Direct measurements were made on 2,166 lumbar vertebrae of 433 adult negro and caucasoid skeletons. On statistical analysis, forty-five vertebrae in twenty-seven skeletons were found to be stenotic, the mid-sagittal diameter being the significantly reduced dimension. Whereas spinal stenosis syndromes are rare in South African negroes, the lumbar canal is marginally narrower in the negro. There is a uniformity of configuration and capacity of the lumbar spinal canal, which transcends race and sex. By a new method of determining the dorsal limit of the lumbar canal on lateral plain radiography, the overall average lower limit of normal of the mid-sagittal diameter is established at 15 millimetres, and of the transverse diameter 20 millimetres. Bony degenerative changes are more likely to cause neurological compression in the nerve root tunnel than in the spinal canal. The role of skeletal narrowing of the spinal canal as an exclusive cause of the spinal stenosis syndrome may have been exaggerated.

Objectives

To employ a simple and fast method to evaluate those patients with neurological deficits and misplaced screws in relatively safe lumbosacral spine, and to determine if it is necessary to undertake revision surgery.

Aims. The association of auraptene (AUR), a 7-geranyloxycoumarin, on osteoporosis and its potential pathway was predicted by network pharmacology and confirmed in experimental osteoporotic mice. Methods. The network of AUR was constructed and a potential pathway predicted by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) terms enrichment. Female ovariectomized (OVX) Institute of Cancer Research mice were intraperitoneally injected with 0.01, 0.1, and 1 mM AUR for four weeks. The bone mineral density (BMD) level was measured by dual-energy X-ray absorptiometry. The bone microstructure was determined by histomorphological changes in the femora. In addition, biochemical analysis of the serum and assessment of the messenger RNA (mRNA) levels of osteoclastic markers were performed. Results. In total, 65.93% of the genes of the AUR network matched with osteoporosis-related genes. Osteoclast differentiation was predicted to be a potential pathway of AUR in osteoporosis. Based on the network pharmacology, the BMD and bone mineral content levels were significantly (p < 0.05) increased in the whole body, femur, tibia, and lumbar spine by AUR. AUR normalized the bone microstructure and the serum alkaline phosphatase (ALP), bone-specific alkaline phosphatase (bALP), osteocalcin, and calcium in comparison with the OVX group. In addition, AUR treatment reduced TRAP-positive osteoclasts and receptor activator of nuclear factor kappa-B ligand (RANKL). +. nuclear factor of activated T cells 1 (NFATc1). +. expression in the femoral body. Moreover, the expressions of initiators for osteoclastic resorption and bone matrix degradation were significantly (p < 0.05) regulated by AUR in the lumbar spine of the osteoporotic mice. Conclusion. AUR ameliorated bone loss by downregulating the RANKL/NFATc1 pathway, resulting in improvement of osteoporosis. In conclusion, AUR might be an ameliorative cure that alleviates bone loss in osteoporosis via inhibition of osteoclastic activity. Cite this article: Bone Joint Res 2022;11(5):304–316

Aims. The purpose of this study was to investigate the risk of additional surgery in the lumbar spine and to describe long-term changes in patient-reported outcomes after surgery for lumbar disc herniation in adolescents and young adults. Patients and Methods. We conducted a retrospective study design on prospectively collected data from a national quality register. The 4537 patients were divided into two groups: adolescents (≤ 18 years old, n = 151) and young adults (19 to 39 years old, n = 4386). The risk of additional lumbar spine surgery was surveyed for a mean of 11.4 years (6.0 to 19.3) in all 4537 patients. Long-term patient-reported outcomes were available at a mean of 7.2 years (5.0 to 10.0) in up to 2716 patients and included satisfaction, global assessment for leg and back pain, Oswestry Disability Index, visual analogue scale for leg and back pain, EuroQol five-dimension questionnaire (EQ-5D), and 36-Item Short-Form Health Survey (SF-36) Mental Component Summary and Physical Component Summary scores. Statistical analyses were performed with Cox proportional hazard regression, chi-squared test, McNemar’s test, Welch–Satterthwaite t-test, and Wilcoxon’s signed-rank test. Results. Any type of additional lumbar spine surgery was seen in 796 patients (18%). Surgery for lumbar disc herniation accounted for more than half of the additional surgeries. The risk of any additional surgery was 0.9 (95% confidence interval (CI) 0.6 to 1.4) and the risk of additional lumbar disc herniation surgery was 1.0 (0.6 to 1.7) in adolescents compared with the young adult group. Both age groups improved their patient-reported outcome data after surgery (all p < 0.001). Changes between short- (mean 1.9 years (1.0 to 2.0)) and long-term follow-up (mean 7.2 years (5.0 to 10.0)) were small. Conclusion. The risk of any additional lumbar spine surgery and additional lumbar disc herniation surgery was similar in adolescents and young adults. All patient-reported outcomes improved from preoperative to the short-term follow-up, while no likely clinically important differences between the short- and long-term follow-up were seen within both groups. Cite this article: Bone Joint J 2019;101-B:1534–1541

The June 2023 Spine Roundup. 360. looks at: Characteristics and comparative study of thoracolumbar spine injury and dislocation fracture due to tertiary trauma; Sublingual sufentanil for postoperative pain management after lumbar spinal fusion surgery; Minimally invasive bipolar technique for adult neuromuscular scoliosis; Predictive factors for degenerative lumbar spinal stenosis; Lumbosacral transitional vertebrae and lumbar fusion surgery at level L4/5; Does recall of preoperative scores contaminate trial outcomes? A randomized controlled trial; Vancomycin in fibrin glue for prevention of SSI; Perioperative nutritional supplementation decreases wound healing complications following elective lumbar spine surgery: a randomized controlled trial

Aims. Osteoporosis is common in total hip arthroplasty (THA) patients. It plays a substantial factor in the surgery’s outcome, and previous studies have revealed that pharmacological treatment for osteoporosis influences implant survival rate. The purpose of this study was to examine the prevalence of and treatment rates for osteoporosis prior to THA, and to explore differences in osteoporosis-related biomarkers between patients treated and untreated for osteoporosis. Methods. This single-centre retrospective study included 398 hip joints of patients who underwent THA. Using medical records, we examined preoperative bone mineral density measures of the hip and lumbar spine using dual energy X-ray absorptiometry (DXA) scans and the medications used to treat osteoporosis at the time of admission. We also assessed the following osteoporosis-related biomarkers: tartrate-resistant acid phosphatase 5b (TRACP-5b); total procollagen type 1 amino-terminal propeptide (total P1NP); intact parathyroid hormone; and homocysteine. Results. The prevalence of DXA-proven hip osteoporosis (T-score ≤ -2.5) among THA patients was 8.8% (35 of 398). The spinal osteoporosis prevalence rate was 4.5% (18 of 398), and 244 patients (61.3%; 244 of 398) had osteopenia (-2.5 < T-score ≤ -1) or osteoporosis of either the hip or spine. The rate of pharmacological osteoporosis treatment was 22.1% (88 of 398). TRACP-5b was significantly lower in the osteoporosis-treated group than in the untreated group (p < 0.001). Conclusion. Osteoporosis is common in patients undergoing THA, but the diagnosis and treatment for osteoporosis were insufficient. The lower TRACP-5b levels in the osteoporosis-treated group — that is, osteoclast suppression — may contribute to the reduction of the postoperative revision rate after THA. Cite this article: Bone Joint Res 2022;11(12):873–880

Aims. Radiotherapy is a well-known local treatment for spinal metastases. However, in the presence of postoperative systemic therapy, the efficacy of radiotherapy on local control (LC) and overall survival (OS) in patients with spinal metastases remains unknown. This study aimed to evaluate the clinical outcomes of post-surgical radiotherapy for spinal metastatic non-small-cell lung cancer (NSCLC) patients, and to identify factors correlated with LC and OS. Methods. A retrospective, single-centre review was conducted of patients with spinal metastases from NSCLC who underwent surgery followed by systemic therapy at our institution from January 2018 to September 2022. Kaplan-Meier analysis and log-rank tests were used to compare the LC and OS between groups. Associated factors for LC and OS were assessed using Cox proportional hazards regression analysis. Results. Overall, 123 patients with 127 spinal metastases from NSCLC who underwent decompression surgery followed by postoperative systemic therapy were included. A total of 43 lesions were treated with stereotactic body radiotherapy (SBRT) after surgery and 84 lesions were not. Survival rate at one, two, and three years was 83.4%, 58.9%, and 48.2%, respectively, and LC rate was 87.8%, 78.8%, and 78.8%, respectively. Histological type was the only significant associated factor for both LC (p = 0.007) and OS (p < 0.001). Treatment with targeted therapy was significantly associated with longer survival (p = 0.039). The risk factors associated with worse survival were abnormal laboratory data (p = 0.021), lesions located in the thoracic spine (p = 0.047), and lumbar spine (p = 0.044). This study also revealed that postoperative radiotherapy had little effect in improving OS or LC. Conclusion. Tumour histological type was significantly associated with the prognosis in spinal NSCLC metastasis patients. In the presence of post-surgical systemic therapy, radiotherapy appeared to be less effective in improving LC, OS, or quality of life in spinal NSCLC metastasis patients. Cite this article: Bone Jt Open 2024;5(4):350–360

Aims. The aim of this study was to report the long-term prognosis of patients with multiple Langerhans cell histiocytosis (LCH) involving the spine, and to analyze the risk factors for progression-free survival (PFS). Methods. We included 28 patients with multiple LCH involving the spine treated between January 2009 and August 2021. Kaplan-Meier methods were applied to estimate overall survival (OS) and PFS. Univariate Cox regression analysis was used to identify variables associated with PFS. Results. Patients with multiple LCH involving the spine accounted for 15.4% (28/182 cases) of all cases of spinal LCH: their lesions primarily involved the thoracic and lumbar spines. The most common symptom was pain, followed by neurological dysfunction. All patients presented with osteolytic bone destruction, and 23 cases were accompanied by a paravertebral soft-tissue mass. The incidence of vertebra plana was low, whereas the oversleeve-like sign was a more common finding. The alkaline phosphatase was significantly higher in patients with single-system multifocal bone LCH than in patients with multisystem LCH. At final follow-up, one patient had been lost to follow-up, two patients had died, three patients had local recurrence, six patients had distant involvement, and 17 patients were alive with disease. The median PFS and OS were 50.5 months (interquartile range (IQR) 23.5 to 63.1) and 60.5 months (IQR 38.0 to 73.3), respectively. Stage (hazard ratio (HR) 4.324; p < 0.001) and chemotherapy (HR 0.203; p < 0.001) were prognostic factors for PFS. Conclusion. Pain is primarily due to segmental instability of the spine from its destruction by LCH. Chemotherapy can significantly improve PFS, and radiotherapy has achieved good results in local control. The LCH lesions in some patients will continue to progress. It may initially appear as an isolated or single-system LCH, but will gradually involve multiple sites or systems. Therefore, long-term follow-up and timely intervention are important for patients with spinal LCH. Cite this article: Bone Joint J 2023;105-B(6):679–687

Aims. The aim of this study was to determine the influence of pelvic parameters on the tendency of patients with adolescent idiopathic scoliosis (AIS) to develop flatback deformity (thoracic hypokyphosis and lumbar hypolordosis) and its effect on quality-of-life outcomes. Patients and Methods. This was a radiological study of 265 patients recruited for Boston bracing between December 2008 and December 2013. Posteroanterior and lateral radiographs were obtained before, immediately after, and two-years after completion of bracing. Measurements of coronal and sagittal Cobb angles, coronal balance, sagittal vertical axis, and pelvic parameters were made. The refined 22-item Scoliosis Research Society (SRS-22r) questionnaire was recorded. Association between independent factors and outcomes of postbracing ≥ 6° kyphotic changes in the thoracic spine and ≥ 6° lordotic changes in the lumbar spine were tested using likelihood ratio chi-squared test and univariable logistic regression. Multivariable logistic regression models were then generated for both outcomes with odds ratios (ORs), and with SRS-22r scores. Results. Reduced T5-12 kyphosis (mean -4.3° (. sd. 8.2); p < 0.001), maximum thoracic kyphosis (mean -4.3° (. sd. 9.3); p < 0.001), and lumbar lordosis (mean -5.6° (. sd. 12.0); p < 0.001) were observed after bracing treatment. Increasing prebrace maximum kyphosis (OR 1.133) and lumbar lordosis (OR 0.92) was associated with postbracing hypokyphotic change. Prebrace sagittal vertical axis (OR 0.975), prebrace sacral slope (OR 1.127), prebrace pelvic tilt (OR 0.940), and change in maximum thoracic kyphosis (OR 0.878) were predictors for lumbar hypolordotic changes. There were no relationships between coronal deformity, thoracic kyphosis, or lumbar lordosis with SRS-22r scores. Conclusion. Brace treatment leads to flatback deformity with thoracic hypokyphosis and lumbar hypolordosis. Changes in the thoracic spine are associated with similar changes in the lumbar spine. Increased sacral slope, reduced pelvic tilt, and pelvic incidence are associated with reduced lordosis in the lumbar spine after bracing. Nevertheless, these sagittal parameter changes do not appear to be associated with worse quality of life. Cite this article: Bone Joint J 2019;101-B:1370–1378

Low-energy fractures of the proximal humerus indicate osteoporosis and it is important to direct treatment to this group of patients who are at high risk of further fracture. Data were prospectively collected from 79 patients (11 men, 68 women) with a mean age of 69 years (55 to 86) with fractures of the proximal humerus in order to determine if current guidelines on the measurement of the bone mineral density at the hip and lumbar spine were adequate to stratify the risk and to guide the treatment of osteoporosis. Bone mineral density measurements were made by dual-energy x-ray absorptiometry at the proximal femur, lumbar spine (L2-4) and contralateral distal radius, and the T-scores were generated for comparison. Data were also collected on the use of steroids, smoking, the use of alcohol, hand dominance and comorbidity. The mean T-score for the distal radius was −2.97 (. sd. 1.56) compared with −1.61 (. sd. 1.62) for the lumbar spine and −1.78 (. sd. 1.33) for the femur. There was a significant difference between the mean lumbar and radial T scores (1.36 (1.03 to 1.68); p < 0.001) and between the mean femoral and radial T-scores (1.18 (0.92 to 1.44); p < 0.001). The inclusion of all three sites in the determination of the T-score increased the sensitivity to 66% compared with that of 46% when only the proximal femur and lumbar spine were used. This difference between measurements in the upper limb compared with the axial skeleton and lower limb suggests that basing risk assessment and treatment on only the bone mineral density taken at the hip or lumbar spine may misrepresent the extent of osteoporosis in the upper limb and the subsequent risk of fracture at this site. The assessment of osteoporosis must include measurement of the bone mineral density at the distal radius to avoid underestimation of osteoporosis in the upper limb

Aims. The aim of this study was to assess the accuracy of pedicle screw placement, as well as intraoperative factors, radiation exposure, and complication rates in adult patients with degenerative disorders of the thoracic and lumbar spines who have undergone robotic-navigated spinal surgery using a contemporary system. Methods. The authors reviewed the prospectively collected data on 196 adult patients who had pedicle screws implanted with robot-navigated assistance (RNA) using the Mazor X Stealth system between June 2019 and March 2022. Pedicle screws were implanted by one experienced spinal surgeon after completion of a learning period. The accuracy of pedicle screw placement was determined using intraoperative 3D fluoroscopy. Results. A total of 1,123 pedicle screws were implanted: 1,001 screws (89%) were placed robotically, 63 (6%) were converted from robotic placement to a freehand technique, and 59 (5%) were planned to be implanted freehand. Of the robotically placed screws, 942 screws (94%) were determined to be Gertzbein and Robbins grade A with median deviation of 0.8 mm (interquartile range 0.4 to 1.6). Skive events were noted with 20 pedicle screws (1.8%). No adverse clinical sequelae were noted in the 90-day follow-up. The mean fluoroscopic exposure per screw was 4.9 seconds (SD 3.8). Conclusion. RNA is highly accurate and reliable, with a low rate of abandonment once mastered. No adverse clinical sequelae occurred after implanting a large series of pedicle screws using the latest generation of RNA. Understanding of patient-specific anatomical features and the real-time intraoperative identification of risk factors for suboptimal screw placement have the potential to improve accuracy further. Cite this article: Bone Joint J 2023;105-B(5):543–550

Aims. This study of patients with osteoarthritis (OA) of the hip aimed to: 1) characterize the contribution of the hip, spinopelvic complex, and lumbar spine when moving from the standing to the sitting position; 2) assess whether abnormal spinopelvic mobility is associated with worse symptoms; and 3) identify whether spinopelvic mobility can be predicted from static anatomical radiological parameters. Patients and Methods. A total of 122 patients with end-stage OA of the hip awaiting total hip arthroplasty (THA) were prospectively studied. Patient-reported outcome measures (PROMs; Oxford Hip Score, Oswestry Disability Index, and Veterans RAND 12-Item Health Survey Score) and clinical data were collected. Sagittal spinopelvic mobility was calculated as the change from the standing to sitting position using the lumbar lordosis angle (LL), sacral slope (SS), pelvic tilt (PT), pelvic-femoral angle (PFA), and acetabular anteinclination (AI) from lateral radiographs. The interaction of the different parameters was assessed. PROMs were compared between patients with normal spinopelvic mobility (10° ≤ ∆PT ≤ 30°) or abnormal spinopelvic mobility (stiff: ∆PT < ± 10°; hypermobile: ∆PT > ± 30°). Multiple regression and receiver operating characteristic (ROC) curve analyses were used to test for possible predictors of spinopelvic mobility. Results. Standing to sitting, the hip flexed by a mean of 57° (. sd. 17°), the pelvis tilted backwards by a mean of 20° (. sd. 12°), and the lumbar spine flexed by a mean of 20° (. sd. 14°); strong correlations were detected. There was no difference in PROMs between patients in the different spinopelvic mobility groups. Maximum hip flexion, standing PT, and standing AI were independent predictors of spinopelvic mobility (R. 2. = 0.42). The combined thresholds for standing was PT ≥ 13° and hip flexion ≥ 88° in the clinical examination, and had 90% sensitivity and 63% specificity of predicting spinopelvic stiffness, while SS ≥ 42° had 84% sensitivity and 67% specificity of predicting spinopelvic hypermobility. Conclusion. The hip, on average, accounts for three-quarters of the standing-to-sitting movement, but there is great variation. Abnormal spinopelvic mobility cannot be screened with PROMs. However, clinical and standing radiological features can predict spinopelvic mobility with good enough accuracy, allowing them to be used as reliable screening tools. Cite this article: Bone Joint J 2019;101-B:902–909

Aims. The purpose of this study was to evaluate spinopelvic mechanics from standing and sitting positions in subjects with and without femoroacetabular impingement (FAI). We hypothesize that FAI patients will experience less flexion at the lumbar spine and more flexion at the hip whilst changing from standing to sitting positions than subjects without FAI. This increase in hip flexion may contribute to symptomatology in FAI. Patients and Methods. Male subjects were prospectively enrolled to the study (n = 20). Mean age was 31 years old (22 to 41). All underwent clinical examination, plain radiographs, and dynamic imaging using EOS. Subjects were categorized into three groups: non-FAI (no radiographic or clinical FAI or pain), asymptomatic FAI (radiographic and clinical FAI but no pain), and symptomatic FAI (patients with both pain and radiographic FAI). FAI was defined as internal rotation less than 15° and alpha angle greater than 60°. Subjects underwent standing and sitting radiographs in order to measure spine and femoroacetabular flexion. Results. Compared with non-FAI controls, symptomatic patients with FAI had less flexion at the spine (mean 22°, . sd. 12°, vs mean 35°, . sd. 8°; p = 0.04) and more at the hip (mean 72°, . sd. 6°, vs mean 62°, . sd. 8°; p = 0.047). Subjects with asymptomatic FAI had more spine flexion and similar hip flexion when compared to symptomatic FAI patients. Both FAI groups also sat with more anterior pelvic tilt than control patients. There were no differences in standing alignment among groups. Conclusion. Symptomatic patients with FAI require more flexion at the hip to achieve sitting position due to their inability to compensate through the lumbar spine. With limited spine flexion, FAI patients sit with more anterior pelvic tilt, which may lead to impingement between the acetabulum and proximal femur. Differences in spinopelvic mechanics between FAI and non-FAI patients may contribute to the progression of FAI symptoms. Cite this article: Bone Joint J 2018;100-B:1275–9

Objectives. Many studies have investigated the kinematics of the lumbar spine and the morphological features of the lumbar discs. However, the segment-dependent immediate changes of the lumbar intervertebral space height during flexion-extension motion are still unclear. This study examined the changes of intervertebral space height during flexion-extension motion of lumbar specimens. Methods. First, we validated the accuracy and repeatability of a custom-made mechanical loading equipment set-up. Eight lumbar specimens underwent CT scanning in flexion, neural, and extension positions by using the equipment set-up. The changes in the disc height and distance between adjacent two pedicle screw entry points (DASEP) of the posterior approach at different lumbar levels (L3/4, L4/5 and L5/S1) were examined on three-dimensional lumbar models, which were reconstructed from the CT images. Results. All the vertebral motion segments (L3/4, L4/5 and L5/S1) had greater changes in disc height and DASEP from neutral to flexion than from neutral to extension. The change in anterior disc height gradually increased from upper to lower levels, from neutral to flexion. The changes in anterior and posterior disc heights were similar at the L4/5 level from neutral to extension, but the changes in anterior disc height were significantly greater than those in posterior disc height at the L3/4 and L5/S1 levels, from neutral to extension. Conclusions. The lumbar motion segment showed level-specific changes in disc height and DASEP. The data may be helpful in understanding the physiologic dynamic characteristics of the lumbar spine and in optimising the parameters of lumbar surgical instruments. Cite this article: M. Fu, Q. Ye, C. Jiang, L. Qian, D. Xu, Y. Wang, P. Sun, J. Ouyang. The segment-dependent changes in lumbar intervertebral space height during flexion-extension motion. Bone Joint Res 2017;6:245–252. DOI: 10.1302/2046-3758.64.BJR-2016-0245.R1

Aims. Cross-table lateral (CTL) radiographs are commonly used to measure acetabular component anteversion after total hip arthroplasty (THA). The CTL measurements may differ by > 10° from CT scan measurements but the reasons for this discrepancy are poorly understood. Anteversion measurements from CTL radiographs and CT scans are compared to identify spinopelvic parameters predictive of inaccuracy. Methods. THA patients (n = 47; 27 males, 20 females; mean age 62.9 years (SD 6.95)) with preoperative spinopelvic mobility, radiological analysis, and postoperative CT scans were retrospectively reviewed. Acetabular component anteversion was measured on postoperative CTL radiographs and CT scans using 3D reconstructions of the pelvis. Two cohorts were identified based on a CTL-CT error of ≥ 10° (n = 11) or < 10° (n = 36). Spinopelvic mobility parameters were compared using independent-samples t-tests. Correlation between error and mobility parameters were assessed with Pearson’s coefficient. Results. Patients with CTL error > 10° (10° to 14°) had stiffer lumbar spines with less mean lumbar flexion (38.9°(SD 11.6°) vs 47.4° (SD 13.1°); p = 0.030), different sagittal balance measured by pelvic incidence-lumbar lordosis mismatch (5.9° (SD 18.8°) vs -1.7° (SD 9.8°); p = 0.042), more pelvic extension when seated (pelvic tilt -9.7° (SD 14.1°) vs -2.2° (SD 13.2°); p = 0.050), and greater change in pelvic tilt between supine and seated positions (12.6° (SD 12.1°) vs 4.7° (SD 12.5°); p = 0.036). The CTL measurement error showed a positive correlation with increased CTL anteversion (r = 0.5; p = 0.001), standing lordosis (r = 0.23; p = 0.050), seated lordosis (r = 0.4; p = 0.009), and pelvic tilt change between supine and step-up positions (r = 0.34; p = 0.010). Conclusion. Differences in spinopelvic mobility may explain the variability of acetabular anteversion measurements made on CTL radiographs. Patients with stiff spines and increased compensatory pelvic movement have less accurate measurements on CTL radiographs. Flexion of the contralateral hip is required to obtain clear CTL radiographs. In patients with lumbar stiffness, this movement may extend the pelvis and increase anteversion of the acetabulum on CTL views. Reliable analysis of acetabular component anteversion in this patient population may require advanced imaging with a CT scan. Cite this article: Bone Joint J 2021;103-B(7 Supple B):59–65

Low bone mass and osteopenia have been described in the axial and peripheral skeleton of patients with adolescent idiopathic scoliosis (AIS). Recently, many studies have shown that gene polymorphism is related to osteoporosis. However, no studies have linked the association between IL6 gene polymorphism and bone mass in AIS. This study examined the association between bone mass and IL6 gene polymorphism in 198 girls with AIS. The polymorphisms of IL6-597 G→A, IL6-572 G→C and IL6-174 G→A and the bone mineral density in the lumbar spine and femoral neck were analysed and compared with their levels in healthy controls. The mean bone mineral density at both sites in patients with AIS was decreased compared with controls (p = 0.0022 and p = 0.0013, respectively). Comparison of genotype frequencies between AIS and healthy controls revealed a statistically significant difference in IL6-572 G→C polymorphism (p = 0.0305). There was a significant association between the IL6-572 G→C polymorphism and bone mineral density in the lumbar spine, with the CC genotype significantly higher with the GC (p = 0.0124) or GG (p = 0.0066) genotypes. These results suggest that the IL6-572 G→C polymorphism is associated with bone mineral density in the lumbar spine in Korean girls with AIS

Objectives. Several genome-wide association studies (GWAS) of bone mineral density (BMD) have successfully identified multiple susceptibility genes, yet isolated susceptibility genes are often difficult to interpret biologically. The aim of this study was to unravel the genetic background of BMD at pathway level, by integrating BMD GWAS data with genome-wide expression quantitative trait loci (eQTLs) and methylation quantitative trait loci (meQTLs) data. Method. We employed the GWAS datasets of BMD from the Genetic Factors for Osteoporosis Consortium (GEFOS), analysing patients’ BMD. The areas studied included 32 735 femoral necks, 28 498 lumbar spines, and 8143 forearms. Genome-wide eQTLs (containing 923 021 eQTLs) and meQTLs (containing 683 152 unique methylation sites with local meQTLs) data sets were collected from recently published studies. Gene scores were first calculated by summary data-based Mendelian randomisation (SMR) software and meQTL-aligned GWAS results. Gene set enrichment analysis (GSEA) was then applied to identify BMD-associated gene sets with a predefined significance level of 0.05. Results. We identified multiple gene sets associated with BMD in one or more regions, including relevant known biological gene sets such as the Reactome Circadian Clock (GSEA p-value = 1.0 × 10. -4. for LS and 2.7 × 10. -2. for femoral necks BMD in eQTLs-based GSEA) and insulin-like growth factor receptor binding (GSEA p-value = 5.0 × 10. -4. for femoral necks and 2.6 × 10. -2. for lumbar spines BMD in meQTLs-based GSEA). Conclusion. Our results provided novel clues for subsequent functional analysis of bone metabolism, and illustrated the benefit of integrating eQTLs and meQTLs data into pathway association analysis for genetic studies of complex human diseases. Cite this article: W. Wang, S. Huang, W. Hou, Y. Liu, Q. Fan, A. He, Y. Wen, J. Hao, X. Guo, F. Zhang. Integrative analysis of GWAS, eQTLs and meQTLs data suggests that multiple gene sets are associated with bone mineral density. Bone Joint Res 2017;6:572–576

Aims. Low-energy distal radius fractures (DRFs) are the most common upper arm fractures correlated with bone fragility. Vitamin D deficiency is an important risk factor associated with DRFs. However, the relationship between DRF severity and vitamin D deficiency is not elucidated. Therefore, this study aimed to identify the correlation between DRF severity and serum 25-hydroxyvitamin-D level, which is an indicator of vitamin D deficiency. Methods. This multicentre retrospective observational study enrolled 122 female patients aged over 45 years with DRFs with extension deformity. DRF severity was assessed by three independent examiners using 3D CT. Moreover, it was categorized based on the AO classification, and the degree of articular and volar cortex comminution was evaluated. Articular comminution was defined as an articular fragment involving three or more fragments, and volar cortex comminution as a fracture in the volar cortex of the distal fragment. Serum 25-hydroxyvitamin-D level, bone metabolic markers, and bone mineral density (BMD) at the lumbar spine, hip, and wrist were evaluated six months after injury. According to DRF severity, serum 25-hydroxyvitamin-D level, parameters correlated with bone metabolism, and BMD was compared. Results. The articular comminuted group (n = 28) had a significantly lower median serum 25-hydroxyvitamin-D level than the non-comminuted group (n = 94; 13.4 ng/ml (interquartile range (IQR) 9.8 to 17.3) vs 16.2 ng/ml (IQR 12.5 to 20.4); p = 0.005). The AO classification and volar cortex comminution were not correlated with the serum 25-hydroxyvitamin-D level. Bone metabolic markers and BMD did not significantly differ in terms of DRF severities. Conclusion. Articular comminuted DRF, referred to as AO C3 fracture, is significantly associated with low serum 25-hydroxyvitamin-D levels. Therefore, vitamin D. 3. supplementation for vitamin D deficiency might prevent articular comminuted DRFs. Nevertheless, further studies must be conducted to validate the results of the current study. Cite this article: Bone Jt Open 2022;3(3):261–267