Objectives. Osteoporosis has become an increasing concern for older people as it may potentially lead to osteoporotic fractures. This study is designed to assess the efficacy and safety of ten therapies for post-menopausal women using network meta-analysis. Methods. We conducted a systematic search in several databases, including PubMed and Embase. A random-effects model was employed and results were assessed by the odds ratio (OR) and corresponding 95% confidence intervals (CI). Furthermore, with respect to each outcome, each intervention was ranked according to the surface under the cumulative ranking curve (SUCRA) value. Results. With respect to preventing new vertebral fractures (NVF), all ten drugs outperformed placebo, and etidronate proved to be the most effective treatment (OR 0.24, 95% CI 0.14 to 0.39). In addition, zoledronic acid and parathyroid hormone ranked higher compared with the other drugs. With respect to preventing clinical vertebral fractures (CVF), zoledronic acid proved to be the most effective drug (OR = 0.25, 95% CI 0.08 to 0.92), with denosumab as a desirable second option (OR = 0.48, 95% CI 0.22 to 0.96), when both were compared with placebo. As for adverse events (AE) and severe adverse events (SAE), no significant difference was observed. According to SUCRA, etidronate ranked first in preventing CVF; parathyroid hormone and zoledronic acid ranked highly in preventing NVF and CVF. Raloxifene was safe with a high rank in preventing AEs and SAEs though performed unsatisfactorily in efficacy. Conclusions. This study suggests that, taking efficacy and safety into account, parathyroid hormone and zoledronic acid had the highest probability of satisfactory performance in preventing osteoporotic fractures. Cite this article: G. Wang, L. Sui, P. Gai, G. Li, X. Qi, X. Jiang. The efficacy and safety of vertebral fracture prevention therapies in post-menopausal osteoporosis treatment: Which therapies work best? a network meta-analysis. Bone Joint Res 2017;6:452–463. DOI: 10.1302/2046-3758.67.BJR-2016-0292.R1

Introduction Vertebral fractures in the elderly frequently involve the anterior and superior regions of the vertebral body. We hypothesise that vertebral fracture patterns reflect regional variations in bone mineral density (BMD). Methods Nineteen motion segments (aged 48–90 yrs) were obtained from thoracic and lumbar regions of cadaver spines. Specimens were compressed to failure while positioned in moderate flexion (to simulate someone lifting in a stooped posture). Superior and inferior vertebrae were dissected and the site of fracture identified by visual inspection. The volume of each vertebral body was measured by water immersion, and BMD was measured using dual X-ray absorptiometry (DXA). BMD was also calculated for the following regions: superior and inferior end-plates; upper, middle and lower thirds of the vertebral body between the end-plates; anterior, middle and posterior thirds of the vertebral body. Results In 16 of the 19 specimens, an obvious fracture was located in the anterior or central region of the superior end-plate of the inferior vertebral body, accompanied by collapse of supporting trabeculae. BMD of the superior end-plate was significantly lower than that of the inferior end-plate. Similarly, BMD of the upper third of the vertebral body was less than that of the lower third, and BMD increased significantly from anterior to posterior regions in the vertebral body. Discussion Low BMD in the superior and anterior regions of old vertebral bodies predisposes them to fracture. Altered load-sharing in old spines secondary to disc degeneration may explain these regions of low BMD

Spinal fractures are common following underbody blast. Most injuries occur at the thoracolumbar junction, and fracture patterns suggest the spine is flexed at the moment of injury. However, current mechanistic descriptions of vertebral fractures are based on low energy injuries, and there is no evidence to correlate fracture pattern with posture at the loading rates seen in blast injury. The T12-L1 segment of 4 human spines was dissected to preserve the paraspinal ligaments and potted in polymethylmecrylate. The specimens were impacted with a 14 kg mass at 3.5m/s in a drop tower; two specimens were impacted in neutral posture, one in flexion, and one in extension. A load cell measured the load history. CT scans and dissection identified the injury patterns. Each specimen sustained a burst fracture. The neutral specimens demonstrated superior burst fractures, the flexed specimen demonstrated a superior burst fracture with significant anterior involvement, and the extended specimen showed a posterior vertebral body burst fracture. At high loading rates, the posture of the spine at the moment of injury appears to affect the resulting fracture. This supports understanding the behaviour of the spine in blast injury and will allow improved mitigation system design in the future

To explore a novel machine learning model to evaluate the vertebral fracture risk using Decision Tree model and train the model by Bone Mineral Density (BMD) of different compartments of vertebral body. We collected a Computed Tomography image dataset, including 10 patients with osteoporotic fracture and 10 patients without osteoporotic fracture. 40 non-fracture Vertebral bodies from T11 to L5 were segmented from 10 patients with osteoporotic fracture in the CT database and 53 non-fracture Vertebral bodies from T11 to L5 were segmented from 10 patients without osteoporotic fracture in the CT database. Based on the biomechanical properties, 93 vertebral bodies were further segmented into 11 compartments: eight trabecular bone, cortical shell, top and bottom endplate. BMD of these 11 compartments was calculated based on the HU value in CT images. Decision tree model was used to build fracture prediction model, and Support Vector Machine was built as a compared model. All BMD data was shuffled to a random order. 70% of data was used as training data, and 30% left was used as test data. Then, training prediction accuracy and testing prediction accuracy were calculated separately in the two models. The training accuracy of Decision Tree model is 100% and testing accuracy is 92.14% after trained by BMD data of 11 compartments of the vertebral body. The type I error is 7.14% and type II error is 0%. The training accuracy of Support Vector Machine model is 100% and the testing accuracy is 78.57%. The type I error is 17.86% and type II error is 3.57%. The performance of vertebral body fracture prediction using Decision Tree is significantly higher than using Support Vector Machine. The Decision Tree model is a potential risk assessment method for clinical application. The pilot evidence showed that Decision Tree prediction model overcomes the overfitting drawback of Support Vector Machine Model. However, larger dataset and cohort study should be conducted for further evidence

Residual kyphotic deformity is considered the main factor for the increased risk of new fractures after an osteoporotic vertebral fracture. We hypothesized that even in the absence of kyphotic deformity, the altered pressure profile of the disc after a fracture will increase the risk for subsequent fractures. Materials and Methods: Six fresh-frozen, human thoracolumbar specimens, consisting of 5 adjacent vertebrae, were used. A void was randomly created under the upper (n=3) or the lower (n=3) endplate of the middle vertebra. The specimen was then compressed in flexion until a selective fracture of the weakened endplate was observed. Vertebral kyphosis was reduced with extension. After cementation of the fracture, the rest of the trabecular content was evacuated and was filled with cement. Specimens were tested in flexion-extension (±6Nm) under 400N preload before and after the index fracture. Pressure was recorded at the discs above and below the fractured VB and strain at the anterior wall of the adjacent VBs. Finally, the specimen was loaded in flexion until a subsequent fracture was observed on fluoroscopy. Results: In the intact specimens, nucleus pressure increased by 26.4±13.9% in full flexion compared to neutral posture. After the index fracture, the pressure in full flexion increased by 15.2±11 % in the discs with unfractured endplates, but decreased by 19±26.7% in the discs with the fractured endplate (p< 0.05). Anterior wall strain at the VB adjacent to the fractured endplate increased by 94.2%±22.8% (p=0.02), compared to an 18.2%±7.1% (p=0.98) increase at the VB adjacent to the unfractured endplate. Subsequent loading of the specimens after cementation of the index fracture resulted in a fracture of the adjacent VB close to the fractured endplate of the middle vertebra in 4 specimens and at the upper potted VB in one specimen. Maximum load applied with the actuators failed to create a fracture in one specimen. Discussion: The effects of the fractured endplate were isolated by eliminating other known parameters. Vertebral kyphosis was reduced and cement was similarly distributed under both endplates. In the intact specimens, nucleus pressure gradually increased during flexion. This can more evenly distribute the load during flexion to the entire surface of the endplate and avoid excessive load concentration to the anterior portion. After an endplate fracture, the nucleus pressure gradually decreased during flexion, meaning that the anterior annulus was forced to bear more load. This uneven load transfer to the anterior part of the VB resulted in doubling the strain at the VB adjacent to the fractured end plate. All adjacent factures were observed at the vertebra next to the damaged endplate. The altered mechanical behavior of the nucleus can be ascribed to the increased available space after the endplate depression

Introduction: Pathological changes in the elderly spine include intervertebral disc degeneration, apophyseal joint arthritis and osteoporotic fracture of the vertebral body. Such changes are likely to be inter-related through alterations in the sharing of load between the apophyseal joints and the intervertebral disc unit. We describe an accurate, non-destructive method for calculating the load sharing based on measurements of the distribution of stress within the intervertebral disc.

Materials and Methods: Twenty three motion segments, consisting of two vertebrae and the intervening disc and ligaments, were dissected from 17 human lumbar spines. A preliminary “creep” test was used to reduce disc height and water content by an amount equivalent to the diurnal variation seen in vivo. Then, a constant load was applied to each motion segment, using a computer-controlled hydraulic materials testing machine, for a period of 20s while a pressure-transducer, sensitive to spatial variations in compressive stress, was pulled through the disc along its mid-sagittal diameter. Profiles of vertically-acting compressive stress were obtained in each disc positioned in 2° of extension (appropriate for an erect standing posture). The total compressive force acting on the intervertebral disc was calculated by modelling the disc using approximately 20 elliptical rings of known cross-sectional area. The force acting on each ring was given by the product of area and the average compressive stress acting on it, which was obtained from the appropriate region of the stress profile. The total force acting through the disc was obtained by summing up the force contribution from each ring. The force acting on the apophyseal joints was calculated from the difference between applied (known) load and the calculated load acting on the disc. A correction factor was obtained separately for each disc to account for deviations in the cross-section from the elliptical, and variations in the sensitivity of the transducer in disc tissues of different ages. The correction factor was obtained by comparing the applied force with the force calculated from a stress profile measured before creep loading while the disc was in a neutral position, when the load passing through the apophyseal joints is negligible.

Results: The proportion of load passing through the apophyseal joints increased significantly with age (r²=0.48, p< 0.01), from 7% at age 27 yrs to 42% at 82yrs. Similarly, the proportion of load passing through the apophyseal joints increased with degree of disc degeneration (r²=0.5, p< 0.05 Pearson, Chi-square) from 8% in “grade 1” discs to 40% in “grade 4” discs.

Discussion: The compressive load passing through the apophyseal joints is higher than that predicted by previous, inaccurate, methods, or by experiments which failed to reduce the height and water content of the intervertebral disc. Increased load-bearing may be a contributing factor in apophyseal joint degeneration. Also, in lordotic postures, “stress shielding” by the apophyseal joints could contribute to bone loss in the vertebral body, leaving it vulnerable to osteoporotic fracture when the spine is loaded in flexion.

Purpose: To identify local and systemic risk factors for the development of pathologic fractures and determine the value of the Tokuhashi Score in patients with known asymptomatic lytic spinal metastases secondary to breast cancer.

Method: A prospective cohort study was carried out on 51 patients with lytic spinal metastases secondary to breast cancer identified as having either purely lytic or mixed disease. The Tokuhashi Score, developed to estimate life expectancy for patients with symptomatic spinal metastases being considered for surgery, was calculated for each of the 51 patients. The score consists of six parameters each of which is rated from 0–2. Initial and follow up CT images and pain and function data were obtained every four months for one year. A final review of patient charts was performed two years later to determine if each patient was still alive.

Results: Tumour burden was predominantly blastic and mixed rather than lytic. There was no progression of lytic tumour burden over the 12-month period, however there was progression of blastic tumour load. Eleven compression fractures occurred in seven patients; no burst fractures occurred during the study. No correlation between tumour burden (lytic, blastic or both) and risk of fracture was found. A weak correlation between bone mineral density and length of time elapsed from diagnosis of metastatic disease and fracture risk was found. Pain and functional data results were not related to tumour load. Tokuhashi score did correlate with survival, however actual survival in our population was far longer than that found in previous studies. Negative progesterone status was found to be negatively associated with life expectancy.

Conclusion: Metastatic vertebral disease in breast cancer patients has a predominantly blastic and mixed appearance with current pharmacologic therapies. Pathologic fracture risk appears to be more related to bone mineral density than tumour burden in this population. Tokuhashi score does correlate with life expectancy in patients with relatively asymptomatic spinal metastases. Having a progesterone receptor negative tumour has a significantly negative impact on life expectancy.

Purpose: Apoptosis of osteoblasts and osteoclasts regulates bone homeostasis. Vertebral osteoporotic insufficiency fractures are characterised by pathological rates of osteoblast apoptosis. Skeletal injury in humans results in ‘angiogenic’ responses primarily mediated by vascular endothelial growth factor(VEGF), a protein essential for bone repair in animal models. Osteoblasts release VEGF in response to a number of stimuli and express receptors for VEGF in a differentiation dependent manner. This study investigates the putative role of VEGF in regulating the lifespan of primary human vertebral osteoblasts (PHVO) in-vitro.

Method: PHVO were cultured from biopsies taken at time of therapeutic vertebroplasty and were examined for VEGF receptors. Cultures were supplemented with VEGF(0–50ng/mL), a neutralising antibody to VEGF, mAB VEGF(0.3ug/mL) and Placental Growth Factor (PlGF), an Flt-1 receptor-specific VEGF ligand(0–100 ng/mL) to examine their effects on mineralised nodule assay, alkaline phosphatase assay and apoptosis. The role of the VEGF specific antiapoptotic gene target BCl2 in apoptosis was determined.

Results: PHVO expressed functional VEGF receptors. VEGF 10 and 25 ng/mL increased nodule formation 2.3- and 3.16-fold and alkaline phosphatase release 2.6 and 4.1-fold respectively while 0.3ug/mL of mAB VEGF resulted in approx 40% reductions in both. PlGF 50ng/mL had greater effects on alkaline phosphatase release (103% increase) than on nodule formation (57% increase). 10ng/mL of VEGF inhibited spontaneous and pathological apoptosis by 83.6% and 71% respectively, while PlGF had no significant effect. Pretreatment with mAB VEGF, in the absence of exogenous VEGF resulted in a significant increase in apoptosis (14 versus 3%). BCl2 transfection gave a 0.9% apoptotic rate. VEGF 10 ng/mL increased BCl2 expression four fold while mAB VEGF decreased it by over 50%.

Conclusion: VEGF is a potent regulator of osteoblast life-span in-vitro. This autocrine feedback regulates survival of these cells, mediated via the KDR receptor and expression of BCl2 antiapoptotic gene. This mechanism may represent a novel therapeutic model for the treatment of osteoporosis.

Study Purpose

To review systematically review literature on the early diagnosis of spinal metastases and prediction of spinal cord compression (SCC) due to spinal metastases

Introduction/Aims

An increased mortality associated with hip fractures has been recognized, but the impact of vertebral osteoporotic compression fractures (VCF) is still underestimated. The aim of this study was to report on the difference in survival for VCF patients following non-operative and operative [Balloon Kyphoplasty (BKP) or Vertebroplasty (VP)] treatments.

Introduction. Most common osteoporotic fracture. 20-30% of patients with OVFs are presented to hospital while 2.2 million remain undiagnosed, as diagnosis is usually opportunistic. 66,000 OVFs occur annually in the UK with increase by 18,000 cases a year until 2025. 20% chance of another OVF in next 12 months and 3 times risk of hip fracture. Acute painful OVFs poorly tolerated by infirm elderly patients, leading to significant morbidity and 8 times increase in age-adjusted mortality. Materials and Methods. Classify fracture severity and patents with ovfs in 12-month period. To assess follow-up status and if kyphoplasty was offered within 6 weeks as per NICE guidelines. To introduce Royal Osteoporosis Society and GIRFT guidelines on management of symptomatic osteoporotic vertebral fractures. Results. Total no. of patients- 62. Initial pain assessment=40. Pain assessed at ≤6 weeks- 21. Duration from decision to operate to kyphoplasty 8.7 weeks. 11% had kyphoplasty of which 50% noted improvement in pain. 11 deaths. Nearly similar findings to NoSH study. Conclusion. To improve pain assessment on admission of patients with acute osteoporotic vertebral fractures. To follow GIRFT guidelines for early assessment and intervention in patients with acute osteoporotic vertebral fractures to improve pain, mobility and early discharge from hospital. Conflicts of interest. None. Sources of funding. None

Introduction and Objective. Up to 30% of thoracolumbar (TL) fractures are missed in the emergency room. Failure to identify these fractures can result in neurological injuries up to 51% of the casesthis article aimed to clarify the incidence and risk factors of traumatic fractures in China. The China National Fracture Study (CNFS. Obtaining sagittal and anteroposterior radiographs of the TL spine are the first diagnostic step when suspecting a traumatic injury. In most cases, CT and/or MRI are needed to confirm the diagnosis. These are time and resource consuming. Thus, reliably detecting vertebral fractures in simple radiographic projections would have a significant impact. We aim to develop and validate a deep learning tool capable of detecting TL fractures on lateral radiographs of the spine. The clinical implementation of this tool is anticipated to reduce the rate of missed vertebral fractures in emergency rooms. Materials and Methods. We collected sagittal radiographs, CT and MRI scans of the TL spine of 362 patients exhibiting traumatic vertebral fractures. Cases were excluded when CT and/or MRI where not available. The reference standard was set by an expert group of three spine surgeons who conjointly annotated (fracture/no-fracture and AO Classification) the sagittal radiographs of 171 cases. CT and/or MRI were used confirm the presence and type of the fracture in all cases. 302 cropped vertebral images were labelled “fracture” and 328 “no fracture”. After augmentation, this dataset was then used to train, validate, and test deep learning classifiers based on the ResNet18 and VGG16 architectures. To ensure that the model's prediction was based on the correct identification of the fracture zone, an Activation Map analysis was conducted. Results. Vertebras T12 to L2 were the most frequently involved, accounting for 48% of the fractures. Accuracies of 88% and 84% were obtained with ResNet18 and VGG16 respectively. The sensitivity was 89% with both architectures but ResNet18 had a significantly higher specificity (88%) compared to VGG16 (79%). The fracture zone used was precisely identified in 81% of the heatmaps. Conclusions. Our AI model can accurately identify anomalies suggestive of TL vertebral fractures in sagittal radiographs precisely identifying the fracture zone within the vertebral body

Aims. The current pandemic caused by COVID-19 is the biggest challenge for national health systems for a century. While most medical resources are allocated to treat COVID-19 patients, several non-COVID-19 medical emergencies still need to be treated, including vertebral fractures and spinal cord compression. The aim of this paper is to report the early experience and an organizational protocol for emergency spinal surgery currently being used in a large metropolitan area by an integrated team of orthopaedic surgeons and neurosurgeons. Methods. An organizational model is presented based on case centralization in hub hospitals and early management of surgical cases to reduce hospital stay. Data from all the patients admitted for emergency spinal surgery from the beginning of the outbreak were prospectively collected and compared to data from patients admitted for the same reason in the same time span in the previous year, and treated by the same integrated team. Results. A total of 19 patients (11 males and eight females, with a mean age of 49.9 years (14 to 83)) were admitted either for vertebral fracture or spinal cord compression in a 19-day period, compared to the ten admitted in the previous year. No COVID-19 patients were treated. The mean time between admission and surgery was 1.7 days, significantly lower than 6.8 days the previous year (p < 0.001). Conclusion. The structural organization and the management protocol we describe allowed us to reduce the time to surgery and ultimately hospital stay, thereby maximizing the already stretched medical resources available. We hope that our early experience can be of value to the medical communities that will soon be in the same emergency situation. Cite this article: Bone Joint J 2020;102-B(6):671–676

The aim of our study is to investigate the relation between the intensity of pain in the thoracic and lumbar spine and morphometric parameters of vertebrae in postmenopausal women. Materials and methods. We have examined 250 postmenopausal women aged 50–79 years divided into two groups: 171 women without vertebral deformations and 79 women with confirmed vertebral fractures. The duration of pain syndrome after fracture was over 6 months. The presence and intensity of pain syndrome in the thoracic and lumbar spine were assessed using a visual analog scale (VAS). Morphometric analysis of the vertebral parameters was carried out using the VFA software of the dual-energy X-ray densitometer «Prodigy» (GE Medical systems, Lunar, model 8743, 2005). Results. The intensity of pain syndrome in the lumbar spine significantly correlates with L1 vertebral indices: A/P (r=−0.37, p=0.01) and M/P (r=−0.29, p=0.03) in women with normal BMD. The intensity of pain in the thoracic region correlates with Th10 vertebral indices: A/P (r=−0.45, p=0.0004) and M/P (r=−0.35, p=0.01) in women with osteopenia. We have not determined any significant relationship between the level of back pain and vertebral body size index in women with osteoporosis and without vertebral fractures. In 11% patients with confirmed wedge and compression vertebral fractures chronic pain syndrome is absent, and the presence of other fractures does not increase the frequency of back pain syndrome (14%). The presence of vertebral fractures significantly increases the risk of pain in the thoracic spine (RR=1.32; 95% CI: 1.09–1.60, p= 0.004). In patients with vertebral fractures the intensity of pain in the thoracic spine significantly correlates with indices of Th11-Th12vertebrae, and relates to the number and localisation of vertebral fractures. The level of pain in the lumbar region does not depend on the location and number of damaged vertebrae. Conclusion. In postmenopausal women without osteoporosis and vertebral fractures level of pain may be associated with initial vertebral deformation, limiting the spine transition zone. The presence of vertebral fractures increases the risk of pain syndrome in the thoracic region depending on the location and number of damaged vertebrae

Quantitative ultrasound (QUS) is a promising tool to estimate bone structure characteristics and predict fragile fracture. The aim of this pilot cross-sectional study was to evaluate the performance of a multi-channel residual network (MResNet) based on ultrasonic radiofrequency (RF) signal to discriminate fragile fractures retrospectively in postmenopausal women. Methods. RF signal and speed of sound (SOS) were obtained using an axial transmission QUS at one‐third distal radius for 246 postmenopausal women. Based on the involved RF signal, we conducted a MResNet, which combines multi-channel training with original ResNet, to classify the high risk of fragility fractures patients from all subjects. The bone mineral density (BMD) at lumber, hip and femoral neck acquired with DXA was recorded on the same day. The fracture history of all subjects in adulthood were collected. To assess the ability of the different methods in the discrimination of fragile fracture, the odds ratios (OR) calculated using binomial logistic regression analysis and the area under the receiver operator characteristic curves (AUC) were analyzed. Results. Among the 246 postmenopausal women, 170 belonged to the non-fracture group, 50 to the vertebral group, and 26 to the non-vertebral fracture group. MResNet was discriminant for all fragile fractures (OR = 2.64; AUC = 0.74), for Vertebral fracture (OR = 3.02; AUC = 0.77), for non-vertebral fracture (OR = 2.01; AUC = 0.69). MResNet showed comparable performance to that of BMD of hip and lumbar with all types of fractures, and significantly better performance than SOS all types of fractures. Conclusions. the MResNet model based on the ultrasonic RF signal can significantly improve the ability of QUS device to recognize previous fragile fractures. Moreover, the performance of the proposed model modified by age, weight, and height is further optimized. These results open perspectives to evaluate the risk of fragile fracture applying a deep learning model to analyze ultrasonic RF signal

Introduction: Osteoporosis is a disease characterized by a low bone mass and the development of nontraumatic fractures. Approximately 700,000 elderly women in the US are newly diagnosed with osteoporotic vertebral fractures every year. Noninvasive measurements of bone mineral density (BMD) are central to the diagnosis and management of osteoporosis. However, BMD alone is not completely satisfactory in vertebral fracture risk assessment. The aim of this study was to identify clinical and laboratoristic factors associated with an increased risk of vertebral fractures in osteoporotic Caucasian women and to define a new clinically relevant scale of risk. Methods: 475 patients consecutively admitted at our ambulatory for the treatment of vertebral osteoporosis were included in the study. All patients were affected by post-menopausal osteoporosis according to the WHO classification criteria. Exclusion criteria were major infectious diseases, tumors and major diseases of sense organs. We attempted to determine whether parameters such as age, body mass index, smoking and alcohol habitudes, femoral and lumbar T-scores, femoral and lumbar Z-scores, femoral and lumbar BMD, total and bone alkaline phosphatase and L3 and T7 vertebral volumes were associated with the risk of vertebral fractures. Results: 173 patients of the entire population presented at least one vertebral fracture for a total of 488 fractures (238 thoracic and 250 lumbar collapses). When considered alone, age (> 65 years-p=0,0001), lumbar T-score (≤-3,5-p=0,0001), lumbar Z-score (≤-2,5-p=0,0050), lumbar BMD (≤0,800-p=0,0017), femoral T-score (≤-3,5-p=0,0090), femoral Z-score (≤-2,5-p=0,0127), L3 volume (≤-2,0SD–p=0,0023) and T7 volume (≤-2,0SD–p=0,0075) were significantly associated with an increased risk of vertebral fractures. Considering only the patients with two fractures or more, the same parameters with the exception of the femoral T-score resulted strongly associated with the risk of new vertebral fractures. Moreover, there was a significantly increased risk of vertebral fractures when two or more of these parameters were present together (p = 0.02). On the base of the obtained data we have then defined a new scale of risk (from grade I-low risk to grade IV-very high risk-p=0.0123) confirmed in a prospective study conducted on 71 osteoporotic patients followed for 30 months. Conclusion: We propose a new clinical scale to easily identify the osteoporotic patient at risk of new vertebral fractures

One out of nine Canadian males would suffer prostate cancer (PC) during his lifetime. Life expectancy of males with PC has increased with modern therapy and 90% live >10 years. However, 20% of PC-affected males would develop incurable metastatic diseases. Bone metastases (BM) are present in ~80% of metastatic PC patients, and are the most severe complication of PC, generating severe pain, fractures, spinal cord compression, and death. Interestingly, PC-BMs are mostly osteoblastic. However, the structure of this newly formed bone and how it relates to pain and fracture are unknown. Due to androgen antagonist treatment, different PC phenotypes develop with differential dependency on androgen receptor (AR) signaling: androgen-dependent (AR+), double negative (AR-) and neuroendocrine. How these phenotypes are related to changes in bone structure has not been studied. Here we show a state-of-the-art structural characterization of PCBM and how PC phenotypes are associated to abnormal bone formation in PCBM. Cadaveric samples (n=14) obtained from metastases of PC in thoracic or lumbar vertebrae (mean age 74yo) were used to analyze bone structure. We used micro-computed tomography (mCT) to analyze the three-dimensional structure of the bone samples. After imaging, the samples were sectioned and one 3mm thick section was embedded in epoxy-resin, ground and polished. Scanning electron microscopy (SEM)/energy-dispersive X-ray spectroscopy (EDS) and quantitative backscattering electron (qBSE) imaging were used to determine mineral morphology and composition. Another section was used for histological analysis of the PC-affected bone. Collagen structure, fibril orientation and extracellular matrix composition were characterized using histochemistry. Additionally, we obtained biopsies of 3 PCBM patients undergoing emergency decompression surgery following vertebral fracture and used them for immunohistological characterization. By using mCT, we observed three dysmorphic bone patterns: osteolytic pattern with thinned trabecula of otherwise well-organized structures, osteoblastic pattern defined as accumulation of disorganized matrix deposited on pre-existing trabecula, and osteoblastic pattern with minimum residual trabecula and bone space dominated by accumulation of disorganized mineralized matrix. Comparing mCT data with patho/clinical parameters revealed a trend for higher bone density in males with larger PSA increase. Through histological sections, we observed that PC-affected bone, lacks collagen alignment structure, have a higher number of lacunae and increased amount of proteoglycans as decorin. Immunohistochemistry of biopsies revealed that PC-cells inside bone organize into two manners: i) glandular-like structures where cells maintain their polarization in the expression of prostate markers, ii) diffuse infiltrate that spreads along bone surfaces, with loss of cell polarity. These cells take direct contact with osteoblasts in the surface of trabecula. We define that PCBM are mostly composed by AR+ with some double negative cells. We did not observe neuroendocrine phenotype cells. PCBMs generate predominantly osteoblastic lesions that are characterized by high lacunar density, lack of collagen organization and elevated proteoglycan content. These structural changes are associated with the infiltration of PC cells that are mostly androgen-dependent but have lost their polarization and contact directly with osteoblasts, perhaps altering their function. These changes could be associated with lower mechanical properties that led to fracture and weakness of the PCBM affected bone

Mechanical failure of spine posterior fixation in the lumbar region Is suspected to occur more frequently when the sagittal balance is not properly restored. While failures at the proximal extremity have been studied in the literature, the lumbar distal junctional pathology has received less attention. The aim of this work was to investigate if the spinopelvic parameters, which characterize the sagittal balance, could predict the mechanical failure of the posterior fixation in the distal lumbar region. All the spine surgeries performed in 2017-2019 at Rizzoli Institute were retrospectively analysed to extract all cases of lumbar distal junctional pathology. All the revision surgeries performed due to the pedicle screws pull-out, or the breakage of rods or screws, or the vertebral fracture, or the degenerative disc disease, in the distal extremity, were included in the junctional (JUNCT) group. A total of 83 cases were identified as JUNCT group. All the 241 fixation surgeries which to date have not failed were included in the control (CONTROL) group. Clinical data were extracted from both groups, and the main spinopelvic parameters were assessed from sagittal standing preoperative (pre-op) and postoperative (post-op) radiographs with the software Surgimap (Nemaris). In particular, pelvic incidence (PI), sagittal vertical axis (SVA), pelvic tilt (PT), T1 pelvic angle (TPA), sacral slope (SS) and lumbar lordosis (LL) have been measured. In JUNCT, the main failure cause was the screws pull-out (45%). Spine fixation with 7 or more levels were the most common in JUNCT (52%) in contrast to CONTROL (14%). In CONTROL, PT, TPA, SS and PI-LL were inside the recommended ranges of good sagittal balance. For these parameters, statistically significant differences were observed between pre-op and post-op (p<0.0001, p=0.01, p<0.0001, p=0.004, respectively, Wilcoxon test). In JUNCT, the spinopelvic parameters were out of the ranges of the good sagittal balance and the worsening of the balance was confirmed by the increase in PT, TPA, SVA, PI-LL and by the decrease of LL (p=0.002, p=0.003, p<0.0001, p=0.001, p=0.001, respectively, paired t-test) before the revision surgery. TPA (p=0.003, Kolmogorov-Smirnov test) and SS (p=0.03, unpaired t-test) differed significantly in pre-op between JUNCT and CONTROL. In post-op, PI-LL was significantly different between JUNCT and CONTROL (p=0.04, unpaired t-test). The regression model of PT vs PI was significantly different between JUNCT and CONTROL in pre-op (p=0.01, Z-test). These results showed that failure is most common in long fused segments, likely due to long lever arms leading to implant failure. If the sagittal balance is not properly restored, after the surgery the balance is expected to worsen, eventually leading to failure: this effect was confirmed by the worsening of all the spinopelvic parameters before the revision surgery in JUNCT. Conversely, a good sagittal balance seems to avoid a revision surgery, as it is visible is CONTROL. The mismatch PI-LL after the fixation seems to confirm a good sagittal balance and predict a good correction. The linear regression of PT vs PI suggests that the spine deformity and pelvic conformation could be a predictor for the failure after a fixation

Background. Balloon kyphoplasty has been established as an effective minimal invasive method to treat vertebral fractures of osteoporotic and pathologic etiology. Objectives. Comparative analysis of the clinical and radiographic outcomes of balloon kyphoplasty for treatment of osteoporotic and pathologic vertebral fractures. Study design. Prospective comparative study. Materials-Methods. Twenty five patients (14 women and 11 men) aged (average + SD) 73 + 8 years (range 52–83 years) with vertebral fracture were treated with kyphoplasty and were sampled into three groups: 14 patients (Group A) suffered from osteoporotic fractures and underwent percutaneous kyphoplasty, 5 patients (Group B) suffered from fractures caused from malignancy were treated with percutaneous kyphoplasty, and 6 patients (Group C, hybrid) who underwent combined operation (open kyphoplasty plus instrumented fusion). These patients underwent 25 operations to treat 38 vertebral fractures located between T11 and L5. Preoperative and postoperative radiographs were compared to calculate the changes of vertebral body height ratio (AVBHr, PVBHr) and Gardner kyphotic deformity angle. Sagittal spine alignment was analyzed on whole spine standing radiographs. The VAS, the Oswestry Disability Index (ODI) and the SF-36 surveys were used to evaluate the clinical results. The average time of follow-up was 31.5 + 7 months (range 25–40 months). The average preoperatively SF-36 score (Domain Bodily pain) was 8+ 16, The VAS was 9+1.3 while the ODI was 28+ 17. Results. The average SF-36 (Bodily Pain) score did not significantly differ among the groups and was improved postoperatively to (average, SD) 40+14. VAS improved postoperatively in an similar way in all three groups to 4+1.4 and the ODI was improved in all three groups to 49+ 17, without significant differences among groups. The AVBHr improved significantly only in group A (p=0.01), while there was no change in PVBHr in any group. The Gardner angle improved significantly in groups A (p=0.006) and C (p=0.05) respectively. Discussion. The inflatable bone tamp placed percutaneous or open in combination with spinal instrumentation was efficacious in the treatment of osteoporotic and pathologic vertebral fractures. Kyphoplasty alone or as hybrid was associated with early clinical improvement of pain and function in the treatment of painful pathologic compression fractures, as well as with reduction of Gardner angle

Aim: Urinary C-terminal telopeptide of type I collagen (u-CTx) has been reported to be a sensitive biochemical marker of bone turnover. There have been two assays for urinary CTx, which are u-aCTx and u-BCTx. A newly developed immunoassay for serum CTx (s-CTx) is now available for assessment of bone resorption. We have both evaluated the effects of menopause, and osteoporosis on the measurements of serum CTx and compared them to urinary CTx assays. Subjects: 79 premenopausal healthy women, 80 post-menopausal healthy women, 61 osteoporotic patients with vertebral fractures and 34 osteoporotic patients with hip fractures. Results: Bone resorption markers were increased after menopause. There was no significant difference among s-CTx, u-aCTx and u-BCTx in the T-scores of post-menopausal group over premenopausal group (T -score; s-CTx:2.3, u-aCTx:1.8, u-BCTx:2.1). Patients with vertebral fractures and patients with hip fracture had elevated levels of bone resorption markers compared to age-matched healthy postmenopousal women. There was no significant difference among s-CTx, u-aCTx and u-BCTx in the T-scores against postmenopausal group in vertebral fracture group (T -score; s-CTx:0.8, u-aCTx:0.9, u-BCTx:0.7) and in hip fracture group women (T-score; s-CTx:1.1, u-aCTx: 1.3 u-BCTx: 1.3). Conclusions: These findings indicate that s-CTx reflects the increase of bone resorption associated with menopause and osteoporosis with vertebral fractures and hip fractures