Effects of Etelcalcetide on Bone Microstructure in the Adenine-Induced Chronic Kidney Disease Rat Model

Objective: Chronic kidney disease (CKD) with secondary hyperparathyroidism (SHPT) increases the risk of fragility fractures with deterioration of cortical and trabecular bone microstructure. Etelcalcetide (EC), which is used to treat SHPT, reduces parathyroid hormone (PTH) levels in the blood. However, the details of the effects of EC on the microstructure of cortical and trabecular bone remain unclear. This study investigated whether EC improved the cortical and trabecular bone microstructure in CKD model rats. Methods: Eight-week-old, male Wistar rats were fed with a 0.75% adenine diet for 4 weeks to establish the CDK model rats. At 20 weeks of age, the rats were divided into two groups (n = 9 - 11 in each group): CKD group (vehicle administration) and EC group (0.6 mg/kg, daily). EC was injected for 4 weeks starting at 20 weeks of age. After treatment, the biochemical tests, measurement of bone mineral density and bone strength, and evaluation of cortical and trabecular bone microstructure were performed. Results: Compared with the CKD group, the EC group showed significantly lower serum blood urea nitrogen, calcium, and inorganic phosphorus levels (p p p p p Conclusions: EC significantly improved cortical microstructure and cortical porosity, suppressing deterioration of cortical bone strength and loss of trabecular bone in the adenine-induced CKD model rats.

Effects of Teriparatide and Aerobic Exercise on Lumbar Spine Microstructure in Ovariectomized and Tail-Suspended Rats

Osteoporosis is an increasingly prevalent malady of the elderly that is associated with bone fragility and increased risk of fractures. Osteoporosis treatments focus on restoring bone strength and quality. Teriparatide (TPTD) is a therapeutic agent that has been shown to increase bone strength by improving the volume and connectivity of trabecular bone. Exercise is also known to have pro-osteogenic effects. Here we used a rat model of severe osteoporosis (ovariectomized and tail-suspension) to evaluate the effects of TPTD, exercise and a combination of TPTD and exercise on the microstructure of trabecular bone. TPTD mono-therapy and TPTD combined with exercise treatment significantly increased bone mineral density (BMD) in the whole body. Micro-computed tomography analysis revealed that a combination of exercise and TPTD treatment significantly decreased bone surface to volume and trabecular separation compared with those of the control and exercise groups. Node-strut analysis indicated that exercise or TPTD alone did not affect trabecular bone connectivity. However, the combination of exercise and TPTD treatment significantly decreased measures of trabecular bone connectivity (node number) that are consistent with a transition from rod-like to plate-like of trabecular bone microstructures. The combination treatment with exercise and TPTD improved microstructure of trabecular bone in the OVX and tail-suspended rats. These results indicate that combining exercise with TPTD represents a viable means to improve cancellous bone strength in osteoporosis populations.

Quantitative Evaluation of Fat Composition in Lumbar Vertebral Body and Paraspinal Muscle by Proton Density Fat Fraction with MRI

Purpose: Bone marrow and muscle adiposity have been considered to correlate with osteoporosis and Sarcopenia. Proton Density Fat Fraction (PDFF) can be measured by Magnetic Resonance Imaging (MRI). The purpose of the present study was to measure PDFF in the lumbar spine, paraspinal muscle and subcutaneous fat tissue. Methods: Participants were comprised of 30 patients (18 males, 12 females;age range, 14 - 87 years) who underwent MRI due to low back symptoms. PDFFs for the body of the fourth lumbar vertebra (L4), paraspinal muscle, and subcutaneous fat were measured. Results: PDFFs of the vertebral body and subcutaneous fat were significantly higher than that of paraspinal muscle (p < 0.001). PDFF was significantly higher for subcutaneous fat than for the vertebral body (p < 0.001). Although no significant differences in PDFF of the vertebral body, paraspinal muscle, and subcutaneous fat between females and males, PDFFs of the vertebral body and paraspinal muscle were significantly higher in older subjects (>63 years) than in younger subjects (Conclusions: PDFF of the vertebral body was significantly higher than that of paraspinal muscle. PDFFs of the vertebral body and paraspinal muscle were significantly lower in younger subjects than in older subjects.

Adjacent Segment Disease after Long Spinal Fusion Ending at L5 for Adult Spinal Deformity: A Retrospective Cohort Study

Study Design: This is a retrospective cohort study using data from the adult spinal deformity (ASD) database of a single institution. Purpose: To investigate the incidence of proximal junctional failure and distal junctional failure (DJF) after ASD surgery with a lower instrumented vertebra (LIV) at L5. Overview of Literature: Spinopelvic fixation from the lower thoracic vertebra to the pelvis is the current gold standard treatment for ASD. However, the LIV at L5 is acceptable in some cases. Methods: Fifty-six patients who underwent corrective surgery for ASD with LIV at L5 were included. The upper instrumented vertebra (UIV) was T7 in one patient, T9 in 14, T10 in three, T11 in four, T12 in eight, L1 in 10, and L2 in 16. Regarding clinical parameters, age, sex, curve types of Scoliosis Research Society-Schwab classification, number of levels fused, follow-up period, hip bone mallow density, revision surgery rate, and radiographic measurements were compared between the T (UIV: T7 - 10) and TL (UIV: T11 - L2) groups. Results: The revision surgery rate was 19.6% overall. In the T and TL groups, it was 27.8%, and 15.8%, respectively (p = 0.305). The rate of DJF in the T group (33.3%) was significantly higher than in the TL group (5.3%). The rate of proximal junctional kyphosis in the T group (55.6%) was higher than in the TL group (28.9%), with no significant difference. The mean global alignment, sagittal vertical axis, and C7 plumb line-central sacral vertical line were not different between both groups. Conclusions: ASD surgery with LIV set at L5 and UIV set at the thoracic vertebrae (T7 - T10) has a risk of adjacent segment disease.

Pedicle Screw Insertion for Concave Side of Proximal Thoracic Curve in Adolescent Idiopathic Scoliosis

Background: Insertion of the pedicle screws (PS) into the proximal thoracic spine is occasionally challenging owing to the small size of the pedicles and the proximity to the spinal cord. An appropriate anchor placement method for the concave side of the proximal thoracic curve has not been established yet. This study aimed to evaluate the pedicle size and position of PS on the concave side of the proximal thoracic curve in patients with adolescent idiopathic scoliosis (AIS). Methods: Forty consecutive patients with AIS who underwent correction and fusion with all PS constructs, including the proximal thoracic curve in the fusion area, were included. After identifying the screws inserted on the concave side of the proximal thoracic curve, the pre-operative morphology and postoperative position of the inserted PS, including the end vertebrae, were analyzed using computed tomography (CT). Screw perforations were categorized into four grades depending on the degree of perforation from the pedicle wall on postoperative CT and were classified using an outcome-based classification. Results: A total of 109 screws were inserted on the concave side of the proximal thoracic curve. The average width of all pedicles was 3.5 ± 1.1 mm. The width of 90 pedicles (83%) was Conclusion: Perforations were found in 84% of the PS on the concave side of the proximal thoracic curve;however, 93% of the PS were considered acceptable in the outcome-based classification. Thus, we conclude that the in-out-in technique may be both feasible and effective.

The Serum 25(OH)D Level in Patients with Atypical Femoral Fracture

Objective: Excessive curvature of the femur has been considered to be one of the factors associated with atypical femoral fracture (AFF). Although we clarified that femoral curvature was markedly influenced by a low vitamin D level, very few studies have been conducted on the direct relationship between AFF and a serum low level of vitamin D. Therefore, we compared the serum vitamin D level between AFF and osteoporosis patients. Methods: A total of 48 consecutive AFFs in 36 Japanese patients were retrospectively reviewed using the medical records, and 12 consecutive AFFs in 9 patients (AFF group) whose 25-hydroxyvitamin D (25(OH)D) levels were examined were included in this study. As a non-AFF control group, 45 consecutive age-matched female patients with osteoporosis (Osteoporosis group) were enrolled. We compared some laboratory examination items, the bone mineral density, and curvature of the femur. Results: When univariate logistic regression analysis was performed to compare the 2 groups, Ca levels and lateral and anterior curvatures in the AFF group were significantly greater than in the Osteoporosis group (P < 0.05, P < 0.01, and P < 0.01, respectively), and the 25(OH)D level in the AFF group was significantly lower than in the Osteoporosis group (P < 0.01). We used discriminant analysis of these extracted items to exclude the mutual influence of factors and identify factors closely associated with AFF, and 25(OH)D, Ca and anterior curvature were identified as significant items to differentiate these diseases (P < 0.05, P < 0.01, and P < 0.01, respectively). Conclusion: AFF patients showed low vitamin D levels and marked femoral curvatures.

Pediatric Primary Malignant Lymphoma of the Spine: A Case Report

Background: Cases of primary malignant lymphomas of the bone are rare and account for about <1% of all lymphomas and 5% of extranodal non-Hodgkin’s lymphomas. Furthermore, most reports have described the occurrence of this disease in the middle-aged population, pediatric malignant lymphomas originating in the bone, particularly in the spine is rare. Methods: A 10-year-old boy presented with low back pain caused by T12 vertebral compression fracture due to sustaining a fall. A month later, he still presented with prolonged low back pain that intensified after exercise. A neoplastic lesion in T12 vertebral body was identified after spine computed tomography (CT) and magnetic resonance imaging. Results: We performed CT-guided biopsy, and he was diagnosed with primary malignant lymphoma of the vertebral body. He was treated with multiagent chemotherapy without irradiation, and complete remission was maintained at the 5-year follow-up. Moreover, the height of the deformed vertebral body improved as he grew. Conclusions: Herein, we report a rare case of pediatric primary malignant lymphoma of the spine with successful clinical and radiological outcome.

Prevalence of Non-Responders to Both Oral Bisphosphonate Monotherapy and Intravenous Ibandronate in Patients with Postmenopausal Osteoporosis

Objectives: Although bisphosphonates (BPs) are effective for the majority of patients with osteoporosis, some individuals do not adequately respond to these drugs. The objective of this study was to estimate the prevalence of true BP non-responders who showed insufficient response after both oral BPs and intravenous ibandronate. Methods: Among 146 consecutive patients with postmenopausal osteoporosis who received oral BP monotherapy for more than 12 months, insufficient responders to oral BP monotherapy were switched to intravenous ibandronate injection and followed for more than 12 months. Serum N-terminal telopeptide of type I collagen (NTX) and bone alkaline phosphatase (BAP) concentrations were measured. Patients who also showed insufficient response to intravenous ibandronate were defined as true BP non-responders. Insufficient response to BP therapy was evaluated based on the serum NTX reduction cut-off for minimum significant change. Results: Sixty-one patients (41.8%) were diagnosed as oral BP non-responders. Fourteen patients who switched to intravenous ibandronate and had complete data available were used for final analysis. After switching to intravenous ibandronate, both NTX and BAP decreased significantly (p Conclusion: These results estimated that as few as 9% - 15% (i.e., 21.4% - 35.7% of 41.8%) or as many as 24% - 27% (i.e., 57.1% - 64.3% of 41.8%) of patents might be true BP non-responders.

Spinal Epidural Myeloid Sarcoma with Paraplegia in Acute Myeloid Leukemia Treated with Radiation and Chemotherapy: A Case Report

Myeloid sarcoma occurs in 1% - 9% of patients with myelogenous leukemia. Spinal epidural myeloid sarcoma is particularly rare, and its treatment has not been established. A 27-year-old woman complained of pain on her left chest, back around the scapula, and neck. Magnetic resonance imaging (MRI) showed a thoracic epidural tumor. One week after her visit, she developed motor weakness of her lower extremities and dysuria, and she was diagnosed with acute myelogenous leukemia (AML) on peripheral blood analysis. The epidural tumor was strongly suspected to be myeloid sarcoma. The paralysis of the lower extremities and bladder dysfunction were not progressive, and chemotherapy and local radiation therapy to the spine were performed. Improvement of paralysis and complete reduction of tumor volume were achieved by the combination of local low-dose radiation therapy and chemotherapy.

Effects of Povidone-Iodine or Ethanol Exposure on Bone Formation at the Osteotomy Site of the Proximal Tibia in Rats

Background: Povidone-iodine (PVI) irrigation is currently used to decrease the frequency of postoperative surgical site infections. Ethanol (EtOH) is sometimes applied to prevent local recurrence after curettage of benign bone tumors. However, the effects of PVI and EtOH on surrounding soft tissue and on bone union are unclear. The purpose of this study was to determine whether PVI or EtOH adversely affects the cancellous bone healing of the osteotomy site at the proximal tibia in rats. Methods: A cancellous bone osteotomy was performed at the right proximal tibia in 4-month-old, female, Sprague Dawley rats. Vehicle, 10% PVI, or 95% EtOH-soaked gauze was inserted into the osteotomy site and maintained for 6 minutes. The rats were euthanized 2 or 4 weeks after the osteotomy. Results: Two weeks after treatment, the bone union rate was significantly higher in the vehicle group than in the PVI group and the EtOH group (p < 0.001). However, the bone union rate was not significantly different between the PVI and EtOH groups. There was no significant difference among the three groups in the bone union rate 4 weeks after treatment. Conclusion: PVI or EtOH delayed bone union of the cancellous bone osteotomy site of the proximal tibia in the early phase (2 weeks), but not at 4 weeks, in rats.

Eosinophilic Granuloma Arising from the Sacrum: A Case Report

Introduction: Osseous eosinophilic granulomas commonly occur in the skull, pelvis, vertebrae, mandible, and ribs. However, the eosinophilic granuloma in the sacrum is rare. Case presentation: We present the case of a 13-year-old Japanese boy, who presented with left low-back pain, and was diagnosed with eosinophilic granuloma arising in the sacrum. Computed tomography (CT) and magnetic resonance imaging demonstrated an osteolytic lesion with interruption of the cortex, and signal intensity changes at the left sacral body and wing. Histologic examination indicated an eosinophilic granuloma. Two years after CT-guided biopsy, the tumor had spontaneously healed completely, with no residual pain.Conclusion: The present case was eosiophilic granuloma arising from the rare site of sacrum. The tumor was completely remodeled two years after biopsy.