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BACKGROUND CONTEXT: Bone morphogenetic proteins (BMPs) have potent osteoinductivity and have been applied clinically for challenging musculoskeletal conditions. However, the supraphysiological doses of BMPs used in clinical settings cause various side effects that prevent widespread use, and therefore the BMP dosage needs to be reduced. PURPOSE: To address this problem, we synthesized 7C, a retinoic acid receptor γ antagonist-loaded nanoparticle (NP), and investigated its potential application in BMP-based bone regeneration therapy using a rat spinal fusion model. STUDY DESIGN: An experimental animal study. METHODS: Fifty-three male 8-week-old Sprague-Dawley rats underwent posterolateral spinal fusion and were divided into the following five treatment groups: (1) no recombinant human (rh)BMP-2 and blank-NP (Control), (2) no rhBMP-2 and 1 µg 7C-NP (7C group), (3) low-dose rhBMP-2 (0.5 µg) and 1 µg blank-NP (L-BMP group), (4) low-dose rhBMP-2 (0.5 µg) and 1 µg 7C-NP (L-BMP + 7C group), and (5) high-dose rhBMP-2 (5.0 µg) and 1 µg blank-NP (H-BMP group). Micro-computed tomography and histologic analysis were performed 2 and 6 weeks after the surgery. RESULTS: The spinal fusion rates of the Control and 7C groups were both 0%, and those of the L-BMP, L-BMP + 7C, and H-BMP groups were 55.6%, 94.4%, and 100%, respectively. The L-BMP + 7C group markedly promoted cartilaginous tissue formation during BMP-induced endochondral bone formation that resulted in a significantly better spinal fusion rate and bone formation than in the L-BMP group. Although spinal fusion was slower in the L-BMP + 7C group, the L-BMP + 7C group formed a spinal fusion mass with better bone quality than the spinal fusion mass in the H-BMP group. CONCLUSIONS: The combined use of 7C-NP with rhBMP-2 in a rat posterolateral lumbar fusion model increased spinal fusion rate and new bone volume without deteriorating the quality of newly formed bone. CLINICAL SIGNIFICANCE: 7C-NP potentiates BMP-2-induced bone regeneration and has the potential for efficient bone regeneration with low-dose BMP-2, which can reduce the dose-dependent side effects of BMP-2 in clinical settings.
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Ossification of the posterior longitudinal ligament (OPLL) is a heterotopic ossification that may cause spinal cord compression. With the recent development of computed tomography (CT) imaging, it is known that patients with OPLL often have complications related to ossification of other spinal ligaments, and OPLL is now considered part of ossification of the spinal ligaments (OSL). OSL is known to be a multifactorial disease with associated genetic and environmental factors, but its pathophysiology has not been clearly elucidated. To elucidate the pathophysiology of OSL and develop novel therapeutic strategies, clinically relevant and validated animal models are needed. In this review, we focus on animal models that have been reported to date and discuss their pathophysiology and clinical relevance. The purpose of this review is to summarize the usefulness and problems of existing animal models and to help further the development of basic research on OSL.
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OBJECTIVE: Although several reports have described adjacent-segment disease (ASD) after posterior lumbar interbody fusion (PLIF), there have been only a few reports focusing on early-onset ASD occurring within 3 years after primary PLIF. The purpose of this study was to investigate the prevalence and postoperative pathologies of early-onset ASD and its relation with radiological parameters such as segmental lordosis (SL). METHODS: The authors reviewed a total of 256 patients who underwent single-segment PLIF at L4-5 for degenerative lumbar spondylolisthesis (DLS) and were followed up for at least 5 years. The definition of ASD was a symptomatic condition requiring an additional operation at the adjacent fusion segment in patients who had undergone PLIF. ASD occurring within 3 years after primary PLIF was categorized as early-onset ASD. As a control group, 54 age- and sex-matched patients who had not suffered from ASD for more than 10 years were selected from this series. RESULTS: There were 42 patients with ASD at the final follow-up. ASD prevalence rates at 3, 5, and 10 years postoperatively and at the final follow-up were 5.0%, 8.2%, 14.1%, and 16.4%, respectively. With respect to ASD pathologies, lumbar disc herniation (LDH) was significantly more common in early-onset ASD, while lumbar spinal stenosis and DLS occurred more frequently in late-onset ASD. Significant differences were detected in the overall postoperative range of motion (ROM) and in the changes in ROM (ΔROM) at L3-4 (the cranial adjacent fusion segment) and changes in SL (ΔSL) at L4-5 (the fused segment), while there were no significant differences in other pre- and postoperative parameters. In stepwise logistic regression analysis, ΔSL was identified as an independent variable (p = 0.008) that demonstrated significant differences, especially in early-onset ASD (control 1.1° vs overall ASD -2.4°, p = 0.002; control 1.1° vs early-onset ASD -6.6°, p = 0.00004). CONCLUSIONS: The study results indicated that LDH was significantly more common as a pathology in early-onset ASD and that ΔSL was a major risk factor for ASD, especially early-onset ASD.
