Glucocorticoids Increase Fracture Risk and Fracture Prevalence Independently from Bone Mineral Density and Clinical Risk Factors: Results from the Gliwice Osteoporosis (GO) Study.

The aim of the study was to establish the influence of glucocorticoids (GC) on fracture risk, probability, and prevalence. A set of 1548 postmenopausal women were divided into study group - treated with GC (n=114, age 66.48±7.6 years) and controls (n=1434, age 66.46±6.83 years). Data on clinical risk factors for osteoporosis and fractures were collected. Hip bone densitometry was performed using a device Prodigy (GE, USA). Fracture probability was established by FRAX, and fracture risk by Garvan algorithm and POL-RISK. Fracture risk and fracture probability were significantly greater for GC-treated women in comparison to controls. In the study group, there were 24, 3, 24, and 6 fractures noted at spine, hip, forearm, and arm, respectively. The respective numbers of fractures reported in controls at those skeletal sites were: 186, 23, 240, and 25. The use of GCs increased significantly prevalence of all major, spine and arm fractures. Also the number of all fractures was affected by GC use. Following factors significantly increased fracture probability: age (OR 1.04 per each year; 95% CI: 1.03-1.06), GC use (OR 1.54; 95% CI: 1.03-2.31), falls (OR 2.09; 95% CI: 1.60-2.73), and FN T-score (OR 0.62 per each unit; 95% CI: 0.54-0.71). In conclusion, in patients treated with GCs the fracture risk, probability, and prevalence were increased. This effect was evident regardless of whether GC therapy is included in the algorithm as a risk factor (FRAX, POL-RISK) or not taken into consideration (Garvan nomogram).

Serum levels of irisin in postmenopausal women with osteoporotic hip fractures.

OBJECTIVE: The purpose of this study was to evaluate the role of circulating serum levels of irisin in predicting hip fracture occurrence in a cohort of Chinese postmenopausal women. METHODS: This was a cross-section and case-control study. Four hundred and thirty postmenopausal women aged 50-90 years were included (215 with hip fractures and 215 age-matched cases without fracture). Clinical features, bone mineral density (BMD) and serum biomarkers levels including irisin were measured at baseline. Cox proportional hazards regression analysis was used to assess the correlation between irisin and fracture risk. RESULTS: The mean age of those participants was 68.7 (S.D. 11.7) and 53.0% were order than 65. The irisin serum levels were positively related to total body BMD and total hip BMD. Women with hip fractures showed lower mean serum levels of irisin compared normal control women (457.6 ± 172.6 ng/ml vs. 602.2 ng/ml; P < 0.001). The irisin levels in third and fourth quartiles were associated with the risk of hip fracture (the lowest quartile of irisin levels as the reference), and risk of fracture reduced by 67% (hazard ratio [HR] = 0.33; 95 %CI: 0.18-0.54; P < 0.001) and 84% (HR = 0.16; 95 %CI: 0.09-0.29; P < 0.001). The irisin levels in third and fourth quartiles were also associated with the risk of osteoporosis, and risk of fracture reduced by 55% (HR = 0.45; 95 %CI: 0.21-0.63; P = 0.003) and 73% (HR = 0.27; 95 %CI: 0.15-0.47; P < 0.001). CONCLUSION: Decreased serum levels of circulating irisin are associated with high risk of osteoporosis-related hip fractures and osteoporosis.

Biomechanics of the Femoral Head Cartilage and Subchondral Trabecular Bone in Osteoporotic and Osteopenic Fractures.

This study aimed to investigate the relationship between the micro structural properties of the subchondral trabecular bone (STB) and the macro mechanical properties of the articular cartilage (AC) in patients with osteoporotic (OP) and osteopenic (OPE) fractures. Sixteen femoral head samples (OP;OPE, n = 8 each) were obtained from female patients who underwent hip hemiarthroplasty. STB and AC specimens were harvested from those heads. Bone specimens were scanned using µ-CT to determine the micro structural properties. In-situ nondestructive compressive tests were performed for the cartilages to obtain elastic properties. The finite element technique was implemented on STB models created from µ-CT data to compute apparent elastic modulus. In addition, dynamic cyclic destructive tests were performed on STB and AC specimens to assess failure cycles. The results demonstrated that STB specimens in OPE group have more interconnected structure and higher cyclic dynamic strength than those in OP group. Furthermore, bone mineral density, failure cycle, and trabecular number of STB were positively correlated with the cartilage failure cycle, which indicates that STB alteration may affect the macroscopic mechanical properties of AC. The findings suggest that STB loss correlates with a decrease in cartilage strength and that improving of bone quality may prevent cartilage weakness.

Marine n-3 Polyunsaturated Fatty Acids and Bone Mineral Density in Kidney Transplant Recipients: A Randomized, Placebo-Controlled Trial.

Kidney transplant recipients are at high risk of progressive bone loss and low-energy fractures in the years following transplantation. Marine n-3 polyunsaturated fatty acids (n-3 PUFA) supplementation may have beneficial effects on bone strength. The Omega-3 fatty acids in Renal Transplantation (ORENTRA) trial was an investigator initiated, randomized, placebo-controlled trial investigating the effects of marine n-3 PUFA supplementation after kidney transplantation. Effects of supplementation on bone mineral density (BMD) and calcium metabolism were pre-defined secondary endpoints. Adult kidney transplant recipients (n = 132) were randomized to 2.6 g marine n-3 PUFA supplement or olive oil (control) from 8 to 52 weeks post-transplant. Dual energy X-ray absorptiometry was performed to assess changes in bone mineral density of hip, spine, and forearm, as well as trabecular bone score (TBS) of the lumbar spine. Student's t test was used to assess between-group differences. There were no differences in ΔBMD between the two groups (intervention vs. control) at lumbar spine (-0.020 ± 0.08 vs. -0.007 ± 0.07 g/cm², p = 0.34), total hip (0.001 ± 0.03 vs. -0.005 ± 0.04, p = 0.38), or other skeletal sites in the intention-to-treat analyses. There was no difference in the change in TBS score (0.001 ± 0.096 vs. 0.009 ± 0.102, p = 0.62). Finally, no effect on biochemical parameters of mineral metabolism was seen. Results were similar when analyzed per protocol. In conclusion, we found no significant effect of 44 weeks of supplementation with 2.6 g of marine n-3 PUFA on BMD in kidney transplant recipients.

Low Bone Mineral Density and Risk for Osteoporotic Fractures in Patients with Chronic Pancreatitis.

Introduction: Chronic pancreatitis (CP) can lead to malnutrition, an established risk factor for low bone mineral density (BMD) and fractures. This study aims to determine the prevalence of low BMD, assess fracture incidence and explore risk factors for fractures in patients with CP. Patients and methods: We performed a retrospective analysis of all patients treated for CP at Karolinska University Hospital between January 1999 and December 2020. Electronic medical records were retrieved to assess demographic, laboratory and clinical data. Patients subjected to dual-energy X-ray absorptiometry (DXA) were categorised as either low BMD or normal BMD. We investigated whether the rate of fractures, defined by chart review, differed between these groups using Cox regression, adjusting the model for age, sex and body mass index (BMI). Additional within-group survival analysis was conducted to identify potential risk factors. Results: DXA was performed in 23% of patients with definite CP. Some 118 patients were included in the final analysis. Low BMD was present in 63 (53.4%) patients. Mean age at CP diagnosis in the total cohort was 53.1 years and was significantly lower in patients with normal BMD than in patients with low BMD (45.5 vs. 59.8, p < 0.001). Significant differences were observed in smoking status and disease aetiology, i.e., a higher proportion of patients with low BMD were current or former smokers, with nicotine or alcohol being a more common cause of CP (p < 0.05). Total follow-up time was 898 person-years. Fractures were found in 33 (28.0%) patients: in 5 of 55 patients (16.7%) with normal DXA and in 28 of 63 patients (44.4%) with low BMD (adjusted hazard ratio = 3.4, 95% confidence interval (CI) = 1.2-9.6). Patients with at least 3 months of consecutive pancreatic enzyme replacement therapy (PERT) or vitamin D treatment had a longer median time to fracture after CP diagnosis. Conclusion: DXA was only performed in 23% of patients with definite CP in this study, indicating a low adherence to current European guidelines. A low BMD was found in 53.4% of patients with CP, and 44% of the patients with a low BMD experienced a fracture during follow-up. Moreover, the fracture rate in patients with low BMD increased compared to those with normal BMD.

Exosomes: A Friend or Foe for Osteoporotic Fracture?

The clinical need for effective osteoporotic fracture therapy and prevention remains urgent. The occurrence and healing of osteoporotic fracture are closely associated with the continuous processes of bone modeling, remodeling, and regeneration. Accumulating evidence has indicated a prominent role of exosomes in mediating multiple pathophysiological processes, which are essential for information and materials exchange and exerting pleiotropic effects on neighboring or distant bone-related cells. Therefore, the exosomes are considered as important candidates both in the occurrence and healing of osteoporotic fracture by accelerating or suppressing related processes. In this review, we collectively focused on recent findings on the diagnostic and therapeutic applications of exosomes in osteoporotic fracture by regulating osteoblastogenesis, osteoclastogenesis, and angiogenesis, providing us with novel therapeutic strategies for osteoporotic fracture in clinical practice.

Trans-sacral bar osteosynthesis provides low mortality and high mobility in patients with fragility fractures of the pelvis.

Operative treatment of osteoporosis-associated fragility fractures of the pelvis (FFP) and the sacrum is advocated with immobilizing or longstanding pain, fracture progression and displacement. We analyzed clinical outcomes regarding mobility, quality of life, and mortality of patients with FFP treated with trans-sacral bar (TB) osteosynthesis through S1. Demographics, clinical data, and operation-related data of patients with an FFP treated with TB were acquired from chart review. We assessed mortality, quality of life (EQ-5D), mobility, and residential status at follow-up. Seventy-nine females and six males with a median age of 78.0 years (IQR 73-84) were included, median follow-up was 3.2 years. Medical complications during hospitalization occurred in 28%. Operative revision was carried out in 15% of patients. One-year survival was 90.4%, this was associated with shorter preoperative and total length of stay in hospital (p 0.006 and 0.025, respectively). At follow-up, 85% lived at home and 82% walked with or without walking aid. Higher EQ-5D was reached with higher mobility status and living at home (p < 0.001 and < 0.001, respectively). TB osteosynthesis is an adequate and reliable method for fixation of FFP in the posterior pelvic ring to ensure timely mobilization. Shorter preoperative and total length of stay had lower mortality rates, advocating a standardized management protocol to limit time delay to operative therapy. Patients treated with TB osteosynthesis had low 1-year mortality of less than 10%.

Pulsed Electromagnetic Field Affects the Development of Postmenopausal Osteoporotic Women with Vertebral Fractures.

BACKGROUND: Postoperative pain, dysfunction, and significant bone loss may occur after vertebral fractures, which will lead to the occurrence of refractures and shorten the survival time, so postoperative rehabilitation is very important. Pulsed electromagnetic field therapy is noninvasive, pain-relieving, and beneficial to reduce bone loss and is an important treatment for patients to recover after surgery. Therefore, this study analyzed the effect of postmenopausal women's vertebral fracture rehabilitation after pulsed electromagnetic field treatment. METHOD: This study uses a randomized controlled study, respectively, in the pulsed electromagnetic field treatment group (40 cases) and the control group (42 cases), respectively. We studied the results of health-related quality of life scores (HRQOL), back pain, body function, hip bone density, bone microstructure of tibia, and radius after 1 month and 3 months after surgery. RESULTS: Compared with the control group, the pulsed electromagnetic field treatment group (PEMF) can improve significantly the psychological score, 6-minute walk test, and Chair Sit-and-Reach one month after the operation. And at 3 months after surgery, the pulsed electromagnetic field treatment group can improve significantly in health-related quality of life scores (HRQOL), back pain, and body function. Regarding the effect of changes in bone mass, compared with the control group, pulsed electromagnetic field treatment had no significant effect on changes in hip bone density. As a result of changes in bone microstructure, pulsed electromagnetic field treatment can significantly improve the bone microstructure of the radius and tibia three months after vertebral fractures. CONCLUSION: Pulsed electromagnetic field therapy has positive significance for improving pain, body functional changes, and bone loss after vertebral fracture surgery.

Loss of longitudinal superiority marks the microarchitecture deterioration of osteoporotic cancellous bones.

Osteoporosis (OP), a skeletal disease making bone mechanically deteriorate and easily fracture, is a global public health issue due to its high prevalence. It has been well recognized that besides bone loss, microarchitecture degradation plays a crucial role in the mechanical deterioration of OP bones, but the specific role of microarchitecture in OP has not been well clarified and quantified from mechanics perspective. Here, we successfully decoupled and identified the specific roles of microarchitecture, bone mass and tissue property in the failure properties of cancellous bones, through µCT-based digital modeling and finite element method simulations on bone samples from healthy and ovariectomy-induced osteoporotic mice. The results show that the microarchitecture of healthy bones exhibits longitudinal superiority in mechanical properties such as the effective stiffness, strength and toughness, which fits them well to bearing loads along their longitudinal direction. OP does not only reduce bone mass but also impair the microarchitecture topology. The former is mainly responsible for the mechanical degradation of bones in magnitude, wherever the latter accounts for the breakdown of their function-favorable anisotropy, the longitudinal superiority. Hence, we identified the microarchitecture-deterioration-induced directional mismatch between material and loading as a hazardous feature of OP and defined a longitudinal superiority index as measurement of the health status of bone microarchitecture. These findings provide useful insights and guidelines for OP diagnosis and treat assessment.

Discriminative ability of trabecular bone score over bone mineral density for vertebral and fragility fracture in patients treated with long-term and low-dose glucocorticoid.

AIM: To evaluate the ability of the trabecular bone score (TBS) to discriminate vertebral fracture (VF) and fragility fracture (FF) in patients with chronic inflammatory rheumatic diseases on long-term and low-dose glucocorticoid (GC) treatment and those without exposure to GC. METHODS: This study assessed TBS and bone mineral density (BMD) in chronic GC users, defined as ≥2.5 mg/d of prednisone for >3 months (n = 89, mean age: 62.5 ± 11 years), and in controls (n = 59, mean age: 60.3 ± 9.6 years). Osteoporosis risk factors, radiographs of the thoracolumbar spine, non-VF history, osteoporosis drugs, and current/cumulative GC doses were collected. Patients were classified as high (TBS <1.23), intermediate (1.23-1.31), or low risk (>1.31), according to the fracture risk based on a recent meta-analysis. RESULTS: The mean current dose and duration of GC treatment were 3.9 ± 1.9 mg/d and 3.9 ± 4.2 years, respectively. The prevalence of VF was significantly higher in chronic GC users than in controls (20.2% vs 5.1%, P = .010), although the prevalence of non-VF was similar (11.2% vs 5.1%). The GC group had significantly lower L1-L4 TBS and femur total BMD than did the controls (all with P < .01) without significantly different lumbar BMD. TBS (<1.31) showed a higher sensitivity for patients with VF and FF (83.3% and 81.8%, respectively) than with densitometric osteoporosis in the GC group (61.1% and 59.1%, respectively). Using the receiver operating characteristic curve, TBS <1.31 showed better diagnostic accuracy than TBS <1.23 and BMD in chronic GC users. CONCLUSION: TBS is more sensitive than BMD in detecting VF and FF in chronic GC users, even at a lower dose.

The effect of whole-body vibration exercise on postmenopausal women with osteoporosis: A protocol for systematic review and meta-analysis.

BACKGROUND: Osteoporosis (OP) is an age-related disease characterized by reduced bone mass and increased bone fragility. It is more common in older people and postmenopausal women. As a new type of exercise training for OP, whole-body vibration (WBV) exercise has been proved to have a good effect on postmenopausal women with OP. It can increase bone density and improve strength and balance in postmenopausal population, which has certain clinical value, but lacks evidence-based medicine evidence. This study aims to systematically study the effectiveness of WBV exercise on postmenopausal women with OP. METHODS: The English databases (PubMed, Embase, Web of Science, The Cochrane Library) and Chinese databases (China National Knowledge Network, Wanfang, Weipu, China Biomedical Database) were searched by computer. From the establishment of the database to February 2021, the randomized controlled clinical studies on WBV exercise on postmenopausal women with OP were conducted. The quality of the included studies was independently extracted by 2 researchers and literature quality was evaluated. Meta-analysis of the included studies was performed using RevMan5.3 software. RESULTS: In this study, the efficacy and safety of WBV exercise on postmenopausal women with OP were evaluated by lumbar spine bone density, femoral neck bone density, pain, incidence of falls, incidence of fractures, and quality of life scale score, etc. CONCLUSION: This study will provide reliable evidences for the clinical application of WBV exercise on postmenopausal women with OP. ETHICS AND DISSEMINATION: Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval will not be required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/WPYT9.

Integrating real-world data and modeling to project changes in femoral neck bone mineral density and fracture risk in premenopausal women.

Decline of bone mineral density (BMD) during menopause is related to increased risk of fractures in postmenopausal women, however, this relationship in premenopausal women has not been established. To quantify this relationship, real-world data (RWD) from the National Health and Nutrition Examination Survey (NHANES), and longitudinal data from the elagolix phase III clinical trials were modeled across a wide age range, and covariates were evaluated. The natural changes in femoral neck BMD (FN-BMD) were well-described by a bi-exponential relationship with first-order BMD formation (k1 ) and resorption (k2 ) rate constants. Body mass index (BMI) and race (i.e., Black) were significant predictors indicating that patients with high BMI or Black race experience a relatively lower BMD loss. Simulations suggest that untreated premenopausal women with uterine fibroids (UFs) from elagolix phase III clinical trials (median age 43 years [minimum 25-maximum 53]) lose 0.6% FN-BMD each year up to menopausal age. For clinical relevance, the epidemiological FRAX model was informed by the simulation results to predict the 10-year risk of major osteoporotic fracture (MOF). Premenopausal women with UFs, who received placebo only in the elagolix phase III trials, have a projected FN-BMD of 0.975 g/cm2 at menopause, associated with a 10-year risk of MOF of 2.3%. Integration of modeling, RWD, and clinical trials data provides a quantitative framework for projecting long-term postmenopausal risk of fractures, based on natural history of BMD changes in premenopausal women. This framework enables quantitative evaluation of the future risk of MOF for women receiving medical therapies (i.e., GnRH modulators) that adversely affect BMD.

Bone Material Strength Index as Measured by Impact Microindentation is Low in Patients with Primary Hyperparathyroidism.

CONTEXT: In primary hyperparathyroidism (PHPT) bone mineral density (BMD) is typically decreased in cortical bone and relatively preserved in trabecular bone. An increased fracture rate is observed however not only at peripheral sites but also at the spine, and fractures occur at higher BMD values than expected. We hypothesized that components of bone quality other than BMD are affected in PHPT as well. OBJECTIVE: To evaluate bone material properties using impact microindentation (IMI) in PHPT patients. METHODS: In this cross-sectional study, the Bone Material Strength index (BMSi) was measured by IMI at the midshaft of the tibia in 37 patients with PHPT (28 women), 11 of whom had prevalent fragility fractures, and 37 euparathyroid controls (28 women) matched for age, gender, and fragility fracture status. RESULTS: Mean age of PHPT patients and controls was 61.8 ±â€…13.3 and 61.0 ±â€…11.8 years, respectively, P = .77. Calcium and PTH levels were significantly higher in PHPT patients but BMD at the lumbar spine (0.92 ±â€…0.15 vs 0.89 ±â€…0.11, P = .37) and the femoral neck (0.70 ±â€…0.11 vs 0.67 ±â€…0.07, P = .15) were comparable between groups. BMSi however was significantly lower in PHPT patients than in controls (78.2 ±â€…5.7 vs 82.8 ±â€…4.5, P < .001). In addition, BMSi was significantly lower in 11 PHPT patients with fragility fractures than in the 26 PHPT patients without fragility fractures (74.7 ±â€…6.0 vs 79.6 ±â€…5.0, P = .015). CONCLUSION: Our data indicate that bone material properties are altered in PHPT patients and most affected in those with prevalent fractures. IMI might be a valuable additional tool in the evaluation of bone fragility in patients with PHPT.

Factors Affecting Quality of Life at Discharge among Patients with Osteoporotic Vertebral Fractures.

OBJECTIVES: This study aimed to identify factors, including physical functions and activities that affect quality of life (QOL) at discharge among patients with osteoporotic vertebral fractures. METHODS: Patients with osteoporotic vertebral fractures were included in our prospective cohort study. Multiple regression analysis was performed to determine the predictors of QOL at discharge using two models: model 1, basic medical information and physical functions at admission, and model 2, basic medical information, physical function, and activity after 4 weeks of admission. RESULTS: Multiple regression analysis (standard partial regression coefficients) using model 1 identified L2 to L4 bone mineral density (-0.2), Visual Analog Scale for pain during activity at admission (-0.31), and Revised Hasegawa Dementia Scale (HDS-R) score at admission (0.64) as factors affecting QOL at discharge. Multiple regression analysis using model 2 identified HDS-R at admission (0.64), Pain Catastrophizing Scale score at 4 weeks (-0.34), and knee extension muscle strength at 4 weeks (0.28) as factors affecting QOL at discharge. CONCLUSIONS: Our results suggest that if patients have high bone mineral density, intense pain, and low cognitive function at admission, then low QOL at discharge will be predicted; however, improvement of pain catastrophizing and knee extension muscle strength during first the 4 weeks of admission may be able to improve QOL at discharge. Because patients in this study were Japanese only, it is important to exercise caution when applying our results to other populations.

Comparison of the Characteristics of Back Pain in Women with Postmenopausal Osteoporosis with and without Vertebral Compression Fracture: A Retrospective Study at a Single Osteoporosis Center in Poland.

BACKGROUND The incidence of unspecific back pain and osteoporotic vertebral compression fractures increases significantly with age. Considering the difficulties in the diagnosis of spontaneous osteoporotic vertebral fractures, this retrospective study aimed to compare the characteristics of back pain in women with postmenopausal osteoporosis with and without vertebral compression fractures. MATERIAL AND METHODS This study enrolled 334 women with postmenopausal osteoporosis; 150 had vertebral fractures, and 184 had no vertebral fractures. Densitometric vertebral fracture assessment and bone mineral density measurements in the central skeleton were performed for each patient. The participants completed a survey about features of their back pain. RESULTS Patients with vertebral fractures had more severe back pain based on the numeric rating scale: 6.14 vs. 4.33 (P<0.001, odds ratio [OR]=1.43, 95% confidence interval [CI]: 1.29-1.59). Among these individuals, back pain caused reduction in normal activity during the day (P<0.001, OR=4.68, 95% CI: 2.86-7.68), and pain occurred more often (P<0.001, OR=1.77, 95% CI: 1.47-2.13), lasted longer (P<0.001, OR=2.01, 95% CI: 1.65-2.46), predominantly occurred in the lumbar spine (P<0.001, OR=4.70, 95% CI: 1.96-11.29), and intensified during normal everyday activities (P<0.001). Based on these results, a new survey was created. It demonstrated a sensitivity of 70.67% and a specificity of 67.37% in predicting a current compression fracture. CONCLUSIONS Patients with vertebral compression fractures experience higher pain intensity and exhibit specific features of back pain. The new survey can be considered a supportive tool in assessing the possibility of vertebral compression fractures.

Long-Term Follow-Up of Denosumab Discontinuers with Multiple Vertebral Fractures in the Real-World: A Case Series.

Denosumab discontinuation is associated with rapid reversal of bone turnover suppression and with a considerable increase in fracture risk, including a risk for multiple vertebral fractures (MVF). Long-term follow-up of patients who sustained MVF after denosumab discontinuation has not been reported. This case-series was aimed to provide a long-term follow-up on the management and outcome of denosumab discontinuers who initially presented with multiple vertebral fractures. Denosumab discontinuers were identified from a computerized database of a large healthcare provider. Baseline and follow-up clinical, laboratory, and imaging data were obtained from the computerized database and electronic medical records. The post-denosumab discontinuers MVF patients consisted of 12 women aged 71±12. Osteoporotic fractures were prevalent before denosumab discontinuation in 6 of the patients. The majority received bisphosphonates before denosumab. MVF occurred 134±76 days after denosumab discontinuation. The patients were followed for a median of 36.5 (IQR 28.2, 42.5) months after MVF. Two patients passed-away. Two patients suffered recurrent vertebral fractures. Following MVF, patients were treated inconsistently with denosumab, teriparatide, oral, and intravenous bisphosphonates, in various sequences. Two patients underwent vertebroplasty/kyphoplasty. This long-term follow-up of real-world patients with MVF following denosumab discontinuation reveals that management is inconsistent, and recurrent fractures are not uncommon. It calls for clear management guidelines for patients with MVF after denosumab discontinuation and for special attention to this high-risk group.

Finite element analysis of wedge and biconcave deformity in four different height restoration after augmentation of osteoporotic vertebral compression fractures.

PURPOSE: Biomechanical comparison of wedge and biconcave deformity of different height restoration after augmentation of osteoporotic vertebral compression fractures was analyzed by three-dimensional finite element analysis (FEA). METHODS: Three-dimensional finite element model (FEM) of T11-L2 segment was constructed from CT scan of elderly osteoporosis patient. The von Mises stresses of vertebrae, intervertebral disc, facet joints, displacement, and range of motion (ROM) of wedge and biconcave deformity were compared at four different heights (Genant 0-3 grade) after T12 vertebral augmentation. RESULTS: In wedge deformity, the stress of T12 decreased as the vertebral height in neutral position, flexion, extension, and left axial rotation, whereas increased sharply in bending at Genant 0; L1 and L2 decreased in all positions excluding flexion of L2, and T11 increased in neutral position, flexion, extension, and right axial rotation at Genant 0. No significant changes in biconcave deformity. The stress of T11-T12, T12-L1, and L1-L2 intervertebral disc gradually increased or decreased under other positions in wedge fracture, whereas L1-L2 no significant change in biconcave fracture. The utmost overall facet joint stress is at Genant 3, whereas there is no significant change under the same position in biconcave fracture. The displacement and ROM of the wedge fracture had ups and downs, while a decline in all positions excluding extension in biconcave fracture. CONCLUSIONS: The vertebral restoration height after augmentation to Genant 0 affects the von Mises stress, displacement, and ROM in wedge deformity, which may increase the risk of fracture, whereas restored or not in biconcave deformity.

Bone strain index as a predictor of further vertebral fracture in osteoporotic women: An artificial intelligence-based analysis.

BACKGROUND: Osteoporosis is an asymptomatic disease of high prevalence and incidence, leading to bone fractures burdened by high mortality and disability, mainly when several subsequent fractures occur. A fragility fracture predictive model, Artificial Intelligence-based, to identify dual X-ray absorptiometry (DXA) variables able to characterise those patients who are prone to further fractures called Bone Strain Index, was evaluated in this study. METHODS: In a prospective, longitudinal, multicentric study 172 female outpatients with at least one vertebral fracture at the first observation were enrolled. They performed a spine X-ray to calculate spine deformity index (SDI) and a lumbar and femoral DXA scan to assess bone mineral density (BMD) and bone strain index (BSI) at baseline and after a follow-up period of 3 years in average. At the end of the follow-up, 93 women developed a further vertebral fracture. The further vertebral fracture was considered as one unit increase of SDI. We assessed the predictive capacity of supervised Artificial Neural Networks (ANNs) to distinguish women who developed a further fracture from those without it, and to detect those variables providing the maximal amount of relevant information to discriminate the two groups. ANNs choose appropriate input data automatically (TWIST-system, Training With Input Selection and Testing). Moreover, we built a semantic connectivity map usingthe Auto Contractive Map to provide further insights about the convoluted connections between the osteoporotic variables under consideration and the two scenarios (further fracture vs no further fracture). RESULTS: TWIST system selected 5 out of 13 available variables: age, menopause age, BMI, FTot BMC, FTot BSI. With training testing procedure, ANNs reached predictive accuracy of 79.36%, with a sensitivity of 75% and a specificity of 83.72%. The semantic connectivity map highlighted the role of BSI in predicting the risk of a further fracture. CONCLUSIONS: Artificial Intelligence is a useful method to analyse a complex system like that regarding osteoporosis, able to identify patients prone to a further fragility fracture. BSI appears to be a useful DXA index in identifying those patients who are at risk of further vertebral fractures.

Long-term safety and effectiveness of denosumab in Japanese patients with osteoporosis: 3-year post-marketing surveillance study.

INTRODUCTION: Denosumab is a humanized IgG2 monoclonal antibody that was approved for the treatment of osteoporosis in Japan in 2013. This study aimed to investigate the long-term safety and effectiveness of denosumab in Japanese patients with osteoporosis in daily clinical practice. MATERIALS AND METHODS: This 3-year, prospective, observational, post-marketing study included patients who initiated treatment with denosumab (60 mg/6 months) for osteoporosis. Data were assessed at baseline, 3, 6, 12, 24 and 36 months. Key endpoints were adverse events (AEs), adverse drug reactions (ADRs), occurrence of osteoporotic fractures, bone mineral density (BMD), and bone turnover markers. Multivariate analyses were conducted to identify predictors of hypocalcaemia and percent change in BMD. RESULTS: Overall, 3534 patients were assessed (mean 75.7 years; 89.8% women). In total, 298 patients (8.4%) developed ADRs; the most common was hypocalcaemia (3.9%). Hypocalcaemia risk was significantly increased in patients with creatinine clearance < 30 mL/min, no prior use of bisphosphonates, prior use of calcium and vitamin D preparations, baseline serum calcium < 8.5 mg/dL, and no concomitant use of calcium or vitamin D preparations. Six patients had adjudicated osteonecrosis of the jaw. Lumbar spine BMD increased significantly from baseline (mean percent change: 11.4% at 36 months). All bone turnover markers decreased significantly from baseline. Over 3 years, 3.3% of patients developed a new osteoporotic fracture. CONCLUSIONS: This study confirmed the long-term safety and effectiveness of denosumab in Japanese patients with osteoporosis in daily clinical practice. No new safety signals were identified.