Patterns of Lumbar Disc Degeneration: Magnetic Resonance Imaging Analysis in Symptomatic Subjects

Study Design: Cross-sectional study. Purpose: To evaluate lumbar disc degeneration (LDD) on magnetic resonance imaging (MRI) in symptomatic subjects to accumulate baseline data on the pattern of degeneration. Overview of Literature: LDD plays an important role in the diagnosis and treatment of low-back pain in patients. Few studies have focused on the pattern of LDD to understand how the lumbar spine ages. Methods: This study included 1,095 patients (mean age, 44.29 years; range, 16–85 years) who underwent upright lumbar MRI. LDD was graded into five categories (I–V). Positive LDD was defined as grade III or greater. The prevalence and pattern of LDD were ana-lyzed, and the correlations between age and total grade of LDD were evaluated. Results: The average number of LDD levels and the total grade of LDD increased with age. LDD moved cephalad with age. The rate of LDD increased rapidly during the decade before the prevalence of LDD and became \u3e 50%. In the single-level LDD group, the levels L5–S1 were the most common levels (60.3%). In the two-level group, L4–L5 and L5–S1 were the most common levels (53.5%). In the three-level group, L3–L4, L4–L5, and L5–S1 were the most common levels (55.7%). In the multilevel LDD group, contiguous multilevel disc degeneration (CMDD) was more common than the skipped level disc degeneration (SLDD). The levels L4–L5 were the most com-mon levels in the CMDD group, and L5–S1 were the most common levels among SLDD. Conclusions: LDD was found to correlate with age, and the specific patterns and rates of LDD depended on lumbar disc level and age. These LDD pattern data can be used before spinal procedures to predict the probability of natural LDD progression with age

Secreted Phosphoprotein 24 kD (Spp24) and Spp14 Affect TGF-β Induced Bone Formation Differently

Transforming growth factor-β (TGF-β) and bone morphogenetic proteins (BMPs) have opposing but complementary functions in directing bone growth, repair, and turnover. Both are found in the bone matrix. Proteins that bind to and affect the activity of these growth factors will determine the relative abundance of the growth factors and, therefore, regulate bone formation. Secreted phosphoprotein 24 kD (Spp24) is a bone matrix protein that has been demonstrated to bind to and affect the activity of BMPs. The arginine-rich carboxy terminus of Spp24 is proteolytically processed to produce three other predictable truncation products (Spp18.1, Spp16.0, and Spp14.5). In this work, we report that kinetic data obtained by surface plasmon resonance demonstrate that Spp24 and the three C-terminal truncation products all bind to TGF-β1 and TGF-β2 with a similar but somewhat less affinity than they bind BMP-2; that, as in the case of BMP-2, the full-length (FL) form of Spp24 binds TGF-β with greater affinity than do the truncation products; that FL-Spp24 inhibits TGF-β2 induced bone formation in vivo, but Spp14.5 does not; and that co-administration of FL-Spp24 or Spp14.5 with TGF-β2 in vivo is associated with a reduction in the amount of cartilage, relative to new bone, present at the site of injection. This finding is consistent with the observation that low-dose TGF-β administration in vivo is associated with greater bone formation than high-dose TGF-β administration, and suggests that one function of Spp24 and its truncation products is to down-regulate local TGF-β activity or availability during bone growth and development. The similarities and differences of the interactions between Spp24 proteins and TGF-β compared to the interaction of the Spp24 proteins and BMPs have significant implications with respect to the regulation of bone metabolism and with respect to engineering therapeutic proteins for skeletal disorders. © 2013 Tian et al

Bone Morphogenetic Protein-2 Promotes Osteosarcoma Growth by Promoting Epithelial-Mesenchymal Transition (EMT) Through the Wnt/b-Catenin Signaling Pathway

The correlation between BMP-2 and osteosarcoma growth has gained increased interest in the recent years, however, there is still no consensus. In this study, we tested the effects of BMP-2 on osteosarcoma cells through both in vitro and in vivo experiments. The effect of BMP-2 on the proliferation, migration and invasion of osteosarcoma cells was tested in vitro. Subcutaneous and intratibial tumor models were used for the in vivo experiments in nude mice. The effects of BMP-2 on EMT of osteosarcoma cells and the Wnt/β-catenin signaling pathway were also tested using a variety of biochemical methods. In vitro tests did not show a significant effect of BMP-2 on tumor cell proliferation. However, BMP-2 increased the mobility of tumor cells and the invasion assay demonstrated that BMP-2 promoted invasion of osteosarcoma cells in vitro. In vivo animal study showed that BMP-2 dramatically enhanced tumor growth. We also found that BMP-2 induced EMT of osteosarcoma cells. The expression levels of Axin2 and Dkk-1 were both down regulated by BMP-2 treatment, while β-catenin, c-myc and Cyclin-D1 were all upregulated. The expression of Wnt3α and p-GSK-3β were also significantly upregulated indicating that the Wnt/β-catenin signaling pathway was activated during the EMT of osteosarcoma driven by BMP-2. From this study, we can conclude that BMP-2 significantly promotes growth of osteosarcoma cells (143B, MG63), and enhances mobility and invasiveness of tumor cells as demonstrated in vitro. The underlying mechanism might be that BMP-2 promotes EMT of osteosarcoma through the Wnt/β-catenin signaling pathway. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1638–1648, 2019. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc

Minimizing Blood Loss in Spine Surgery.

Study Design: Broad narrative review. Objective: To review and summarize the current literature on guidelines, outcomes, techniques and indications surrounding multiple modalities of minimizing blood loss in spine surgery. Methods: A thorough review of peer-reviewed literature was performed on the guidelines, outcomes, techniques, and indications for multiple modalities of minimizing blood loss in spine surgery. Results: There is a large body of literature that provides a consensus on guidelines regarding the appropriate timing of discontinuation of anticoagulation, aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and herbal supplements prior to surgery. Additionally, there is a more heterogenous discussion the utility of preoperative autologous blood donation facilitated by erythropoietin and iron supplementation for healthy patients slated for procedures with high anticipated blood loss and for whom allogeneic transfusion is likely. Intraoperative maneuvers available to minimize blood loss include positioning and maintaining normothermia. Tranexamic acid (TXA), bipolar sealer electrocautery, and topical hemostatic agents, and hypotensive anesthesia (mean arterial pressure (MAP)Hg) should be strongly considered in cases with larger exposures and higher anticipated blood loss. There is strong level 1 evidence for the use of TXA in spine surgery as it reduces the overall blood loss and transfusion requirements. Conclusion: As the volume and complexity of spinal procedures rise, intraoperative blood loss management has become a pivotal topic of research within the field. There are many tools for minimizing blood loss in patients undergoing spine surgery. The current literature supports combining techniques to use a cost- effective multimodal approach to minimize blood loss in the perioperative period

Patterns of Cervical Disc Degeneration: Analysis of Magnetic Resonance Imaging of Over 1000 Symptomatic Subjects

The aim of this study was to evaluate cervical disc degeneration on magnetic resonance imaging (MRI) in a large population of symptomatic patients and to provide baseline data on the pattern of degeneration in order to understand how the cervical spine ages. Methods: We performed a cross-sectional study of 1059 patients who underwent upright cervical MRI for neck pain with and without neurological symptoms. A total of 6354 cervical discs from C2/3 to C7/TI were evaluated. Cervical disc degeneration was evaluated on T2-weighted MRI and graded into 4 categories (Grades 0-111). Positive degeneration was defined as greater than Grade II. The correlation between age and total grade of degeneration of each patient was evaluated, as well as the prevalence and pattern of degeneration. Results: The average number of degenerated disc levels and the total grade of cervical disc degeneration significantly increase with age. In the patient group with 1-level degeneration, C5/6 was the most common degenerated level followed by C4/5 and C6/7. In the group with 2-level degeneration, C5/6 & C6/7 was most common followed by C4/5 & C5/6 and C3/4 & C4/5. Skip level degeneration was significantly rarer than contiguous level degeneration, and C7/TI and C2/3 were the most unlikely to degenerate in multilevel degeneration. Conclusion: Disc degeneration is most common in the middle cervical spine (C516) and progresses to contiguous levels, except for C7/TI and C2/3. This pattern may play a role in adjacent-level disc degeneration associated with spinal fusion

Secreted phosphoprotein 24 kD (Spp24) and Spp14 affect TGF-β induced bone formation differently.

Transforming growth factor-β (TGF-β) and bone morphogenetic proteins (BMPs) have opposing but complementary functions in directing bone growth, repair, and turnover. Both are found in the bone matrix. Proteins that bind to and affect the activity of these growth factors will determine the relative abundance of the growth factors and, therefore, regulate bone formation. Secreted phosphoprotein 24 kD (Spp24) is a bone matrix protein that has been demonstrated to bind to and affect the activity of BMPs. The arginine-rich carboxy terminus of Spp24 is proteolytically processed to produce three other predictable truncation products (Spp18.1, Spp16.0, and Spp14.5). In this work, we report that kinetic data obtained by surface plasmon resonance demonstrate that Spp24 and the three C-terminal truncation products all bind to TGF-β1 and TGF-β2 with a similar but somewhat less affinity than they bind BMP-2; that, as in the case of BMP-2, the full-length (FL) form of Spp24 binds TGF-β with greater affinity than do the truncation products; that FL-Spp24 inhibits TGF-β2 induced bone formation in vivo, but Spp14.5 does not; and that co-administration of FL-Spp24 or Spp14.5 with TGF-β2 in vivo is associated with a reduction in the amount of cartilage, relative to new bone, present at the site of injection. This finding is consistent with the observation that low-dose TGF-β administration in vivo is associated with greater bone formation than high-dose TGF-β administration, and suggests that one function of Spp24 and its truncation products is to down-regulate local TGF-β activity or availability during bone growth and development. The similarities and differences of the interactions between Spp24 proteins and TGF-β compared to the interaction of the Spp24 proteins and BMPs have significant implications with respect to the regulation of bone metabolism and with respect to engineering therapeutic proteins for skeletal disorders

Sensogram from the surface plasmon resonance analysis of the interaction between TGF-β1, β2 and different Spps.

<p>The response (RU or response units) is plotted on the Y-axis, while time (seconds) is plotted on the X-axis.</p