[Latest Findings on the Role of RUNX1 in Bone Development and Disorders]. / RUNX1åœ¨éª¨å‘è‚²åŠéª¨ç›¸å ³ç–¾ç— ä¸­çš„ä½œç”¨ç ”ç©¶è¿›å±•.

Runt-related transcription factor (RUNX1) is a transcription factor closely involved in hematopoiesis. RUNX1 gene mutation plays an essential pathogenic role in the initiation and development of hematological tumors, especially in acute myeloid leukemia. Recent studies have shown that RUNX1 is also involved in the regulation of bone development and the pathological progression of bone-related diseases. RUNX1 promotes the differentiation of mesenchymal stem cells into chondrocytes and osteoblasts and modulates the maturation and extracellular matrix formation of chondrocytes. The expression of RUNX1 in mesenchymal stem cells, chondrocytes, and osteoblasts is of great significance for maintaining normal bone development and the mass and quality of bones. RUNX1 also inhibits the differentiation and bone resorptive activities of osteoclasts, which may be influenced by sexual dimorphism. In addition, RUNX1 deficiency contributes to the pathogenesis of osteoarthritis, delayed fracture healing, and osteoporosis, which was revealed by the RUNX1 conditional knockout modeling in mice. However, the roles of RUNX1 in regulating the hypertrophic differentiation of chondrocytes, the sexual dimorphism of activities of osteoclasts, as well as bone loss in diabetes mellitus, senescence, infection, chronic inflammation, etc, are still not fully understood. This review provides a systematic summary of the research progress concerning RUNX1 in the field of bone biology, offering new ideas for using RUNX1 as a potential target for bone related diseases, especially osteoarthritis, delayed fracture healing, and osteoporosis.

Young osteocyte-derived extracellular vesicles facilitate osteogenesis by transferring tropomyosin-1.

BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) can undergo inadequate osteogenesis or excessive adipogenesis as they age due to changes in the bone microenvironment, ultimately resulting in decreased bone density and elevated risk of fractures in senile osteoporosis. This study aims to investigate the effects of osteocyte senescence on the bone microenvironment and its influence on BMSCs during aging. RESULTS: Primary osteocytes were isolated from 2-month-old and 16-month-old mice to obtain young osteocyte-derived extracellular vesicles (YO-EVs) and senescent osteocyte-derived EVs (SO-EVs), respectively. YO-EVs were found to significantly increase alkaline phosphatase activity, mineralization deposition, and the expression of osteogenesis-related genes in BMSCs, while SO-EVs promoted BMSC adipogenesis. Neither YO-EVs nor SO-EVs exerted an effect on the osteoclastogenesis of primary macrophages/monocytes. Our constructed transgenic mice, designed to trace osteocyte-derived EV distribution, revealed abundant osteocyte-derived EVs embedded in the bone matrix. Moreover, mature osteoclasts were found to release osteocyte-derived EVs from bone slices, playing a pivotal role in regulating the functions of the surrounding culture medium. Following intravenous injection into young and elderly mouse models, YO-EVs demonstrated a significant enhancement of bone mass and biomechanical strength compared to SO-EVs. Immunostaining of bone sections revealed that YO-EV treatment augmented the number of osteoblasts on the bone surface, while SO-EV treatment promoted adipocyte formation in the bone marrow. Proteomics analysis of YO-EVs and SO-EVs showed that tropomyosin-1 (TPM1) was enriched in YO-EVs, which increased the matrix stiffness of BMSCs, consequently promoting osteogenesis. Specifically, the siRNA-mediated depletion of Tpm1 eliminated pro-osteogenic activity of YO-EVs both in vitro and in vivo. CONCLUSIONS: Our findings suggested that YO-EVs played a crucial role in maintaining the balance between bone resorption and formation, and their pro-osteogenic activity declining with aging. Therefore, YO-EVs and the delivered TPM1 hold potential as therapeutic targets for senile osteoporosis.

The association of FRAX with predictors of falls in the assessment of postmenopausal osteoporosis in Turkey: the fracture study of Turkey (FRACT study).

Although FRAX is used for fracture risk evaluation, this tool does not include balance and fall risk. The association between the predictors of falls and high FRAX scores we found in this study suggests that risk indicators for falls may add substantial value to FRAX by improving fracture risk prediction. PURPOSE: This observational, descriptive, and cross-sectional study aimed to assess the fall risk predictors and explore their association with FRAX in Turkish patients with postmenopausal osteoporosis. METHODS: Two hundred and nine (209) women with postmenopausal osteoporosis referred to the Fracture Liaison Service (FLS) at Istanbul University-Cerrahpasa were enrolled in the FRACT study (The Fracture Study of Turkey). Clinical risk factors were assessed using the FRAX tool. Tandem stance, Tandem walking, Timed up and go (TUG), and Chair stand tests were performed to assess balance and fall risk. RESULTS: Among patients with a mean age of 67.6 (± 9.7) years, 66 patients (31.6%) had osteoporosis without fractures and 143 patients (68.4%) had fragility fractures. The proportion of patients with poor performance of fall prediction tests was significantly higher in patients with a fragility fracture than those with osteoporosis alone. There was an inverse relationship between dynamic balance tests and the reported number of prior falls in the past year. FRAX score was higher in patients with impaired Tandem stance, Tandem walking, and TUG tests (p = 0.008, p = 0.035, p = 0.001, respectively). CONCLUSION: Assessment of fall risk predictors should be one of the major pillars in the physical evaluation of osteoporotic patients in the FLS setting. FRAX is a useful tool to determine the fracture risk of patients with both static and dynamic balance impairments. Combining balance assessment with FRAX may be an important step to optimize osteoporosis risk assessment.

Sex- and Age-Specific Prevalence of Osteopenia and Osteoporosis: Sampling Survey.

BACKGROUND: Osteopenia and osteoporosis are posing a long-term influence on the aging population's health contributing to a higher risk of mortality, loss of autonomy, hospitalization, and huge health system costs and social burden. Therefore, more pertinent data are needed to demonstrate the current state of osteoporosis. OBJECTIVE: This sampling survey seeks to assess the trends in the prevalence of osteopenia and osteoporosis in a Chinese Han population. METHODS: A community-based cross-sectional study involving 16,377 participants used a multistage sampling method. Bone mineral density was measured using the quantitative ultrasonic densitometry. Student t test and Mann-Whitney U test were used to test the difference between normally and nonnormally distributed quantitative variables between male and female participants. A chi-square (χ2) test was used to compare categorized variables. Stratified analysis was conducted to describe the prevalence rates of osteoporosis (T score ≤-2.5) and osteopenia (T score -2.5 to -1.0) across age, sex, calcium intake, and menopause. A direct standardization method was used to calculate the age-standardized prevalence rates of osteoporosis and osteopenia. T-score was further categorized into quartiles (T1-T4) by age- and sex-specified groups. RESULTS: The prevalence rates of osteopenia and osteoporosis were 40.5% (6633/16,377) and 7.93% (1299/16,377), respectively, and the age-standardized prevalence rates were 27.32% (287,877,129.4/1,053,861,940) and 3.51% (36,974,582.3/1,053,861,940), respectively. There was an increase in osteopenia and osteoporosis prevalence from 21.47% (120/559) to 56.23% (754/1341) and 0.89% (5/559) to 17.23% (231/1341), respectively, as age increased from 18 years to 75 years old. The prevalence rates of osteopenia and osteoporosis were significantly higher in female participants (4238/9645, 43.94% and 1130/9645, 11.72%) than in male participants (2395/6732, 35.58% and 169/6732, 2.51%; P<.001), and in postmenopausal female participants (3638/7493, 48.55% and 1053/7493, 14.05%) than in premenopausal female participants (538/2026, 26.55% and 53/2026, 2.62%; P<.001). In addition, female participants with a history of calcium intake had a lower osteoporosis prevalence rate than female participants without any history of calcium intake in all age groups (P=.004). From low quartile to high quartile of T-score, the prevalence of diabetes mellitus (752/4037, 18.63%; 779/4029, 19.33%; 769/3894, 19.75%; and 869/3879, 22.4%) and dyslipidemia (2228/4036, 55.2%; 2304/4027, 57.21%; 2306/3891, 59.26%; and 2379/3878, 61.35%) were linearly increased (P<.001), while the prevalence of cancer (112/4037, 2.77%; 110/4029, 2.73%; 103/3894, 2.65%; and 77/3879, 1.99%) was decreased (P=.03). CONCLUSIONS: Our data imply that as people age, osteopenia and osteoporosis are more common in females than in males, particularly in postmenopausal females than in premenopausal females, and bone mineral density significantly affects the prevalence of chronic diseases. These findings offer information that can be applied to intervention programs meant to prevent or lessen the burden of osteoporosis in China.

Etidronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women.

BACKGROUND: Osteoporosis is an abnormal reduction in bone mass and bone deterioration, leading to increased fracture risk. Etidronate belongs to the bisphosphonate class of drugs which act to inhibit bone resorption by interfering with the activity of osteoclasts - bone cells that break down bone tissue. This is an update of a Cochrane review first published in 2008. For clinical relevance, we investigated etidronate's effects on postmenopausal women stratified by fracture risk (low versus high). OBJECTIVES: To assess the benefits and harms of intermittent/cyclic etidronate in the primary and secondary prevention of osteoporotic fractures in postmenopausal women at lower and higher risk of fracture, respectively. SEARCH METHODS: We searched the Cochrane Central Register of Control Trials (CENTRAL), MEDLINE, Embase, two clinical trial registers, the websites of drug approval agencies, and the bibliographies of relevant systematic reviews. We identified eligible trials published between 1966 and February 2023. SELECTION CRITERIA: We included randomized controlled trials that assessed the benefits and harms of etidronate in the prevention of fractures for postmenopausal women. Women in the experimental arms must have received at least one year of etidronate, with or without other anti-osteoporotic drugs and concurrent calcium/vitamin D. Eligible comparators were placebo (i.e. no treatment; or calcium, vitamin D, or both) or another anti-osteoporotic drug. Major outcomes were clinical vertebral, non-vertebral, hip, and wrist fractures, withdrawals due to adverse events, and serious adverse events. We classified a study as secondary prevention if its population fulfilled one or more of the following hierarchical criteria: a diagnosis of osteoporosis, a history of vertebral fractures, a low bone mineral density T-score (≤ -2.5), or aged 75 years or older. If none of these criteria were met, we considered the study to be primary prevention. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. The review has three main comparisons: (1) etidronate 400 mg/day versus placebo; (2) etidronate 200 mg/day versus placebo; (3) etidronate at any dosage versus another anti-osteoporotic agent. We stratified the analyses for each comparison into primary and secondary prevention studies. For major outcomes in the placebo-controlled studies of etidronate 400 mg/day, we followed our original review by defining a greater than 15% relative change as clinically important. For all outcomes of interest, we extracted outcome measurements at the longest time point in the study. MAIN RESULTS: Thirty studies met the review's eligibility criteria. Of these, 26 studies, with a total of 2770 women, reported data that we could extract and quantitatively synthesize. There were nine primary and 17 secondary prevention studies. We had concerns about at least one risk of bias domain in each study. None of the studies described appropriate methods for allocation concealment, although 27% described adequate methods of random sequence generation. We judged that only 8% of the studies avoided performance bias, and provided adequate descriptions of appropriate blinding methods. One-quarter of studies that reported efficacy outcomes were at high risk of attrition bias, whilst 23% of studies reporting safety outcomes were at high risk in this domain. The 30 included studies compared (1) etidronate 400 mg/day to placebo (13 studies: nine primary and four secondary prevention); (2) etidronate 200 mg/day to placebo (three studies, all secondary prevention); or (3) etidronate (both dosing regimens) to another anti-osteoporotic agent (14 studies: one primary and 13 secondary prevention). We discuss only the etidronate 400 mg/day versus placebo comparison here. For primary prevention, we collected moderate- to very low-certainty evidence from nine studies (one to four years in length) including 740 postmenopausal women at lower risk of fractures. Compared to placebo, etidronate 400 mg/day probably results in little to no difference in non-vertebral fractures (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.20 to 1.61); absolute risk reduction (ARR) 4.8% fewer, 95% CI 8.9% fewer to 6.1% more) and serious adverse events (RR 0.90, 95% CI 0.52 to 1.54; ARR 1.1% fewer, 95% CI 4.9% fewer to 5.3% more), based on moderate-certainty evidence. Etidronate 400 mg/day may result in little to no difference in clinical vertebral fractures (RR 3.03, 95% CI 0.32 to 28.44; ARR 0.02% more, 95% CI 0% fewer to 0% more) and withdrawals due to adverse events (RR 1.41, 95% CI 0.81 to 2.47; ARR 2.3% more, 95% CI 1.1% fewer to 8.4% more), based on low-certainty evidence. We do not know the effect of etidronate on hip fractures because the evidence is very uncertain (RR not estimable based on very low-certainty evidence). Wrist fractures were not reported in the included studies. For secondary prevention, four studies (two to four years in length) including 667 postmenopausal women at higher risk of fractures provided the evidence. Compared to placebo, etidronate 400 mg/day may make little or no difference to non-vertebral fractures (RR 1.07, 95% CI 0.72 to 1.58; ARR 0.9% more, 95% CI 3.8% fewer to 8.1% more), based on low-certainty evidence. The evidence is very uncertain about etidronate's effects on hip fractures (RR 0.93, 95% CI 0.17 to 5.19; ARR 0.0% fewer, 95% CI 1.2% fewer to 6.3% more), wrist fractures (RR 0.90, 95% CI 0.13 to 6.04; ARR 0.0% fewer, 95% CI 2.5% fewer to 15.9% more), withdrawals due to adverse events (RR 1.09, 95% CI 0.54 to 2.18; ARR 0.4% more, 95% CI 1.9% fewer to 4.9% more), and serious adverse events (RR not estimable), compared to placebo. Clinical vertebral fractures were not reported in the included studies. AUTHORS' CONCLUSIONS: This update echoes the key findings of our previous review that etidronate probably makes or may make little to no difference to vertebral and non-vertebral fractures for both primary and secondary prevention.

Deep learning in the radiologic diagnosis of osteoporosis: a literature review.

OBJECTIVE: Osteoporosis is a systemic bone disease characterized by low bone mass, damaged bone microstructure, increased bone fragility, and susceptibility to fractures. With the rapid development of artificial intelligence, a series of studies have reported deep learning applications in the screening and diagnosis of osteoporosis. The aim of this review was to summary the application of deep learning methods in the radiologic diagnosis of osteoporosis. METHODS: We conducted a two-step literature search using the PubMed and Web of Science databases. In this review, we focused on routine radiologic methods, such as X-ray, computed tomography, and magnetic resonance imaging, used to opportunistically screen for osteoporosis. RESULTS: A total of 40 studies were included in this review. These studies were divided into three categories: osteoporosis screening (n = 20), bone mineral density prediction (n = 13), and osteoporotic fracture risk prediction and detection (n = 7). CONCLUSIONS: Deep learning has demonstrated a remarkable capacity for osteoporosis screening. However, clinical commercialization of a diagnostic model for osteoporosis remains a challenge.

Pregnancy and lactation-associated osteoporosis as a major type of premenopausal osteoporosis: a retrospective cohort study based on real-world data.

BACKGROUND: Pregnancy and lactation-associated osteoporosis (PLO), as well as premenopausal osteoporosis, might be a predictor of future fracture. This study aimed to describe the clinical features of PLO as a subtype of premenopausal osteoporosis and to evaluate medical interventions for it. METHODS: From an administrative claims database including 4,224,246 people in Japan, we classified women for whom the date of childbirth had been defined and who had suffered low-trauma fracture between the ages of 18-47 years as the premenopausal osteoporosis group. A fracture site for which the odds ratio for fractures occurring between 5 months before and 12 months after childbirth (around childbirth) was greater than 1 was considered the PLO site. We classified patients with a fracture at the PLO site around childbirth as the PLO group. The control group consisted of 500 women without fragility fractures. We investigated some drugs and diseases to explore fracture-causing factors, as well as medical interventions such as osteoporosis diagnosis, bone densitometry, anti-osteoporosis pharmacotherapy, and lactation inhibitors. RESULTS: In total, 231 parous women were classified into the premenopausal osteoporosis group. The most common fracture was vertebral fracture and was likely to occur around childbirth, followed by distal radius and sacral fractures, which were rare around childbirth. Considering vertebral, pelvic, and proximal femoral fractures as PLO sites, 56 women with 57 PLO fractures were classified into the PLO group. The incidence of PLO was estimated at 460 per million deliveries. Ovulation disorder and high maternal age were associated with the development of PLO. Vertebral fracture was the most common PLO fracture. It was mainly diagnosed a few months, and possibly up to 1 year, postpartum. PLO patients with vertebral fractures underwent more medical interventions than did those with other fractures, but they were still inadequate. CONCLUSIONS: PLO with vertebral fracture was one of the major types of premenopausal osteoporosis. The prevalence of PLO is considered to be higher than previously thought, indicating the presence of potentially overlooked patients. More timely interventions for PLO might lead to the improved management of latent patients with premenopausal osteoporosis and reduce future fracture risk.

Lactobacillus plantarum 45 activates SHP2 through inhibition of oxidative stress to regulate osteoblast and osteoclast differentiation.

BACKGROUND: The purpose of this study is to observe LP45 (Lactobacillus plantarum 45) to investigate the mechanism by which LP45 attenuates oxidative stress-induced damage and regulates the osteoblast-osteoclast balance. MATERIALS AND METHODS: The oxidative stress level and osteoblast- and osteoclast-related proteins were detected by immunofluorescence staining, Western blotting, ROS fluorescent probe and ELISA. Osteoblast cell proliferation capacity was determined by the CCK-8 assay. X-ray observation and HE staining were used to detect the effect of LP45 on osteoporosis. RESULTS: The expression level of SHP2 and Src was significantly increased, and the expression levels of NOX4, P22, P47, IL-1ß, NLRP3, IRF3, RANK, ß-catenin and INF-ß were inhibited in LP45 group and LPS + LP45 group as compared to those in LPS group. Compared with that in LPS group, the concentration of SOD was increased and the concentration of MDA was decreased in LPS + LP45 group. The protein expressions of OPG, RANKL, RUNX3, RANK and ß-catenin in LP45 group and LPS + LP45 group increased. The protein expressions of NF-κB, CREB and AP-1 in LP45 group and LPS + LP45 group decreased significantly. The results were also confirmed by immunofluorescence staining and ROS fluorescent probe. X-ray observation and HE staining showed that LP45 could inhibit the progression of osteoporosis. CONCLUSION: LP45 can exert its antioxidant effect by inhibiting the production of oxidative stress to activate the SHP2 signaling pathway, thus promoting osteoblast differentiation and repressing osteoclast formation to maintain bone homeostasis and improve bone metabolism.

Bone evaluation study-2: update on the epidemiology of osteoporosis in Germany.

Osteoporosis is the most common bone disorder. Our data gives an estimate of around 5.87 million cases of osteoporosis in the general German population in 2018. Only 30% of insured individuals who suffered an osteoporotic fracture and/or had a confirmed diagnosis of osteoporosis, received an appropriate prescription. PURPOSE: Osteoporosis is the most common bone disorder. It particularly affects elderly people and increases the risk of atraumatic fractures. The aim of this study was to estimate the prevalence of osteoporosis in the general German population aged ≥ 50 years and to collect data on the frequency of prescription of osteoporosis-specific medication in order to assess the treatment gap. METHODS: Retrospective analysis of anonymized data of individuals aged ≥ 50 years insured under statutory healthcare schemes from the database of the Institute for Applied Health Research Berlin (InGef) for 2018 (study population). Insured individuals with osteoporosis were identified based on osteoporosis diagnoses, osteoporosis-specific prescriptions, or osteoporotic fractures. Thus, we estimated the prevalence of osteoporosis in the general German population aged ≥ 50 years. The prevalence of diagnoses, fractures, and prescriptions was determined for the study population and stratified by age and gender. RESULTS: Within the study population of 1,599,299 insured individuals, a prevalence of osteoporosis of 15.9% was determined. This estimated approximately 5.87 million cases of osteoporosis for the general German population. 81.6% of the cases were women. Osteoporosis-specific prescriptions were received by 30.0% of the insured individuals in the study population who had been diagnosed with osteoporosis and/or suffered an osteoporotic fracture. CONCLUSIONS: Germany has a high prevalence of osteoporosis. Only a small portion of individuals who may require osteoporosis-specific treatment actually receive it.

Influence of anti-sclerostin monoclonal antibody in the repair of post-extraction sockets of ovariectomized rats.

OBJECTIVE: This study assessed the impact of an anti-sclerostin monoclonal antibody (Scl-Ab)-based osteoporosis drug on the post-extraction alveolar repair of ovariectomized rats. DESIGN: Fifteen female rats were randomly distributed into three groups: CTR (healthy animals), OST (osteoporosis induced by ovariectomy), and OST+Scl-Ab (osteoporosis induction followed by Scl-Ab treatment). Ovariectomy or sham surgery was performed 30 days before baseline, and Scl-Ab or a vehicle was administered accordingly in the groups. After seven days, all rats underwent the first lower molar extraction and were euthanized 15 days later. Computed microtomography, histological analysis, and collagen content measurement were performed on post-extraction sockets and intact mandibular and maxillary bone areas. RESULTS: Microtomographic analyses of the sockets and mandibles did not reveal significant differences between groups on bone morphometric parameters (p > 0.05), while maxillary bone analyses resulted in better maintenance of bone architecture in OST+Scl-Ab, compared to OST (p < 0.05). Descriptive histological analysis and polarization microscopy indicated better post-extraction socket repair characteristics and collagen content in OST+Scl-Ab compared to OST (p < 0.05). CONCLUSIONS: Scl-Ab-based medication did not accelerate alveolar bone formation but exhibited better post-extraction repair characteristics, and collagen content compared to ovariectomized animals only.

Radiological manifestations and clinical findings of patients with oncologic and osteoporotic medication-related osteonecrosis of the jaw.

Medication-related osteonecrosis of the jaw (MRONJ) poses a challenging form of osteomyelitis in patients undergoing antiresorptive therapies in contrast to conventional osteomyelitis. This study aimed to compare the clinical and radiological features of MRONJ between patients receiving low-dose medications for osteoporosis and those receiving high-dose medications for oncologic purposes. The clinical, panoramic radiographic, and computed tomography data of 159 patients with MRONJ (osteoporotic group, n = 120; oncologic group, n = 39) who developed the condition after using antiresorptive medications for the management of osteoporosis or bone malignancy were analyzed. The osteoporotic group was older (75.8 vs. 60.4 years, p < 0.01) and had a longer duration of medication usage than the oncologic group (58.1 vs. 28.0 months, p < 0.01). Pus discharge and swelling were more common in the osteoporotic group (p < 0.05), whereas bone exposure was more frequent in the oncologic group (p < 0.01). The mandibular cortical index (MCI) in panoramic radiographs was higher in the osteoporotic group (p < 0.01). The mean sequestra size was larger in the oncologic group than in the osteoporotic group (15.3 vs. 10.6 mm, p < 0.05). The cured rate was significantly higher in the osteoporotic group (66.3% vs. 33.3%, p < 0.01). Oncologic MRONJ exhibited distinct clinical findings including rapid disease onset, fewer purulent signs, and lower cure rates than osteoporotic MRONJ. Radiological features such as sequestrum size on CT scan, and MCI values on panoramic radiographs, may aid in differentiating MRONJ in osteoporotic and oncologic patients.

FRAX predicts cardiovascular risk in women undergoing osteoporosis screening: the Manitoba bone mineral density registry.

Osteoporosis and cardiovascular disease (CVD) are highly prevalent in older women, with increasing evidence for shared risk factors and pathogenesis. Although FRAX was developed for the assessment of fracture risk, we hypothesized that it might also provide information on CVD risk. To test the ability of the FRAX tool and FRAX-defined risk factors to predict incident CVD in women undergoing osteoporosis screening with DXA, we performed a retrospective prognostic cohort study which included women aged 50 yr or older with a baseline DXA scan in the Manitoba Bone Mineral Density Registry between March 31, 1999 and March 31, 2018. FRAX scores for major osteoporotic fracture (MOF) were calculated on all participants. Incident MOF and major adverse CV events (MACE; hospitalized acute myocardial infarction [AMI], hospitalized non-hemorrhagic cerebrovascular disease [CVA], or all-cause death) were ascertained from linkage to population-based healthcare data. The study population comprised 59 696 women (mean age 65.7 ± 9.4 yr). Over mean 8.7 yr of observation, 6021 (10.1%) had MOF, 12 277 women (20.6%) had MACE, 2274 (3.8%) had AMI, 2061 (3.5%) had CVA, and 10 253 (17.2%) died. MACE rates per 1000 person-years by FRAX risk categories low (10-yr predicted MOF <10%), moderate (10%-19.9%) and high (≥20%) were 13.5, 34.0, and 64.6, respectively. Although weaker than the association with incident MOF, increasing FRAX quintile was associated with increasing risk for MACE (all P-trend <.001), even after excluding prior CVD and adjusting for age. HR for MACE per SD increase in FRAX was 1.99 (95%CI, 1.96-2.02). All FRAX-defined risk factors (except parental hip fracture and lower BMI) were independently associated with higher non-death CV events. Although FRAX is intended for fracture risk prediction, it has predictive value for cardiovascular risk.

Bone loss after discontinuation of denosumab: the devil is in the details.

A 47-year-old postmenopausal woman with osteoporosis was treated with denosumab, which was discontinued due to side effects. She was therefore transitioned to a yearly intravenous infusion of zoledronic acid. An increase in bone turnover markers together with bone loss at the lumbar spine was observed before the second infusion, suggesting an overshooting of bone resorption due to denosumab discontinuation. On physical examination, the patient was restless and reported having lost about 10 kg since the last visit. A solitary left inferior thyroid nodule was noted on neck palpation. Circulating thyroid hormone levels were elevated, with suppressed thyroid-stimulating hormone. A thyroid scan showed increased uptake in the left inferior nodule with suppression of the remainder of the thyroid gland. A diagnosis of hyperthyroidism due to toxic adenoma was made. The patient was treated with radioactive iodine ablation, with consequent complete normalization of thyroid function. She continued yearly treatment with zoledronic acid. She remained clinically well with no further fractures. Bone turnover markers were appropriately suppressed and bone mineral density increased in the spine and hip. This case illustrates how the overshooting phenomenon following denosumab discontinuation may be compounded by the development of secondary conditions, which can result in suboptimal response to antiresorptive osteoporosis medications.

Raman spectroscopic analysis for osteoporosis identification in humans with hip fractures.

Osteoporosis is a significant health concern. While multiple techniques have been utilized to diagnose this condition, certain limitations still persist. Raman spectroscopy has shown promise in predicting bone strength in animal models, but its application to humans requires further investigation. In this study, we present an in vitro approach for predicting osteoporosis in 10 patients with hip fractures using Raman spectroscopy. Raman spectra were acquired from exposed femoral heads collected during surgery. Employing a leave-one-out cross-validated linear discriminant analysis (LOOCV-LDA), we achieved accurate classification (90 %) between osteoporotic and osteopenia groups. Additionally, a LOOCV partial least squares regression (PLSR) analysis based on the complete Raman spectra demonstrated a significant prediction (r2 = 0.84, p < 0.05) of bone mineral density as measured by dual X-ray absorptiometry (DXA). To the best of our knowledge, this study represents the first successful demonstration of Raman spectroscopy correlating with osteoporotic status in humans.

Systematical mutational analysis of teriparatide on anti-osteoporosis activity by alanine scanning.

Osteoporosis is a progressive systemic skeletal disease that decreases bone density and bone quality, making them fragile and easy to break. In spite of effective anti-osteoporosis potency, teriparatide, the first anabolic medications approved for the treatment of osteoporosis, was proven to exhibit various side effects. And the relevant structure-activity relationship (SAR) of teriparatide was in need. In this work, we performed a systematical alanine scanning against teriparatide and synthesized 34 teriparatide derivatives. Their biological activities were evaluated and the importance of each residue for anti-osteoporosis activity was also revealed. A remarkable decrease in activity was observed for alanine replacement of the residue Gly12, His14, Ser17, Arg20 and Leu24, showcasing the important role of these residues in teriparatide on anti-osteoporosis activity. On contrary, when Gly13 and Gln30 were mutated to Ala, the peptide derivatives exhibited the significantly increased activities, demonstrating that these two residues could be readily replaced. Our research expanded the peptide library of teriparatide analogues and presented a potential opportunity for designing the more powerful anti-osteoporosis peptide agents.

Three-year follow-up of a novel orthopedic ward fracture liaison services (OWFLS) model.

OBJECTIVE: We established an orthopedic ward fracture liaison services (OWFLS) model and evaluated its role in improving detection rates of bone metabolic markers, treatment rates, and long-term treatability. METHODS: This observational retrospective cohort study included 120 patients aged >50 years hospitalized for primary osteoporotic fracture from January 2018 to January 2019 (group A: not included in OWFLS). Group B (included in OWFLS) comprised 120 patients from February 2019 to February 2020. We compared rates of bone metabolic index testing, treatment, and adherence; symptomatic improvement; and recurrent fracture between groups. RESULTS: Rates of bone metabolism index testing (50% vs. 0%) and medication use (94.2% vs. 64.2%) were significantly higher after OWFLS implementation. There was no significant difference in adherence rates at 3 months between groups (97.3% vs. 93.5%). Adherence rates at 1 and 3 years were better in group B than A (73.5% vs. 51.9%; 57.5% vs. 26%, respectively). Recurrence of bone pain at 1 and 3 years was significantly lower in group B than A (20.4% vs. 46.8%; 45.1% vs. 76.6%, respectively). CONCLUSIONS: OWFLS improved the detection rate of bone metabolism indicators, treatment rate, and patient adherence and reduced recurrence of bone pain. OWFLS may be suitable for settings lacking human resources.

Correlation of serum anti-Mullerian hormone and Inhibin-B levels with osteoporosis of menopausal woman in Chinese Daur ethnic group.

PURPOSE: To investigate the diagnostic value of anti-Mullerian hormone (AMH) and Inhibin B (InhB) in menopausal women with osteoporosis from the Chinese Daur ethnic group. METHODS: A total of 175 menopausal women were selected and divided into the osteoporosis group (N = 90) and the control group (N = 85). BMD was measured by dual-energy X-ray absorptiometry, and laboratory indicators of osteoporosis, for example, serum osteocalcin (OC), ß-collagen special sequence (ß-CTX), and procollagen type I amino-terminal propeptide (PINP), bone alkaline phosphatase (BALP), AMH, and InhB were measured by commercial kits. The relationship between osteoporosis and AMH or InhB was analyzed. The predictive values of AMH and InhB were reflected by the ROC curve and logistic regression. RESULTS: The level of BMD was decreased and the levels of OC, ß-CTX, PINP, and BALP of the menopausal osteoporosis group were increased. The concentration of AMH and InhB in the menopausal osteoporosis group was decreased and they had connections with each other. AMH and InhB could be used as independent indicators for the occurrence of osteoporosis in menopausal women and their combination had a higher diagnostic value. CONCLUSION: AMH and InhB measurements in menopausal women had a certain clinical significance in the detection of osteoporosis. The occurrence of osteoporosis was related to BMD, OC, ß-CTX, BALP, AMH, and InhB.

SIRT1 and ZNF350 as novel biomarkers for osteoporosis: a bioinformatics analysis and experimental validation.

BACKGROUND: Osteoporosis (OP) is characterized by bone mass decrease and bone tissue microarchitectural deterioration in bone tissue. This study identified potential biomarkers for early diagnosis of OP and elucidated the mechanism of OP. METHODS: Gene expression profiles were downloaded from Gene Expression Omnibus (GEO) for the GSE56814 dataset. A gene co-expression network was constructed using weighted gene co-expression network analysis (WGCNA) to identify key modules associated with healthy and OP samples. Functional enrichment analysis was conducted using the R clusterProfiler package for modules to construct the transcriptional regulatory factor networks. We used the "ggpubr" package in R to screen for differentially expressed genes between the two samples. Gene set variation analysis (GSVA) was employed to further validate hub gene expression levels between normal and OP samples using RT-PCR and immunofluorescence to evaluate the potential biological changes in various samples. RESULTS: There was a distinction between the normal and OP conditions based on the preserved significant module. A total of 100 genes with the highest MM scores were considered key genes. Functional enrichment analysis suggested that the top 10 biological processes, cellular component and molecular functions were enriched. The Toll-like receptor signaling pathway, TNF signaling pathway, PI3K-Akt signaling pathway, osteoclast differentiation, JAK-STAT signaling pathway, and chemokine signaling pathway were identified by Kyoto Encyclopedia of Genes and Genomes pathway analysis. SIRT1 and ZNF350 were identified by Wilcoxon algorithm as hub differentially expressed transcriptional regulatory factors that promote OP progression by affecting oxidative phosphorylation, apoptosis, PI3K-Akt-mTOR signaling, and p53 pathway. According to RT-PCR and immunostaining results, SIRT1 and ZNF350 levels were significantly higher in OP samples than in normal samples. CONCLUSION: SIRT1 and ZNF350 are important transcriptional regulatory factors for the pathogenesis of OP and may be novel biomarkers for OP treatment.