Denosumab vs. bisphosphonates in primary osteoporosis: a meta-analysis of comparative safety in randomized controlled trials.

Denosumab and bisphosphonates for primary osteoporosis are generally well-tolerated, but their comparative safety remains unclear. We aimed to explore the comparative safety of denosumab and bisphosphonates in primary osteoporosis. Databases such as PubMed and Google Scholar were searched for relevant peer-reviewed randomized controlled trials published in English (as of December 2023). Trials comparing adverse events (AE) between denosumab and bisphosphonates in patients with primary osteoporosis were investigated. Data were pooled using a fixed- or random-effects model to determine the risk ratios (RR) and 95% confidence intervals (CIs) for various AEs in patients treated with denosumab in comparison to patients treated with bisphosphonates. Eleven trials (5,545 patients; follow-up period: 12-24 months) were included in this meta-analysis. All trials had a risk of bias (e.g., reporting bias linked to secondary endpoints and selection bias linked to random allocation). In comparison to bisphosphonates, denosumab was significantly associated with less withdrawal due to AEs (RR = 0.49; 95% CI 0.34-0.71), more five-point major adverse cardiovascular events (RR = 2.05; 95% CI 1.03-4.09), more cardiovascular AEs (RR = 1.61; 95% CI 1.07-2.41), more infections (RR = 1.14; 95% CI 1.02-1.27), more upper respiratory tract infections (RR = 1.56; 95% CI 1.08-2.25), less vertebral fractures (RR = 0.54; 95% CI 0.31-0.93), and less abdominal pain (RR = 0.44;95% CI 0.22-0.87). We explored the comparative safety of denosumab and bisphosphonates for primary osteoporosis, some of which could be attributed to their beneficial effects. However, all trials had a risk of bias. Further investigations are required to confirm our results.

Spinal magnetic resonance imaging artifacts in lumboperitoneal shunt surgery using adjustable valve implantation on the paravertebral spinal muscles.

BACKGROUND: Adjustable shunt valves that have been developed for managing hydrocephalus rely on intrinsically magnetic components ; thus, artifacts with these valves on magnetic resonance imaging (MRI) are inevitable. No studies on valve-induced artifacts in lumboperitoneal shunt (LPS) surgery have been published. Therefore, this study aimed to evaluate valve-induced artifacts in LPS. METHODS: We retrospectively reviewed all MRIs obtained between January 2023 and June 2023 in patients with an implanted Codman CERTAS Plus adjustable shunt valve (Integra Life Sciences, Princeton, New Jersey, USA). The valve was placed <1 cm subcutaneously on the paravertebral spinal muscle of the back, with its long axis perpendicular to the body axis. The scans were performed using a Toshiba Medical Systems 1.5 Tesla scanner. The in-plane artifact sizes were assessed as the maximum distance of the artifact from the expected region of the back. RESULTS: All spinal structures or spinal cords can be recognized, even with valve-induced artifacts. The median maximum valve-induced artifact distance on T1-weighted axial imaging was 25.63 mm (mean, 25.98 mm ; range, 22.24-30.94 mm). The median maximum valve-induced artifact distance on T2-weighted axial imaging was 25.56 mm (mean, 26.27 mm ; range, 21.83-29.53 mm). CONCLUSION: LPS surgery with adjustable valve implantation on paravertebral muscles did not cause valve-induced artifacts in the spine and spinal cord. We considered that LPS could simplify the postoperative care of these patients. J. Med. Invest. 71 : 154-157, February, 2024.

A new era in the management of spinal metastasis.

Despite the recent advances in cancer treatment, the incidence of patients with spinal metastases continues to grow along with the total number of cancer patients. Spinal metastases can significantly impair activities of daily living (ADL) and quality of life (QOL), compared with other types of bone metastases, as they are characterized with severe pain and paralysis caused by skeletal-related events. Reduced ADL can also lead to treatment limitations as certain anticancer agents and radiation therapy are not compatible treatments; thus, leading to a shorter life expectancy. Consequently, maintaining ADLs in patients with spinal metastases is paramount, and spine surgeons have an integral role to play in this regard. However, neurosurgeon, orthopedic and spinal surgeons in Japan do not have a proactive treatment approach to spinal metastases, which may prevent them from providing appropriate treatment when needed (clinical inertia). To overcome such endemic inertia, it is essential for 1) spine surgeons to understand and be more actively involved with patients with musculoskeletal disorders (cancer locomo) and cancer patients; 2) the adoption of a multidisciplinary approach (coordination and meetings not only with the attending oncologist but also with spine surgeons, radiologists, rehabilitation specialists, and other professionals) to preemptive treatment such as medication, radiotherapy, and surgical treatment; and 3) the integration of the latest findings associated with minimally invasive spinal treatments that have expanded the indications for treatment of spinal metastases and improved treatment outcomes. This heralds a new era in the management of spinal metastases.

Academic Engagement of Women as Orthopaedic Surgeons at the Annual Meetings of the Japanese Orthopaedic Association From 2012 to 2022.

BACKGROUND: Higher gender diversity correlates with higher patient satisfaction, higher-quality medical education, increased research productivity, and higher revenues. Although the field of Japanese orthopaedic surgery includes the lowest proportion of women and lags in gender diversity, reports on the current gender diversity status in academic activities are scarce. We investigated changes in women's participation in academic activities at the Japanese Orthopaedic Association (JOA) annual meetings over the past 11 years. METHODS: Data on the percentage of women in the JOA membership during 2012-2022 were analyzed to ascertain the proportion of women as first authors of oral and poster presentations, abstract reviewers, invited lecturers, seminar lecturers, general abstract oral chairpersons, symposium chairpersons, and speakers. Regarding the ratio of women among the JOA members during 2012-2022, we relied on data provided by the JOA. Data related to other categories were collected from the abstract book presented at the JOA Annual Meetings between 2012 and 2022. We analyzed the time trend for women's proportions using the Cochran-Armitage trend test. A p-value < 0.05 was considered statistically significant. RESULTS: During 2012-2022, the percentage of female members (4.9-6.7%), poster first authors (2.7-4.3%), abstract reviewers (0-1.5%), general abstract oral chairpersons (0-2.3%), symposium chairpersons (0-3.6%), and symposium speakers (1.6-6.8%) had increased significantly (p < 0.05). Oral first authors (2.2-4.1%), invited lecturers (0-6.8%), or seminar lecturers (0%-6.7%) showed no trend. Women engaged in academic activities at all annual association meetings did not exceed the women's proportion among the association members. CONCLUSION: Although the proportion of women members of the JOA has gradually increased and more women are involved in its annual meetings, the proportion of female presenters, invited speakers, symposiasts, and chairpersons of oral and poster presentations is generally lower than that of women as JOA members. Members should be asked to raise awareness, including more active education of women as physicians in educational institutions and the creation of positive actions to select women as physicians for more important roles (chairpersons, educational speakers, and symposiasts) in the organization of annual meetings.

Spinal subdural hematoma with sudden onset of paraplegia in a patient on oral anticoagulant therapy.

Spinal subdural hematoma is uncommon but may become more prevalent with increasing anticoagulant use. Early diagnosis from symptoms like lower back pain and leg paralysis is crucial for timely intervention.

The Usefulness of Deep Tendon Reflexes in the Diagnosis of Lumbar Spine Diseases: A Narrative Review.

The deep tendon reflex (DTR) is a more objective indicator than sensory and muscle assessments for lumbar spine disorders. Further, unlike sensory and muscle assessments that require patient cooperation, the DTR can be assessed even in patients with impaired consciousness or cognition. Therefore, DTR assessment with a hammer is an essential neurological test for lumbar spinal diseases. However, despite the usefulness of DTR assessment, few reports have described the significance of increased, diminished, or absent deep lower extremity reflexes in lumbar spine diseases. This review outlines the history of DTR of the lower limbs and describes the techniques, evaluation, and interpretation of DTR for the diagnosis of lumbar spine diseases. The patellar tendon reflex (PTR) was the first parameter of lower extremity DTR identified to have clinical usefulness, followed by the Achilles tendon reflex (ATR), pathological reflexes (Babinski reflex), and reflex enhancement (Jendrassik maneuver). They have now become an integral part of clinical examination. To determine whether an increase or decrease in DTR is pathological, it is necessary to determine left-right differences, differences between the upper and lower extremities, and the overall balance of the limb. There are several critical limitations and pitfalls in interpreting DTRs for lumbar spine diseases. Attention should be paid to examiner and patient factors that make the DTR assessment less objective. When there is a discrepancy between clinical and imaging findings and the level of the lumbosacral nerve root disorder is difficult to diagnose, the presence of a lumbosacral transitional vertebra, nerve root malformation, or furcal nerve should be considered. In addition, assessing the DTR after the gait loading test and standing extension loading test, which induce lumbosacral neuropathy, will help provide a rationale for the diagnosis.

Perioperative Cerebrovascular Accidents in Spine Surgery: A Retrospective Descriptive Study and A Systematic Review with Meta-Analysis.

Introduction: Perioperative cerebrovascular accidents (CVAs) related to spine surgery, although rare, can lead to significant disabilities. More studies on spine surgeries are required to identify those at risk of perioperative CVAs. The characteristics and outcomes of patients that experienced CVAs during spine surgery were assessed through a retrospective descriptive study and meta-analysis. Methods: Patients aged ≥18 years who underwent spine surgery under general anesthesia at a hospital between April 2011 and March 2023 were examined. Of the 2,391 initially identified patients, 2,346 were included after excluding 45 who underwent debridement for surgical site infections. Subsequently, a meta-analysis including the present retrospective descriptive study was conducted. Databases such as PubMed and Google Scholar were searched for original peer-reviewed articles written in English. Results: Of the 2,346 patients, 4 (0.17%) (three men, one woman) exhibited perioperative CVAs associated with spine surgery. The CVAs were diverse in nature: one case of cerebral hemorrhage resulting from dural injury during posterior occipitocervical fusion, two cases of cerebral infarctions after lumbar laminectomy and anterior thoracic fusion due to anticoagulant discontinuation, and one case of posterior reversible encephalopathy syndrome following microscopic lumbar discectomy due to gestational hypertension. The subsequent meta-analysis included three studies (n=186,860). It showed several risk factors for perioperative CVAs, including cervical level (pooled odds ratio [OR]=1.33), hypertension (pooled OR=2.27), atrial fibrillation (pooled OR=8.78), history of heart disease (pooled OR=2.47), and diabetes (pooled OR=2.13). Conclusions: It was speculated that the potential risk factors for the four perioperative CVA cases of spine surgery in this retrospective descriptive study were intraoperative dural injury, preoperative anticoagulant discontinuation, and gestational hypertension history. The meta-analysis revealed that cervical spine surgery, hypertension, atrial fibrillation, heart disease, and diabetes increased the CVA risk. This highlights the need for risk assessment, preoperative optimization, and postoperative care to reduce spine surgery-associated perioperative CVAs.

Analyzing lumbar vertebral shape and alignment in female patients with degenerative spondylolisthesis: Comparisons with spinal stenosis and risk factor exploration.

PURPOSE: This study aimed to examine the vertebral body shape characteristics and spondylopelvic alignment in L4 degenerative spondylolisthesis (DS) as well as the risk factors for the development of DS. METHODS: This cross-sectional study compared vertebral morphology and sagittal spinopelvic alignment in female patients with lumbar DS and lumbar spinal stenosis (LSS). The degree of lumbar lordosis (LL), pelvic incidence (PI), cross-sectional area (CSA), and vertebral body height ratio (ha/hp) of the lumbar spine were compared using full-length spine radiographs and computed tomography in 60 females with DS and in 60 women with LSS. RESULTS: No significant differences in age or body mass index were observed between the two groups; however, the DS and LSS groups significantly differed in PI (mean, 58.9±10.8 vs. 47.2±11.6, P < 0.001), L4 CSA (mean, 1,166.2 m2 vs. 1,242.0 m2, P = 0.002) and ha/hp (mean, 1.134 vs. 1.007, P < 0.001). The L4 ha/hp was significantly higher in the DS group than in the LSS group. Additionally, LL values were negatively correlated with vertebral L5 CSA in the DS group (r = -0.28, P < 0.05). The LSS and DS groups demonstrated positive correlations between LL and L2, L3, and L4 ha/hp (r = 0.331, 0.267, and 0.317; P < 0.01, < 0.05, and < 0.05, respectively) and between LL and L4 and L5 ha/hp (r = 0.333, 0.331; P < 0.01, respectively). Multivariate regression analyses revealed that PI and ha/hp ratio may be independent predictors of DS development. CONCLUSION: The DS group had significantly larger LL, PI, and L4 ha/hp and smaller L4 CSA than the LSS group. The lumbar vertebral body shape and sagittal spinopelvic alignment in females might be independent predictors of DS development.

Adjacent vertebral fractures in the lumbar and thoracic spine after balloon kyphoplasty: A finite element analysis.

The purpose of the present study was to mechanically verify after vertebral augmentation (AVA) scores using a finite element method (FEM) with accurate material constants of balloon kyphoplasty (BKP) cement. Representative cases with AVA scores of 1 (case 1), 3 (case 2), and 5 (case 3) among patients with vertebral body fractures who underwent BKP were analyzed. A FEM model consisting of 5 vertebral bodies was created, including the injured vertebral body in each case. The amount of displacement for each load (up to 4000 N) between the upper and lower vertebral bodies of each model was measured. Young modulus of the BKP cement was calculated from actual measurements using the EZ-Test EZ-S (Shimadzu Corporation, Kyoto, Japan). In all cases, the number of shell elements (209,296-299,876), solid elements (1913,029-2417,671), and nodes (387,848-487,756) were similar, indicating that FEM modeling was comparable among the cases. Young modulus of BKP cement, calculated using EZ-Test EZ-S, was 572 MPa. Fractures were detected by compressive forces of 3300 N (upper) and 3300 N (lower), 3000 N (upper) and 3100 N (lower), and 1200 N (upper) and 1200 N (lower) in cases 1, 2, and 3, respectively. The AVA scoring system was mechanically verified using the accurate material constants of BKP cement. A multicenter survey and external validation are therefore required for the clinical implementation of the AVA score.

Conservative management of spontaneous spinal epidural hematoma: A case report with favorable prognosis.

Sudden spinal epidural hematoma (SSEH) is relatively rare. Sudden pain from the neck to the back and subsequent extremity paralysis necessitate immediate head and cervical magnetic resonance imaging or computed tomography, keeping SSEH in mind. Although surgery is recommended for progressive paralysis, conservative treatment is indicated for mildly symptomatic cases.

Infected charcot spine.

Patients with an infected charcot spine (ICS) may experience little or no back pain despite severe vertebral destruction. Understanding the pathophysiology underlying ICS and its differential diagnoses is crucial for its accurate diagnosis. Worsening symptoms of chronic charcot spine should raise suspicions of an infection.

A view on the skin-bone axis: unraveling similarities and potential of crosstalk.

The phrase "skin as a mirror of internal medicine," which means that the skin reflects many of the diseases of the internal organs, is a well-known notion. Despite the phenotypic differences between the soft skin and hard bone, the skin and bone are highly associated. Skin and bone consist of fibroblasts and osteoblasts, respectively, which secrete collagen and are involved in synthesis, while Langerhans cells and osteoclasts control turnover. Moreover, the quality and quantity of collagen in the skin and bone may be modified by aging, inflammation, estrogen, diabetes, and glucocorticoids. Skin and bone collagen are pathologically modified by aging, drugs, and metabolic diseases, such as diabetes. The structural similarities between the skin and bone and the crosstalk controlling their mutual pathological effects have led to the advocacy of the skin-bone axis. Thus, the skin may mirror the health of the bones and conversely, the condition of the skin may be reflected in the bones. From the perspective of the skin-bone axis, the similarities between skin and bone anatomy, function, and pathology, as well as the crosstalk between the two, are discussed in this review. A thorough elucidation of the pathways governing the skin-bone axis crosstalk would enhance our understanding of disease pathophysiology, facilitating the development of new diagnostics and therapies for skin collagen-induced bone disease and of new osteoporosis diagnostics and therapies that enhance skin collagen to increase bone quality and density.

Experimental Study of Failures of the Rigid Spinal Posterior Fixation System Under Compressive Load Conditions: A Cadaver Study.

Background Many studies have been conducted on the biomechanics of the spine to elucidate the fixation properties of spinal fusion surgery and the causes of instrumentation failure. Among these studies, there are some studies on load sharing in the spine and measurement using strain gauges and pressure gauges, but there is a lack of research on axial compressive loads. Methods Axial compressive load tests were performed on human cadaveric injured lumbar vertebrae fixed with pedicle screws (PS). Both the strain generated in the PS rod and the intradiscal pressure were measured. Subsequently, the stress generated in the PS rod and the load sharing of the spine and instrumentation were calculated. Results Even when only compressive load is applied, bending stress of more than 10 times the compression stress was generated in the rod, and the stress tended to concentrate on one rod. Rod deformation becomes kyphotic, in contrast to the lordotic deformation behavior of the lumbar spine. The stress shielding rate was approximately 40%, less than half. Conclusions This study obtained basic data useful for constructing and verifying numerical simulations that are effective for predicting and elucidating the causes of dislodgement and failure of spinal implants.

The first case of methotrexate-associated lymphoproliferative disorder in the sacrum: a case report.

Methotrexate (MTX) is a drug used for treating rheumatoid arthritis. Recently, the reported incidence of methotrexate-associated lymphoproliferative disease (MTX-LPD) has increased, especially in Japan. Extranodal involvement is observed in half of MTX-LPD cases. However, only a few spinal lesions have been reported, with none in the sacrum. Additionally, Epstein-Barr virus (EBV) infection has also been implicated in the pathogenesis of MTX-LPD. Herein, we describe the case of a 74-year-old woman with MTX-LPD in the sacral spine who complained of severe back pain and nocturnal pain. Radiographs revealed a tumour on the right wing of the sacrum and a positive EBV immunoglobulin G antibody titre. MTX-LPD was suspected based on imaging findings and a history of MTX administration. A pathological examination was performed on the CT-guided biopsy specimen. The histopathological diagnosis was MTX-LPD, and MTX was discontinued. Three months after MTX administration ended, the tumour tended to shrink, and 1 year later, significant tumour shrinkage was observed. This experience suggests that MTX-LPD can be treated by discontinuing MTX administration. Therefore, early and accurate diagnosis is required, as is avoiding unnecessary treatment such as surgery. MTX-LPD should be considered, especially in spinal origin tumours in EBV-infected patients on MTX.

Clinical and oncologic outcomes of posterior only total en bloc spondylectomy for spinal metastasis involving third lumbar vertebra: A case series.

INTRODUCTION: A posterior-only total en bloc spondylectomy (TES) of the L3 level was deemed a highly intricate surgical procedure, necessitating the preservation of the L3 nerve root to prevent neurological deterioration. Despite bilateral preservation efforts of the L3 nerve roots, neurological deterioration proved unavoidable. This study aims to present the clinical, neurologic, and oncologic outcomes of spinal metastasis patients who underwent a posterior-only approach TES, encompassing the L3 vertebra. MATERIALS AND METHODS: All patients with L3-involved spinal metastasis undergoing posterior TES between January 2018 and January 2022 were investigated. The primary outcomes considered were the local recurrence rate and manual muscle testing of the lumbar myotome. Secondary outcomes included Frankel neurological status, operative time, blood loss, perioperative and postoperative complications, and Eastern Cooperative Oncology Group score. RESULTS: Five patients with TES involving L3 (three females) met the inclusion criteria. All patients had solitary metastases (three in the lungs, 2 in the breasts). Postoperatively, all patients experienced weakness of the hip flexors, but they were able to ambulate independently 12 months after surgery. One patient exhibited adjacent segment (L2) disease progression and underwent corpectomy 18 months after TES. No local recurrences at the surgical site were detected on magnetic resonance imaging at the 1-year follow-up. CONCLUSION: Posterior-only TES for L3-involved vertebrae yielded excellent results in the local control of metastatic disease. Despite hip flexor weakness, all patients were able to regain independent ambulation after 12 months. TES can offer favorable clinical and oncological outcomes in patients with solitary spinal metastases.

Delayed Diagnosis of Spinal Dural Arteriovenous Fistula: A Case Report and Scoping Review.

Spinal dural arteriovenous fistula (SDAVF) is among the most common arterial shunt diseases typically found in middle aged or older men. Herein, we aimed to clarify the reasons for misdiagnoses and delayed diagnoses of SDAVF, determine how these affect prognoses, and establish how they can be prevented. We conducted a PubMed/MEDLINE literature search using "spinal dural arteriovenous fistula", "delayed diagnosis", "late diagnosis", and "misdiagnosis" terms. We identified 18 articles, including 965 SDAVF cases. Patients were predominantly males (71.8-100.0%) (mean age: 53.5-71.0 years). Misdiagnoses rates varied (17.5-100.0%) and encompassed many conditions. The mean time between early manifestations and confirmed diagnosis was approximately 10-15 months and from the first radiologic image revealing dural arteriovenous fistula (DAVF) features to diagnosis was 9.2-20.7 months. Posttreatment outcomes showed a significant improvement in motor functions, gait, and micturition, particularly in patients exhibiting preoperative symptoms over a short period. SDAVF is frequently misdiagnosed or subject to delayed diagnosis, causing poor clinical outcomes. SDAVF symptoms including progressive lower-limb weakness, paresthesia, and vesicorectal dysfunction are indications for spinal magnetic resonance imaging with subsequent spinal angiography, wherein DAVF is evidenced by extensive T2 hyperintensity and flow-void abnormalities. We reported a representative case with delayed diagnosis.