Postero-lateral fusion was graded using Lenke's criteria. A detailed description of the criteria is available in their original work. They divide postero lateral fusion mass into 4 grades based on the appearance in an AP radiograph. Grade A represents definitive fusion with bilateral thick bony masses, Grade B represents probable fusion with unilateral thick bony mass and thin bony mass on other side, Grade C represents no probable fusion with thin bony mass on the one side and pseudo-arthrosis on the other side, Grade D represents no fusion with thin bony mass on both the sides showing obvious pseudo-arthrosis or resorption of graft bilaterally.
We interpreted Grade 1 and Grade 2 of Lenke's criteria as solid fusion which is explained as unilateral or bilateral bridging bone formation across the transverse process of adjacent vertebra showing continuous trabeculation in an AP radiograph. Grade 3 and 4 will be interpreted as nonunion. Although most of the patients had long fixations, segmental cobb's angle change involving the upper and lower ends of the construct as seen in dynamic (flexion and extension) stress lateral views will also be considered as nonunion. Screw loosening was determined when there was occurrence of radiolucency (Halo sign) around the pedicle screws in either AP or lateral view radiographs. Change in the screw position noticed in dynamic stress lateral view radiographs will additionally be considered as screw loosening, which may occur at the cephalic and caudal ends of the construct.
Evaluation of radiographs were blinded and performed by 3 surgeons. Their observations were taken only if at least 2 of them concurred. Results were tabulated and statistical analyses were carried out using Graph Pad Prism 5 (GraphPad Software Inc., San Diego, CA). Analyses were done using Unpaired T test for continuous variables and Fisher's exact test for categorical variables. Probability values of less than 0.05 were considered statistically significant. Written informed consent was obtained from all patients including acceptance of daily usage of teriparatide delivery device from those in the experimental group. This study was approved by the institutional review board of Chang Gung Memorial Hospital with IRB Registry No - 201600800B0 and was performed in accordance with the ethical standards stated in the most recent version of the 1964 Declaration of Helsinki.
Sixty-two elderly patients (age = 65–78 years; mean = 70.11 years; male = 9, female = 53) are divided into 2 groups based on teriparatide administration following surgery. Group 1 or the experimental group (n = 30; mean age ± SD = 69.8 ± 3.8 years) was those in whom teriparatide was administered and Group 2 (n = 32; mean age ± SD = 70.4 ± 3.6 years) was the control group. Mean age and sex ratio in the groups are similar (Table 1). Considering their age, patients in both groups are presumed to have poor BMD. The presence of concomitant medical comorbidities in Group 1 (DM = 14; BA = 4) and Group 2 (DM = 11; BA = 4) was matched. The demographic variation in characteristics of the groups is statistically insignificant (Table 1).
Surgical parameters of the experimental group (fusion levels = 137; pedicle screws = 269) and the control group (fusion levels = 144; pedicle screws = 283) had no statistically significant variance. Duration of teriparatide administration averaged 7.4 ± 2.4 months in the experimental group. Follow-up data were available for a mean duration of 25.4 months for those in the experimental group and 27 months for those in the control group. Even though follow-up was done for a longer duration, analyzing outcome further after 1 year may not be related to teriparatide use. Considering the duration of administration of teriparatide, radiological outcome analysis was decided to be done at 1 year follow-up. None of our patients missed the 1st year follow-up and required x-rays were available in our database for all the patients.
Radiological outcome analysis was done using AP, lateral, and dynamic stress lateral view radiographs taken at 12 months follow-up. Two or more observers concurred stating that there was unilateral or bilateral bridging bone formation across the transverse process of adjacent vertebras showing continuous trabeculation confirming solid fusion in 20 patients (66.7%) of the teriparatide group and 16 patients (50%) in the control group. Nonunion was noted in 10 patients (33.3%) of teriparatide group and 16 patients (50%) in the control group. The 16.7% advantage procured with teriparatide use was not statistically significant (P = 0.20) (Table 2). Screw loosening was calculated comparing the number of screws showing signs of loosening to total number of screws in each group. The incidence of screw loosening was 13.4% in the teriparatide group and 24.4% in the control group. This difference was statistically significant with P = 0.001 (Table 2).
Elderly patients with chronic unresolving symptoms due to degenerative spine disease are prone to have poor surgical outcomes. They also predispose for more hardware-related complications, especially following long spinal fusions. Considering the possibility of poor outcomes, treating these conditions cannot be ignored but rather a potential solution needs to be developed which effectively supplements the mainstay surgical management. Teriparatide seemed to be a promising solution for this difficult problem. It is said to play a reasonable role in treatment of osteoporosis.[1–4] Apart from being used in osteoporotic individuals, insights into its action on many other conditions are unraveling. Animal studies yielded promising results for teriparatide usage to enhance postero-lateral fusion mass in rat models. In human studies relating to teriparatide, most authors studied its effect only in osteoporotic individuals.[10,11] In our sample, patients were between 65 and 78 years of age and are more susceptible to have poor BMD. Patients had comorbidities such as DM and bronchial asthma that have negative influence over BMD.[14–16] DM is said to reduce BMD at a higher rate in elderly women, even if the baseline BMD was high. Patients with bronchial asthma are also prone to have reduced BMD.
All available potentially confounding variables were matched among both the groups of our sample. We followed similar standardized surgical technique of posterolateral fusion and instrumentation. Along with postero-lateral fusion, additional interbody cages were used especially at very insufficient discs often seen in the caudal end of the construct. Thorough decortication of transverse process was done before placing the graft. This promotes fusion by exposing the underlying cancellous bone rich in vascular supply. This step also allows the graft to access the pluripotent stem cells of the bone marrow. Since a large amount of graft is required for long fusions, there usually is a lack of host bone. We preferred fresh frozen allografts along with local bone chips for this purpose. These allografts can yield greater quantity of bone that gets completely incorporated. Donor site morbidity can be significantly overcome by using allografts. Teriparatide could be a supplement for enhancing osteogenesis and bio-integration of allografts.
Static and dynamic radiographs are used for radiological assessment of spinal fusion by many authors, but computerized tomography (CT) is considered more accurate. Most of the radiographic criteria developed to assess fusion mass consider movement in dynamic radiographs as a main component for assessment. Dynamic radiographs include flexion and extension lateral views. They lack reliability as the absence of motion does not confirm fusion, especially in the case of long instrumented levels. Based on AP radiographs, we considered Grade A (definitive fusion; bilateral thick bony mass) and Grade B (probable fusion; unilateral thick bony mass) described by Lenke et al as solid fusion. Fusion masses that did not favorably appear to have definitive or probable fusion were considered as nonunion. We also considered change in segmental Cobb's angle, visualized in dynamic stress lateral view radiographs as an additional criterion to interpret as nonunion. Formation of a radiolucent zone (halo sign) around the pedicle screws seen in conventional AP/lateral view radiographs and change in screw position seen in dynamic stress lateral view radiographs were considered definitive indicators for screw loosening.
Being a retrospective study, there are few methodological shortcomings that may have influenced our outcome. The lack of preoperative BMD data, variation in surgical indications, and differential treatment durations of teriparatide administration may have biased the sample. Use of CT as an evaluation tool to assess bone graft union could have been more empirical. Considering the selected sample size, the study may be underpowered to draw potential conclusions. These limitations need to be considered and results be interpreted with caution.
. Kleerekoper M, Greenspan SL, Lewiecki EM, et al. Assessing the effects of teriparatide
treatment on bone mineral density bone microarchitecture, and bone strength. J Bone Joint Surg Am 2014;96:e90.
. Ma YL, Zeng Q, Donley DW, et al. Teriparatide
increases bone formation in modeling and remodelling osteons and enhances IGF-II immunoreactivity in postmenopausal women with osteoporosis. J Bone Miner Res 2006;21:855–64.
. Jiang Y, Zhao JJ, Mitlak BH, et al. Recombinant human parathyroid hormone (1-34) [teriparatide
] improves both cortical and cancellous bone structure. J Bone Miner Res 2003;18:1932–41.
. Chen P, Satterwhite JH, Licata AA, et al. Early changes in biochemical markers of bone formation predict BMD response to teriparatide
in postmenopausal women with osteoporosis. J Bone Miner Res 2005;20:962–70.
. Hodsman AB, Bauer DC, Dempster DW, et al. Parathyroid hormone and teriparatide
for the treatment of osteoporosis: a review of the evidence and suggested guidelines for its use. Endocr Rev 2005;26:688–703.
. Cheng ML, Gupta V. Teriparatide
—indications beyond osteoporosis. Indian J Endocrinol Metab 2012;16:343–8.
. Bhandari M, Jin L, See K, et al. Does teriparatide
improve femoral neck fracture healing: results from a randomized placebo-controlled trial. Clin Orthop Relat Res 2016;474:1234–44.
. Takahata M, Schwarz EM, Chen T, et al. Delayed short course treatment with teriparatide
(PTH1-34) improves femoral allograft healing by enhancing intramembranous bone formation at the graft-host junction. J Bone Miner Res 2012;27:26–37.
. Kuchler U, Luvizuto ER, Tangl S, et al. Short-term teriparatide
delivery and osseointegration: a clinical feasibility study. J Dent Res 2011;90:1001–6.
. Ohtori S, Inoue G, Orita S, et al. Teriparatide
accelerates lumbar posterolateral fusion
in women with postmenopausal osteoporosis: prospective study. Spine (Phila Pa 1976) 2012;37:E1464–1468.
. Ohtori S, Inoue G, Orita S, et al. Comparison of teriparatide
and bisphosphonate treatment to reduce pedicle screw loosening
after lumbar spinal fusion surgery in postmenopausal women with osteoporosis from a bone quality perspective. Spine (Phila Pa 1976) 2013;38:E487–92.
. Lenke LG, Bridwell KH, Bullis D, et al. Results of in situ fusion for isthmic spondylolisthesis. J Spinal Disord 1992;5:433–42.
. Sugiura T, Kashii M, Matsuo Y, et al. Intermittent administration of teriparatide
enhances graft bone healing and accelerates spinal fusion in rats with glucocorticoid-induced osteoporosis. Spine J 2015;15:298–306.
. Schwartz AV, Ewing SK, Porzig AM, et al. Diabetes and change in bone mineral density at the hip, calcaneus, spine, and radius in older women. Front Endocrinol (Lausanne) 2013;00062doi: 10. 3389/fendo. 2013.
. Katsura H, Kida K. A comparison of bone mineral density in elderly female patients with COPD and bronchial asthma. Chest 2002;122:1949–55.
. Slappey G, Toribatake Y, Ganey TM, et al. Guidelines to decortication in posterolateral spine fusion. J Spinal Disord 1998;11:102–9.
. Dhillon RS, Schwarz EM. Teriparatide
therapy as an adjuvant for tissue engineering and integration of biomaterials. J Mater Res 2011;4:1117–31.
. Brodsky AE, Kovalsky ES, Khalil MA. Correlation of radiologic assessment of lumbar spine fusions with surgical exploration. Spine (Phila Pa 1976) 1991;16:S261–5.
. Lee CK, Vessa P, Lee JK. Chronic disabling low back pain syndrome caused by internal disc derangements. The results of disc excision and posterior lumbar interbody fusion. Spine (Phila Pa 1976) 1995;20:356–61.
. Selby MD, Clark SR, Hall DJ, et al. Radiologic assessment of spinal fusion. J Am Acad Orthop Surg 2012;20:694–703.
. Sandén B, Olerud C, Petrén-Mallmin M, et al. The significance of radiolucent zones surrounding pedicle screws. Definition of screw loosening
in spinal instrumentation. J Bone Joint Surg Br 2004;86:457–61.
. Inoue G, Ueno M, Nakazawa T, et al. Teriparatide
increases the insertional torque of pedicle screws during fusion surgery in patients with postmenopausal osteoporosis. J Neurosurg Spine 2014;21:425–31.
. Graeff C, Timm W, Nickelsen TN, et al. EUROFORS High Resolution Computed Tomography Substudy Group. Monitoring teriparatide
-associated changes in vertebral microstructure by high-resolution CT in vivo: results from the EUROFORS study. J Bone Miner Res 2007;22:1426–33.
. Ohtori S, Orita S, Yamauchi K, et al. More than 6 months of teriparatide
treatment was more effective for bone union than shorter treatment following lumbar posterolateral fusion
surgery. Asian Spine J 2015;9:573–80.