Fusion mass bone quality after uninstrumented spinal fusion in older patients

doi:10.1007/s00586-010-1373-2

Eur Spine J. 2010 December; 19(12): 2200–2208.

Published online 2010 April 29. doi: 10.1007/s00586-010-1373-2

PMCID: PMC2997208

Fusion mass bone quality after uninstrumented spinal fusion in older patients

Thomas Andersen,¹ Finn B. Christensen,¹ Bente L. Langdahl,⁷ Carsten Ernst,² Søren Fruensgaard,³ Jørgen Østergaard,⁴ Jens Langer Andersen,² Sten Rasmussen,⁵ Bent Niedermann,¹ Kristian Høy,¹ Peter Helmig,¹ Randi Holm,¹ Bent Erling Lindblad,¹ Ebbe Stender Hansen,¹ Niels Egund,⁶ and Cody Bünger¹

¹Spine Section, Orthopaedic Research Laboratory, Orthopaedic Department E, Aarhus University Hospital, Building 1A, Nørrebrogade 44, 8000 Aarhus C, Denmark

²Orthopaedic Department, Esbjerg County Hospital, Esbjerg, Denmark

³Orthopaedic Department, Holstebro County Hospital, Holstebro, Denmark

⁴Orthopaedic Department, Viborg County Hospital, Viborg, Denmark

⁵Orthopaedic Department, Vejle County Hospital, Vejle, Denmark

⁶Department of Radiology R, Aarhus University Hospital, Aarhus, Denmark

⁷Department C of Endocrinology and Metabolism, Aarhus University Hospital, Aarhus, Denmark

Thomas Andersen, Phone: +45-89494122, Fax: +45-89494150, Email: tba/at/dadlnet.dk.

Corresponding author.

Received August 18, 2009; Revised February 22, 2010; Accepted March 7, 2010.

Abstract

Older people are at increased risk of non-union after spinal fusion, but little is known about the factors determining the quality of the fusion mass in this patient group. The aim of this study was to investigate fusion mass bone quality after uninstrumented spinal fusion and to evaluate if it could be improved by additional direct current (DC) electrical stimulation. A multicenter RCT compared 40 and 100 μA DC stimulation with a control group of uninstrumented posterolateral fusion in patients older than 60 years. This report comprised 80 patients who underwent DEXA scanning at the 1 year follow-up. The study population consisted of 29 men with a mean age of 72 years (range 62–85) and 51 women with a mean age of 72 years (range 61–84). All patients underwent DEXA scanning of their fusion mass. Fusion rate was assessed at the 2 year follow-up using thin slice CT scanning. DC electrical stimulation did not improve fusion mass bone quality. Smokers had lower fusion mass BMD (0.447 g/cm²) compared to non-smokers (0.517 g/cm²) (P = 0.086). Women had lower fusion mass BMD (0.460 g/cm²) compared to men (0.552 g/cm²) (P = 0.057). Using linear regression, fusion mass bone quality, measured as BMD, was significantly influenced by gender, age of the patient, bone density of the remaining part of the lumbar spine, amount of bone graft applied and smoking. Fusion rates in this cohort was 34% in the control group and 33 and 43% in the 40 and 100 μA groups, respectively (not significant). Patients classified as fused after 2 years had significant higher fusion mass BMD at 1 year (0.592 vs. 0.466 g/cm², P = 0.0001). Fusion mass bone quality in older patients depends on several factors. Special attention should be given to women with manifest or borderline osteoporosis. Furthermore, bone graft materials with inductive potential might be considered for this patient population.

Keywords: Spinal fusion, Randomised clinical trial, Bone mineral density, Electrical stimulation, Bone graft, Age, Smoking

Introduction

One of the main goals when performing posterolateral spinal fusion is the achievement of bridging bone between the transverse processes. The most common method for assessment of this is plain radiographs, followed by CT scanning. Previous studies have shown the fusion rate to be dependent on several factors: age [5, 36], smoking [5, 16], use of instrumentation [14] and also the amount of bone graft used [26]. The majority of fusion studies have focused on fusion rates, some have used semi-quantitative scoring techniques to describe the quality of the fusion mass, but few have investigated the quality beyond this. Microscopically, the fusion mass in humans have been investigated by Kleiner et al. [23] who performed a large study where they took biopsies from the fusion mass in connection with surgery for hardware removal or pseudoarthrosis. They found instrumented fusions to have significant higher mineralised volume and trabecular thickness as compared to uninstrumented fusions. Using a radiographic microdensitometry technique, An et al. [1] compared fusion qualities of various allografts with autografts. The same techniques were applied by Jenis et al. [18] in a comparison of direct current electrical stimulation (DC stimulation) and pulsed electromagnetic fields (PEMF) as an adjunct to instrumented posterolateral fusion with autograft. They demonstrated a small decrease in fusion mass bone density from 3 to 12 months in the control group who received no stimulation, compared to the two stimulated groups who both had an increase in bone density in the period. Using dual energy X-ray absorptiometry (DEXA), Lipscomb et al. [28] reported that the density of the grafted area increased in a cyclical pattern after uninstrumented fusion. In experimental studies, bone density of healing fractures has been shown to correlate well with measures of mechanical strength [9]. Also, the bone mineral density (BMD) of tricortical iliac crest bone grafts has been shown to correlate with biomechanical strength [2]. Thus, DEXA scanning might be one method to investigate fusion mass quality in posterolateral spinal fusion.

In the study by Jenis et al. [18] DC stimulation was shown to prevent loss of bone density of the fusion mass. DC stimulation has been shown to increase fusion rates in posterolateral fusion, both with and without instrumentation, as well as in “high-risk” patients [20, 25, 39, 41]. However, these studies investigated fusions using autograft. Only one study demonstrated a positive effect on fusion rates using allograft in interbody fusions [34].

Aim

The aim of the present study was to investigate fusion mass bone quality 1 year after uninstrumented spinal fusion performed in patients above 60 years and to investigate the effect of DC stimulation on fusion mass bone density.

Materials and methods

Study design

The patient cohort in this study was taken from a Danish multicenter randomised trial on the effect of DC electrical stimulation in adjunct to uninstrumented spinal fusion. The main results of the study are reported elsewhere [3, 4]. The study included patients of 60 years or above, eligible for spinal fusion. The main indication for surgery was spinal stenosis, where additional fusion was deemed necessary due to instability or the need for extensive decompression, or a significant degree of back pain indicating that additional fusion could be beneficial. The patients were randomised to posterolateral spinal fusion using fresh frozen allograft with or without 40 μA DC electrical stimulation in a 1:1 fashion. The electrical stimulation was delivered by the SpF-XL IIb spinal fusion stimulator (former EBI, now BiometSpine). The study was initiated in 2001. In 2004, the manufacturer launched a more powerful new device delivering 100 μA stimulation, as the number of patients already included was acceptable. This new device was incorporated into the study as a third arm with a 1:1:2 randomisation between control, 40 and 100 μA. In 2005, the manufacturer stopped producing the 100 μA device and the study was discontinued. The study and subsequent changes were approved by the regional ethical committees.

Patient population

The original study included 98 patients. Three patients died before the 1 year control leaving 95 patients accessible for the 1 year follow-up. This study included 80 patients (84% follow-up) who underwent bone densitometry of their fusion mass 1 year post-operatively. Patient demographics are seen in Table 1. Characteristics of the patients missing in the study are seen in Table 2. Surgery was a standard posterolateral spinal fusion. The allograft used was a fresh frozen femoral head obtained during total hip replacement; it was milled and mixed with any local bone obtained from the decompression procedure, just prior to insertion. Before insertion, the amount of graft was quantified by weighing. The properties of the femoral head are very similar to those described by Gibson et al. [15]. Battery life in the stimulator was at least 6 months and the stimulator battery (not the electrodes) was removed with local anaesthesia within 6 months to 1 year after the primary operation. To allow for blinded evaluation in all radiographic evaluations, dummy electrodes were utilised in the control group. They were completely identical to those coming with the stimulator device and were provided by the manufacturer of the stimulator. They were placed in a similar fashion as in the intervention groups, but were not coupled to a stimulator battery. As the control patients did not need to be scheduled for battery removal, they were aware that they did not get active stimulation. All patients were braced postoperatively for 3 months in a BOB brace.

Table 1

Baseline characteristics according to study group

Table 2

Baseline characteristics of patients who completed 1 year clinical control, but missed 1 year DEXA scanning

Eight patients missed the weight of the bone graft (five in the control group, two in the 40 μA group and one in the 100 μA group). In 54 patients, weight of any used local bone as well as used allograft was measured separately and could be combined into the total weight of the graft used.

Bone densitometry

Bone mineral density (BMD, g/cm²) and bone mineral content (BMC, g) were measured by dual energy X-ray apsortiometry (DEXA) using a Hologic QDR-2000 densitometer (Hologic Inc., Waltham, MA, USA). BMC and BMD of the fusion mass were assessed with an anteroposterior regional scan using the scanner’s “subregion forearm” programme. A region of interest was placed over the posterolateral fusion mass at each side of the spine and the values calculated by the scanner (Fig. 1). This was done both by the technician performing the scan and by the first author (TA), and a mean of these two measurements was used for the statistical analysis. Lumbar spine BMD and BMC were assessed using a standard anteroposterior L1–L4 scanning including only the lumbar vertebrae above the fused levels, e.g. L1–L3 in a patient with an L4–S1 fusion.

Fig. 1

A Lumbar AP DEXA scanning showing the selected vertebrae above the fusion used for lumbar spine BMD measurements. B Fusion mass subregion scanning with regions of interest placed at each side over the fusion mass area

Radiology

To correlate DEXA scanning results with the final fusion status, data obtained by thin slice CT scanning at the 2 year follow-up was used. All CT scans were performed using 0.8 mm slice thickness and a 0.4 mm overlap and reviewed blinded to the treatment group. Classification of fusion was based on the study by Carreon et al. [11]. For a segment to be categorised as fused, there had to be a continuous bony bridge between the transverse processes or at the lateral side of the facet joints on at least one side or a bilateral fusion of the facet joints. If there was only unilateral facet joint fusion, questionable bilateral facet fusion or possible presence of a cleft in the bony bridge, the fusion was categorised as doubtfully fused. Segments with a clearly definable cleft in the bony bridge, questionable fusion in one facet joint and none in the contralateral or with resorption of most of the fusion mass were classified as non-unions. For the patients to be categorised as fused, fusion had to be achieved at all intended levels. A total of five patients (four in the control group and one in the 100 μA group) had missing CT scan data.

Functional outcome

Functional outcome was assessed using the Dallas pain questionnaire (DPQ) [27], which assesses the functional impact of chronic spinal pain in four categories: daily activities, work–leisure activities, anxiety and depression and social concerns. A high score indicates a high influence of back pain on the daily life of the patient and thus a poor outcome. Pain was assessed using the pain assessment index from the low back pain rating scale (LBPRS) [29]. It is measured using 11-box numerical rating scales ranging from 0 representing no pain to 10 representing worst possible pain. It comprises three scales for back and leg pain separately (pain now, worst and average pain in the last 14 days). Each response scale is added giving a scale ranging from 0 to 60. General health was assessed using the SF-36 [7]. The SF-36 yields a profile of scores in eight scales, covering different physical and mental components of health [42]. The score in each scale ranges from 0 (poorest health) to 100 (best health). Additionally, two summary measures are produced: a physical component summary (PCS) and a mental component summary (MCS).

Statistics

Between-group comparisons of continuous variables were done using non-parametric testing (Mann–Whitney rank-sum test or Kruskal–Wallis test without correction for ties). Significance of proportions was calculated using χ² test. The level of significance was set to 0.05 (two-sided testing). Correlations were assessed by linear regression. Applicability of the linear regression procedure was tested using Lowess regression and analysis of Studentised residuals. Coefficient of variation (CV) was calculated both for the fusion mass BMC and BMD measurements using the method proposed by Bland and Altman [8]. Stata Intercooled version 9.2 was the software used for the statistical analysis.

Results

Coefficient of variation (CV) for the graft BMC measurements was quite high at 39.5%; however, the CV for the graft BMD measurement was 8.8%. The average amount of bone graft used in the three treatment groups are seen in Table 3. The total amount of bone used ranged between 30 and 186 g. Out of this, the local bone constituted between 0 and 40 g. The average amount of graft applied at each level ranged between 15 and 114 g.

Table 3

Fusion mass parameters according to study group

There was no difference between the three treatment groups with respect to fusion mass BMD or BMC (Table 3). The 100 μA group received more graft due to more multilevel fusions; the amount of graft per level did not differ from the two other groups (Table 3). Compared to non-smokers, smokers had lower fusion mass BMD [Mean (SD): 0.447 g/cm² (0.155) vs. 0.517 g/cm² (0.168), P = 0.0864] and BMC [Mean (SD): 4.06 g (3.32) vs. 7.08 g (5.60), P = 0.0163]. Also, women had lower fusion mass BMD compared to men [Mean (SD): 0.460 g/cm² (0.128) vs. 0.552 g/cm² (0.207), P = 0.0566]. There was a linear relation between fusion mass BMD, BMD of the intact lumbar spine and the amount of bone graft applied. The latter relation was significantly stronger in men than in women (Fig. 2). Multivariate regression analysis showed fusion mass BMD to be dependent on the amount of bone graft applied (but with a significant gender difference), BMD of the lumbar spine, age and smoking (Table 4). Fusion mass BMD did not correlate significantly with functional outcome, except for pain, as measured with the LBPRS, which was higher in patients with the lowest fusion mass BMD (Fig. 3).

Fig. 2

a Correlation between amount of bone graft applied at operation and fusion mass BMD at 1 year follow-up. Correlation coefficient (r) is 0.6386 for men (P = 0.0006) and 0.2254 for women (P = 0.1277). There is significant (more ...)

Table 4

Linear regression with fusion mass BMD as dependent variable

Fig. 3

Functional outcome at the time of DEXA scanning depending on bone mineral density of the fusion mass. Bars represent mean, error bars represent standard error of mean

CT-based fusion rate in this cohort was 34% (11/32) in the control group, 34% in the 40 μA group (12/36) and 43% (3/7) in the 100 μA group (not significant). The amount of graft amount applied at each level was significantly larger in patients classified as fused, based on CT scanning (Mean 54 g; range 24–114 g) compared to patients classified as non- or doubtful fusions (mean 40 g; range 15–72 g) (P = 0.0078). Patients classified as fused after 2 years had significantly higher fusion mass BMD at their 1 year DEXA scanning compared to their non-union counterparts [Mean (SD): 0.592 g/cm² (0.190) vs. 0.446 g/cm² (0.130), P = 0.0001]. The mean spinal BMD at the 1 year DEXA scanning was also higher in fused patients (0.974 g/cm²) compared to non-union patients (0.905 g/cm²; not significant).

Discussion

We assessed fusion mass quality 1 year after uninstrumented spinal fusion using DEXA scanning. DEXA was chosen as it is the most widely used non-invasive bone quality test used today and has excellent precision with a small radiation dose [35]. In experimental studies, DEXA has been used to evaluate the bone quality of healing fractures [9, 31, 32]. These studies have shown acceptable correlation of the DEXA results with mechanical properties of the healing fracture [9, 31, 32]. One study has also shown that DEXA scanning was able to predict the development of atrophic pseudoarthroses in a canine osteotomy model [30]. Thus, we felt DEXA could provide some indication of the mechanical status of the fusion mass together with information on the bone status of the fusion mass.

We could not demonstrate any effect of DC stimulation on fusion mass behaviour assessed by DEXA. In the study by Jenis et al. [18], which demonstrated a positive effect of DC stimulation on bone density, the assessment was performed using image analysis of the X-rays and not by DEXA or any other validated method. Thus, DC stimulation either has no effect or the effect is too small to overcome the influencing factors observed in this study.

We found that the fusion mass quality, measured as BMD, depended significantly on several factors. One of them was age, probably reflecting factors involved with the age-related decline in bone mass seen at all skeletal sites. Also, a linear correlation was found between fusion mass BMD and BMD of the lumbar spine not involved in the fusion. It could indicate that the fusion mass was remodelled to obtain characteristics similar to the spinal bone mass in that particular patient. Thus, each patient might have a “set point” of bone quality at which the fusion mass will end. Experimental studies on fracture healing in rats have investigated the effect of osteoporosis and reported different findings [13]. Studies looking into long-term changes have shown few differences at early time points, but development of differences in the late periods of fracture healing when remodelling begins to occur [24, 33, 43]. These and other studies have demonstrated remodelling of the fracture callus towards characteristics equal to those observed in osteoporotic bone. They have coupled the decreased strength of fracture healing in osteoporotic bone to a finding of irregular formation of the trabeculae and less mineral acquisition [13, 24, 33, 43]. Another factor found to influence the fusion mass negatively was smoking. Smoking has been shown to result in lower BMD, especially in the spine, probably by depressing the vitamin D/PTH system [10, 12, 19, 38], and it is a well-documented risk factor for lower fusion rates after spinal surgery [5, 16].

The amount of graft applied at the operation was linearly related to the fusion mass BMD after 1 year, however with a strong interacting effect of sex, as the relation was far more pronounced in men than in women. Only one study so far has looked into volume changes of the spinal fusion mass. Kim and Ha et al. performed a CT study in which they demonstrated a loss of initial bone graft volume of more than 30% from 2 weeks to 1 year postoperatively in instrumented posterolateral fusions using autograft. From 1 to 5 year postoperatively, the fusion mass volume remained stable. Any effect of gender was, however, not investigated in their study [17, 22]. The differences between genders observed in our study could be explained by an up-regulation in osteoclast activity in women, due to postmenopausal changes leading to greater bone resorption [21]. Furthermore, it has been shown that oestrogen can modulate mechano-sensitivity of bone cells [6]. Thus, oestrogen might play a role via mechanical stimuli or by an effect on resorption in explaining the difference in dependency of graft amount on final fusion mass BMD observed in this study. Another factor could be that men are better adapted to incorporate the fusion mass, as shown by an increased ability of periostal apposition by men compared to women of the same age [40]. Thus, there simply might be more viable bone cells at the posterolateral fusion bed in men compared to women leading to incorporation of a larger amount of the graft material present. Preparation of the fusion bed was one of the factors we did not control for in this study and it could be thought to vary between surgeons. It has been proven in experimental studies to influence the fusion result.

Another limitation to this study is its cross-sectional design, which prevents conclusions on longitudinal changes and whether the fusion mass has matured. In the only study so far that has applied DEXA for the assessment of fusion mass status after spinal fusion, Libscomb et al. [28] found that the majority of patients had reached a “steady state” after 1 year, suggesting that the results obtained in this study should be representative of the end status of bony fusion.

We found both the amount of bone graft used as well as spinal BMD to influence fusion rate. In her thesis, Laursen demonstrated that 25 g of autograft per segment included in the fusion seemed to be a critical size to achieve a solid posterolateral fusion as determined from X-rays [26]. Compared to this, our data suggest that a larger amount of allograft is needed to secure a solid fusion, but also that no “security limit” can be given due to the spread of the data. Regarding spinal BMD, Okuyama et al. [37] showed patients with a clearly defined fusion after a PLIF to have significantly higher BMD than patients with undetermined union or non-union. They suggested a spinal BMD of 0.674 (±0.104) g/cm² to be a critical threshold below which non-union starts occurring [37]. As seen from our result, non-unions can occur well above this threshold in older patients undergoing uninstrumented fusion.

One difference between the assessment of the fusion mass BMD and the CT-based fusion evaluation is that DEXA measures the amount of bone mineral at the fusion site at all levels together and does not reveal anything about the presence of pseudoarthrosis of any kind. Thus, fusions with a significant amount of bone present might be classified as non-unions because of a single transverse line through the fusion mass at one level. Nevertheless significant less bone mineral was present at the fusion site in the non-unions as compared to those solidly fused. This might also explain why the association between fusion mass BMD and functional outcome was weaker than that observed in the primary report between CT-based fusion rate and functional outcome [3].

This study demonstrates that the quality of the posterolateral fusion mass is dependant on several factors. Special attention should be given to women and patients with manifest or borderline osteoporosis. Besides optimal preparation of the fusion bed, graft amount should be sufficient when using fresh frozen allograft. But, fusion rates are low and not changeable by DC stimulation using the current magnitudes tested in this study. Other graft materials and stimulatory devices should be tested in a proper fashion in this patient category to prove their efficiency, and the use of autograft might be considered in these patients until more effective fusion methods have been found.

Acknowledgments

The study was approved by the regional ethical committees (case number): 20000262, 2000/149mc, M-2200-00, 20000235. This study received unrestricted support from Biomet approximately 24.000 €.

References

1. An HS, Lynch K, Toth J. Prospective comparison of autograft vs. allograft for adult posterolateral lumbar spine fusion: differences among freeze-dried, frozen, and mixed grafts. J Spinal Disord. 1995;8:131–135. doi: 10.1097/00002517-199504000-00007. [PubMed] [Cross Ref]

2. An HS, Xu R, Lim TH, McGrady L, Wilson C. Prediction of bone graft strength using dual-energy radiographic absorptiometry. Spine. 1994;19:2358–2362. [PubMed]

3. Andersen T, Christensen FB, Egund N, Ernst C, Fruensgaard S, Ostergaard J, Andersen JL, Rasmussen S, Niedermann B, Hoy K, Helmig P, Holm R, Lindblad BE, Hansen ES, Bunger C. The effect of electrical stimulation on lumbar spinal fusion in older patients: a randomized, controlled, multi-center trial: part 2: fusion rates. Spine. 2009;34:2248–2253. doi: 10.1097/BRS.0b013e3181b02c59. [PubMed] [Cross Ref]

4. Andersen T, Christensen FB, Ernst C, Fruensgaard S, Ostergaard J, Andersen JL, Rasmussen S, Niedermann B, Hoy K, Helmig P, Holm R, Lindblad BE, Hansen ES, Egund N, Bunger C. The effect of electrical stimulation on lumbar spinal fusion in older patients: a randomized, controlled, multi-center trial. Part 1. Functional outcome. Spine. 2009;34:2241–2247. doi: 10.1097/BRS.0b013e3181b02988. [PubMed] [Cross Ref]

5. Andersen T, Christensen FB, Laursen M, Hoy K, Hansen ES, Bunger C. Smoking as a predictor of negative outcome in lumbar spinal fusion. Spine. 2001;26:2623–2628. doi: 10.1097/00007632-200112010-00018. [PubMed] [Cross Ref]

6. Augat P, Simon U, Liedert A, Claes L. Mechanics and mechano-biology of fracture healing in normal and osteoporotic bone. Osteoporos Int. 2005;16(Suppl 2):S36–S43. doi: 10.1007/s00198-004-1728-9. [PubMed] [Cross Ref]

7. Bjørner JB, Damsgaard MT, Watt T, Bech P, Rasmussen NK, Kristensen TS, Modvig J, Thunedborg K (1997) Dansk manual til SF-36. Lif.

8. Bland JM, Altman DG. Measurement error proportional to the mean. BMJ. 1996;313:106. [PMC free article] [PubMed]

9. Blokhuis TJ, den Boer FC, Bramer JA, van Lingen A, Roos JC, Bakker FC, Patka P, Haarman HJ (2000) Evaluation of strength of healing fractures with dual energy X-ray absorptiometry. Clin Orthop :260–268. [PubMed]

10. Brot C, Jorgensen NR, Sorensen OH. The influence of smoking on vitamin D status and calcium metabolism. Eur J Clin Nutr. 1999;53:920–926. doi: 10.1038/sj.ejcn.1600870. [PubMed] [Cross Ref]

11. Carreon LY, Djurasovic M, Glassman SD, Sailer P. Diagnostic accuracy and reliability of fine-cut CT scans with reconstructions to determine the status of an instrumented posterolateral fusion with surgical exploration as reference standard. Spine. 2007;32:892–895. doi: 10.1097/01.brs.0000259808.47104.dd. [PubMed] [Cross Ref]

12. Egger P, Duggleby S, Hobbs R, Fall C, Cooper C. Cigarette smoking and bone mineral density in the elderly. J Epidemiol Community Health. 1996;50:47–50. doi: 10.1136/jech.50.1.47. [PMC free article] [PubMed] [Cross Ref]

13. Giannoudis P, Tzioupis C, Almalki T, Buckley R. Fracture healing in osteoporotic fractures: is it really different? A basic science perspective. Injury. 2007;38(Suppl 1):S90–S99. doi: 10.1016/j.injury.2007.02.014. [PubMed] [Cross Ref]

14. Gibson JN, Waddell G. Surgery for degenerative lumbar spondylosis: updated Cochrane review. Spine. 2005;30:2312–2320. doi: 10.1097/01.brs.0000182315.88558.9c. [PubMed] [Cross Ref]

15. Gibson S, McLeod I, Wardlaw D, Urbaniak S. Allograft versus autograft in instrumented posterolateral lumbar spinal fusion: a randomized control trial. Spine. 2002;27:1599–1603. doi: 10.1097/00007632-200208010-00002. [PubMed] [Cross Ref]

16. Glassman SD, Anagnost SC, Parker A, Burke D, Johnson JR, Dimar JR. The effect of cigarette smoking and smoking cessation on spinal fusion. Spine. 2000;25:2608–2615. doi: 10.1097/00007632-200010150-00011. [PubMed] [Cross Ref]

17. Ha KY, Lee JS, Kim KW. bone graft volumetric changes and clinical outcomes after instrumented lumbar or lumbosacral fusion: a prospective cohort study with a five-year follow-up. Spine. 2009;34:1663–1668. doi: 10.1097/BRS.0b013e3181aacab5. [PubMed] [Cross Ref]

18. Jenis LG, An HS, Stein R, Young B. Prospective comparison of the effect of direct current electrical stimulation and pulsed electromagnetic fields on instrumented posterolateral lumbar arthrodesis. J Spinal Disord. 2000;13:290–296. doi: 10.1097/00002517-200008000-00004. [PubMed] [Cross Ref]

19. Jenkins LT, Jones AL, Harms JJ. Prognostic factors in lumbar spinal fusion. Contemp Orthop. 1994;29:173–180. [PubMed]

20. Kane WJ. Direct current electrical bone growth stimulation for spinal fusion. Spine. 1988;13:363–365. doi: 10.1097/00007632-198803000-00026. [PubMed] [Cross Ref]

21. Khosla S, Melton LJ, III, Riggs BL. Osteoporosis: gender differences and similarities. Lupus. 1999;8:393–396. doi: 10.1177/096120339900800513. [PubMed] [Cross Ref]

22. Kim KW, Ha KY, Moon MS, Kim YS, Kwon SY, Woo YK. Volumetric change of the graft bone after intertransverse fusion. Spine. 1999;24:428–433. doi: 10.1097/00007632-199903010-00003. [PubMed] [Cross Ref]

23. Kleiner JB, Odom JA, Jr, Moore MR, Wilson NA, Huffer WE. The effect of instrumentation on human spinal fusion mass. Spine. 1995;20:90–97. doi: 10.1097/00007632-199501000-00016. [PubMed] [Cross Ref]

24. Kubo T, Shiga T, Hashimoto J, Yoshioka M, Honjo H, Urabe M, Kitajima I, Semba I, Hirasawa Y. Osteoporosis influences the late period of fracture healing in a rat model prepared by ovariectomy and low calcium diet. J Steroid Biochem Mol Biol. 1999;68:197–202. doi: 10.1016/S0960-0760(99)00032-1. [PubMed] [Cross Ref]

25. Kucharzyk DW. A controlled prospective outcome study of implantable electrical stimulation with spinal instrumentation in a high-risk spinal fusion population. Spine. 1999;24:465–468. doi: 10.1097/00007632-199903010-00012. [PubMed] [Cross Ref]

26. Laursen M (2001) Predictive parameters of autologous iliac crest bone graft for lumbar spinal fusion: quantitative and in vitro qualitative aspects. Thesis, Faculty of Health Sciences, Aarhus University.

27. Lawlis GF, Cuencas R, Selby D, McCoy CE. The development of the Dallas pain questionnaire. An assessment of the impact of spinal pain on behavior. Spine. 1989;14:511–516. doi: 10.1097/00007632-198905000-00007. [PubMed] [Cross Ref]

28. Lipscomb HJ, Grubb SA, Talmage RV. Spinal bone density following spinal fusion. Spine. 1989;14:477–479. doi: 10.1097/00007632-198904000-00028. [PubMed] [Cross Ref]

29. Manniche C, Asmussen K, Lauritsen B, Vinterberg H, Kreiner S, Jordan A. Low back pain rating scale: validation of a tool for assessment of low back pain. Pain. 1994;57:317–326. doi: 10.1016/0304-3959(94)90007-8. [PubMed] [Cross Ref]

30. Markel MD, Bogdanske JJ, Xiang Z, Klohnen A. Atrophic nonunion can be predicted with dual energy X-ray absorptiometry in a canine ostectomy model. J Orthop Res. 1995;13:869–875. doi: 10.1002/jor.1100130610. [PubMed] [Cross Ref]

31. Markel MD, Wikenheiser MA, Morin RL, Lewallen DG, Chao EY. Quantification of bone healing. Comparison of QCT, SPA, MRI, and DEXA in dog osteotomies. Acta Orthop Scand. 1990;61:487–498. doi: 10.3109/17453679008993569. [PubMed] [Cross Ref]

32. Markel MD, Wikenheiser MA, Morin RL, Lewallen DG, Chao EY. The determination of bone fracture properties by dual-energy X-ray absorptiometry and single-photon absorptiometry: a comparative study. Calcif Tissue Int. 1991;48:392–399. doi: 10.1007/BF02556452. [PubMed] [Cross Ref]

33. McCann RM, Colleary G, Geddis C, Clarke SA, Jordan GR, Dickson GR, Marsh D (2007) Effect of osteoporosis on bone mineral density and fracture repair in a rat femoral fracture model. J Orthop Res. [PubMed]

34. Meril AJ. Direct current stimulation of allograft in anterior and posterior lumbar interbody fusions. Spine. 1994;19:2393–2398. doi: 10.1097/00007632-199411000-00004. [PubMed] [Cross Ref]

35. Miller PD, Bonnick SL, Rosen CJ. Consensus of an international panel on the clinical utility of bone mass measurements in the detection of low bone mass in the adult population. Calcif Tissue Int. 1996;58:207–214. [PubMed]

36. Okuda S, Oda T, Miyauchi A, Haku T, Yamamoto T, Iwasaki M. Surgical outcomes of posterior lumbar interbody fusion in elderly patients. J Bone Joint Surg Am. 2006;88:2714–2720. doi: 10.2106/JBJS.F.00186. [PubMed] [Cross Ref]

37. Okuyama K, Abe E, Suzuki T, Tamura Y, Chiba M, Sato K. Influence of bone mineral density on pedicle screw fixation: a study of pedicle screw fixation augmenting posterior lumbar interbody fusion in elderly patients. Spine J. 2001;1:402–407. doi: 10.1016/S1529-9430(01)00078-X. [PubMed] [Cross Ref]

38. Rapuri PB, Gallagher JC, Balhorn KE, Ryschon KL. Smoking and bone metabolism in elderly women. Bone. 2000;27:429–436. doi: 10.1016/S8756-3282(00)00341-0. [PubMed] [Cross Ref]

39. Rogozinski A, Rogozinski C. Efficacy of implanted bone growth stimulation in instrumented lumbosacral spinal fusion. Spine. 1996;21:2479–2483. doi: 10.1097/00007632-199611010-00014. [PubMed] [Cross Ref]

40. Seeman E. The growth and age-related origins of bone fragility in men. Calcif Tissue Int. 2004;75:100–109. [PubMed]

41. Tejano NA, Puno R, Ignacio JM. The use of implantable direct current stimulation in multilevel spinal fusion without instrumentation. A prospective clinical and radiographic evaluation with long-term follow-up. Spine. 1996;21:1904–1908. doi: 10.1097/00007632-199608150-00015. [PubMed] [Cross Ref]

42. Ware JE., Jr SF-36 health survey update. Spine. 2000;25:3130–3139. doi: 10.1097/00007632-200012150-00008. [PubMed] [Cross Ref]

43. Yingjie H, Ge Z, Yisheng W, Ling Q, Hung WY, Kwoksui L, Fuxing P. Changes of microstructure and mineralized tissue in the middle and late phase of osteoporotic fracture healing in rats. Bone. 2007;41:631–638. doi: 10.1016/j.bone.2007.06.006. [PubMed] [Cross Ref]

Articles from European Spine Journal are provided here courtesy of
Springer-Verlag