of the evidence for a specific outcome was based on the study design, risk of bias, consistency of results, directness (generalizability), precision (sufficient data) and potential bias for the reporting of results across all studies that measured that particular outcome. ITT, intention to treat.

Discussion

The objective of this systematic review and meta-analysis was to compare chemotherapy plus surgery with chemotherapy alone for treatment of spinal TB. There was no statistically significant benefit of routine surgery, and surgery had no effect on kyphosis angle. The incidence of progressive kyphosis and the kyphosis angle at study entry were high (>30°) for all participants.^48–54 Spinal surgeons generally consider kyphosis >30° to be unacceptably high and an indication for surgical correction.¹⁸

The current review revealed no between-group difference in bony fusion, which is often considered the best evidence of healing.^46,47 Data on the speed of bony fusion were not provided in either trial, and it was therefore not possible to assess differences during early phases of treatment. The amount of bone is considered important for the stability of the spine; as both studies excluded patients with >3 U total bone loss, the role of surgery in these more severe cases could not be assessed. A small number of participants had neurological deficit at study entry, but there were no statistically significant between-group differences in the improvement of this deficit. Deterioration of neurological deficit or persisting deficit with spinal cord compression can be an indication for surgery,¹⁷ and a small group of patients (n = 5/130) in the chemotherapy group required surgery to decompress the spinal cord.^48–52

The current analysis has several limitations, the most important of which is the availability of only two relevant studies, severely restricting the value of the meta-analysis findings. In addition, there was inadequate follow-up data for the MRC trial^48,49 at any time point, and at 10 years in the ICMR/MRC trial.^50–54 Finally, both trials were performed almost three decades ago and their current clinical relevance is difficult to determine given the advances in medical and surgical management of spinal TB. It is therefore imperative that randomized controlled trials are initiated to assess the benefits of surgery in spinal TB in the current setting. Several small-scale non-randomized studies have been performed more recently,^21-47 but the results of the present analysis suggest that routine surgery cannot be recommended unless within the context of a large, well conducted randomized controlled trial.

Footnotes

Declaration of conflicting interest

The authors declare that there is no conflict of interest.

Funding

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Acknowledgements

We thank everyone who helped with this study.

References

Sai Kiran

Vaishya

Kale

. Surgical results in patients with tuberculosis of the spine and severe lower-extremity motor deficits: a retrospective study of 48 patients. J Neurosurg Spine 2007; 6: 320–326.

Rezai

Lee

Cooper

. Modern management of spinal tuberculosis. Neurosurgery 1995; 36: 87–97.

Turgut

. Spinal tuberculosis (Pott's disease): its clinical presentation, surgical management, and outcome. A survey study on 694 patients. Neurosurg Rev 2001; 24: 8–13.

Barnes

Bloch

Davidson

. Tuberculosis in patients with human immunodeficiency virus infection. N Engl J Med 1991; 324: 1644––1650.

Bass

Jr Farer

Hopewell

. Treatment of tuberculosis and tuberculosis infection in adults and children. American Thoracic Society and the Centers for Disease Control and Prevention. Am J Respir Crit Care Med 1994; 149: 1359–1374.

Chemotherapy and management of tuberculosis in the United Kingdom: recommendations 1998. Joint Tuberculosis Committee of the British Thoracic Society. Thorax 1998; 53: 536–548.

Van Loenhout-Rooyackers

Verbeek

Jutte

. Chemotherapeutic treatment for spinal tuberculosis. Intl J Tubercul Lung Dis 2002; 6: 259–265.

Kirkaldy-Willis

Thomas

. Anterior approaches in the diagnosis and treatment of infections of the vertebral bodies. J Bone Joint Surg Am 1965; 47: 87–110.

Arct

. Operative treatment of tuberculosis of the spine in old people. J Bone Joint Surg Am 1968; 50: 255–267.

10.

Wilkinson

. Tuberculosis of the spine treated by chemotherapy and operative débridement. A long-term follow-up study. J Bone Joint Surg Am 1969; 51: 1331–1342.

11.

Rajasekaran

Shanmugasundaram

Prabhakar

. Tuberculous lesions of the lumbosacral region: A 15-year follow-up of patients treated by ambulant chemotherapy. Spine (Phila Pa 1976) 1998; 23: 1163–1167.

12.

Hodgson

Stock

. Anterior spinal fusion for the treatment of tuberculosis of the spine. J Bone Joint Surg Am 1960; 42: 1147–1156.

13.

Kohli

. Radical surgical approach to spinal tuberculosis. J Bone Joint Surg Br 1967; 49: 668–673.

14.

Albee

. Transplantation of a portion of the tibia into the spine for Pott's disease: a preliminary report. JAMA 1911; 11: 885–886.

15.

Hibbs

. An operation for Pott's disease of the spine. JAMA 1912; 59: 433–436.

16.

Huo

Xiao

. Combination of intensified anti-tuberculosis with operation for treatment of thoracolumbar tuberculosis. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2009; 23: 1427–1430.

17.

Jutte

Van Loenhout-Rooyackers

. Routine surgery in addition to chemotherapy for treating spinal tuberculosis. Cochrane Database Syst Rev 2006, pp. CD004532–CD004532.

18.

Rasouli

Mirkoohi

Vaccaro

. Spinal tuberculosis: diagnosis and management. Asian Spine J 2012; 6: 294–308.

19.

Critical Appraisal Skills Programme Guidelines. Available at: http://www.casp-uk.net/.

20.

Moher

Cook

Eastwood

. Improving the quality of reports of meta-analyses of randomized controlled trials: the QUOROM statement: quality of reporting of meta-analyses. Lancet 1999; 354: 1896–1900.

21.

Bakhsh

. Medical management of spinal tuberculosis: an experience from Pakistan. Spine (Phila Pa 1976) 2010; 35: E787–E791.

22.

Guo

Chen

. Clinical study of short-course chemotherapy combined with radical operation in retreating spinal tuberculosis. Zhongguo Gu Shang 2010; 23: 491–494.

23.

Park

Sohn

Kim

. Outcome and management of spinal tuberculosis according to the severity of disease: a retrospective study of 137 adult patients at Korean teaching hospitals. Spine (Phila Pa 1976) 2007; 32: E130–E135.

24.

Wang

Jin

. Treatment of spinal tuberculosis with ultrashort-course chemotherapy in conjunction with partial excision of pathologic vertebrae. Spine J 2007; 7: 671–681.

25.

Sai Kiran

Vaishya

Kale

. Surgical results in patients with tuberculosis of the spine and severe lower-extremity motor deficits: a retrospective study of 48 patients. J Neurosurg Spine 2007; 6: 320–326.

26.

Chadha

Agarwal

Singh

. Craniovertebral tuberculosis: a retrospective review of 13 cases managed conservatively. Spine (Phila Pa 1976) 2007; 32: 1629–1634.

27.

Kotil

Alan

Bilge

. Medical management of Pott disease in the thoracic and lumbar spine: a prospective clinical study. J Neurosurg Spine 2007; 6: 222–228.

28.

Jain

Aggarwal

Arora

. Behavior of the kyphotic angle in spinal tuberculosis. Intl Orhtop 2004; 28: 110–114.

29.

Loembe

. Medico-surgical treatment of Pott’s disease. Our attitude in Gabon. Can J Neurol Sci 1994; 21: 339–345. [In French, English abstract].

30.

A controlled trial of ambulant out-patient treatment and in-patient rest in bed in the management of tuberculosis of the spine in young Korean patients on standard chemotherapy a study in Masan, Korea. First report of the Medical Research Council Working Party on Tuberculosis of the Spine. J Bone Joint Surg Br 1973; 55: 678–697.

31.

A controlled trial of plaster-of-paris jackets in the management of ambulant outpatient treatment of tuberculosis of the spine in children on standard chemotherapy. A study in Pusan, Korea. Second report of the Medical Research Council Working Party on Tuberculosis of the Spine. Tubercle 1973; 54: 261–282.

32.

A controlled trial of anterior spinal fusion and debridement in the surgical management of tuberculosis of the spine in patients on standard chemotherapy: a study in Hong Kong. Br J Surg 1974; 61: 853–866.

33.

A five-year assessment of controlled trials of in-patient and out-patient treatment and of plaster-of-Paris jackets for tuberculosis of the spine in children on standard chemotherapy. Studies in Masan and Pusan, Korea. Fifth report of the Medical Research Council Working Party on tuberculosis of the spine. J Bone Joint Surg Br 1976; 58-B: 399–411.

34.

A controlled trial of anterior spinal fusion and debridement in the surgical management of tuberculosis of the spine in patients on standard chemotherapy: a study in two centres in South Africa. Seventh Report of the Medical Research Council Working Party on tuberculosis of the spine. Tubercle 1978; 59: 79–105.

35.

A 10-year assessment of a controlled trial comparing debridement and anterior spinal fusion in the management of tuberculosis of the spine in patients on standard chemotherapy in Hong Kong. Eighth Report of the Medical Research Council Working Party on Tuberculosis of the Spine. J Bone Joint Surg 1982; 64: 393–398.

36.

A 10-year assessment of controlled trials of inpatient and outpatient treatment and of plaster-of-Paris jackets for tuberculosis of the spine in children on standard chemotherapy. Studies in Masan and Pusan, Korea. Ninth report of the Medical Research Council Working Party on Tuberculosis of the Spine. J Bone Joint Surg 1985; 67: 103–110.

37.

A controlled trial of six-month and nine-month regimens of chemotherapy in patients undergoing radical surgery for tuberculosis of the spine in Hong Kong. Tenth report of the Medical Research Council Working Party on Tuberculosis of the Spine. Tubercle 1986; 67: 243–259.

38.

Controlled trial of short-course regimens of chemotherapy in the ambulatory treatment of spinal tuberculosis. Results at three years of a study in Korea. Twelfth report of the Medical Research Council Working Party on Tuberculosis of the Spine. J Bone Joint Surg Br 1993; 75: 240–248.

39.

A 15-year assessment of controlled trials of the management of tuberculosis of the spine in Korea and Hong Kong. Thirteenth Report of the Medical Research Council Working Party on Tuberculosis of the Spine. J Bone Joint Surg 1998; 80: 456–462.

40.

Rajasekaran

Shanmugasundaram

Prabhakar

. Tuberculous lesions of the lumbosacral region. A 15-year follow-up of patients treated by ambulant chemotherapy. Spine (Phila Pa 1976) 1998; 23: 1163–1167.

41.

Rajeswari

Balasubramanian

Venkatesan

. Short-course chemotherapy in the treatment of Pott’s paraplegia: report on five year follow-up. Intl J Tuberc Lung Dis 1997; 1: 152–158.

42.

Seddon

. The choice of treatment in Pott’s disease. J Bone Joint Surg Br 1976; 58-B: 395–397.

43.

Upadhyay

Sell

Saji

. 17-year prospective study of surgical management of spinal tuberculosis in children. Hong Kong operation compared with debridement surgery for short- and long-term outcome of deformity. Spine (Phila Pa 1976) 1993; 18: 1704–1711.

44.

Upadhyay

Saji

Sell

. Spinal deformity after childhood surgery for tuberculosis of the spine. A comparison of radical surgery and debridement. J Bone Joint Surg Br 1994; 76: 91–98.

45.

Upadhyay

Saji

Sell

. Longitudinal changes in spinal deformity after anterior spinal surgery for tuberculosis of the spine in adults. A comparative analysis between radical and debridement surgery. Spine (Phila Pa 1976) 1994; 19: 542–549.

46.

Upadhyay

Sell

Saji

. Surgical management of spinal tuberculosis in adults. Hong Kong operation compared with debridement surgery for short and long term outcome of deformity. Clin Orthop Relat Res 1994; 302: 173–182.

47.

Upadhyay

Saji

Yau

. Duration of antituberculosis chemotherapy in conjunction with radical surgery in the management of spinal tuberculosis. Spine (Phila Pa 1976) 1996; 21: 1898–1903.

48.

A controlled trial of debridement and ambulatory treatment in the management of tuberculosis of the spine in patients on standard chemotherapy. A study in Bulawayo, Rhodesia. J Trop Med Hyg 1974; 77: 72–92.

49.

Five-year assessments of controlled trials of ambulatory treatment, debridement and anterior spinal fusion in the management of tuberculosis of the spine. Studies in Bulawayo (Rhodesia) and in Hong Kong. Sixth report of the Medical Research Council Working Party on Tuberculosis of the Spine. J Bone Joint Surg Br 1978; 60-B: 163–177.

50.

Balasubramanian

Sivasubramanian

Parthasarathy

. Prevalence, incidence and resolution of abscesses and sinuses in patients with tuberculosis of the spine: 5-year results of patients treated with short-course chemotherapy with or without surgery in Madras. Indian J Tuberc 1994; 41: 151–160.

51.

Five-year assessment of controlled trials of short-course chemotherapy regimens of 6, 9 or 18 months’ duration for spinal tuberculosis in patients ambulatory from the start or undergoing radical surgery. Fourteenth report of the Medical Research Council Working Party on Tuberculosis of the Spine. Intl Orthop 1999; 23: 73–81.

52.

Indian Council of Medical Research/British Medical Research Council Working Party Study. A controlled trial of short-course regimens of chemotherapy in patients receiving ambulatory treatment or undergoing radical surgery for tuberculosis of the spine. Indian J Tubercu 1989; 36: 1–21.

53.

Parthasarathy

Sriram

Santha

. Short-course chemotherapy for tuberculosis of the spine. A comparison between ambulant treatment and radical surgery – ten-year report. J Bone Joint Surg Br 1999; 81-B: 464–471.

54.

Reetha

Sivasubramanian

Parthasarathy

. Five-year findings of a comparison of ambulatory short-course chemotherapy with radical surgery plus chemotherapy for tuberculosis of the spine in Madras. Ind J Orthop 1994; 28: 7–13.

Management of spinal tuberculosis: a systematic review and meta-analysis

Abstract

Objective

Methods

Results

Conclusions

Keywords

Introduction

Materials and methods

Data sources and searches

Assessment of methodological quality

Data extraction, synthesis and analysis

Statistical analyses

Results

Discussion

Footnotes

Declaration of conflicting interest

Funding

Acknowledgements

References