Bone fractures are a global public health issue; however, to date, no comprehensive study of their incidence and burden has been done. We aimed to measure the global, regional, and national incidence, prevalence, and years lived with disability (YLDs) of fractures from 1990 to 2019. Using the framework of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we compared numbers and age-standardised rates of global incidence, prevalence, and YLDs of fractures across the 21 GBD regions and 204 countries and territories, by age, sex, and year, from 1990 to 2019. We report estimates with 95% uncertainty intervals (UIs). Globally, in 2019, there were 178 million (95% UI 162–196) new fractures (an increase of 33·4% [30·1–37·0] since 1990), 455 million (428–484) prevalent cases of acute or long-term symptoms of a fracture (an increase of 70·1% [67·5–72·5] since 1990), and 25·8 million (17·8–35·8) YLDs (an increase of 65·3% [62·4–68·0] since 1990). The age-standardised rates of fractures in 2019 were 2296·2 incident cases (2091·1–2529·5) per 100 000 population (a decrease of 9·6% [8·1–11·1] since 1990), 5614·3 prevalent cases (5286·1–5977·5) per 100 000 population (a decrease of 6·7% [5·7–7·6] since 1990), and 319·0 YLDs (220·1–442·5) per 100 000 population (a decrease of 8·4% [7·2–9·5] since 1990). Lower leg fractures of the patella, tibia or fibula, or ankle were the most common and burdensome fracture in 2019, with an age-standardised incidence rate of 419·9 cases (345·8–512·0) per 100 000 population and an age-standardised rate of YLDs of 190·4 (125·0–276·9) per 100 000 population. In 2019, age-specific rates of fracture incidence were highest in the oldest age groups, with, for instance, 15 381·5 incident cases (11 245·3–20 651·9) per 100 000 population in those aged 95 years and older. The global age-standardised rates of incidence, prevalence, and YLDs for fractures decreased slightly from 1990 to 2019, but the absolute counts increased substantially. Older people have a particularly high risk of fractures, and more widespread injury-prevention efforts and access to screening and treatment of osteoporosis for older individuals should help to reduce the overall burden. Bill & Melinda Gates Foundation.

Background: Bones are one of the most common metastatic sites for solid malignancies. Bone metastases can significantly increase mortality and decrease the quality of life of cancer patients. In the United States, around 350,000 people die each year from bone metastases. This study aimed to analyze and update the incidence and prognosis of bone metastases with solid tumors at the time of cancer diagnosis and its incidence rate for each solid cancer. Methods: We used the Surveillance, Epidemiology, and End Results (SEER) database to find patients diagnosed with solid cancers originating from outside the bones and joints between 2010 and 2016. Data were stratified by age, sex, and race. Patients with a tumor in situ or with an unknown bone metastases stage were excluded. We then selected most of the sites where cancer often occurred, leaving 2,207,796 patients for the final incidence analysis. For the survival analysis, patients were excluded if they were diagnosed at their autopsy or on their death certificate, or had unknown follow-ups. The incidence of bone metastases and overall survival was compared between patients with different primary tumor sites. Results: We identified 2,470,634 patients, including 426,594 patients with metastatic disease and 113,317 patients with bone metastases, for incidence analysis. The incidence of bone metastases among the metastatic subset was 88.74% in prostate cancer, 53.71% in breast cancer, and 38.65% in renal cancer. In descending order of incidence, there were patients with other cancers in the genitourinary system (except for renal, bladder, prostate, and testicular cancer) (37.91%), adenocarcinoma of the lung (ADC) (36.86%), other gynecologic cancers (36.02%), small-cell lung cancer (SCLC) (34.56%), non-small cell lung cancer not otherwise specified and others [NSCLC (NOS/others)] (33.55%), and bladder (31.08%) cancers. The rate of bone metastases is 23.19% in SCLC, 22.50% in NSCLC (NOS/others), 20.28% in ADC, 8.44% in squamous cell carcinoma of the lung (SCC), and 4.11% in bronchioloalveolar carcinoma [NSCLC (BAC)]. As for the digestive system, the overall bone metastases rate was 7.99% in the esophagus, 4.47% in the gastric cancer, 4.42% in the hepatobiliary cancer, 3.80% in the pancreas, 3.26% in other digestive organs, 1.24% in the colorectum, and 1.00% in the anus. Overall, the incidence rate of bone metastases among the entire cohort in breast and prostate cancer was 3.73% and 5.69%, respectively. Conclusions: The results of this study provide population-based estimates for the incidence rates of patients with bone metastases at initial diagnosis of their solid tumor. The findings can help clinicians to early detect bone metastases by bone screening to anticipate the occurrence of symptoms and favorably improve the prognosis.

Cancer-induced Bone Pain (CIBP) is an important factor affecting their quality of life of cancer survivors. In addition, current clinical practice and scientific research suggest that neuropathic pain is a representative component of CIBP. However, given the variability of cancer conditions and the complexity of neuropathic pain, related mechanisms have been continuously supplemented but have not been perfected. Therefore, the current review highlights the latest progress in basic research on the field and proposes potential therapeutic targets, representative drugs and upcoming therapies. Notably, factors such as central sensitization, neuroinflammation, glial cell activation and an acidic environment are considered to be related to neuropathic pain in CIBP. Nonetheless, further research is needed to ascertain the mechanism of CIBP in order to develop highly effective drugs. Moreover, more attention needs to be paid to the care of patients with advanced cancer.

Intervertebral disc degeneration (IVDD) is a chronic degenerative disease involving the aging and loss of proliferative capacity of nucleus pulposus cells (NPCs), processes heavily dependent on mitochondrial dynamics and autophagic flux. This study finds that the absence of BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) is associated with senescence‐related NPC degeneration, disrupting mitochondrial quality control. Bone marrow mesenchymal stem cells (BMSCs) have multidirectional differentiation potential and produce extracellular vesicles containing cellular activators. Therefore, in this study, BMSCs are induced under hypoxic stimulation to deliver BNIP3‐rich extracellular vesicles to NPCs, thereby alleviating aging‐associated mitochondrial autophagic flux, promoting damaged mitochondrial clearance, and restoring mitochondrial quality control. Mechanistically, BNIP3 is shown to interact with the membrane‐bound protein annexin A2 (ANXA2), enabling the liberation of the transcription factor EB (TFEB) from the ANXA2‐TFEB complex, promoting TFEB nuclear translocation, and regulating autophagy and lysosomal gene activation. Furthermore, a rat model of IVDD is established and verified the in vivo efficacy of the exosomes in repairing disc injuries, delaying NPC aging, and promoting extracellular matrix (ECM) synthesis. In summary, hypoxia‐induced BMSC exosomes deliver BNIP3‐rich vesicles to alleviate disc degeneration by activating the mitochondrial BNIP3/ANXA2/TFEB axis, providing a new target for IVDD treatment.

Intervertebral disc degeneration (IVDD) is a major cause of low back pain (LBP), and excessive senescence and apoptosis of nucleus pulposus (NP) cells are major pathological changes in IVDD. Physical exercise could effectively delay the process of intervertebral disc degeneration; however, its mechanism is still largely unknown. Irisin is an exercise-induced myokine released upon cleavage of the membrane-bound precursor protein fibronectin type III domain-containing protein 5 (FNDC5), and its levels increase after physical exercise. Here, we show that after physical exercise, FNDC5/irisin levels increase in the circulation and NP, senescence and apoptosis are reduced, autophagy is activated in NP tissue, and the progression of IVDD is delayed. Conversely, after knocking out FNDC5, the benefits of physical exercise are compromised. Moreover, the overexpression of FNDC5 in NP tissue effectively alleviated the degeneration of the intervertebral disc (IVD) in rats. By showing that FNDC5/irisin is an important mediator of the beneficial effects of physical exercise in the IVDD model, the study proposes FNDC5/irisin as a novel agent capable of activating autophagy and protecting NP from senescence and apoptosis.

Background: Bone is one of the common metastatic sites of lung cancer, and its prognosis is not optimistic. We performed a study to evaluate the incidence, survival, and prognostic factors of lung cancer with bone metastasis (LCBM) at initial diagnosis, and to develop a nomogram to predict its outcomes. Methods: We conducted a retrospective study choosing 13,541 patients with LCBM from the Surveillance, Epidemiology, and End Results (SEER) 18 registry database. An X-tile analysis provided the optimal age cutoff point. The incidence, overall survival, and prognosis of bone metastasis were evaluated according to the patient information, characteristics of the tumor, and therapy. We also used multivariable Cox regression to estimate mortality hazard ratios (HRs) among patients with LCBM, while a visual nomogram was established to judge the prognosis. Results: The incidence of disease increased with age, but survival rates show the opposite trend. The median survival time was about 4 months. In addition, although the differences for patient race is not significant (P=0.445), White patients are prone to have bone metastases from lung cancer according to the incidence analysis. The difference for laterality is also not significant (P=0.534), while the factors of age, gender, the total number of sites, histological types, grade, tumor size, and treatment are significantly related to the outcome of patients with LCBM. Furthermore, our nomogram could predict the probability of surviving to the median survival time of the population with a c-index of 0.72. Conclusions: Age, characteristics of the tumor, and therapy should be considered for prediction of prognosis for patients with lung cancer bone metastasis. Putatively, the younger patients and the patients with chemotherapy and surgery may indicate improved survival.