Study Design.: A retrospective cohort study. Objective.: The authors aimed to estimate the incidence, prevalence and years lived with disability (YLDs) of spinal cord injury (SCI) by location, sex, age, injury site and socio-demographic index (SDI) based on the data of the Global Burden of Disease Study (GBD) 2019. Summary of Background Data.: GBD 2019 estimates the burden of 369 diseases and injuries worldwide in 2019 and the temporal trends in the past 30 years. SCI is estimated as a result of injury from various causes. Methods.: A Bayesian meta-regression tool, DisMod-MR2.1, was used to produce the estimates. Estimated annual percentage change (EAPC) was calculated based on a linear regression mode of the age standardized rates and the calendar year to represent the temporal trends of the age standardized rates. Spearman rank order correlation was used to determine the correlation between SDI and the incidence and burden of SCI. Results.: Globally, there were 0.9 [95% uncertainty interval (UI), 0.7 to 1.2] million incident cases, 20.6 (95% UI, 18.9–23.6) million prevalent cases and 6.2 (95% UI, 4.5–8.2) million YLDs of total SCI in 2019. The ASPR increased (EAPC, 0.1; 95% confidence interval, −0.01 to 0.2), while the age standardized incidence rate (ASIR) (EAPC, −0.08; 95% UI, −0.24 to 0.09) and age standardized YLD rate (ASYR) (EAPC, −0.08; 95% confidence interval, −0.24 to 0.09) decreased. Males had higher ASIR and ASYR, and the rate of incidence, prevalence and YLD increased with age. Spinal injuries at neck level caused higher ASYR than injuries below neck level. A positive correlation existed between SDI and ASIR (ρ=0.1626, P<0.05), while a negative correlation was observed between SDI and EAPC of ASYR (ρ=−0.2421, P<0.01). Conclusion.: Conclusively, the incidence and burden of SCI has increased over the last 30 years. Males and the elderly were affected to a greater degree than females and younger individuals. Level of Evidence.: Level III.

Background: Hip fractures are associated with a high risk of death; among those who survive a hip fracture, many experience substantial decreases in quality of life. A comprehensive understanding of the epidemiology and burden of hip fractures by country, age, gender, and sociodemographic factors would provide valuable information for healthcare policymaking and clinical practice. The Global Burden of Disease (GBD) study 2019 was a global-level study estimating the burden of 369 diseases and injuries in 204 countries and territories. An exploration and additional analysis of the GBD 2019 would provide a clearer picture of the incidence and burden of hip fractures. Questions/purposes: Using data from the GBD 2019, we asked, (1) What are the global, regional, and national incidences of hip fractures, and how did they change over a recent 30-year span? (2) What is the global, regional, and national burden of hip fractures in terms of years lived with disability, and how did it change over that same period? (3) What is the leading cause of hip fractures? (4) How did the incidence and years lived with disability of patients with hip fractures change with age, gender, and sociodemographic factors? Methods: This was a cross-sectional study. Participant data were obtained from the GBD 2019 (http://ghdx.healthdata.org/gbd-results-tool). The GBD study is managed by the WHO, coordinated by the Institute of Health Metrics and Evaluation, and funded by the Bill and Melinda Gates Foundation. It estimates the burden of disease and injury for 204 countries by age, gender, and sociodemographic factors, and can serve as a valuable reference for health policymaking. All estimates and their 95% uncertainty interval (UI) were produced using DisMod-MR 2.1, a Bayesian meta-regression tool in the GBD 2019. In this study, we directly pulled the age-standardized incidence rate and years lived with disability rate of hip fractures by location, age, gender, and cause from the GBD 2019. Based on these data, we analyzed the association between the incidence rate and latitude of each country. Then, we calculated the estimated annual percentage change to represent trends from 1990 to 2019. We also used the Spearman rank-order correlation analysis to determine the correlation between the incidence or burden of hip fractures and the sociodemographic index, a composite index of the income per capita, average years of educational attainment, and fertility rates in a country. Results: Globally, hip fracture incidences were estimated to be 14.2 million (95% UI 11.1 to 18.1), and the associated years lived with disability were 2.9 million (95% UI 2.0 to 4.0) in 2019, with an incidence of 182 (95% UI 142 to 231) and 37 (95% UI 25 to 50) per 100,000, respectively. A strong, positive correlation was observed between the incidence rate and the latitude of each country (rho = 0.65; p < 0.001). From 1990 to 2019, the global incidence rate for both genders remained unchanged (estimated annual percentage change 0.01 [95% confidence interval -0.08 to 0.11]), but was slightly increased in men (estimated annual percentage change 0.11 [95% CI 0.01 to 0.2]). The years lived with disability rate decreased slightly (estimated annual percentage change 0.66 [95% CI -0.73 to -0.6]). These rates were standardized by age. Falls were the leading cause of hip fractures, accounting for 66% of all patients and 55% of the total years lived with disability. The incidence of hip fractures was tightly and positively correlated with the sociodemographic index (rho 0.624; p < 0.001), while the years lived with disability rate was slightly negatively correlated (rho -0.247; p < 0.001). Most hip fractures occurred in people older than 70 years, and women had higher incidence rate (189.7 [95% UI 144.2 to 247.2] versus 166.2 [95% UI 133.2 to 205.8] per 100,000) and years lived with disability (38.4 [95% UI 26.9 to 51.6] versus 33.7 [95% UI 23.1 to 45.5] per 100,000) than men. Conclusion: Hip fractures are common, devastating to patients, and economically burdensome to healthcare systems globally, with falls being the leading cause. The age-standardized incidence rate has slightly increased in men. Many low-latitude countries have lower incidences, possibly because of prolonged sunlight exposure. Policies should be directed to promoting public health education about maintaining bone-protective lifestyles, enhancing the knowledge of osteoporosis management in young resident physicians and those in practice, increasing the awareness of osteoporosis screening and treatment in men, and developing more effective antiosteoporosis drugs for clinical use. Level of Evidence: Level III, prognostic study.

Due to the unique physical characteristics of intervertebral disc degeneration (IVDD) and the pathological microenvironment that it creates, including inflammation and oxidative stress, effective self-repair is impossible. During the process of intervertebral disc degeneration, there is an increase in the infiltration of M1 macrophages and the secretion of proinflammatory cytokines. Here, we designed a novel injectable composite hydrogel scaffold: an oligo [poly (ethylene glycol) fumarate]/sodium methacrylate (OPF/SMA) hydrogel scaffold loaded with dual-drug/sustained-release PLGA microspheres containing IL-4 (IL-4-PLGA) and kartogenin (KGN-PLGA). This scaffold exhibited good mechanical properties and low immunogenicity while also promoting the sustained release of drugs. By virtue of the PLGA microspheres loaded with IL-4 (IL-4-PLGA), the composite hydrogel scaffold induced macrophages to transition from the M1 phenotype into the M2 phenotype during the early induced phase and simultaneously exhibited a continuous anti-inflammatory effect through the PLGA microspheres loaded with kartogenin (KGN-PLGA). Furthermore, we investigated the mechanisms underlying the immunomodulatory and anti-inflammatory effects of the composite hydrogel scaffold. We found that the scaffold promoted cell proliferation and improved cell viability in vitro. While ensuring mechanical strength, this composite hydrogel scaffold regulated the local inflammatory microenvironment and continuously repaired tissue in the nucleus pulposus via the sequential release of drugs in vivo. When degenerative intervertebral discs in a rat model were injected with the scaffold, there was an increase in the proportion of M2 macrophages in the inflammatory environment and higher expression levels of type II collagen and aggrecan; this was accompanied by reduced levels of MMP13 expression, thus exhibiting long-term anti-inflammatory effects. Our research provides a new strategy for promoting intervertebral disc tissue regeneration and a range of other inflammatory diseases.

Bone metastasis is a severe complication associated with various carcinomas. It causes debilitating pain and pathologic fractures and dramatically impairs patients' quality of life. Drugs aimed at osteoclast formation significantly reduce the incidence of skeletal complications and are currently the standard treatment for patients with bone metastases. Here, we reported that serum- and glucocorticoid-inducible kinase 1 (SGK1) plays a pivotal role in the formation and function of osteoclasts by regulating the Ca2+ release-activated Ca2+ channel Orai1. We showed that SGK1 inhibition represses osteoclastogenesis in vitro and prevents bone loss in vivo. Furthermore, we validated the effect of SGK1 on bone metastasis by using an intracardiac injection model in mice. Inhibition of SGK1 resulted in a significant reduction in bone metastasis. Subsequently, the Oncomine and the OncoLnc database were employed to verify the differential expression and the association with clinical outcome of SGK1 gene in patients with breast cancer. Our data mechanistically demonstrated the regulation of the SGK1 in the process of osteoclastogenesis and revealed SGK1 as a valuable target for curing bone metastasis diseases.

Background: (I) To determine whether patients with malignant bone tumors had a higher risk of dying from pneumonia compared with the general US population; (II) to identify the independent risk factor associated with fatal pneumonia among these patients. Methods: We identified 18,583 patients diagnosed with primary malignant bone tumors between 1973 and 2016 from the Surveillance, Epidemiology, and End Results (SEER) database. Standardized mortality ratios (SMRs) were calculated based on the mortality data of the general population gathered by the National Center for Health Statistics, which provided the risk of death from pneumonia among cancer patients relative to that of the general population. Given that other causes of death were considered as competing events, we also designed the Fine-Gray model to identify demographic and tumor-related characteristics associated with a higher risk of dying from pneumonia among these patients. Results: Patients with primary malignant bone tumors had a higher risk of dying from pneumonia than the general population after adjusting the distribution difference of age, sex, and race among them (SMR =2.79; 95% CI: 2.17–3.59). The older age, Black and earlier period of diagnosis were found to be the independent prognostic factor for a higher risk of death from pneumonia for these patients. Additionally, amputation due to malignant bone tumors significantly increased the risk of death from pneumonia compared with non-surgery. The highest mortality rate of pneumonia was observed among patients with chordoma. Interaction tests demonstrated that amputation only increased the relative risk of fatal pneumonia among patients with osteosarcoma. Throughout the follow-up period, the mortality rate of fatal pneumonia was the highest within the first year after diagnosis, and the highest relative suicide risks persisted over time in patients with osteosarcoma. Conclusions: To mitigate the risk of fatal pneumonia among patients with bone tumors, we call for long-term clinical monitoring of the lung condition among these patients, especially for those after amputation for bone tumors.

The biodegradable scaffolds based on biomedical polymeric materials have attracted the wide interest in bone transplantation for clinical treatment to bone defects without the second operation. The composite materials of poly(trimethylene carbonate), poly(L-lactic acid) and hydroxyapatite (PTMC/PLA/HA) were prepared by the modification and blending of poly(trimethylene carbonate) (PTMC) with poly(L-lactic acid) (PLA) and hydroxyapatite nanoparticles (HA). The PTMC/PLA/HA scaffolds were further prepared by additive manufacturing using the biological 3D printing method. The PTMC/PLA/HA composite materials and scaffolds were also characterized by fourier transform infrared spectroscopy (FT-IR), GPC, automatic contact-angle, SEM, XRD, differential scanning calorimetry (DSC) and thermogravimetry (TG). Subsequently, their properties, such as the mechanic, biodegradation, drug controlled release, cell cytotoxicity, cell compatibility in vitro and proliferation/differentiation assay in vivo, were also investigated. Experiment results indicated that PTMC/PLA/HA scaffolds possessed the low toxicity, good biodegradability and good biocompatibility and then improved the cell proliferation of osteoblast cells (MC3T3-E1). Moreover, PTMC/PLA/HA enhanced the adhesion and proliferation of MC3T3-E1 cells, allowing penetration of host cells within the construct boundaries, and then can enable the growing of bone cells and induction of bone tissue regeneration. Therefore, PTMC/PLA/HA composite materials can be used as the potential biodegradable scaffolds for bone regeneration and tissue engineering in vivo.