Identification of the Human Skeletal Stem Cell.

Stem cell regulation and hierarchical organization of human skeletal progenitors remain largely unexplored. Here, we report the isolation of a self-renewing and multipotent human skeletal stem cell (hSSC) that generates progenitors of bone, cartilage, and stroma, but not fat. Self-renewing and multipotent hSSCs are present in fetal and adult bones and can also be derived from BMP2-treated human adipose stroma (B-HAS) and induced pluripotent stem cells (iPSCs). Gene expression analysis of individual hSSCs reveals overall similarity between hSSCs obtained from different sources and partially explains skewed differentiation toward cartilage in fetal and iPSC-derived hSSCs. hSSCs undergo local expansion in response to acute skeletal injury. In addition, hSSC-derived stroma can maintain human hematopoietic stem cells (hHSCs) in serum-free culture conditions. Finally, we combine gene expression and epigenetic data of mouse skeletal stem cells (mSSCs) and hSSCs to identify evolutionarily conserved and divergent pathways driving SSC-mediated skeletogenesis. VIDEO ABSTRACT.

Stretchable Ultrasound Metalens for Biomedical Zoom Imaging and Bone Quality Assessment with Subwavelength Resolution.

Ultrasound imaging is extensively used in biomedical science and clinical practice. Imaging resolution and tunability of imaging plane are key performance indicators, but both remain challenging to be improved due to the longer wavelength compared with light and the lack of zoom lens for ultrasound. Here, the ultrasound zoom imaging based on a stretchable planar metalens that simultaneously achieves the subwavelength imaging resolution and dynamic control of the imaging plane is reported. The proposed zoom imaging ultrasonography enables precise bone fracture diagnosis and comprehensive osteoporosis assessment. Millimeter-scale microarchitectures of the cortical bones at different depths can be selectively imaged with a 0.6-wavelength resolution. The morphological features of bone fractures, including the shape, size and position, are accurately detected. Based on the extracted ultrasound information of cancellous bones with healthy matrix, osteopenia and osteoporosis, a multi-index osteoporosis evaluation method is developed. Furthermore, it provides additional biological information in aspects of bone elasticity and attenuation to access the comprehensive osteoporosis assessment. The soft metalens also features flexibility and biocompatibility for preferable applications on wearable devices. This work provides a strategy for the development of high-resolution ultrasound biomedical zoom imaging and comprehensive bone quality diagnosis system.

Effect of recreational cannabis use on bone mineral density: a systematic review.

The recreational use of cannabis products has risen considerably worldwide over the past decade. As the cannabis legal market grows, a critical challenge has been to make substantiated claims about the benefits and adverse health problems triggered by cannabis exposure. Despite accumulating evidence from animal studies demonstrating the role of cannabinoids on bone metabolism, there are conflicting results in clinical literature regarding their effects on bone health outcomes.We undertook a systematic review to assess the evidence for the safety of cannabis use on bone health. We searched the databases MEDLINE, EMBASE, Cochrane Library, and Web of Science up to March 2023 for studies evaluating the effect of the recreational use of cannabis on the bone mineral density (BMD) of adults.Among the 2620 studies reviewed, three cross-sectional studies and one randomized controlled trial comprised 4032 participants from 18 to 60 years who met the inclusion criteria. Two studies showed that cannabis exposure decreased BMD, while the other 2 indicated no alteration. Despite the different study designs, the included studies showed a low risk of bias according to the Joanna Briggs Institute tool.Eligible studies present differences in cannabis products, administration routes, and exposure determination. Further longitudinal research is needed to establish multiple clinical predictors associated with potentially negative consequences of cannabis exposure, especially in vulnerable populations such as elderly individuals.

Time-dependent risk of fracture in adults with type 2 diabetes receiving anti-diabetic drug: A one-stage network meta-analysis.

AIMS: To assess the time-dependent risk of fracture in adults with type 2 diabetes receiving anti-diabetic drugs. MATERIALS AND METHODS: We searched MEDLINE, EMBASE, and Cochrane Library up to 18 November 2021, for randomized controlled trials (RCTs) and propensity-score-matched non-randomized studies (NRSs) comparing all anti-diabetic drugs with standard treatment or with each other on fracture in adults with type 2 diabetes. The study performed a one-stage network meta-analysis using discrete-time hazard regression with reconstructed individual time-to-event data. RESULTS: This network meta-analysis involved seven RCTs (65,051 adults with type 2 diabetes) with a median follow-up of 36 months and three propensity-score-based NRSs (17,954 participants) with a median follow-up of 27.3 months. Among anti-diabetic drugs, thiazolidinediones increased the overall hazard of fracture by 42% (95% credible interval [CrI], 3%-97%) and almost tripled the risk after 4 years (hazard ratio [HR], 2.74; 95% CrI, 1.53-4.80). Credible subgroup analysis suggested that thiazolidinediones increased the hazard of fracture only in females (HR, 2.19; 95% CrI, 1.26-3.74) but not among males (HR, 0.81; 95% CrI, 0.45-1.40). Moderate certainty evidence established that thiazolidinediones increase 92 fractures in five years per 1000 female patients. We did not find the risk of fractures with other anti-diabetic drugs including metformin, sulfonylureas, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and dipeptidyl peptidase-4 (DPP-4) inhibitors. CONCLUSIONS: Long-term use of thiazolidinediones elevates the risk of fracture among females with type 2 diabetes. There is no evidence eliciting fracture risk associated with other anti-diabetic drugs.

History of fragility fracture is associated with cardiovascular mortality in hemodialysis patients: the Q-Cohort study.

INTRODUCTION: In patients undergoing dialysis, major bone fracture is associated with a high risk of mortality, including death of cardiovascular (CV) origin. In the present study, we aimed to determine whether a history of fragility fracture is a predictor of CV death in patients undergoing hemodialysis with long-term follow-up. MATERIALS AND METHODS: In total, 3499 patients undergoing hemodialysis were analyzed for 10 years. We evaluated the history of fragility fracture in each patient at enrollment. The primary outcome was CV death. A Cox proportional hazard model and a competing risk approach were applied to determine the association between a history of fragility fracture and CV death. RESULTS: A total of 346 patients had a history of fragility fracture at enrollment. During a median follow-up of 8.8 years, 1730 (49.4%) patients died. Among them, 621 patients experienced CV death. Multivariable Cox analyses after adjustment for confounding variables showed that a history of fragility fracture was associated with CV death (hazard ratio, 1.47; 95% confidence interval, 1.16-1.85). In the Fine-Gray regression model, a history of fragility fracture was an independent risk factor for CV death (subdistribution hazard ratio, 1.36; 95% confidence interval, 1.07-1.72). CONCLUSION: In a large cohort of patients undergoing hemodialysis, a history of fragility fracture was an independent predictor of CV death.

WNT-modulating gene silencers as a gene therapy for osteoporosis, bone fracture, and critical-sized bone defects.

Treating osteoporosis and associated bone fractures remains challenging for drug development in part due to potential off-target side effects and the requirement for long-term treatment. Here, we identify recombinant adeno-associated virus (rAAV)-mediated gene therapy as a complementary approach to existing osteoporosis therapies, offering long-lasting targeting of multiple targets and/or previously undruggable intracellular non-enzymatic targets. Treatment with a bone-targeted rAAV carrying artificial microRNAs (miRNAs) silenced the expression of WNT antagonists, schnurri-3 (SHN3), and sclerostin (SOST), and enhanced WNT/ß-catenin signaling, osteoblast function, and bone formation. A single systemic administration of rAAVs effectively reversed bone loss in both postmenopausal and senile osteoporosis. Moreover, the healing of bone fracture and critical-sized bone defects was also markedly improved by systemic injection or transplantation of AAV-bound allograft bone to the osteotomy sites. Collectively, our data demonstrate the clinical potential of bone-specific gene silencers to treat skeletal disorders of low bone mass and impaired fracture repair.

Osteoimmunology of Fracture Healing.

PURPOSE OF REVIEW: The purpose of this review is to summarize what is known in the literature about the role inflammation plays during bone fracture healing. Bone fracture healing progresses through four distinct yet overlapping phases: formation of the hematoma, development of the cartilaginous callus, development of the bony callus, and finally remodeling of the fracture callus. Throughout this process, inflammation plays a critical role in robust bone fracture healing. RECENT FINDINGS: At the onset of injury, vessel and matrix disruption lead to the generation of an inflammatory response: inflammatory cells are recruited to the injury site where they differentiate, activate, and/or polarize to secrete cytokines for the purposes of cell signaling and cell recruitment. This process is altered by age and by sex. Bone fracture healing is heavily influenced by the presence of inflammatory cells and cytokines within the healing tissue.

Macrophage membrane-reversibly camouflaged nanotherapeutics accelerate fracture healing by fostering MSCs recruitment and osteogenic differentiation.

The fracture healing outcome is largely dependent on the quantities as well as osteogenic differentiation capacities of mesenchymal stem cells (MSCs) at the lesion site. Herein, macrophage membrane (MM)-reversibly cloaked nanocomplexes (NCs) are engineered for the lesion-targeted and hierarchical co-delivery of short stromal derived factor-1α peptide (sSDF-1α) and Ckip-1 small interfering RNA (Ckip-1 siRNA, siCkip-1) to promote bone repair by concurrently fostering recruitment and osteogenic differentiation of endogenous MSCs. To construct the NCs, a membrane-penetrating α-helical polypeptide first assembles with siCkip-1, and the cationic NCs are sequentially coated with catalase and an outer shell of sSDF-1α-anchored MM. Due to MM-assisted inflammation homing, intravenously injected NCs could efficiently accumulate at the fractured femur, where catalase decomposes the local hydrogen peroxide to generate oxygen bubbles that drives the shedding of sSDF-1α-anchored MM in the extracellular compartment. The exposed, cationic inner core thus enables robust trans-membrane delivery into MSCs to induce Ckip-1 silencing. Consequently, sSDF-1α-guided MSCs recruitment cooperates with siCkip-1-mediated osteogenic differentiation to facilitate bone formation and accelerate bone fracture healing. This study provides an enlightened strategy for the hierarchical co-delivery of macromolecular drugs into different cellular compartments, and it also renders a promising modality for the management of fracture healing.

Bone fracture is associated with incident myocardial infarction in long-term follow-up.

BACKGROUND: The association between bone fracture and cardiovascular diseases is examined in this study. While basic research has established a connection between fractures and heart attacks through the linkage between bones and arteries, population studies have not provided clear evidence. The aim of the present study is to investigate the association between bone fracture and the occurrence of myocardial infarction in a natural population during long-term follow-up. METHODS: A total of 13,196 adult participants with bone fracture history at baseline from the China Health and Nutrition Survey (CHNS) prospective cohort were included in this study. Baseline investigation was performed in 1997-2009 and the outcome was followed up till 2015. Hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. RESULTS: From 1997 to 2015, a total of 329 incident myocardial infarction cases were identified. In univariate and multivariate Cox regression analysis, a history of bone fracture was associated with an increased risk of myocardial infarction incidence in the total population (for the crude model: HR = 2.56, 95% CI 1.83-3.53, P < 0.001; for the multivariate model: HR = 1.43, 95% CI 1.02-1.99, P = 0.036). In the stratified analysis, bone fracture was not associated with an increased risk of incident myocardial infarction in subjects with age < 50 years (HR = 0.71, 95% CI 0.34-1.47, P = 0.356), but significantly associated with an increased risk of incident myocardial infarction in subjects with age ≥ 50 years (HR = 1.80, 95% CI 1.23-2.63, P = 0.003). CONCLUSIONS: It is suggested by the present study that bone fracture may be associated with an increased risk of incident myocardial infarction in the elderly population during long-term follow-up.

Comparing intravenous lidocaine and pethidine for pain management in emergency department patients with femoral bone fracture: a randomized controlled trial.

BACKGROUND: Intravenous lidocaine has shown promise as an effective analgesic in various clinical settings, but its utility for pain management in emergency departments, especially for bone fractures, remains relatively understudied. OBJECTIVE: This study compared intravenous lidocaine to pethidine for femoral bone fracture pain management. METHODS: This double-blind, randomized, controlled clinical trial was conducted in the emergency department of AJA University of Medical Sciences affiliated hospitals. Patients aged 18-70 years-old with femoral bone fracture and experiencing severe pain, defined as a numerical rating scale (NRS) of pain ≥ 7, were included in the study. One group received intravenous pethidine (25 mg), while the other group received intravenous lidocaine (3 mg/kg, not exceeding 200 mg), infused with 250 ml saline over 20 min. Pain levels were evaluated before treatment administration (0 min) and at 10, 20, 30, 40, 50, and 60 min after treatment administration using the NRS. RESULTS: Seventy-two patients were enrolled in the study. Demographic characteristics and pain scores were similar between the two groups. The mean pain scores upon arrival for the lidocaine and pethidine groups were 8.50 ± 1 and 8.0 ± 1, respectively; after one hour, they were 4.0 ± 1 and 4.0 ± 1, respectively. While there was a statistically significant reduction in pain in both groups after one hour, there were no clinically or statistically significant differences between the two groups (p = 0.262). Pethidine had a higher incidence of adverse events, though not statistically significant. Additionally, females required more rescue analgesics. CONCLUSION: The administration of intravenous lidocaine is beneficial for managing pain in femoral bone fractures, suggesting that lidocaine could be a potent alternative to opioids. TRIAL REGISTRATION: IRCT20231213060355N1 ( https://irct.behdasht.gov.ir/trial/74624 ) (30/12/2023).

A self-powered implantable and bioresorbable electrostimulation device for biofeedback bone fracture healing.

Electrostimulation has been recognized as a promising nonpharmacological treatment in orthopedics to promote bone fracture healing. However, clinical applications have been largely limited by the complexity of equipment operation and stimulation implementation. Here, we present a self-powered implantable and bioresorbable bone fracture electrostimulation device, which consists of a triboelectric nanogenerator for electricity generation and a pair of dressing electrodes for applying electrostimulations directly toward the fracture. The device can be attached to irregular tissue surfaces and provide biphasic electric pulses in response to nearby body movements. We demonstrated the operation of this device on rats and achieved effective bone fracture healing in as short as 6 wk versus the controls for more than 10 wk to reach the same healing result. The optimized electrical field could activate relevant growth factors to regulate bone microenvironment for promoting bone formation and bone remodeling to accelerate bone regeneration and maturation, with statistically significant 27% and 83% improvement over the control groups in mineral density and flexural strength, respectively. This work provided an effective implantable fracture therapy device that is self-responsive, battery free, and requires no surgical removal after fulfilling the biomedical intervention.

Post-traumatic cortical cystic lesions in children: three case reports and a systematic review of the literature.

Post-traumatic cortical cystic lesions are rare radiolucent lesions that appear as a complication of low-severity fractures in children. Their relevance lies in the fact that few cases of these lesions have been described to date, so they are little known among clinicians caring for children. Three case reports of well-circumscribed cortical lytic lesions detected at 2-4 months during the follow-up of non-displaced distal radius fractures in children aged 9, 7, and 2 years are presented. The consistent clinical history and typical radiological features allowed the accurate diagnosis of post-traumatic cortical cystic lesion, without the need for advanced imaging tests or biopsy. At 12-, 8- and 11-month follow-ups, respectively, the lesions either disappeared or decreased in size. This benign and self-limited lesion should be correctly recognized to avoid confusion with other diagnoses, advanced imaging tests or biopsies, and unnecessary parental concerns.

Cerebral fat embolism with turbid urine as the initial sign.

BACKGROUND: Cerebral fat embolism (CFE) is a rare but potentially fatal complication that can occur after long bone fractures. It represents one subcategory of fat embolisms (FE). Diagnosing CFE can be challenging due to its variable and nonspecific clinical manifestations. We report a case of CFE initially presenting with turbid urine, highlighting an often neglected sign. CASE PRESENTATION: A 69-year-old male was admitted after a traffic accident resulting in bilateral femoral fractures. Sixteen hours post-admission, grossly turbid urine was noted but received no special attention. Four hours later, he developed rapid deterioration of consciousness and respiratory distress. Neurological examination revealed increased upper limb muscle tone and absent voluntary movements of lower limbs. Brain MRI demonstrated a 'starfield pattern' of diffuse punctate lesions, pathognomonic for CFE. Urine microscopy confirmed abundant fat droplets. Supportive treatment and fracture fixation were performed. The patient regained consciousness after 3 months but had residual dysphasia and limb dyskinesia. CONCLUSION: CFE can present with isolated lipiduria preceding overt neurological or respiratory manifestations. Heightened awareness of this subtle sign in high-risk patients is crucial for early diagnosis and intervention. Prompt urine screening and neuroimaging should be considered when gross lipiduria occurs after long bone fractures.

Low-dose short infusion ketamine as adjunct to morphine for acute long bone fracture in the emergency department: a randomized controlled trial.

BACKGROUND: Ketamine is recognized as an alternative for pain management; however, concerns about emergent adverse reactions have limited its widespread adoption. This study aimed to assess the efficacy of a short infusion of low-dose ketamine (LDK) compared to intravenous morphine (MOR) as adjunctive analgesia for acute long bone fracture pain. METHODS: This single-blinded, randomized controlled trial was conducted in a single emergency department. Patients with acute long bone fractures and numerical rating scale (NRS) pain scores ≥ 6 following an initial dose of intravenous morphine were assigned to receive either a LDK (0.3 mg/kg) over 15 min or intravenous MOR at a dose of 0.1 mg/kg administered over 5 min. Throughout a 120-min observation period, patients were regularly evaluated for pain level (0-10), side effects, and the need for additional rescue analgesia. RESULTS: A total of 58 subjects participated, with 27 in the MOR group and 31 in the LDK group. Demographic variables and baseline NRS scores were comparable between the MOR (8.3 ± 1.3) and LDK (8.9 ± 1.2) groups. At 30 min, the LDK group showed a significantly greater mean reduction in NRS scores (3.1 ± 2.03) compared to the MOR group (1.8 ± 1.59) (p = 0.009). Similarly, at 60 min, there were significant differences in mean NRS score reductions (LDK 3.5 ± 2.17; MOR mean reduction = 2.4, ± 1.84) with a p-value of 0.04. No significant differences were observed at other time intervals. The incidence of dizziness was higher in the LDK group at 19.4% (p = 0.026). CONCLUSION: Short infusion low-dose ketamine, as an adjunct to morphine, is effective in reducing pain during the initial 30 to 60 min and demonstrated comparability to intravenous morphine alone in reducing pain over the subsequent 60 min for acute long bone fractures. However, it was associated with a higher incidence of dizziness. TRIAL REGISTRATION: NMRR17318438970 (2 May 2018; www.nmrr.gov.my ).

Persistent Mesodermal Differentiation Capability of Bone Marrow MSCs Isolated from Aging Patients with Low-Energy Traumatic Hip Fracture and Osteoporosis: A Clinical Evidence.

A low-energy hit, such as a slight fall from a bed, results in a bone fracture, especially in the hip, which is a life-threatening risk for the older adult and a heavy burden for the social economy. Patients with low-energy traumatic bone fractures usually suffer a higher level of bony catabolism accompanied by osteoporosis. Bone marrow-derived stem cells (BMSCs) are critical in osteogenesis, leading to metabolic homeostasis in the healthy bony microenvironment. However, whether the BMSCs derived from the patients who suffered osteoporosis and low-energy traumatic hip fractures preserve a sustained mesodermal differentiation capability, especially in osteogenesis, is yet to be explored in a clinical setting. Therefore, we aimed to collect BMSCs from clinical hip fracture patients with osteoporosis, followed by osteogenic differentiation comparison with BMSCs from healthy young donors. The CD markers identification, cytokines examination, and adipogenic differentiation were also evaluated. The data reveal that BMSCs collected from elderly osteoporotic patients secreted approximately 122.8 pg/mL interleukin 6 (IL-6) and 180.6 pg/mL vascular endothelial growth factor (VEGF), but no PDGF-BB, IL-1b, TGF-b1, IGF-1, or TNF-α secretion. The CD markers and osteogenic and adipogenic differentiation capability in BMSCs from these elderly osteoporotic patients and healthy young donors are equivalent and compliant with the standards defined by the International Society of Cell Therapy (ISCT). Collectively, our data suggest that the elderly osteoporotic patients-derived BMSCs hold equivalent differentiation and proliferation capability and intact surface markers identical to BMSCs collected from healthy youth and are available for clinical cell therapy.

Long-term outcomes after capitate fractures: a median 16-year follow-up.

INTRODUCTION: The long-term effects of a capitate fracture are unknown. The aim of this study was to assess both clinical and radiological long-term outcomes after a capitate fracture. MATERIALS AND METHODS: From a cohort of 526 consecutive patients with post traumatic radial sided wrist pain, 23 were identified diagnosed with a capitate fracture. 16 of these (11 males and 5 females) with a median age at injury of 17.5 years (range 11-27 years) were eligible for a follow-up after a median of 16 years (range 8 to 17 years). In this study patients were examined using conventional radiographs, computed tomography (CT) and magnetic resonance imaging (MRI) at the time of injury and with CT at the follow-up. At follow-up radiological signs of osteoarthritis were graded in four stages and clinical outcome was evaluated by measuring range of wrist motion and grip and pinch strength. The subjective outcome was assessed using DASH and PRWE questionnaires. RESULTS: Five patients had isolated capitate fractures and 11 had concomitant fractures, 10 of which had a simultaneous scaphoid fracture. 14 patients had been treated non-surgically in a cast and two patients were treated surgically. None of the fractures were visible on conventional radiographs at the time of injury. At follow-up all fractures had healed without signs of avascular necrosis. In one patient, CT examination revealed osteoarthritis between the capitate and lunate. This did not cause clinical symptoms. Functional impairments and pain scores were low: median DASH score 0, median PRWE 3 and median VAS pain score 0. We found no impairment in range of motion or grip and pinch strength. CONCLUSIONS: At a median of 16-year follow-up, patients with a capitate fracture report normal self-assessed hand function as well as good wrist motion and strength. The risk of development of posttraumatic arthritis in the joints around the capitate is low.

Does the type of lower extremity fracture affect long-term opioid usage? A meta-analysis.

INTRODUCTION:  Patients recovering from musculoskeletal trauma have a heightened risk of opioid dependence and misuse, as these medications are typically required for pain management. The purpose of this meta-analysis was to examine the association between fracture type and chronic opioid use following fracture fixation in patients who sustain lower extremity trauma. MATERIALS AND METHODS: A meta-analysis was performed using PubMed and Web of Science to identify articles reporting chronic opioid use in patients recovering from surgery for lower extremity fractures. 732 articles were identified using keyword and MeSH search functions, and 9 met selection criteria. Studies were included in the final analysis if they reported the number of patients who remained on opioids 6 months after surgery for a specific lower extremity fracture (chronic usage). Logistic regressions and descriptive analyses were performed to determine the rate of chronic opioid use within each fracture type and if age, year, country of origin of study, or pre-admission opioid use influenced chronic opioid use following surgery. RESULTS: Bicondylar and unicondylar tibial-plateau fractures had the largest percentage of patients that become chronic opioid users (29.7-35.2%), followed by hip (27.8%), ankle (19.7%), femoral-shaft (18.5%), pilon (17.2%), tibial-shaft (13.8%), and simple ankle fractures (2.8-4.7%).Most opioid-naive samples had significantly lower rates of chronic opioid use after surgery (2-9%, 95% CI) when compared to samples that allowed pre-admission opioid use (13-50%, 95% CI). There were no significant associations between post-operative chronic opioid use and age, year, or country of origin of study. CONCLUSIONS:  Patients with lower extremity fractures have substantial risk of becoming chronic opioid users. Even the lowest rates of chronic opioid use identified in this meta-analysis are higher than those in the general population. It is important that orthopedic surgeons tailor pain-management protocols to decrease opioid usage after lower extremity trauma.

Risk of fractures and postfracture mortality in 3980 people with primary biliary cholangitis: A population-based cohort study.

BACKGROUND: Morbidity in primary biliary cholangitis (PBC) is multifactorial. Osteoporosis related to cholestasis is an extrahepatic complication of PBC. It is not fully established to what extent people with PBC have an increased risk for fractures, and if mortality after a fracture is increased, compared to the general population. METHODS: All Swedish people with PBC diagnosed between 2001 and 2016 were identified from the National Swedish Patient Register using ICD-10 codes. Incident fractures were ascertained in the same register and compared to matched controls from the Swedish general population (1:10 for age, sex, and municipality). Cox regression was used to investigate the rates of fractures and postfracture mortality. The cumulative incidence of fractures was calculated while accounting for competing risks (death or liver transplantation). RESULTS: People with PBC (n = 3980) showed a higher risk of fractures at all-time points during follow-up compared to matched controls (n = 37,196), which was seen both in men and women. At 5 years of follow-up, the cumulative incidence of any fracture in people with PBC was 16.8% (95% confidence interval [CI] = 15.6-18.1), compared to 11.6% (95%CI = 11.3-12.0) in controls. The rate of osteoporotic fractures was particularly high (adjusted Hazard ratio [aHR] = 1.9; 95% = CI 1.7-2.0). The 30-day as well as the 1-year mortality after a fracture was significantly higher in people with PBC compared to controls that also experienced a fracture (aHR = 2.2; 95%CI = 1.5-3.2; aHR = 2.0; 95%CI 1.7-2.4). CONCLUSION: People with PBC have a significantly higher risk of fractures and postfracture mortality compared to matched controls from the general population.

Low bone mineral density, a neglected condition in North Africa and Middle East: estimates from the Global Burden of Disease Study, 1990-2019.

Due to the high prevalence of low bone mineral density in North Africa and Middle East region, estimating its attributable burden would help to a better understanding of this neglected condition for policymakers and health researchers. This study presented the number of attributable deaths has doubled from 1990 to 2019. PURPOSE: This study provides the latest estimates of the burden of low bone mineral density (BMD) from 1990 to 2019 in North Africa and Middle East (NAME) region. METHODS: The data were extracted from the global burden of disease (GBD) 2019 study to estimate epidemiological indices such as deaths, disability-adjusted life years (DALYs), and summary exposure value (SEV). SEV is a measure of the exposure of the population to a risk factor that considers the amount of exposure by the level of risk. RESULTS: Our findings showed that in 1990-2019, the number of deaths and DALYs attributable to low BMD had almost doubled in the region and caused 20,371 (95% uncertainty intervals: 14,848-24,374) deaths and 805,959 (630,238-959,581) DALYs in 2019. However, DALYs and death rates showed a decreasing trend after age standardization. Saudi Arabia had the highest, and Lebanon had the lowest age-standardized DALYs rates in 2019, with rates of 434.2 (329.6-534.3) and 90.3 (70.6-112.1) per 100,000, respectively. The highest burden attributable to low BMD was in the 90-94 and over 95 age groups. Also, there was a decreasing trend in age-standardized SEV to low BMD for both sexes. CONCLUSION: Despite the decreasing trend of age-standardized burden indices, considerable amounts of deaths and DALYs were attributable to low BMD, especially in the elderly population, in the region in 2019. As the positive effects of proper interventions will be detectable in the long term, robust strategies and comprehensive stable policies are the ultimate solutions to achieving desired goals.

Validation of JSBMR's CTIBL manual for Japanese men receiving androgen deprivation therapy for prostate cancer.

INTRODUCTION: Androgen deprivation therapy (ADT) for prostate cancer causes cancer treatment-induced bone loss (CTIBL), increases the fracture risk 2-3 times, and worsens life prognoses. The Japan Society of Bone and Mineral Research (JSBMR) created a CTIBL treatment manual in 2020; however, no study has validated its use in patients with ADT/CTIBL prostate cancer. MATERIALS AND METHODS: This study classified 124 patients with prostate cancer without bone metastasis who received ADT into high- and low-risk groups using the JSBMR CTIBL algorithm. Comparisons were made with the period to incident vertebral fracture and the existing International Osteoporosis Foundation (IOF) classification. RESULTS: The median age was 74 years; the median observation period was 81 months. At 1, 3, 5, 7, and 9 years, the prevalence of incident vertebral fractures was, respectively, 3.3%, 10.7%, 17.9%, 21.4%, and 31.2% in the entire population; 13%, 27%, 36%, 42%, and 58% in the high-risk group (19%); and 1%, 7%, 14%, 17%, and 25% in the low-risk group (81%). The hazard ratio between the two groups was 3.57 (p = 0.0004). Based on multivariate analysis, age, previous vertebral fracture and femoral neck bone density were significant risk factors for incidental vertebral fracture. The JSBMR had a hazard ratio of 3.26 (p = 0.04) relative to 1.13 (p = 0.84) for the IOF, indicating the JSBMR classification performed better. CONCLUSION: Taking preventive measures against fractures is necessary, including starting bone-modifying agents early in patients with a high fracture risk. The JSBMR CTIBL manual may be useful for this purpose.