Object: The object of this study was to examine the efficacy of preoperative teriparatide treatment for increasing the insertional torque of pedicle screws during fusion surgery in postmenopausal women with osteoporosis. Methods: Fusion surgery for the thoracic and/or lumbar spine was performed in 29 postmenopausal women with osteoporosis aged 65–82 years (mean 72.2 years). The patients were divided into 2 groups based on whether they were treated with teriparatide (n = 13) or not (n = 16) before the surgery. In the teriparatide-treated group, patients received preoperative teriparatide therapy as either a daily (20 μg/day, n = 7) or a weekly (56.5 μg/week, n = 6) injection for a mean of 61.4 days and a minimum of 31 days. During surgery, the insertional torque was measured in 212 screws inserted from T-7 to L-5 and compared between the 2 groups. The correlation between the insertional torque and the duration of preoperative teriparatide treatment was also investigated. Results: The mean insertional torque value in the teriparatide group was 1.28 ± 0.42 Nm, which was significantly higher than in the control group (1.08 ± 0.52 Nm, p < 0.01). There was no significant difference between the daily and the weekly teriparatide groups with respect to mean insertional torque value (1.34 ± 0.50 Nm and 1.18 ± 0.43 Nm, respectively, p = 0.07). There was negligible correlation between insertional torque and duration of preoperative teriparatide treatment (r² = 0.05, p < 0.01). Conclusions: Teriparatide injections beginning at least 1 month prior to surgery were effective in increasing the insertional torque of pedicle screws during surgery in patients with postmenopausal osteoporosis. Preoperative teriparatide treatment might be an option for maximizing the purchase of the pedicle screws to the bone at the time of fusion surgery.

Research suggests that vascular endothelial growth factor (VEGF) levels in the synovial fluid of knee osteoarthritis (KOA) patients are positively correlated with KOA severity. The relationship between synovial VEGF levels and pain in human KOA patients is not fully understood, and the role of VEGF in the pain pathway remains unclear. We harvested synovial membrane (SM) from 102 patients with radiographic evidence of KOA (unilateral Kellgren/Lawrence [K/L] grade 2–4) during total knee arthroplasty. Patients scored their pain on a 0 to 10 cm visual analog scale (VAS). VEGF levels in the SM of KOA patients with strong/severe (VAS ≥ 6) and mild/moderate pain (VAS < 6) were compared. Correlations between VAS and VEGF mRNA expression were investigated. To investigate a possible mechanism for VEGF-induced pain, the distribution of VEGF and the neuropeptide apelin was determined by immunohistochemical analyses. To investigate the role of VEGF in regulating apelin expression, SM cells were exposed to VEGF. VEGF expression in the VAS ≥ 6 group was significantly greater than expression in the VAS < 6 group. Expression levels of VEGF were also positively correlated with VAS. VEGF-positive cells were identified in the lining of the SM. Expression of apelin mRNA and protein were significantly elevated in SM cells treated with exogenous VEGF compared to those treated with vehicle. Synovial VEGF may be involved in pain pathways in KOA and its action may be mediated by apelin.

Chronic inflammation with aging contributes to sarcopenia. Previous studies have suggested that the accumulation of adipose tissue in skeletal muscle, referred to as intermuscular adipose tissue (IMAT), increases with age and is associated with inflammation. However, the mechanism governing ectopic inflammation in skeletal muscle due to aging is not fully understood. Leptin, an adipocytokine derived from adipose tissue, is an important mediator of inflammatory processes. We examined changes in leptin levels with age and whether leptin contributes to ectopic inflammation. To evaluate ectopic inflammation in skeletal muscle, we measured alterations to the expression of inflammatory cytokine genes (Il1b, Il6, and Tnfa) and muscle break down-related gene (MuRF1 and Atrogin1) in the quadricep muscles of young (10 weeks) and aged (48 weeks) female rats using quantitative reverse-transcription polymerase chain reaction (Q-RT-PCR). Histological examination was performed to identify the extent of IMAT. Leptin mRNA and leptin protein expression were examined using Q-RT-PCR and enzyme-linked immunosorbent assay, respectively. The effect of leptin on the mRNA expression of Il1b, Il6, and Tnfa in quadricep muscle-derived cells was also examined by stimulating the cells with 0 (control), 1, or 10 μg/mL rat recombinant leptin using Q-RT-PCR. Aged rats had significantly higher Il6, MuRF1, and Atrogin1 but not Il1b and Tnfa, expression and greater levels of IMAT in their quadricep muscles than young rats. Aged rats also had significantly higher leptin expression and leptin protein concentration in their quadricep muscles than young rats. The addition of exogenous leptin to quadricep muscle-derived cells significantly increased the gene expression of Il1b and Il6 but not Tnfa. Our results suggest that elevated leptin levels due to aging cause ectopic inflammation through IL-6 in the skeletal muscle of aged rats.

Nerve growth factor (NGF) is not only an important factor in nerve growth but also a major contributor to the production of inflammation. It has been reported that inhibiting NGF could reduce several types of pain in several animal models. Here, we aimed to clarify the efficacy of NGF antibody in a knee osteoarthritis (OA) pain model in mice. Six-week-old male C57BR/J mice were used (n = 30). Ten mice comprised the control group, which received saline injection into the right knee joints; the other 20 mice comprised the experimental group, which received monoiodoacetate (MIA) injection into the right knee joints. Three weeks after surgery, the 20 experimental mice were randomly placed into treatment groups which received either sterile saline (non-treat group: 10 mg/kg, i.p.) or an anti-NGF antibody (anti-NGF group: 10 mg/kg, i.p.). Simultaneously, all mice received fluorogold (FG) retrograde neurotracer injection into their right joints. In a behavioral study, we evaluated gait using the CatWalk quantitative gait analysis system before surgery, 3 weeks after surgery (before treatment), 4 weeks after surgery (one week after surgery), and 5 weeks after surgery (2 weeks after surgery). In immunohistochemical analysis, the right dorsal root ganglia (DRGs) from the L4–L6 levels were resected 5 weeks after surgery (2 weeks after surgery). They were immunostained for calcitonin gene-related peptide (CGRP), and the number of FG-labeled or CGRP-immunoreactive (IR) DRG neurons was counted. On gait analysis using the CatWalk system, duty cycle, swing speed, and print area were decreased in non-treat group compared with those in control group and improved in the anti-NGF group compared with those in non-treat group. CGRP expression in DRGs was up-regulated in non-treat group compared with that in control group and suppressed in the anti-NGF group compared with that in non-treat group (both p < 0.05). MIA injection into the knee joint induced gait impairment and the up-regulation of CGRP in DRG neurons in a knee OA pain model in mice. Intraperitoneal injection of anti-NGF antibody suppressed this impairment of gait and up-regulation of CGRP in DRG neurons. These finding suggest that anti-NGF therapy might be valuable in the treatment of OA pain in the knee.

Corrective surgery for kyphoscoliosis patients tend to be highly invasive due to osteotomy. The present case introduce less invasive corrective surgery using anterior oblique lateral interbody fusion (OLIF) technique. An 80-year-old Japanese man with a history of Parkinson’s disease presented to our hospital because of severe kyphoscoliosis and gait disturbance. Considering the postsurgical complications due to osteotomy, we performed an anterior-posterior combined corrective fusion surgery: OLIF of Lumbar (L) 2-3, L3-4, and L4-5 (Medtronic Sofamor Danek, Memphis, TN, USA) followed by L5-Sacral (S) 1 anterior lumbar fusion via the OLIF approach using an anterior intervertebral cage, and posterior L3-4 and L4-5 facetectomy and posterior fusion using percutaneous pedicle screws from Thoracic (T) 10 to S1 with a T-9 hook system. The surgery was performed in a less invasive manner with no osteotomy, and it improved the sagittal alignments with moderate restoration, which improved the patient’s posture and gait disturbance. The patient showed transient muscle weakness of proximal lower extremity contralateral side to the surgical site, which fully recovered by physical rehabilitation 3 months after the surgery. The surgical corrective procedure using the minimally invasive OLIF method including L5-S1 fusion showed a great advantage in treating degenerative kyphoscoliosis in a Parkinson’s disease patient in its less-invasive approac.

Basic fibroblast growth factor 2 (bFGF) accelerates bone formation during fracture healing. Because the efficacy of bFGF decreases rapidly following its diffusion from fracture sites, however, repeated dosing is required to ensure a sustained therapeutic effect. We previously developed a fusion protein comprising bFGF, a polycystic kidney disease domain (PKD; s2b), and collagen-binding domain (CBD; s3) sourced from the Clostridium histolyticum class II collagenase, ColH, and reported that the combination of this fusion protein with a collagen-like peptide, poly(Pro-Hyp-Gly)₁₀, induced mesenchymal cell proliferation and callus formation at fracture sites. In addition, C. histolyticum produces class I collagenase (ColG) with tandem CBDs (s3a and s3b) at the C-terminus. We therefore hypothesized that a bFGF fusion protein containing ColG-derived tandem CBDs (s3a and s3b) would show enhanced collagen-binding activity, leading to improved bone formation. Here, we examined the binding affinity of four collagen anchors derived from the two clostridial collagenases to H-Gly-Pro-Arg-Gly-(Pro-Hyp-Gly)₁₂-NH₂, a collagenous peptide, by surface plasmon resonance and found that tandem CBDs (s3a-s3b) have the highest affinity for the collagenous peptide. We also constructed four fusion proteins consisting of bFGF and s3 (bFGF-s3), s2b-s3b (bFGF-s2b-s3), s3b (bFGF-s3b), and s3a-s3b (bFGF-s3a-s3b) and compared their biological activities to those of a previous fusion construct (bFGF-s2b-s3) using a cell proliferation assay in vitro and a mouse femoral fracture model in vivo. Among these CB-bFGFs, bFGF-s3a-s3b showed the highest capacity to induce mesenchymal cell proliferation and callus formation in the mice fracture model. The poly(Pro-Hyp-Gly)₁₀/bFGF-s3a-s3b construct may therefore have the potential to promote bone formation in clinical settings.