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Background: Few studies focus on the clinical, laboratory, radiological, and biological characteristics of bone and muscle of multiple vertebral fractures, which are associated with a more poor prognosis compared with single fracture., Purpose: To compare the BMD, bone turnover, muscularity, fatty infiltration of muscle, and prevalence of co-morbidities in patients with single and multiple vertebral fractures., Methods: We recruited 100 patients with single fracture (age 66.96 ± 8.24 years) and 100 with multiple fractures (age 69.90 ± 7.80 years); performed dual-energy X-ray absorptiometry of the femoral neck, hip, and lumbar vertebrae; and measured biochemical markers of bone turnover, muscularity, and fatty infiltration., Results: Patients with multiple vertebral fractures had lower hip BMD ( p =0.010) than those with single fractures, but there was no difference in femoral neck and lumbar vertebral BMD nor in muscularity. However, fatty infiltration, an indicator of muscle quality, was significantly higher in participants with multiple fractures ( p =0.006). Diabetes was significantly more common in patients with multiple fractures ( p =0.042). There were no significant differences in markers of bone turnover, and Seperman analyses showed no correlations of CTX-1 or tPINP with the BMD of the hip, femoral neck, or lumbar spine. However, high CTX-1 was associated with high tPINP (r=0.4805; p <0.0001), and marked fatty infiltration was associated with low hip, lumbar vertebral, and femoral neck BMD. Cox regression analyses showed that age (OR 1.057; 95% CI 1.016-1.101; p =0.006) and low hip BMD (OR 0.016; 95% CI, 0.000-0.549; p =0.022) were associated with a higher risk of multiple fractures., Conclusion: Patients with multiple fractures tend to have lower hip BMD, a history of type 2 diabetes, and more substantial fatty infiltration of muscle than in those with single fractures. Age and hip BMD rather than lumbar vertebrae BMD were found to be independent risk factors for multiple vertebral compression fractures, implying that hip BMD may be a more sensitive predictor for multiple vertebral fractures. More improvements in hip BMD and focus on older persons may be useful means of preventing multiple fractures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer NW declared a shared affiliation with the author(s) to the handling editor at the time of review., (Copyright © 2024 Zhang, Li, Wang and Sun.)

Objectives: Organ fat may affect bone metabolism and be associated with vertebral fracture (VF). This study aimed to explore relationships between VF, adiposity indexes measured by MRI, and volumetric BMD (vBMD) measured by quantitative CT (QCT)., Methods: Four hundred volunteers, ranging in age from 22 to 83 years, were recruited and underwent same-day abdominal QCT and chemical shift-encoded (CSE) MRI. We used MRI to quantify the fat content of bone marrow (BMF), psoas major and paraspinal muscles, and the liver. Abdominal fat, VF, and vBMD of the lumbar spine were measured by QCT. For VF discrimination analysis, we examined both the whole cohort (60 VF cases in 30 men and 30 women) and a restricted subgroup of those aged over 50 years (50 VF cases in 23 men and 27 women)., Results: Amongst the men, a 1 SD increase in BMF was associated with a 27.67 (95% CI, -32.71 to -22.62) mg/cm 3 decrease in vBMD after adjusting for age and BMI. Amongst women, all adiposity indexes except for liver fat were significantly associated with vBMD, with BMF having the strongest association (β, -24.00; 95% CI, -28.54 to -19.46 mg/cm 3 ). Similar findings were also observed in participants aged over 50 years. The associations of adiposity indexes with vertebral fracture were not significant after adjusting for age in both sexes aged over 50 years., Conclusions: In both sexes, higher bone marrow fat was associated with lower vBMD at the spine. However, marrow fat and other adipose tissues were not associated with radiographic-based prevalent vertebral fractures., Key Points: • In both sexes, higher bone marrow fat was associated with lower vBMD at the spine. • Among women, all adiposity indexes except for liver fat content were significantly associated with vBMD, with bone marrow fat having the strongest association. • Marrow fat and other adipose tissues were not associated with radiographic-based asymptomatic vertebral fractures., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Background: Individuals with pathogenic variants in SATB2 display intellectual disability, speech and behavioral disorders, dental abnormalities and often features of Pierre Robin sequence. SATB2 encodes a transcription factor thought to play a role in bone remodeling. The primary aim of our study was to systematically review the skeletal manifestations of SATB2-associated syndrome. For this purpose, we performed a non-interventional, multicenter cohort study, from 2017 to 2018. We included 19 patients, 9 females and 10 males ranging in age from 2 to 19 years-old. The following data were collected prospectively for each patient: clinical data, bone markers and calcium and phosphate metabolism parameters, skeletal X-rays and bone mineral density., Results: Digitiform impressions were present in 8/14 patients (57%). Vertebral compression fractures affected 6/17 patients (35%). Skeletal demineralization (16/17, 94%) and cortical thinning of vertebrae (15/17) were the most frequent radiological features at the spine. Long bones were generally demineralized (18/19). The distal phalanges were short, thick and abnormally shaped. C-telopeptide (CTX) and Alkaline phosphatase levels were in the upper normal values and osteocalcin and serum procollagen type 1 amino-terminal propeptide (P1NP) were both increased. Vitamin D insufficiency was frequent (66.7%)., Conclusion: We conclude that SATB2 pathogenic variants are responsible for skeletal demineralization and osteoporosis. We found increased levels of bone formation markers, supporting the key role of SATB2 in osteoblast differentiation. These results support the need for bone evaluation in children and adult patients with SATB2-associated syndrome (SAS)., (© 2022. The Author(s).)

Purpose: Hypogonadism and osteoporosis are frequently reported in HIV-infected men and, besides multifactorial pathogenesis, they might be directly linked because of testicular involvement in bone health. We evaluated the prevalence of osteoporosis and vertebral fractures (VFs) in HIV-infected men, and assessed their relationship with gonadal function., Methods: We enrolled 168 HIV-infected men (median age 53). Osteoporosis and osteopenia were defined with T-score ≤  - 2.5SD and T-score between  - 1 and  - 2.5SD, respectively. VFs were assessed by quantitative morphometric analysis. Total testosterone (TT), calculated free testosterone (cFT), Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) were obtained; overt hypogonadism was defined on symptoms and low TT or cFT, and classified into primary and secondary according to gonadotropins; compensated hypogonadism was defined as normal TT and cFT with high LH levels., Results: Overall, osteoporosis and osteopenia were found in 87.5% of patients, and VFs were detected in 25% of them; hypogonadism was identified in 26.2% of cases. Osteoporotic patients had higher SHBG vs those with normal bone mineral density (BMD). Fractured patients were more frequently hypogonadal and with higher SHBG. SHBG showed negative correlation with both spine and femoral BMD, and positive correlation with VFs. In multivariate models, FSH showed negative impact only on femoral BMD, whereas older age and higher SHBG predicted VFs., Conclusion: We found a high burden of bone disease and hypogonadism in HIV-infected men, and we showed that the impact of gonadal function on bone health is more evident on VFs than on BMD., (© 2021. The Author(s).)

Purpose: Hypercortisolism has detrimental effects on bone metabolism with the consequences of bone loss and bone fractures. We aimed to evaluate the frequency of vertebral fragility fractures and to determine the factors associated with Cushing's syndrome (CS)., Methods: A total of 135 patients diagnosed with Cushing's syndrome [108 patients with Cushing's disease and 27 patients with adrenocortical adenoma] and 107 healthy controls were included in this cross-sectional study. The available clinical, laboratory, and radiologic data of patients with CS were recorded, retrospectively. Lateral vertebral radiograms were evaluated for vertebral fragility fractures according to Genant's semi-quantitative method. Bone mineral density (BMD) was determined using a Dual-energy X-ray absorptiometry (DEXA)., Results: Vertebral fragility fractures (VFs) were observed in 75.3% (n = 61) of the patients. The median number of VFs was six (min-max: 2-12). All patients with vertebral fractures had thoracic VF, and 50.7% of the patients had lumbar fragility fractures. Thirty-three (40.7%) patients with vertebral fractures had normal bone densitometry values. Osteoporosis and osteopenia were observed in 16.2% and 40.7% of the patients, respectively. The duration of active disease, the presence of ACTH-secreting pituitary adenoma, and 24-h urinary cortisol did not influence the presence of vertebral fractures. Vertebral fractures were independently associated with age, FSH, LH levels, and lumbar BMD (R 2  = 68.18%, p = 0.028). The femoral neck BMD (but not lumbar BMD) was independently associated with age, BMI, and PTH levels (R 2  = 48.48%, p < 0.001)., Conclusion: Vertebral fracture frequency was higher in CS patients. Most of the patients with vertebral fractures had multiple fractures. Although low lumbar BMD was associated with VF, patients with CS with normal bone densitometry could experience VF. Vertebral radiograph evaluations as a part of routine evaluation for silent vertebral fractures may help to prevent further fractures in patients with CS., (© 2021. Italian Society of Endocrinology (SIE).)

Objective: This study aimed to determine the prevalence of vertebral fractures (VF) in a selected urban population in Malaysia and to explore possible variables associated with VF in the study population., Methods: A cross-sectional study involving community-living, healthy subjects aged between 45-90 years from the state of Selangor, Malaysia, were invited to attend a bone health check-up. Subjects with diseases known to affect bone metabolism or were on treatment for osteoporosis (OP) were excluded. Bone mineral density (BMD) was measured using dual energy X-ray absorptiometry (DXA). Lateral and antero-posterior view lumbar spine x-rays were performed and VF was determined by the semi-quantitative Genant method., Results: A total of 386 subjects were studied. Asymptomatic morphometric VF were found in 44 (11.4%) subjects. T12 was the most common vertebrae to be fractured. The prevalence of VF was significantly higher in menopausal women (12.4%) compared to non-menopausal women, in those above the age of 60 (18.5%), in those of Chinese ethnicity (16.5%), in those with a low body fat percentage (17.1%) and among those with OP (27.0%). The mean (standard deviation) 25-hydroxyvitamin D [25(OH)D] levels were significantly higher in those with VF compared to those without VF, 67.64 (23.50) and 57.47 (21.71) nmol/L, respectively. However, after multiple regression analysis, age over 60 years and OP on DXA BMD measurement were the only significant associated factors for VF., Conclusion: Overall, 11.4% of a selected Malaysian urban population had asymptomatic morphometric VF. Age over 60 years and OP on DXA BMD measurement, but not 25(OH)D levels, were associated with VF., Competing Interests: The authors have declared that no competing interests exist.

Abstract: Prostate-specific membrane antigen (PSMA) is a membrane glycoprotein, which is overexpressed in prostate cancer cells. With its wide use, there is a growing number of case reports describing non-prostate cancer-related benign and malignant lesions showing increased 68Ga-PSMA uptake. We herein present the case of an 89-year-old man with prostate cancer who was referred for 68Ga-PSMA PET/CT for restaging, which revealed incidental 68Ga-PSMA uptake in compression fracture of a vertebral body. This case demonstrates that PSMA expression may occur in acute compression fractures, and it can be a potential pitfall when reporting 68Ga-PSMA PET/CT images., Competing Interests: Conflicts of interest and sources of funding: None., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Vertebral compression fracture is a hallmark of osteoporosis (OP) and by far the most prevalent fragility fracture. It is well proven that patients who develop a vertebral compression fracture are at substantial risk for additional fractures. Diagnosis is based on adequate clinical evaluation, imaging, and laboratory tests. The imaging of OP and fragility fractures includes conventional radiology to evaluate spinal fractures, bone mineral density (BMD) testing by dual energy x-ray densitometry, quantitative computerized tomography, magnetic resonance imaging, bone scintigraphy (if necessary), and ultrasound. Screening and treatment of individuals with high risk of osteoporotic fracture are cost-effective, but approximately two-thirds of the vertebral compression fractures (VCF) that occur each year are not accurately diagnosed and, therefore, not treated. Evaluation of VCFs, even though they may be asymptomatic, seems essential to health-related and/or clinical research on OP., Competing Interests: The authors declare that there is no conflict of interest., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Objectives: To analyze vertebral fractures risk in patients with chest scans by evaluating vertebral hydroxyapatite concentration measured on spectral CT compared to trabecular attenuation value measured on conventional CT., Methods: Our retrospective study reviewed CT of 216 patients. Analysis of vertebral (T11 - L1) hydroxyapatite concentration by spectral imaging and trabecular attenuation value by conventional CT imaging were performed in patients with chest CT examinations. Specificity, sensitivity, negative predictive value (NPV), and positive predictive value (PPV) were performed by using receiver operating characteristic (ROC) curves in patients with and without vertebral fractures., Results: In male patients, vertebral hydroxyapatite concentration had high area under the ROC curve (0.916), by using the optimal threshold of 72.27 mg/cm 3 , specificity, sensitivity, NPV, and PPV were 91.7, 80.2, 36.7, and 98.7%, respectively. In female patients, vertebral hydroxyapatite concentration also had high area under the ROC curve (0.870), by using the optimal threshold of 74.79 mg/cm 3 , specificity, sensitivity, NPV, and PPV were 100.0, 77.8, 47.4, and 100.0%, respectively. Area under the ROC curve was significantly different between spectral CT-measured bone hydroxyapatite concentration and conventional CT-measured attenuation value in distinguishing vertebral fractures ( p = 0.007 for males; p = 0.005 for females)., Conclusions: Quantitative assessment with spectral CT may appear as higher accuracy than that of conventional CT imaging to analyze risk of vertebral fractures. Hydroxyapatite concentration measured with chest spectral CT may be used to evaluate risk of bone fractures., Advances in Knowledge: Hydroxyapatite concentration measured with chest spectral CT may be used to evaluate risk of bone fractures.

Background: Vertebral fractures (VFs) are the most common clinical manifestation of osteoporosis associated with high morbimortality. A personal/familiar history of fractures increases the risk of fractures. The purpose of this study is to identify possible molecular markers associated with osteoporotic VFs in elderly women from community., Methods: Transcriptomic analysis using Affymetrix HTA2 microarray was performed using whole blood samples of 240 subjects from a population-based survey (Sao Paulo Ageing & Health [SPAH] study). Only elderly women with osteoporosis diagnosis by densitometry were analyzed, and divided in two groups: VF: women with osteoporosis and VFs versus no vertebral fracture (NVF): women with osteoporosis and NVFs. They were matched for age, chronic disease, medication use, and bone mineral density (BMD). The logistic regression model adjusted for age was applied for transcriptome data analysis. SYBR green-based quantitative polymerase chain reaction (qPCR) was used to validate the most significant expression changes obtained in the microarray experiment., Results: Microarray analysis identified 142 differentially expressed genes (DEGs, p < .01), 57 upregulated and 85 downregulated, compared VF versus NVF groups. The DEG with the greatest expression difference was the Gamma2-Syntrophin (SNTG2) (β = 31.88, p = .005). Validation by qPCR confirmed increased expression in VF group of Syntrophin (SNTG2, fold change = 2.79, p = .009), TRAF3 Interacting Protein2 (TRAF3IP2, fold change = 2.79, p = .020), and Integrin Subunit Alpha 6 (ITGA6, fold change = 2.86, p = .038)., Conclusion: Our data identified and validated the association of SNTG2 (608715), TRAF3IP2 (607043), and ITGA6 (147556) with osteoporotic VF in elderly women, independently of BMD. These results suggest that these transcripts have potential clinical significance and may help to explain the molecular mechanisms and biological functions of vertebral fracture., (© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

BACKGROUND The incidence of osteoporotic vertebral fractures (OVCFs) has increased significantly in recent years. In order to assess osteoporotic fracture healing process, it is necessary to study the characteristics after this type of vertebral fracture. However, there are few researches on fracture healing process in severe OVCFs. We aim to investigate the histological healing process and the kinetics of bone turnover markers following severe OVCFs. MATERIAL AND METHODS There were 149 patients with severe OVCFs included in this study. Fasting blood samples were obtained to detect bone turnover markers levels. A transpedicular bone biopsy was performed to collect bone biopsy specimens during vertebroplasty surgery. Stratification of healing process was performed: stage I (1-3 days), stage II (4-10 days), stage III (11-20 days), stage IV (21-30 days), stage V (1-3 months), stage VI (3-6 months). RESULTS Quantitative analysis of bone histomorphometry showed that a large amount of necrotic bone tissue was observed in stage VI (12.92±3.66%). Bone turnover markers showed the concentration of ß-isomerized C-terminal telopeptide (ß-CTX) which reflects activity in osteoclast continued to increase in stage VI (0.9±0.33 ng/mL). These results differed from previous reports of other type vertebral fractures. CONCLUSIONS Bone histomorphometric analysis and bone turnover markers showed that severe osteoporotic vertebral compression fractures often associated with delayed union and nonunion during the healing process.

Here I review vertebral fractures (VFs) as an emerging complication of acromegaly through a pathway of key questions in order to help clinicians manage the disease. Peculiarities of acromegalic osteopathy are that VFs are common but not explained by low bone mineral density (BMD) being related to disease duration and activity, and occurring even after remission., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Acromegaly and Growth Hormone Deficiency (GHD) are associated with skeletal fragility and with an increased prevalence of Vertebral Fractures (VFs). In the most recent years, several authors tried to investigate surrogate markers that may predict the risk of bone fragility in these endocrine disorders. The aim of this review is to evaluate the role of GH receptor polymorphisms in skeletal fragility in patients affected by GHD and acromegaly. In fact, until now, two different isoforms of the GH Receptor (GHR) were described, that differ for the presence or the absence of transcription of the exon 3 of the GHR gene. Both the isoforms produce a functioning receptor, but the exon 3-deleted isoforms (d3-GHR) has a higher sensitivity to endogenous and recombinant GH as compared to the full-length isoform (fl-GHR)., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The location of osteoporotic fragility fractures adds crucial information to post-fracture risk estimation. Triaging patients according to fracture site for secondary fracture prevention can therefore be of interest to prioritize patients considering the high imminent fracture risk. The objectives of this cross-sectional study were therefore to explore potential differences between central (vertebral, hip, proximal humerus, pelvis) and peripheral (forearm, ankle, other) fractures. This substudy of the Norwegian Capture the Fracture Initiative (NoFRACT) included 495 women and 119 men ≥50 years with fragility fractures. They had bone mineral density (BMD) of the femoral neck, total hip, and lumbar spine assessed using dual-energy X-ray absorptiometry (DXA), trabecular bone score (TBS) calculated, concomitantly vertebral fracture assessment (VFA) with semiquantitative grading of vertebral fractures (SQ1-SQ3), and a questionnaire concerning risk factors for fractures was answered. Patients with central fractures exhibited lower BMD of the femoral neck (765 versus 827 mg/cm 2 ), total hip (800 versus 876 mg/cm 2 ), and lumbar spine (1024 versus 1062 mg/cm 2 ); lower mean TBS (1.24 versus 1.28); and a higher proportion of SQ1-SQ3 fractures (52.0% versus 27.7%), SQ2-SQ3 fractures (36.8% versus 13.4%), and SQ3 fractures (21.5% versus 2.2%) than patients with peripheral fractures (all p < 0.05). All analyses were adjusted for sex, age, and body mass index (BMI); and the analyses of TBS and SQ1-SQ3 fracture prevalence was additionally adjusted for BMD). In conclusion, patients with central fragility fractures revealed lower femoral neck BMD, lower TBS, and higher prevalence of vertebral fractures on VFA than the patients with peripheral fractures. This suggests that patients with central fragility fractures exhibit more severe deterioration of bone structure, translating into a higher risk of subsequent fragility fractures and therefore they should get the highest priority in secondary fracture prevention, although attention to peripheral fractures should still not be diminished. © 2019 American Society for Bone and Mineral Research. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research., (© 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.)

Purpose: Our purpose was to combine intravoxel incoherent motion diffusion-weighted MR imaging (IVIM-DWI) and magnetic resonance spectroscopy (MRS) to differentiate osteoporotic fractures from osteolytic metastatic vertebral compression fractures (VCFs)., Methods: A total of 70 patients with VCFs were included and divided into two groups, according to their causes of fractures based on pathological findings or clinical follow-up. All patients underwent conventional sagittal T1WI, T2WI, STIR, IVIM-DWI, and single-voxel MRS. The diffusion coefficient (D), pseudo diffusion (D*), and perfusion fraction (f) parameters from IVIM-DWI and the lipid water ratio (LWR) and fat fraction (FF) parameters from MRS were obtained and compared among groups. Furthermore, the diagnostic performance of MRS, IVIM-DWI, and IVIM-DWI combined with MRS for differentiation between osteoporotic and osteolytic metastatic VCFs was assessed by using receiver operating characteristic (ROC) curve analysis., Results: Compared with the osteoporotic group, the metastatic group had significantly lower values for f, D, and FF, but higher D* (all P < 0.05). The area under the receiver operating characteristic (ROC) curve of MRS, IVIM-DWI, and IVIM-DWI combined with MRS were 0.73, 0.88, and 0.94, respectively. Among these, the IVIM-DWI combined with MRS showed the highest sensitivity, specificity, and accuracy, which are 90.63% (29/32), 97.37 % (37/38), and 94.29% (66/70), respectively., Conclusions: IVIM-DWI combined with MRS can be more accurate and efficient for differentiation between osteoporotic and osteolytic metastatic VCFs than single MRS or IVIM-DWI.

Little is known about the function of acid-sensing ion channels (ASICs) in bone cells or osteoporotic vertebral fractures (OVF). This study delineated ASICs expression in adult human bone marrow-mesenchymal stem cells- (BM-MSC-) derived osteoblasts and in OVF bone cells. Adult BM-MSC-derived osteoblasts were isolated and cultured in different pH values. Osteogenic markers as alkaline phosphatase (ALP), osteopontin (OPN), and osteocalcin (OC) mRNA were assessed. Western blots method was applied to analyze ASICs protein expression in different pH values. Amiloride was added into the osteogenic media to analyze the Na + /K + ATPase change. We harvested the vertebral cancellous bone through a bone biopsy needle in 26 OVF patients when performing percutaneous vertebroplasty. Six vertebral bone specimens obtained from 4 patients with high-energy vertebral fractures were used as the control. The reverse transcription polymerase chain reaction was performed to analyze the quantitative mRNA expression of ASICs. Osteogenic markers as ALP, OPN, and OC mRNA were higher expressed in increasing pH values throughout osteoblastogenesis. ASIC proteins were higher expressed in lower pH media, especially ASIC3, and ASIC4. The highest protein expression at days 7, 14, and 21 was ASIC2, ASIC4, and ASIC3, respectively. Expression of Na + /K + ATPase was significantly decreased in cultured osteoblasts by addition of amiloride into the pH 6.9 osteogenic media. ASIC2 mRNA was most highly expressed with a 65.93-fold increase in the biopsied vertebral bone cells in OVF compared with the control. In conclusion, we found osteoblastogenesis was reduced in an acidic environment, and ASIC2, ASIC3, and ASIC4 were most highly expressed in turn during osteoblastogenesis within acidic media. ASIC2 was the most abundantly expressed gene in human bone cells in OVF compared with the control. ASIC2 could be crucial in the pathogenesis of osteoporosis and could serve as a therapeutic target for antiosteoporotic therapies., Competing Interests: The authors have no conflicts of interest and no founding in any product mentioned or concept discussed in this article.

Teriparatide (TPTD) and abaloparatide (ABL) are the only osteoanabolic drugs available, at this time, for treatment of osteoporosis. TPTD is a 34-amino acid fragment that is identical in its primary sequence to the 34 amino acids of full-length human parathyroid hormone [hPTH(1-84)]. ABL is identical to parathyroid hormone-related peptide (PTHrP) through the first 22 residues with significantly different amino acids inserted thereafter, between residues 22 and 34. The osteoanabolic actions of PTH are due directly to its effects on cells of the osteoblast lineage and indirectly by stimulating IGF-I synthesis and suppressing sclerostin and associated enhancement of Wnt signalling. Both TPTD and ABL are ligands that bind to and activate the PTH receptor type 1 (PTHR1) receptor but they appear to do so differently: ABL favours the transient, more anabolic configuration of the receptor. Both TPTD and ABL reduce the risk of vertebral fractures and non-vertebral fractures. Both drugs are administered for a maximum of 24 months, and should be followed by an antiresorptive agent to maintain gains in bone mineral density (BMD). Romosozumab, a monoclonal antibody that binds to and inhibits sclerostin, appears to have dual actions by stimulating bone formation and reducing bone resorption. In the pivotal clinical trial, romosozumab, administered as a 210 mg monthly subcutaneous dose, significantly reduced new vertebral fractures and in a subsequent study reduced both vertebral and non-vertebral fractures., (© 2018 The British Pharmacological Society.)

Meta-analyses conducted >15 years ago reported that improvements in bone mineral density (BMD) were associated with reduction in vertebral and nonvertebral fractures in osteoporosis trials. Numerous studies have been conducted since then, incorporating new therapies with different mechanisms of action and enrolling many more subjects. To extend these prior analyses, we conducted a meta-regression of 38 placebo-controlled trials of 19 therapeutic agents to determine the association between improvements in BMD and reductions in fracture risk. We used a linear model to examine the relationship between mean percent difference in BMD change between treatment and placebo groups and the logarithm of the relative risk. We found that greater improvements in BMD were strongly associated with greater reductions in vertebral and hip fractures but not nonvertebral fractures. For vertebral fracture, the r 2 values for total hip, femoral neck, and lumbar spine BMD change were 0.56, 0.54, and 0.63, respectively (p ≤ 0.0002). For a 2% or 6% improvement in total hip BMD, we might expect a 28% or 66% reduction, respectively, in vertebral fracture risk. For hip fracture, the r 2 values for total hip, femoral neck, and lumbar spine BMD change were 0.48 (p = 0.01), 0.42 (p = 0.02), and 0.22 (ns), respectively. For a 2% or 6% improvement in total hip BMD, we might expect a 16% or 40% reduction in hip fracture risk. In conclusion, our results extend prior observations that larger improvements in dual-energy X-ray absorptiometry (DXA)-based BMD are associated with greater reductions in fracture risk, particularly for vertebral and hip fractures. Although these results cannot be directly applied to predict the treatment benefit in an individual patient, they provide compelling evidence that improvements in BMD with osteoporosis therapies may be useful surrogate endpoints for fracture in trials of new therapeutic agents. © 2019 American Society for Bone and Mineral Research., (© 2019 American Society for Bone and Mineral Research.)

Metastasis of cancer to the spine impacts bone quality. This study aims to characterize vertebral microdamage secondary to metastatic disease considering the pattern of damage and its relationship to stress and strain under load. Osteolytic and mixed osteolytic/osteoblastic vertebral metastases were produced in athymic rats via HeLa cervical or canine Ace-1 prostate cancer cell inoculation, respectively. After 21 days, excised motion segments (T12-L2) were µCT scanned, stained with BaSO 4 and re-imaged. T13-L2 motion segments were loaded in axial compression to induce microdamage, re-stained and re-imaged. L1 (loaded) and T12 (unloaded) vertebrae were fixed, sample blocks cut, polished and BSE imaged. µFE models were generated of all L1 vertebrae with displacement boundary conditions applied based on the loaded µCT images. µCT stereological analysis, BSE analysis and µFE derived von Mises stress and principal strains were quantitatively compared (ANOVA), spatial correlations determined and patterns of microdamage assessed qualitatively. BaSO 4 identified microdamage was found to be spatially correlated with regions of high stress in µFEA. Load-induced microdamage was shown to be elevated in the presence of osteolytic and mixed metastatic disease, with diffuse, crossed hatched areas of microdamage present in addition to linear microdamage and microfractures in metastatic tissue, suggesting diminished bone quality.

The current diagnosis of osteoporosis is limited to a T-score ≤-2.5. However, asymptomatic vertebral fractures (VF) are known to predict a high risk of subsequent fractures and pharmaceutical intervention is known to reduce future fracture risk in these individuals. In a prospective, population-based cohort of ambulant older women, we sought to evaluate the role of VF detection by screening densitometric lateral spine imaging (LSI) for VF at time of bone density testing to the effect on the magnitude of fracture risk. A total of 1084 women (mean age 75 years ± SD 3 years) had baseline LSI that identified 100 (9%) women with VFs and 89 (8%) with femoral neck (FN) T-score osteoporosis ≤-2.5. Follow-up identified incident clinical spine fracture in 73 (7%), 305 (28%) with any fracture-related hospitalization, and 121 (11%) with a hip fracture-related hospitalization. Compared with those without baseline VF, in those with baseline VF, relative risk (RR) for incident clinical spine, hip, and any fracture were 3.46 (95% confidence interval [CI] 2.14-5.60, p < 0.001); 1.72 (95% CI 1.09-2.71, p = 0.02), and 1.4 (95% CI 1.07-1.84, p = 0.02), respectively. In 675 (62%) of women with femoral neck osteopenia (T-score <-1 to >-2.5), 61 (9%) also had a VF. Compared with those without baseline VF, RR for any incident fragility fractures and fractures at spine and hip in those with baseline VF were 1.6 (95% CI 1.2-2.1, p < 0.01), 3.9 (95% CI 2.2-6.9, p < 0.01), and 1.6 (95% CI 0.9-2.8, p = 0.10), respectively. On basis of the prognosis, older women with LSI VF with osteopenia should be diagnosed with osteoporosis and should be considered for pharmaceutical intervention. © 2018 American Society for Bone and Mineral Research., (© 2018 American Society for Bone and Mineral Research.)

Background: Histological and histochemical analyses of muscle samples were used to determine the intensity of paraspinal muscle injury during open (OPEN) and minimally invasive (MIS) procedures due to spinal trauma., Objective: A randomised prospective study design was chosen. According to our hypothesis, OPEN procedures will lead to more intensive microscopic changes than MIS., Methods: Muscle samples were collected during the primary surgery - fracture surgery (FRS) from the left and during material extraction (EXS) from the right side. Complete samples were acquired from 17 OPEN and 18 MIS subjects. We compared them histochemically and histologically; muscle fibre typing and statistical analysis were performed., Results: We statistically confirmed that the increase in fibrosis in the OPEN EXS sample was significantly higher than in the MIS EXS sample, with p< 0.05 (p= 0.000322453). Fibre types in MIS did not differ almost at all in both samples; the changes were statistically insignificant.In OPEN samples, the number of type I fibres differed significantly. In EXS, it was significantly lower (46.23%) than in FRS (60.63%), at a statistically significant level, p< 0.05 (p= 0.0234375000) especially with the increase of the type IIA fibres, less in IIB fibres., Conclusions: These microscopic findings provide a statistically significant confirmation that OPEN procedures in spinal fracture lead, in most cases, to significant changes in the structure of the corset muscle at the fracture site and surgical access point than MIS procedures.

Background: Percutaneous kyphoplasty (PKP) is the first-line treatment for osteoporotic vertebral compression fractures (OVCFs) that can immediately relieve pain and allow the quick recovery of lost mobility. However, some studies reported that after PKP, the incidence of vertebral refracture, particularly adjacent vertebral fracture (AVF), was high. Our previous meta-analysis suggested that the risks for vertebral refracture and AVF did not increase after percutaneous vertebral augmentation in OVCF patients. Despite the negative results of our meta-analysis, there is still significant evidence regarding the relationship between kyphoplasty and AVF, so a new prospective cohort study is warranted. In addition, in our previous retrospective study, we found that advanced age, female sex and low oestradiol (E 2 ) concentrations might be related to the occurrence of postoperative vertebral refracture after PKP. To sufficiently evaluate the probable factors involved in the occurrence of postoperative vertebral refracture, we designed this prospective study., Methods: This is a prospective cohort study of patients admitted for PKP to treat painful OVCFs. The baseline data, including demographic information, lifestyle, bone metabolic status, sex hormone and sex hormone-binding globulin (SHBG) levels, and clinical characteristics will be collected at the time of enrolment. Surgical features of PKP will be recorded on the operation day. Lifestyle, bone metabolic status, sex hormone levels, and SHBG levels will be assessed during the follow-up period at 1 m, 3 m, 12 m, and 24 m postoperatively. Patients suffering from acutely aggravated back pain will be referred to an orthopaedist, and refractured vertebrae will be confirmed by magnetic resonance imaging and computed tomography. The primary outcome will be the incidence of vertebral refracture. Multivariate analyses will be carried out to evaluate the variables that are independently correlated with vertebral refracture., Discussion: To evaluate the risk of postoperative refracture preoperatively and to identify the surgical points related to postoperative refracture, this study will explore the risk factors related to vertebral refracture after PKP. The results may provide new information about defining OVCF patients suitable for PKP treatment., Trial Registration: ChiCTR-ROC-17011562 . Registered on July 4th, 2017.

Background: Observational studies have indicated a high but heterogeneous prevalence of low bone mineral density (BMD) and vertebral fractures (VF) in patients with systemic lupus erythematosus (SLE). Therefore, the objectives of this systematic review and meta-regression were: 1) to compare BMD between SLE patients and healthy controls and 2) to evaluate the relationship between BMD and glucocorticoid therapy and VF in SLE patients., Methods and Findings: Articles were identified from electronic databases (PubMed, Embase, VHL, SciELO and the Cochrane Library). Prospective longitudinal and cross-sectional studies were considered for review. We evaluated the quality of the evidence included using the Oxford Centre for evidence-based medicine (EBM) Levels of Evidence. In total, 38 articles were identified and analyzed (3442 SLE cases and 6198 controls) in the analysis of BMD (9232 women and 408 men). There were significant differences in mean BMD between SLE patients and controls. BMD mean difference in cases/controls: -0.0566 95% CI (-0.071, -0.0439; p = < 0.0001). When only SLE patients were analyzed, the BMD did not significantly differ between patients who had or had not received glucocorticoid (GCT) therapy. 694 SLE patients were included in the analysis of VF (189 with VF vs. 505 without VF). Patients with VF had lower BMD than patients without VF (BMD mean difference without VF/with VF: 0.033 (95%CI: 0.006-0.060); p-value: 0.0156)., Conclusions: Patients with SLE had lower BMD than healthy controls. Moreover, SLE patients with VF had lower BMD than patients without VF. However, our data did not show that GCT therapy had an impact on BMD., Competing Interests: The authors have declared that no competing interests exist.

The 2-year, randomized, double-blind, active-controlled fracture endpoint VERO study included postmenopausal women with established osteoporosis, who had at least 2 moderate or 1 severe baseline vertebral fractures (VFx), and bone mineral density (BMD) T-score ≤-1.5. Patients were treated with either s.c. daily teriparatide 20 μg or oral weekly risedronate 35 mg. As previously reported, the risk of new VFx and clinical fractures (a composite of clinical VFx and nonvertebral fragility fractures [NVFFx]) was statistically significantly reduced with teriparatide compared with risedronate. Here we present the prospectively planned subgroup analyses of fracture data across subgroups, which were predefined by the following baseline characteristics: age, number and severity of prevalent VFx, prevalent nonvertebral fractures (NVFx), glucocorticoid use, prior osteoporosis drugs, recent bisphosphonate use, clinical VFx in the year before study entry, and baseline BMD. Heterogeneity of the treatment effect on the primary endpoint (new VFx), and the four key secondary endpoints (including clinical fractures and NVFFx) were investigated by logistic and Cox proportional hazards regression models. A total of 1360 women were randomized and treated (680 per group). Mean age was 72.1 years, mean (SD) number of prevalent VFx was 2.7 (2.1), 55.4% had a BMD T-score <-2.5, 36.5% had a recent clinical VFx, 28.3% had a prior major NVFx, 43.2% were osteoporosis drug-naïve, 39.3% were recent bisphosphonate users, and 9.3% were taking glucocorticoids at a prednisone-equivalent dose of >5 mg/d. For most fracture endpoints, the risk reduction of teriparatide versus risedronate did not significantly differ in any of the subgroups analyzed (treatment-by-subgroup interaction p > 0.1), with most subgroups mirroring results from the total study population. In conclusion, in postmenopausal women with severe osteoporosis, the antifracture efficacy of teriparatide compared with risedronate was consistent in a wide range of patient settings, including treatment-naïve and previously treated patients. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc., (© 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.)

We compared two methods for osteoporotic vertebral fracture (VF) assessment on lateral spine radiographs, the Genant semiquantitative (GSQ) technique and a modified algorithm-based qualitative (mABQ) approach. We evaluated 4465 women and 1771 men aged ≥50 years from the Canadian Multicentre Osteoporosis Study with available X-ray images at baseline. Observer agreement was lowest for grade 1 VFs determined by GSQ. Among physician readers, agreement was greater for VFs diagnosed by mABQ (ranging from 0.62 [95% confidence interval (CI) 0.00-1.00] to 0.88 [0.76-1.00]) than by GSQ (ranging from 0.38 [0.17-0.60] to 0.69 [0.54-0.85]). GSQ VF prevalence (16.4% [95% CI 15.4-17.4]) and incidence (10.2/1000 person-years [9.2; 11.2]) were higher than with the mABQ method (prevalence 6.7% [6.1-7.4] and incidence 6.3/1000 person-years [5.5-7.1]). Women had more prevalent and incident VFs relative to men as defined by mABQ but not as defined by GSQ. Prevalent GSQ VFs were predominantly found in the mid-thoracic spine, whereas prevalent mABQ and incident VFs by both methods co-localized to the junction of the thoracic and lumbar spine. Prevalent mABQ VFs compared with GSQ VFs were more highly associated with reduced adjusted L 1 to L 4 bone mineral density (BMD) (-0.065 g/cm 2 [-0.087 to -0.042]), femoral neck BMD (-0.051 g/cm 2 [-0.065 to -0.036]), and total hip BMD (-0.059 g/cm 2 [-0.076 to -0.041]). Prevalent mABQ VFs compared with prevalent GSQ were also more highly associated with incident VF by GSQ (odds ratio [OR] = 3.3 [2.2-5.0]), incident VF by mABQ (9.0 [5.3-15.3]), and incident non-vertebral major osteoporotic fractures (1.9 [1.2-3.0]). Grade 1 mABQ VFs, but not grade 1 GSQ VFs, were associated with incident non-vertebral major osteoporotic fractures (OR = 3.0 [1.4-6.5]). We conclude that defining VF by mABQ is preferred to the use of GSQ for clinical assessments. © 2017 American Society for Bone and Mineral Research., (© 2017 American Society for Bone and Mineral Research.)

Background: Impaired bone quality is associated with poor outcome of spinal surgery. The aim of the study was to assess the bone mineral status of patients scheduled to undergo spinal surgery and to report frequencies of bone mineral disorders., Methods: We retrospectively analyzed the bone mineral status of 144 patients requiring spinal surgery including bone mineral density by dual-energy X-ray absorptiometry (DXA) as well as laboratory data with serum levels of 25-hydroxyvitamin D (25-OH-D), parathyroid hormone, calcium, bone specific alkaline phosphate, osteocalcin, and gastrin. High-resolution peripheral quantitative computed tomography (HR-pQCT) was additionally performed in a subgroup of 67 patients with T-Score below - 1.5 or history of vertebral fracture., Results: Among 144 patients, 126 patients (87.5%) were older than 60 years. Mean age was 70.1 years. 42 patients (29.1%) had suffered from a vertebral compression fracture. 12 previously undiagnosed vertebral deformities were detected in 12 patients by vertebral fracture assessment (VFA). Osteoporosis was present in 39 patients (27.1%) and osteopenia in 63 patients (43.8%). Only 16 patients (11.1%) had received anti-osteoporotic therapy, while 54 patients (37.5%) had an indication for specific anti-osteoporotic therapy but had not received it yet. The majority of patients had inadequate vitamin D status (73.6%) and 34.7% of patients showed secondary hyperparathyroidism as a sign for a significant disturbed calcium homeostasis. In a subgroup of 67 patients, severe vertebral deformities were associated with stronger deficits in bone microarchitecture at the distal radius compared to the distal tibia., Conclusions: This study shows that bone metabolism disorders are highly prevalent in elderly patients scheduled for spinal surgery. Vertebral deformities are associated with a predominant deterioration of bone microstructure at the distal radius. As impaired bone quality can compromise surgical outcome, we strongly recommend an evaluation of bone mineral status prior to operation and anti-osteoporotic therapy if necessary.

Purpose/Aim of the study: To evaluate the biomechanical characteristics and biocompatibility of an injectable, biodegradable calcium phosphate cement (CPC) containing poly lactic-co-glycolic acid (PLGA)., Materials and Methods: A vertebral compression fracture model was established using 20 human cadaveric vertebrae (T11-L3) divided into CPC/PLGA composite versus PMMA groups for biomechanical testing. In addition, 35 New Zealand rabbits were used to evaluate biodegradability and osteoconductive properties of CPC/PLGA using a bone defect model. In vitro cytotoxicity was evaluated by culturing with L929 cells., Results: The CPC/PLGA composite effectively restored vertebral biomechanical properties. Compared with controls, the maximum load and compression strength of the CPC/PLGA group were lower, and stiffness was lower after kyphoplasty (all p <.05). Degradation was much slower in the control CPC compared with CPC/PLGA group. The bone tissue percentage in the CPC/PLGA group (44.9 ± 23.7%) was significantly higher compared with control CPC group (25.7 ± 10.9%) (p <.05). The viability of cells cultured on CPC/PLGA was greater than 70% compared with the blanks., Conclusions: Our biodegradable CPC/PLGA composite showed good biomechanical properties, cytocompatibility, and osteoconductivity and may represent an ideal bone substitute for future applications.

Objective: Osteoporosis diagnosis using multidetector CT (MDCT) is limited to relatively high radiation exposure. We investigated the effect of simulated ultra-low-dose protocols on in-vivo bone mineral density (BMD) and quantitative trabecular bone assessment., Materials and Methods: Institutional review board approval was obtained. Twelve subjects with osteoporotic vertebral fractures and 12 age- and gender-matched controls undergoing routine thoracic and abdominal MDCT were included (average effective dose: 10 mSv). Ultra-low radiation examinations were achieved by simulating lower tube currents and sparse samplings at 50%, 25% and 10% of the original dose. BMD and trabecular bone parameters were extracted in T10-L5., Results: Except for BMD measurements in sparse sampling data, absolute values of all parameters derived from ultra-low-dose data were significantly different from those derived from original dose images (p<0.05). BMD, apparent bone fraction and trabecular thickness were still consistently lower in subjects with than in those without fractures (p<0.05)., Conclusion: In ultra-low-dose scans, BMD and microstructure parameters were able to differentiate subjects with and without vertebral fractures, suggesting osteoporosis diagnosis is feasible. However, absolute values differed from original values. BMD from sparse sampling appeared to be more robust. This dose-dependency of parameters should be considered for future clinical use., Key Points: • BMD and quantitative bone parameters are assessable in ultra-low-dose in vivo MDCT scans. • Bone mineral density does not change significantly when sparse sampling is applied. • Quantitative trabecular bone microstructure measurements are sensitive to dose reduction. • Osteoporosis subjects could be differentiated even at 10% of original dose. • Radiation exposure should be considered when comparing quantitative bone parameters.

Objective: Published studies have demonstrated that adding vertebral fracture assessment (VFA) to dual-energy X-ray absorptiometry (DXA) identifies more patients with increased fracture risk than DXA alone. But who needs VFA? This study attempts to determine if some test other than VFA could duplicate the additional information obtained by performing VFA on all first-time patients. This study looked at the Fracture Risk Assessment Tool (FRAX), height loss, age, documented back pain, and nonvertebral fragility fractures., Methods: VFA was performed on 1,259 (all) DXA patients at their first visit from March 2010 through September 2013. All DXA and VFA results were read by the same International Society for Clinical Densitometry-certified clinician., Results: By DXA alone, 44% were osteoporosis. Adding VFA increased clinical osteoporosis by 36% of the original total patients. Eighty-three "normal bone mineral density" patients were changed to clinical osteoporosis. FRAX identified 53% of the patients with diagnosis changes. Historical height loss was not reliable. Increasing age correlated only weakly with clinical osteoporosis., Conclusion: These are modest numbers from a nonacademic referral practice and may not be typical of other populations. Thirty-six percent of our patients were misclassified by DXA alone, with fragility fractures already taken into account for T-scores of -1.5 and lower. FRAX, height loss, age, back pain, and fragility fractures all failed to identify many of the patients identified by VFA. Seeing the lateral spine images obtained by VFA influenced patients and families. VFA on all first-time patients should be reconsidered., Abbreviations: BMD = bone mineral density DXA = dual-energy X-ray absorptiometry FRAX = Fracture Risk Assessment Tool HL = height loss ISCD = International Society for Clinical Densitometry VF = vertebral fracture VFA = vertebral fracture assessment.

The objective of this study was to compare the proportion of patients at high fracture risk according to FRAX® and FRAX® adjusted on TBS in patients hospitalized for a non vertebral fractures. Patients were selected from a Fracture Liaison Service FLS): clinical risk factors, bone mineral density (BMD) and TBS were assessed at the time of the fracture. Without considering the current fracture, we calculated FRAX® and FRAX® adjusted on TBS (TBS-FRAX®), and compared the proportion of patients with a high risk for major osteoporotic fracture (MOF)>20% according to FRAX® and TBS-FRAX®, and the proportion of subjects who should be treated according to current guidelines. Four hundred and thirteen patients were included for a non vertebral fracture (84.5% women, mean age of 73.9±11.7years), Two hundred and eight patients (50.4%) had osteoporosis (T≤-2.5 at least one site) and the mean value of TBS was 1.206 (±0.111). The proportion of patients with a risk of MOF≥20% before the fracture was similar with FRAX® and TBS-FRAX® (24.7% vs 25.4%). The proportion of patients identified with a risk of MOF above the threshold value of therapeutic intervention was higher using TBS-FRAX® than FRAX® for the age categories of 60-70years (38.3% vs 30.9%, p=0.01) and 70-80years (31.2% vs. 26.6%, p=0.04). This study showed that the proportion of patients at high risk of fracture is similar using FRAX® and FRAX® adjusted on TBS in patients hospitalized for a non vertebral fracture in a FLS., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Traumatic odontoid fractures (TOFs) have been described as the most common injury affecting the C-spine in the elderly. Previous studies have identified degenerative changes and bone loss as important predisposing factors. However, their interaction and respective age-adjusted impact needs further clarification. We conducted a retrospective analysis of 5303 patients (aged ≥60 years) admitted to a level I trauma center between January 2008 and January 2016 who underwent CT imaging of the C-spine. Ninety-two patients with TOF and 80 patients with other cervical spine fractures (OCSF) were identified and a respective 3:1 age- and sex-matched control group without fractures after trauma was built. In all groups, cervical bone mineral density (cBMD) was determined using phantom calibration, and degenerative changes were evaluated in a qualitative manner. In all groups, the severity of degenerative changes of the C-spine increased with age (all p < 0.05) and was inversely correlated with cBMD (all p < 0.05). cBMD was the only significant predictor of a TOF in a multivariate logistic regression model (adjusted odds ratio [OR] = 3.066, 95% confidence interval [CI] 1.432-6.563 for cervical osteoporosis). An association between odontoid cysts and TOF reached significance only in Anderson and D'Alonzo (A&D) type II TOFs (aOR = 1.383; 95% CI 1.012-1.890). Patients with OCSFs, compared with patients with TOFs, were younger (median 74 versus 83 years) and had a higher cBMD (median 208 mg/mL versus 172 mg/mL). No differences were observable when comparing cBMD and grades of degenerative changes between OCSFs and their control group (all p >0.1). Decreased cBMD is the major predisposing factor for the occurrence of TOF but not for OCSF in the elderly. The severity of odontoid cysts was found to be a cBMD-independent factor associated with A&D type II TOFs. However, degenerative changes in the odontoid neighboring joints seem to be an epiphenomenon of bone loss and older age but do not independently predispose for TOF. © 2017 American Society for Bone and Mineral Research., (© 2017 American Society for Bone and Mineral Research.)

Background: This study aims to investigate the role of thymic stromal lymphopoietin (TSLP) in the pathogenesis of lumbar disc degeneration (LDD)., Methods: Nucleus pulposus tissues were collected from 77 LDD patients (the case group), in addition, normal tissues were extracted from 21 patients suffering from lumbar fractures (the control group). Immunohistochemistry was applied in order to detect TSLP positive expression. In accordance with varying transfection, the cells were divided into TSLP-siRNA, TSLP-siRNA + TSLPR-siRNA, control, blank, anti-TSLPR, and IgG groups. Western blotting was used in order to detect TSLP expression in tissues, and TSLP and type II collagen (COL2AL) in cell culture media were detected using enzyme linked immunosorbent assay (ELISA). Cell viability was measured using a MTT assay. Aggrecan levels were detected using antonopulos, and cell apoptosis was determined using flow cytometry., Results: TSLP-positive expression was found to be significantly higher in the case group compared with the control group. LDD patients' Pfirrmann grades and preoperative visual analogue scale (VAS) scores were associated with TSLP-positive rate. Cells transfected with TSLP-siRNA and TSLPR-siRNA plasmids exhibited lower TSLP and thymic stromal lymphopoietin receptor (TSLPR) protein expression compared with the control and blank groups. Compared with the control and blank groups, there was significantly higher cell viability, lower cell apoptosis, and higher COL2AL and Aggrecan levels in the TSLP-siRNA, anti-TSLPR, and TSLP-siRNA+TSLPR-siRNA groups; there were significant differences between the TSLP-siRNA, anti-TSLPR, and TSLP-siRNA+TSLPR-siRNA groups and IgG group (all P < .05) CONCLUSION:: Our study provides evidence for the hypothesis that TSLP could reflect the histological severity of LDD, and TSLP-siRNA and, TSLPR-siRNA could inhibit apoptosis of nucleus pulposus cells. The evident information obtained from the investigation could lead the way for new therapeutic approaches regarding LDD treatment.

The association of trabecular bone score (TBS) with incident clinical and radiographic vertebral fractures in older men is uncertain. TBS was estimated from baseline spine dual-energy X-ray absorptiometry (DXA) scans for 5831 older men (mean age 73.7 years) enrolled in the Osteoporotic Fractures in Men (MrOS) study. Cox proportional hazard models were used to determine the association of TBS (per 1 SD decrease) with incident clinical vertebral fractures. Logistic regression was used to determine the association between TBS (per 1 SD decrease) and incident radiographic vertebral fracture among the subset of 4309 men with baseline and follow-up lateral spine radiographs (mean 4.6 years later). We also examined whether any associations varied by body mass index (BMI) category. TBS was associated with a 1.41-fold (95% confidence interval [CI] 1.23 to 1.63) higher aged-adjusted odds of incident radiographic fracture, and this relationship did not vary by BMI (p value = 0.22 for interaction term). This association was no longer significant with further adjustment for lumbar spine bone mineral density (BMD; odds ratio [OR] = 1.11, 95% CI 0.94 to 1.30). In contrast, the age-adjusted association of TBS with incident clinical vertebral fracture was stronger in men with lower BMI (≤ median value of 26.8 kg/m 2 ; hazard ratio [HR] = 2.28, 95% CI 1.82 to 2.87) than in men with higher BMI (> median; HR = 1.60, 95% CI 1.31 to 1.94; p value = 0.0002 for interaction term). With further adjustment for lumbar spine BMD, the association of TBS with incident clinical vertebral fracture was substantially attenuated in both groups (HR = 1.30 [95% CI 0.99 to 1.72] among men with lower BMI and 1.11 [95% CI 0.87 to 1.41] among men with higher BMI). In conclusion, TBS is not associated with incident clinical or radiographic vertebral fracture after consideration of age and lumbar spine BMD, with the possible exception of incident clinical vertebral fracture among men with lower BMI. © 2017 American Society for Bone and Mineral Research., (© 2017 American Society for Bone and Mineral Research.)

A 50-year-old man with recently diagnosed prostate cancer was referred for Ga-prostate-specific membrane antigen (PSMA) PET/CT with elevated prostate-specific antigen. PET/CT demonstrated increased PSMA uptake in an undisplaced transverse fracture of the L1 vertebral body. This case illustrates that PSMA uptake can occur in a transverse vertebral body fracture and is a benign cause of PSMA uptake.

Objective: To test the hypothesis that rebound of bone remodeling is responsible for clinical vertebral fractures reported in a few patients with osteoporosis after cessation of denosumab treatment., Design: In this case-control study we compared clinical and biochemical characteristics of postmenopausal women with clinical vertebral fractures 8-16 months after the last injection of denosumab (Dmab/Fx+, n  = 5) with those of treatment-naïve women with such fractures (Fx+, n  = 5). In addition, 5 women who discontinued denosumab treatment but did not sustain vertebral fractures 18-20 months after the last injection were studied (Dmab/Fx-, n  = 5)., Methods: We measured serum microRNAs, gene expression of mRNAs of factors regulating formation and activity of osteoclasts and biochemical markers of bone and mineral metabolism. In Dmab/Fx+ and Fx+ women, blood was taken 4-8 weeks after the fracture., Results: Compared to Fx+ women, Dmab/Fx+ women had higher serum P1NP and CTx levels, and significantly lower serum miR-503 and miR-222-2 that downregulate osteoclastogenesis and osteoclast activity, and higher RANK (13-fold) and CTSK (2.6-fold) mRNA. The respective values of Dmab/Fx- women were in the same direction as those of Dmab/Fx+ women but of a lesser magnitude., Conclusions: Bone fragility in women with clinical vertebral fractures after stopping denosumab therapy is pathophysiologically different from that of treatment-naïve women with osteoporosis and clinical vertebral fractures and it is associated with upregulation of markers of osteoclast formation and activity. The small number of women with this rare event studied is a limitation., (© 2017 European Society of Endocrinology.)

Low body weight is an established risk factor for osteoporosis and fracture, but the skeletal risks of higher adiposity are unclear and appear sex-specific and site-dependent. The aim of this study was to investigate associations of total fat mass (TFM), visceral adipose tissue (VAT), and C-reactive protein (CRP) with bone mineral density (BMD) and prevalent vertebral fracture (VF) in men and women aged 62 years. A total of 352 men and women aged 62.5 ± 0.5 years from the Newcastle Thousand Families Study cohort received dual-energy X-ray absorptiometry (DXA) evaluations of femoral neck and lumbar spine BMD, of the lateral spine for vertebral fracture assessment, and of the whole body for TFM and VAT (GE Lunar CoreScan, Madison, WI, USA). Plasma CRP, FRAX scores, falls in the last 12 months, and occupation at age 50 years were also included in the analysis. Vertebral fractures were less prevalent in women than in men (odds ratio [OR] = 0.33, p < 0.001) and BMD or FRAX scores did not differ between participants with and without VF. Women with VF were heavier and had higher TFM, VAT, and CRP than women without (p < 0.001). In women, greater (+1 SD) TFM and VAT increased the odds of any grade VF (TFM: OR = 1.06, p = 0.001; VAT: OR = 2.50, p = 0.002), and greater VAT mass increased the odds of prevalent mild VF (OR = 2.60, p = 0.002). In contrast, there were no associations in men. In both sexes, after controlling for body weight, neither VAT nor CRP were associated with BMD. In conclusion, irrespective of BMD, total and visceral adiposity were associated with prevalent VF in women but not in men. High fat mass, particularly if visceral, should be considered when assessing VF risk in women. Risk factors for VF in men require further investigation, particularly given their high prevalence. © 2017 American Society for Bone and Mineral Research., (© 2017 American Society for Bone and Mineral Research.)

Context: We hypothesize that endogenous sex steroids are associated with fracture risk independent of race/ethnicity., Design and Setting: We performed a nested case-control study within the prospective Women's Health Initiative Observational Study. Incident nonspine fractures were identified in 381 black, 192 Hispanic, 112 Asian, and 46 Native American women over an average of 8.6 years. A random sample of 400 white women who experienced an incident fracture was chosen. One control was selected per case and matched on age, race/ethnicity, and blood draw date. Bioavailable estradiol (BioE2), bioavailable testosterone (BioT), and sex hormone-binding globulin (SHBG) were measured using baseline fasting serum. Conditional logistic regression models calculated the odds ratio (OR) and 95% confidence interval (CI) of fracture across tertiles of hormone., Results: In multivariable and race/ethnicity-adjusted models, higher BioE2 (>8.25 pg/mL) and higher BioT (>13.3 ng/dL) were associated with decreased risk of fracture (OR, 0.65; 95% CI, 0.50 to 0.85; P trend = 0.001 and OR, 0.76; 95% CI, 0.60 to 0.96; P trend = 0.02, respectively). The interaction term between race/ethnicity and either BioE2 or BioT was not significant. There was no association between SHBG and fracture risk. In models stratifying by race/ethnicity, higher BioE2 was associated with a lower risk of fracture in both white women (OR, 0.56; 95% CI, 0.36 to 0.87) and black women (OR, 0.61; 95% CI, 0.39 to 0.96). Higher BioT was associated with a significantly lower fracture risk in only black women (OR, 0.65; 95% CI, 0.43 to 1.00), P trend = 0.03., Conclusions: Serum BioE2 and BioT are associated with fracture risk in older women irrespective of race/ethnicity and independent of established risk factors for fracture., (Copyright © 2017 by the Endocrine Society)

This study aims to evaluate the discriminative and predictive capacity of the Fracture Risk Assessment Tool (FRAX) to determine the 10-year risk of osteoporotic fracture in Chinese rheumatoid arthritis (RA) patients.This study included 168 RA patients and 168 healthy individuals as controls. The Chinese mainland FRAX model was applied to calculate the 10-year risk of osteoporotic fractures, defined as fracture of the spine, forearm, hip, or shoulder.The incidence of osteoporosis was significantly increased in RA patients compared to controls (P < .05). Bone mineral density (BMD), lumbar vertebra T-score, and femoral neck T-score were significantly lower in RA patients compared to controls (P < .05). BMD, disease duration, DAS28, and glucocorticoid use were important risk factors for osteoporotic fractures in Chinese RA patients. Ten-year osteoporotic fracture risk in Chinese RA patients was higher when BMD was incorporated in FRAX.There was a higher incidence of osteoporosis and reduced BMD in RA patients compared to controls. The FRAX model should integrate femoral neck BMD with other risk factors to evaluate osteoporotic fracture risk in RA patients, making it a valuable screening tool.

Objective: Accumulating evidence suggests a reciprocal relationship between muscle and bone. Previous in vitro studies showed that the muscle-derived factors, osteoglycin (OGN) and family with sequence similarity 5, member C (FAM5C), regulate osteoblastic differentiation. However, there are no reports investigating the association between circulating OGN and FAM5C and bone metabolism in humans., Design: We conducted a cross-sectional study and investigated the association of serum OGN and FAM5C levels and muscle mass examined by whole-body dual-energy x-ray absorptiometry with bone mineral density (BMD), bone turnover markers, and the presence of vertebral fractures (VFs) in 156 postmenopausal women with type 2 diabetes mellitus (T2DM)., Results: Multiple regression analysis adjusted for age, duration of T2DM, body mass index, serum creatinine, and log(hemoglobin A1c) showed that log(OGN) was negatively associated with BMD at the femoral neck (β=-0.17, p=0.014). Serum OGN levels were higher in subjects with VFs than in those without VFs [mean±standard deviation (SD): 100.2±84.7 vs. 74.4±31.7pg/mL, p=0.013]. Moreover, logistic regression analysis adjusted for the confounding factors described above showed that the serum OGN level was positively associated with the presence of VFs (odds ratio=1.84, 95% confidence interval=1.03-3.29 per SD increase, p=0.039). In contrast, neither the serum FAM5C level nor muscle mass indices were associated with bone turnover markers and the presence of VFs., Conclusions: The present study showed for the first time that higher serum OGN levels were associated with decreased BMD and increased risk of vertebral fractures in postmenopausal women with T2DM., (Copyright © 2016 Elsevier Inc. All rights reserved.)

We examined the efficacy of intravenous (IV) ibandronate 1 mg/month in patient subgroups in the phase III MOVER study. Here we present results of analyses on the incidence of fractures in patients with prevalent vertebral fractures (1 or ≥2, and ≥3) at screening and femoral neck (FN) bone mineral density (BMD) T scores ≥-2.5 or <-2.5, and <-3.0 at baseline. The per-protocol set comprised 1134 patients (ibandronate 0.5 mg/month n = 376; ibandronate 1 mg/month n = 382; risedronate oral 2.5 mg/day n = 376). The incidence of vertebral fractures in patients with 1 or ≥2 prevalent vertebral fractures was 11.2 and 20.4 %, respectively, with ibandronate 1 mg/month, and 12.6 and 22.1 %, respectively, with risedronate. In patients with FN BMD T scores ≥-2.5 or <-2.5, the vertebral fracture incidence was 13.7 and 16.4 %, respectively, with ibandronate 1 mg/month, and 17.3 and 19.1 %, respectively, with risedronate. The incidence of non-vertebral fractures in patients with ≥2 prevalent vertebral fractures or FN BMD T score <-2.5 was 7.6 and 7.6 %, respectively, with ibandronate 1 mg/month, and 9.5 and 9.4 %, respectively, with risedronate. Fracture incidence was consistently lower, but not significant, with ibandronate 1 mg/month than with risedronate in patients with ≥2 prevalent vertebral fractures and FN BMD T score <-2.5. The efficacy of the fracture reduction of monthly IV ibandronate appears consistent and seemingly independent of the number of prevalent vertebral fractures or baseline BMD values.

Spinal osteoarthritis has been suggested as a risk factor for vertebral fractures. However, results are conflicting: most of the data are focused on the lumbar region, and referred to postmenopausal women, whereas data for men are scarce. The aim of this study is to assess the relationship between spinal osteoarthritis and vertebral fractures in men over 50 years of age. We conducted a cross-sectional study, nested in a prospective population-based cohort, including 507 community-dwelling men, 93 of them with at least one vertebral fracture. Vertebral fractures, osteophytosis, and disc space narrowing (DSN) were assessed by lateral thoracic and lumbar radiographs. Anthropometric, clinical, and densitometric variables were also analyzed. A multiple logistic regression model was performed. Eighty-five percent of vertebral fractures were located at the thoracic spine. Osteophytosis and DSN showed a bimodal distribution, with major frequency peaks at mid- and distal lumbar spine. The three distributions overlapped around the T9 vertebra. We did not find any relationship between lumbar osteoarthritis and vertebral fractures. Nevertheless, thoracic osteophytosis (OR, 1.84; 95 % CI, 1.05-3.17; p = 0.03) and DSN (OR, 2.52; 95 % CI, 1.43-4.46; p = 0.001) were found to be independently associated with prevalent vertebral fractures, after adjusting for confounders. Our results suggest a positive relationship between radiologic osteoarthritic changes at the thoracic spine and prevalent vertebral fractures in men more than 50 years of age. Osteoarthritis may act as a local risk factor, in addition to other mechanical factors, resulting in a greater propensity to fracture, especially at the mid-thoracic region.

The aim of this study was to evaluate in a large size cohort of SSc patients bone mineral density (BMD) and to analyze its possible determinants. 106 consecutive outpatients affected by SSc were enrolled and completely evaluated for bone metabolism and SSc characteristics. For the statistical analysis, we preferred Z score to BMD or T score since the population was composed of patients of different ages and of both sexes. Mean neck Z score was significantly lower than 0. No significant differences were found for other sites. Female patients were shown to have a total femur and neck Z score significantly lower than 0 (p = 0.028 and p < 0.001, respectively). 13 % of patients had at least one morphometric non-clinical vertebral fracture. In univariate analysis, total femur Z score was lower in female (p = 0.050) and positively correlates with BMI (p = 0.001), neck Z score positively correlates with age (p = 0.016), and whole body Z score positively correlates with BMI (p < 0.001). No correlations were found for lumbar Z score. The multivariate analysis confirmed the positive correlation between BMI and total femur and whole body Z score and between age and neck femur Z score (p = 0.005, p < 0.001 and p = 0.040, respectively). Lung involvement was shown to correlate with a lower whole body Z score in multivariate analysis (p = 0.037). We found a modest risk of low BMD in patients with SSc and the important protective role of BMI. Patients with lung involvement showed lower whole body Z score.

Osteoporosis affects many men, with significant morbidity and mortality. However, the best osteoporosis screening strategies for men are unknown. We developed an individual-level state-transition cost-effectiveness model with a lifetime time horizon to identify the cost-effectiveness of different osteoporosis screening strategies for US men involving various screening tests (dual-energy X-ray absorptiometry [DXA]; the Osteoporosis Self-Assessment Tool [OST]; or a fracture risk assessment strategy using age, femoral neck bone mineral density [BMD], and Vertebral Fracture Assessment [VFA]); screening initiation ages (50, 60, 70, or 80 years); and repeat screening intervals (5 years or 10 years). In base-case analysis, no screening was a less effective option than all other strategies evaluated; furthermore, no screening was more expensive than all strategies that involved screening with DXA or the OST risk assessment instrument, and thus no screening was "dominated" by screening with DXA or OST at all evaluated screening initiation ages and repeat screening intervals. Screening strategies that most frequently appeared as most cost-effective in base-case analyses and one-way sensitivity analyses when assuming willingness-to-pay of $50,000/quality-adjusted life-year (QALY) or $100,000/QALY included screening initiation at age 50 years with the fracture risk assessment strategy and repeat screening every 10 years; screening initiation at age 50 years with fracture risk assessment and repeat screening every 5 years; and screening initiation at age 50 years with DXA and repeat screening every 5 years. In conclusion, expansion of osteoporosis screening for US men to initiate routine screening at age 50 or 60 years would be expected to be effective and of good value for improving health outcomes. A fracture risk assessment strategy using variables of age, femoral neck BMD, and VFA is likely to be the most effective of the evaluated strategies within accepted cost-effectiveness parameters. DXA and OST are also reasonable screening options, albeit likely slightly less effective than the evaluated fracture risk assessment strategy. © 2016 American Society for Bone and Mineral Research., (© 2016 American Society for Bone and Mineral Research.)

This study aims to explore the effect of microRNA-21 (miR-21) on the proliferation of human degenerated nucleus pulposus (NP) by targeting programmed cell death 4 (PDCD4) tumor suppressor. NP tissues were collected from 20 intervertebral disc degeneration (IDD) patients, and from 5 patients with traumatic spine fracture. MiR-21 expressions were tested. NP cells from IDD patients were collected and divided into blank control group, negative control group (transfected with miR-21 negative sequences), miR-21 inhibitor group (transfected with miR-21 inhibitors), miR-21 mimics group (transfected with miR-21 mimics) and PDCD4 siRNA group (transfected with PDCD4 siRNAs). Cell growth was estimated by Cell Counting Kit-8; PDCD4, MMP-2,MMP-9 mRNA expressions were evaluated by qRT-PCR; PDCD4, c-Jun and p-c-Jun expressions were tested using western blot. In IDD patients, the expressions of miR-21 and PDCD4 mRNA were respectively elevated and decreased (both P<0.05). The miR-21 expressions were positively correlated with Pfirrmann grades, but negatively correlated with PDCD4 mRNA (both P<0.001). In miR-21 inhibitor group, cell growth, MMP-2 and MMP-9 mRNA expressions, and p-c-Jun protein expressions were significantly lower, while PDCD4 mRNA and protein expressions were higher than the other groups (all P<0.05). These expressions in the PDCD4 siRNA and miR-21 mimics groups was inverted compared to that in the miR-21 inhibitor group (all P<0.05). MiR-21 could promote the proliferation of human degenerated NP cells by targeting PDCD4, increasing phosphorylation of c-Jun protein, and activating AP-1-dependent transcription of MMPs, indicating that miR-21 may be a crucial biomarker in the pathogenesis of IDD.

Background and Objectives: The relationship between mineral metabolism disorders, bone fractures and vascular calcifications in kidney transplant recipients has not been established., Method: We performed a cross-sectional study in 727 stable recipients from 28 Spanish transplant clinics. Mineral metabolism parameters, the semi-quantification of vertebral fractures and abdominal aortic calcifications were determined centrally., Results: Vitamin D deficiency (25OHD3<15ng/ml) was more common in female recipients at CKD-T stages I-III (29.6% vs 44.4%; p=0.003). The inverse and significant correlation between 25OHD3 and PTH was gender-specific and women exhibited a steeper slope than men (p=0.01). Vertebral fractures (VFx) with deformity grade ≥2 were observed in 15% of recipients. Factors related to VFx differed by gender; in males, age (OR 1.04; 95% CI 1.01-1.06) and CsA treatment (OR: 3.2; 95% CI: 1.6-6.3); in females, age (OR 1.07; 95% CI: 1.03-1.12) and PTH levels (OR per 100pg/ml increase: 1.27; 95% CI: 1.043-1.542). Abdominal aortic calcifications were common (67.2%) and related to classical risk factors but not to mineral metabolism parameters., Conclusions: Vitamin D deficiency is more common among female kidney transplant recipients at earlier CKD-T stages, and it contributes to secondary hyperparathyroidism. Prevalent vertebral fractures are only related to high serum PTH levels in female recipients., (Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Trabecular bone score (TBS) is a gray-level textural index of bone microarchitecture derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images. TBS is a bone mineral density (BMD)-independent predictor of fracture risk. The objective of this meta-analysis was to determine whether TBS predicted fracture risk independently of FRAX probability and to examine their combined performance by adjusting the FRAX probability for TBS. We utilized individual-level data from 17,809 men and women in 14 prospective population-based cohorts. Baseline evaluation included TBS and the FRAX risk variables, and outcomes during follow-up (mean 6.7 years) comprised major osteoporotic fractures. The association between TBS, FRAX probabilities, and the risk of fracture was examined using an extension of the Poisson regression model in each cohort and for each sex and expressed as the gradient of risk (GR; hazard ratio per 1 SD change in risk variable in direction of increased risk). FRAX probabilities were adjusted for TBS using an adjustment factor derived from an independent cohort (the Manitoba Bone Density Cohort). Overall, the GR of TBS for major osteoporotic fracture was 1.44 (95% confidence interval [CI] 1.35-1.53) when adjusted for age and time since baseline and was similar in men and women (p > 0.10). When additionally adjusted for FRAX 10-year probability of major osteoporotic fracture, TBS remained a significant, independent predictor for fracture (GR = 1.32, 95% CI 1.24-1.41). The adjustment of FRAX probability for TBS resulted in a small increase in the GR (1.76, 95% CI 1.65-1.87 versus 1.70, 95% CI 1.60-1.81). A smaller change in GR for hip fracture was observed (FRAX hip fracture probability GR 2.25 vs. 2.22). TBS is a significant predictor of fracture risk independently of FRAX. The findings support the use of TBS as a potential adjustment for FRAX probability, though the impact of the adjustment remains to be determined in the context of clinical assessment guidelines. © 2015 American Society for Bone and Mineral Research., (© 2015 American Society for Bone and Mineral Research.)

Somewhat paradoxically, fracture risk, which depends on applied loads and bone strength, is elevated in both anorexia nervosa and obesity at certain skeletal sites. Factor-of-risk (Φ), the ratio of applied load to bone strength, is a biomechanically based method to estimate fracture risk; theoretically, higher Φ reflects increased fracture risk. We estimated vertebral strength (linear combination of integral volumetric bone mineral density [Int.vBMD] and cross-sectional area from quantitative computed tomography [QCT]), vertebral compressive loads, and Φ at L4 in 176 women (65 anorexia nervosa, 45 lean controls, and 66 obese). Using biomechanical models, applied loads were estimated for: 1) standing; 2) arms flexed 90°, holding 5 kg in each hand (holding); 3) 45° trunk flexion, 5 kg in each hand (lifting); 4) 20° trunk right lateral bend, 10 kg in right hand (bending). We also investigated associations of Int.vBMD and vertebral strength with lean mass (from dual-energy X-ray absorptiometry [DXA]) and visceral adipose tissue (VAT, from QCT). Women with anorexia nervosa had lower, whereas obese women had similar, Int.vBMD and estimated vertebral strength compared with controls. Vertebral loads were highest in obesity and lowest in anorexia nervosa for standing, holding, and lifting (p < 0.0001) but were highest in anorexia nervosa for bending (p < 0.02). Obese women had highest Φ for standing and lifting, whereas women with anorexia nervosa had highest Φ for bending (p < 0.0001). Obese and anorexia nervosa subjects had higher Φ for holding than controls (p < 0.03). Int.vBMD and estimated vertebral strength were associated positively with lean mass (R = 0.28 to 0.45, p ≤ 0.0001) in all groups combined and negatively with VAT (R = -[0.36 to 0.38], p < 0.003) within the obese group. Therefore, women with anorexia nervosa had higher estimated vertebral fracture risk (Φ) for holding and bending because of inferior vertebral strength. Despite similar vertebral strength as controls, obese women had higher vertebral fracture risk for standing, holding, and lifting because of higher applied loads from higher body weight. Examining the load-to-strength ratio helps explain increased fracture risk in both low-weight and obese women., (© 2015 American Society for Bone and Mineral Research.)