The association between myasthenia gravis and risk of fracture: a systematic review and meta-analysis.

Patients with myasthenia gravis (MG), because of their muscle weakness and exposure to corticosteroids treatment, are generally considered to be at increased risk for osteoporosis or fracture. However, clinical evidence of this issue is lacking. In this review, we systematically searched databases, including Cochrane Library, PubMed, Embase, and Airiti library from inception to the end of November 2023 for cohort studies that compared participants with MG and participants without MG for incidence of osteoporosis or fracture. We used the Newcastle-Ottawa Scale for quality assessment. In total, we included 3 studies with 34,865 participants. The pooled meta-analysis using the random effect model demonstrated no significant difference in risk of fracture in the MG group (odds ratio = 1.52; 95% confidence interval = 0.74 to 3.12; I2 = 93%; between-study variance [τ2] = 0.32) compared with that for the non-MG group. Due to limited studies, we could not perform a quantitative analysis for risk of osteoporosis. In conclusion, we found no robust evidence to support the proposition that patients with MG are at higher risk for fracture than general comparators. The explanations and underlying mechanisms of this finding remain unclear, we therefore conclude that additional studies are warranted.

Association of bone fracture with 30-year body mass index (BMI) trajectories: findings from the Framingham Heart Study : Bone fracture and 30-year BMI trajectories.

A knowledge gap exists in associating later life's osteoporotic fracture and middle adulthood's BMI trajectories. We observed an association showing those transitioning from overweight to normal weight face a higher fracture risk in late adulthood, emphasizing the potential benefits of maintaining a stable BMI to reduce late-life fractures. PURPOSE: Numerous studies on the relationship between obesity and fractures have relied on body mass index (BMI) at a single time point, yielding inconclusive results. This study investigated the association of BMI trajectories over middle adulthood with fracture risk in late adulthood. METHODS: This prospective cohort study analyzed 1772 qualified participants from the Framingham Original Cohort Study, with 292 (16.5%) incident fractures during an average of 17.1-year follow-up. We constructed BMI trajectories of age 35-64 years based on latent class mixed modeling and explored their association with the risk of fracture after 65 years using the Cox regression. RESULTS: The result showed that compared to the BMI trajectory Group 4 (normal to slightly overweight; see "Methods" for detailed description), Group 1 (overweight declined to normal weight) had a higher all-fracture risk after age 65 (hazard ratio [HR], 2.22, 95% CI, 1.13-4.39). The secondary analysis focusing on lower extremity fractures (pelvis, hip, leg, and foot) showed a similar association pattern. CONCLUSIONS: This study suggested that people whose BMI slightly increased from normal weight to low-level overweight during 30 years of middle adulthood confer a significantly lower risk of fracture in later life than those whose BMI declined from overweight to normal weight. This result implies the potentially beneficial effects of avoiding weight loss to normal weight during middle adulthood for overweight persons, with reduced fracture risk in late life.

Understanding the long-term impact of incident osteoporotic fractures on healthcare utilization and costs in Korean postmenopausal women.

This study provides long-term evidence that healthcare resource utilization and costs of care in women who experienced incident osteoporotic fractures remained higher than those in women without fractures over a span of 5 years. These findings emphasize the importance of early diagnostics and treatment for osteoporosis. PURPOSE: To evaluate healthcare resource utilization (HCRU) and costs of care over 5 years after the incident osteoporotic fractures (OF) in postmenopausal women. METHODS: We used data from the National Health Insurance Service databases 2011-2018. Women aged ≥ 50 years with incident OF (OF group) were matched to women without OF (non-OF group). HCRU (inpatient, outpatient, and emergency room [ER] visits) and costs of care (inpatient, outpatient, and ER visits) during the 5-year follow-up period were derived after propensity score matching (PSM). Additionally, we identified women with subsequent fractures within the first 2 years after the incident OF. RESULTS: After PSM, 47,238 OF and 134,813 non-OF women were identified. HCRU rates and costs of care were highest in the first year after OF and decreased substantially, but remained higher in the OF group during the entire follow-up period. The increase in cumulative HCRU rates over 5 years was highest in inpatient admissions with ER visits (138% higher in OF vs non-OF). The cumulative total costs over 5 years were 73% higher in the OF group than in the non-OF group, which was mostly driven by inpatient costs. Trends were similar for women with subsequent fractures, but they generally showed higher HCRU and costs than those in the total OF group. CONCLUSION: OF imposes a substantial and sustained economic burden on women, resulting in an approximately twofold increase in the cumulative cost over 5 years compared to women without fracture, which highlights the need for early diagnostics and treatment of osteoporosis.

Total knee arthroplasty and periprosthetic distal femoral fracture: looking beyond the osteoporosis to previous osteoporotic fracture.

Osteoporosis increases the risk of periprosthetic distal femoral fractures after TKA, especially in patients with a history of osteoporotic fractures. Therefore, careful assessment and proper treatment of osteoporosis need and the importance of taking osteoporotic medication needs to be recognized by the patients following primary TKA. PURPOSE: Osteoporosis is a risk factor for fractures, including those of the hip, vertebrae, and distal radius; however, the association between osteoporosis and periprosthetic fractures after total knee arthroplasty (TKA) has not been much investigated. Therefore, we aimed to investigate the association of the presence of systemic osteoporosis with periprosthetic fractures after TKA. METHODS: This study included 34 patients with periprosthetic fractures following primary TKA and 106 controls matched for age and sex. Bone mineral density was evaluated at the femoral neck, total hip, and lumbar spine using dual X-ray absorptiometry. Medical records were reviewed for age; sex; body mass index; smoking; rheumatoid arthritis, endocrine diseases, and cardiovascular diseases; history of glucocorticoid use; medication for osteoporosis; and history of previous osteoporotic fracture. In addition, anterior femoral notching after TKA was evaluated. Univariable and multivariable logistic regression analysis were used to determine factors associated with periprosthetic fracture. RESULTS: The prevalence of osteoporosis in the fracture group was higher than that in the control group (61.8% vs. 40.6%, p=0.045). The rate of medication for osteoporosis was significantly low in the fracture group (47.6 % vs 76.7%, p=0.026). History of previous osteoporotic fracture (odds ratio [OR], 9.1; p=0.015) and osteoporosis (OR, 3.6; p=0.013) were significant risk factors for periprosthetic fractures after TKA. Medication for osteoporosis could decrease the risk of periprosthetic fracture (OR 0.3; p=0.020). CONCLUSION: Osteoporosis is a major risk factor for periprosthetic distal femoral fractures after TKA. Therefore, careful assessment and proper treatment of osteoporosis need and the importance of taking osteoporotic medication needs to be recognized to the patients following primary TKA, especially in patients with a history of osteoporotic fracture. LEVEL OF EVIDENCE: Prognostic study, level III.

A meta-analysis of previous falls and subsequent fracture risk in cohort studies.

The relationship between self-reported falls and fracture risk was estimated in an international meta-analysis of individual-level data from 46 prospective cohorts. Previous falls were associated with an increased fracture risk in women and men and should be considered as an additional risk factor in the FRAX® algorithm. INTRODUCTION: Previous falls are a well-documented risk factor for subsequent fracture but have not yet been incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between previous falls and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD). METHODS: The resource comprised 906,359 women and men (66.9% female) from 46 prospective cohorts. Previous falls were uniformly defined as any fall occurring during the previous year in 43 cohorts; the remaining three cohorts had a different question construct. The association between previous falls and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture, and hip fracture) was examined using an extension of the Poisson regression model in each cohort and each sex, followed by random-effects meta-analyses of the weighted beta coefficients. RESULTS: Falls in the past year were reported in 21.4% of individuals. During a follow-up of 9,102,207 person-years, 87,352 fractures occurred of which 19,509 were hip fractures. A previous fall was associated with a significantly increased risk of any clinical fracture both in women (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33-1.51) and men (HR 1.53, 95% CI 1.41-1.67). The HRs were of similar magnitude for osteoporotic, major osteoporotic fracture, and hip fracture. Sex significantly modified the association between previous fall and fracture risk, with predictive values being higher in men than in women (e.g., for major osteoporotic fracture, HR 1.53 (95% CI 1.27-1.84) in men vs. HR 1.32 (95% CI 1.20-1.45) in women, P for interaction = 0.013). The HRs associated with previous falls decreased with age in women and with duration of follow-up in men and women for most fracture outcomes. There was no evidence of an interaction between falls and BMD for fracture risk. Subsequent risk for a major osteoporotic fracture increased with each additional previous fall in women and men. CONCLUSIONS: A previous self-reported fall confers an increased risk of fracture that is largely independent of BMD. Previous falls should be considered as an additional risk factor in future iterations of FRAX to improve fracture risk prediction.

Non-osteoporotic fractures are associated with increased risk of subsequent major osteoporotic fractures.

We studied the association between non-osteoporotic fractures and future major osteoporotic fractures, using UK health records. Non-osteoporotic fractures were found to increase the risk of major osteoporotic fractures, although to a lesser extent than osteoporotic fractures. This highlights the importance of considering all previous fractures in assessing future fracture risk. PURPOSE: Previous studies demonstrated that osteoporotic fractures-minor and major-increase the risk for future major osteoporotic fractures; we test whether non-osteoporotic fractures are also associated with such increased risk. METHODS: The study is a retrospective cohort study using UK primary care electronic health records. Exposure groups were defined according to fracture location prior to the year 2011 (index date): major, minor, and non-osteoporotic. The outcome of incident major osteoporotic fractures following the index date was compared between the exposure groups and the general population. RESULTS: The general study population included 1,951,388 patients. The exposure groups included 39,931 patients with a prior major osteoporotic fracture, 19,397 with a prior minor osteoporotic fracture, and 50,115 patients with a prior non-osteoporotic fracture. The standardized Incidence Rate Ratio for future major osteoporotic fractures was 2.73 (95% confidence interval: 2.64-2.82), 2.43 (2.32-2.54), and 1.83 (1.74-1.92), respectively. CONCLUSION: Non-osteoporotic fractures are significantly associated with increased risk for future major osteoporotic fractures relative to the general population, yet to a lesser extent compared to major and minor osteoporotic fractures.

Fracture liaison service-a multidisciplinary approach to osteoporosis management.

A fracture liaison service is a systems-level multidisciplinary approach designed to reduce subsequent fracture risk in patients who recently sustained fragility fractures. It is estimated that one in three women and one in five men over the age of 50 years old have osteoporosis. Nonetheless, only 9 to 20% of patients who sustain an initial fragility fracture eventually receive any osteoporosis treatment. With the aim of preventing subsequent fractures, a fracture liaison service (FLS) works through identifying patients presenting with fragility fractures to the hospital and providing them with easier access to osteoporosis care through referrals for bone health and fracture risk assessment and recommendation or initiation of osteoporosis treatment. Currently, there are four major types of FLS models ranging from services that only identify at-risk patients and inform and educate the patient but take no further part in communicating their findings to other stakeholders in patients' care, to services that identify, investigate, and initiate treatment at the other end of the spectrum. In this article, we review the benefits, challenges, and outcomes of FLS in the American healthcare system with further exploration of the roles each member of the multidisciplinary team can play in improving patients' bone health.

Osteosarcopenia: Prevalence and 10-Year Fracture and Mortality Risk - A Longitudinal, Population-Based Study of 75-Year-Old Women.

Osteosarcopenia is the coexistence of low bone mass and sarcopenia. In older women, its prevalence is not well described, and it is unknown if sarcopenia is additive to low bone mass for fracture and mortality risk. The study investigated prevalence of osteosarcopenia and if osteosarcopenia is associated with higher fracture and mortality risk than low bone mass alone in older community-dwelling women. The longitudinal, population-based OPRA Cohort (n = 1044), all aged 75 at inclusion, followed for 10 years. Using WHO and EWGSOP2 definitions for low bone mass (T-score < -1.0 femoral neck) and sarcopenia (knee strength; appendicular lean muscle mass) women were categorized (1) Normal, (2) Low bone mass (LBM), and 3) Osteosarcopenia (probable; confirmed). Risk of hip, major osteoporotic fracture, and mortality were estimated. Osteosarcopeniaconfirmed prevalence increased from age 75 to 80 and 85 from 3.0% (29/970) to 4.9% (32/656) to 9.2% (33/358) but prevalence is potentially 2-4 times higher (11.8%, 13.4%, 20.3%) based on osteosarcopeniaprobable. Having osteosarcopeniaprobable significantly increased 10-year risk of hip fracture (HRadj 2.67 [1.34-5.32]), major osteoporotic fracture (HRadj 2.04 [1.27-3.27]), and mortality (HRadj 1.91 [1.21-3.04]). In contrast, LBM increased osteoporotic fracture risk (HRadj 2.08 [1.46-2.97], but not hip fracture (HRadj 1.62 [0.92-2.85]) or mortality (HRadj 0.94 [0.64-1.38]). Median time-to-hip fracture was 7.6 years (normal), 6.0 years (LBM), and 5.7 years (osteosarcopeniaprobable). Prevalence of confirmed osteosarcopenia is almost 10% at age 85. Probable osteosarcopenia significantly increased risk of hip and major osteoporotic fractures and mortality more so than low bone mass alone.

Risk of adjacent level fracture after percutaneous vertebroplasty and kyphoplasty vs natural history for the management of osteoporotic vertebral compression fractures: a network meta-analysis of randomized controlled trials.

OBJECTIVES: Percutaneous vertebroplasty and kyphoplasty are common interventions for osteoporotic vertebral compression fractures. However, there is concern about an increased risk of adjacent-level fractures after treatment. This study aimed to compare the risk of adjacent-level fractures after vertebroplasty and kyphoplasty with the natural history after osteoporotic vertebral compression fractures. MATERIALS AND METHODS: A network meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the risk of adjacent-level fractures after vertebroplasty and kyphoplasty compared to the natural history after osteoporotic vertebral compression fractures. Frequentist network meta-analysis was conducted using the "netmeta" package, and heterogeneity was assessed using Q statistics. The pooled risk ratio (RR) and 95% confidence intervals (CI) were calculated using random effects. RESULTS: Twenty-three RCTs with a total of 2838 patients were included in the analysis. The network meta-analysis showed comparable risks of adjacent-level fractures between vertebroplasty, kyphoplasty, and natural history after osteoporotic vertebral compression fractures with a mean follow-up of 21.2 (range: 3-49.4 months). The pooled RR for adjacent-level fractures after kyphoplasty compared to natural history was 1.35 (95% CI, 0.78-2.34, p = 0.23) and for vertebroplasty compared to natural history was 1.16 (95% CI, 0.62-2.14) p = 0.51. The risk of bias assessment showed a low to moderate risk of bias among included RCTs. CONCLUSION: There was no difference in the risk of adjacent-level fractures after vertebroplasty and kyphoplasty compared to natural history after osteoporotic vertebral compression fractures. The inclusion of a large patient number and network meta-analysis of RCTs serve evidence-based clinical practice. CLINICAL RELEVANCE STATEMENT: The risk of adjacent-level fracture following percutaneous vertebroplasty or kyphoplasty is similar to that observed in the natural history after osteoporotic vertebral compression fractures. KEY POINTS: RCTs have examined the risk of adjacent-level fracture after intervention for osteoporotic vertebral compression fractures. There was no difference between vertebroplasty and kyphoplasty patients compared to the natural disease history for adjacent compression fractures. This is strong evidence that interventional treatments for these fractures do not increase the risk of adjacent fractures.

Drug utilization pattern of romosozumab and other osteoporosis treatments in Japan, 2019-2021.

INTRODUCTION: Describe real-world treatment of osteoporosis and romosozumab treatment patterns in Japan. MATERIALS AND METHODS: Data for patients initiating romosozumab or other antiosteoporotic medications between March 01, 2018, and May 31, 2022, were extracted from the Medical Data Vision (MDV) and Japan Medical Data Center (JMDC) databases. Patients were categorized into four cohorts: those who newly initiated romosozumab within the first (MDV: n = 4782; JMDC: n = 2578) or second (MDV: n = 3888; JMDC: n = 2446) year after launch and those who initiated teriparatide (TPTD; MDV: n = 14,576; JMDC: n = 8259) or non-TPTD antiosteoporotic medications within the first year of romosozumab launch (MDV: n = 352,142; JMDC: n = 185,785). RESULTS: Mean age, sex, baseline cardiovascular history, comorbidities, and concomitant medications were similar across cohorts. In the MDV database, fracture history was higher in the romosozumab year-1 (59.3%), year-2 (64.1%), and TPTD (65.5%) cohorts versus the non-TPTD cohort (24.4%). Similar rates were identified in the JMDC database: romosozumab year-1 (64.7%), year-2 (66.6%), TPTD (67.5%), and non-TPTD (27.8%). Vertebral fractures were most common in all cohorts. 12-month romosozumab discontinuation varied between the year-1 and year-2 cohorts in MDV (62.4% and 58.8%) and JMDC (57.1% and 52.7%), whereas mean number of injections remained consistent (MDV: 9.7 and 9.8; JMDC: 7.3 and 7.8). Romosozumab persistence was lower in year-1 versus year-2 (MDV: 37.6% and 42.9%; JMDC: 41.2% and 47.3%). CONCLUSION: Patients initiating romosozumab and TPTD had a high fracture history. Given the dual effects of promoting bone formation and suppressing resorption, improving romosozumab adherence and persistence over time may be important for antiosteoporotic therapy.

Diagnosing Osteoporosis in Diabetes-A Systematic Review on BMD and Fractures.

PURPOSE OF REVIEW: Recently, the American Diabetes Association updated the 2024 guidelines for Standards of Care in Diabetes and recommend that a T-score of - 2.0 in patients with diabetes should be interpreted as equivalent to - 2.5 in people without diabetes. We aimed to evaluate the most recent findings concerning the bone mineral density (BMD)-derived T-score and risk of fractures related to osteoporosis in subjects with diabetes. RECENT FINDINGS: The dual-energy X-ray absorptiometry (DXA) scan is the golden standard for evaluating BMD. The BMD-derived T-score is central to fracture prediction and signifies both diagnosis and treatment for osteoporosis. However, the increased fracture risk in diabetes is not sufficiently explained by the T-score, complicating the identification and management of fracture risk in these patients. Recent findings agree that subjects with type 2 diabetes (T2D) have a higher T-score and higher fracture risk compared with subjects without diabetes. However, the actual number of studies evaluating the direct association of higher fracture risk at higher T-score levels is scant. Some studies support the adjustment based on the 0.5 BMD T-score difference between subjects with T2D and subjects without diabetes. However, further data from longitudinal studies is warranted to validate if the T-score treatment threshold necessitates modification to prevent fractures in subjects with diabetes.

Predicting Osteoporotic Fracture in Patients With Early-Stage Diabetic Kidney Disease Using a Radiomic Model: A Longitudinal Cohort Study.

OBJECTIVE: There is an urgent need for effective predictive strategies to accurately evaluate the risk of fragility fractures in elderly patients in the early stages of diabetic kidney disease (DKD). METHODS: This longitudinal cohort study included 715 older patients in the early stages of DKD diagnosed between January 2015 and August 2019. Patients were randomly allocated to a training cohort (n = 499) and a validation cohort (n = 216). The least absolute shrinkage and selection operator method was used to select key features for dual-energy x-ray absorptiometry-based radiomic analysis. A radiomic model was constructed using Cox proportional hazards regression. The performance of the radiomic model was compared with that of traditional fracture assessment tools through a receiver operating characteristic curve, calibration curve, and decision curve analysis. RESULTS: Over a mean follow-up period of 4.72 ± 1.60 years, 65 participants (9.09%) experienced incident fragility fractures. Seventeen features were ultimately selected to create the radiomic model. The calibration plots of this model demonstrated satisfactory agreement between the observed and predicted outcomes. Moreover, the radiomic model outperformed traditional fracture assessment tools in both the training and validation cohorts according to the area under the receiver operating characteristic curve and decision curve analysis. CONCLUSIONS: The novel radiomic model has demonstrated a more effective prediction of fragility fracture in elderly patients in the early stages of DKDcompared to traditional fracture assessment tools.

Hypoxia preconditioning of adipose stem cell-derived exosomes loaded in gelatin methacryloyl (GelMA) promote type H angiogenesis and osteoporotic fracture repair.

The challenges posed by delayed atrophic healing and nonunion stand as formidable obstacles in osteoporotic fracture treatment. The processes of type H angiogenesis and osteogenesis emerge as pivotal mechanisms during bone regeneration. Notably, the preconditioning of adipose-derived stem cell (ADSC) exosomes under hypoxic conditions has garnered attention for its potential to augment the secretion and functionality of these exosomes. In the present investigation, we embarked upon a comprehensive elucidation of the underlying mechanisms of hypo-ADSC-Exos within the milieu of osteoporotic bone regeneration. Our findings revealed that hypo-ADSC-Exos harboured a preeminent miRNA, namely, miR-21-5p, which emerged as the principal orchestrator of angiogenic effects. Through in vitro experiments, we demonstrated the capacity of hypo-ADSC-Exos to stimulate the proliferation, migration, and angiogenic potential of human umbilical vein endothelial cells (HUVECs) via the mediation of miR-21-5p. The inhibition of miR-21-5p effectively attenuated the proangiogenic effects mediated by hypo-ADSC-Exos. Mechanistically, our investigation revealed that exosomal miR-21-5p emanating from hypo-ADSCs exerts its regulatory influence by targeting sprouly1 (SPRY1) within HUVECs, thereby facilitating the activation of the PI3K/AKT signalling pathway. Notably, knockdown of SPRY1 in HUVECs was found to potentiate PI3K/AKT activation and, concomitantly, HUVEC proliferation, migration, and angiogenesis. The culminating stage of our study involved a compelling in vivo demonstration wherein GelMA loaded with hypo-ADSC-Exos was validated to substantially enhance local type H angiogenesis and concomitant bone regeneration. This enhancement was unequivocally attributed to the exosomal modulation of SPRY1. In summary, our investigation offers a pioneering perspective on the potential utility of hypo-ADSC-Exos as readily available for osteoporotic fracture treatment.

The association between computed tomography-based osteosarcopenia and osteoporotic vertebral fractures: a longitudinal study.

PURPOSE: Osteoporosis and sarcopenia usually coexist in older population. The concept of osteosarcopenia has been proposed in recent years. However, studies on the relationship between osteosarcopenia and the risk of fracture are rare, and the association is unclear at present. This study aimed to investigate the association between osteosarcopenia evaluated based on chest computed tomography (CT) and osteoporotic vertebral fracture (OVF). METHODS: This study recruited 7906 individuals aged 50 years and older who did not have OVFs and underwent chest CT for physical examination between July 2016 and September 2019. Subjects were followed up annually until June 2023. Osteosarcopenia was defined by a low muscle area of the erector spinae (< 25.4 cm2) and the bone attenuation (Hounsfield unit, HU < 135). Genant's grades were used to define OVFs. Control subjects were selected by Propensity Score Matching at a ratio 20:1. Cox proportional hazards models were used to assess the associations between osteosarcopenia and OVFs. RESULTS: Of the 7906 participants included, 95 had a new OVF within a median follow-up of 3 years. A total of 1900 control subjects were matched. Individuals in the osteosarcopenia group had a higher prevalence of spinal fractures than those in normal group (16.4% vs. 0.4%, P < 0.001). Osteosarcopenia was independently associated with OVF (adjusted hazard ratio (aHR): 12.67, 95% confidence interval (CI) 3.79-42.40) and severe OVF (aHR = 14.07, 95% CI 1.84-107.66). Similar trends were observed in males, females and those subjects aged older than 60 years. Osteosarcopenia had good predictive efficacy for OVF (area under the curve = 0.836). A nomogram was also developed for clinical application. CONCLUSION: Osteosarcopenia assessed based on chest CT was associated with OVF, and osteosarcopenia has good performance for vertebral fracture prediction.

Combined Prognostic Impact of Two Quick Frailty Assessments in Acute Heart Failure.

INTRODUCTION: We aimed to investigate the prognostic impact of frailty (defined by the Study of Osteoporotic Fracture [SOF] index and the Clinical Frailty Scale [CFS]) in hospitalized patients with acute decompensated heart failure (HF). METHODS: A total of 1,053 patients over 75 years of age, who were primarily admitted to hospital with a diagnosis of acute decompensated HF, were enrolled. The prognostic value of frailty by the two tools for predicting all-cause mortality was analyzed using multivariate Cox regression models. RESULTS: The incidence of frailty was 57.1% when using the SOF index, 37.6% when using the CFS, and 23.3% when using both tools. Frailty, via the SOF index or CFS, was an independent predictor of all-cause mortality in model 1, after adjustment for significantly associated factors by univariate analysis (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.04-1.84, p = 0.027; HR 1.53, 95% CI 1.15-2.05, p = 0.003, respectively), and in model 2, after adjustment for previously reported prognostic factors (HR 1.42, 95% CI 1.07-1.89, p = 0.015; HR 1.56, 95% CI 1.17-2.07, p = 0.002, respectively). Compared to non-frail patients, frail patients via both tools had a significantly higher incidence of all-cause mortality in models 1 (adjusted HR 2.16, 95% CI 1.42-3.29, p < 0.001) and 2 (adjusted HR 2.30, 95% CI 1.51-3.50, p < 0.001). CONCLUSIONS: Combined frailty screening using the SOF index and CFS contributed to stratify the risk of mortality in patients with acute decompensated HF.

The relation of osteoporotic vertebral fractures and spine degeneration on the occurrence of complications: a systematic review.

STUDY DESIGN: Systematic review. PURPOSE: Osteoporotic vertebral fractures (OVFs) and degenerative spine conditions are age-related and associated with higher morbidity and mortality and greater health care costs. The relationship between OVFs and prevalent spine degeneration is rarely reported. The aim of this study was to systematically review current literature on the influence of preexisting degenerative spine conditions in patients with OVFs on the occurrence of complications during and after treatment. METHODS: A systematic literature review adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was performed using Web of Science and MEDLINE. We considered English and German articles published from January 1990 to December 2022. The inclusion criteria were patients with OVFs and preexisting spinal degeneration with complications such as subsequent fractures, deformity, implant failure and surgical and general complications. The included studies were controlled trials, cohort studies, and case series. RESULTS: Ten articles met the inclusion criteria (two prospective studies, seven retrospective studies and one case series). These were divided into two groups: studies on OVFs in patients with coexisting degenerative spine conditions (n = 5) and studies on OVFs following surgical treatment for degenerative spine conditions (n = 5). Three studies reported more complications in patients with OVFs and severe degeneration. One study stated the opposite. One study did not find any correlation. The remaining studies described complications narratively. Subsequent fractures were the most frequent complications. CONCLUSION: OVFs in patients with preexisting spinal degeneration seem to cause more complications. In addition to subsequent fractures, other complications have rarely been examined. The presence of degenerative changes or undergoing surgical correction may increase the risk of subsequent fractures.

Predictive role of FRAX© for postoperative proximal junctional kyphosis with vertebral fracture after adult spinal deformity surgery.

PURPOSE: To identify risk factors, including FRAX (a tool for assessing osteoporosis) scores, for development of proximal junctional kyphosis (PJK), defined as Type 2 in the Yagi-Boachie classification (bone failure), with vertebral fracture (VF) after surgery for symptomatic adult spinal deformity. METHODS: This was a retrospective, single institution study of 127 adults who had undergone corrective long spinal fusion of six or more spinal segments for spinal deformity and been followed up for at least 2 years. The main outcome was postoperative development of PJK with VF. Possible predictors of this outcome studied included age at surgery, BMI, selected radiographic measurements, bone mineral density, and 10-year probability of major osteoporotic fracture (MOF) as determined by FRAX. We also analyzed use of medications for osteoporosis. Associations between the selected variables and PJK with VF were assessed by the Mann-Whitney, Fishers exact, and Wilcoxon signed-rank tests, and Kaplan-Meier analysis, as indicated. RESULTS: Forty patients (31.5%) developed PJK with VF postoperatively,73% of them within 6 months of surgery. Statistical analysis of the selected variables found that only a preoperative estimate by FRAX of a > 15% risk of MOF within 10 years, pelvic tilt > 30° at first standing postoperatively and lower instrumented level (fusion terminating at the pelvis) were significantly associated with development of PJK with VF. CONCLUSION: Preoperative assessment of severity of osteoporosis using FRAX provides an accurate estimate of risk of postoperative PJK with VF after surgery for adult spinal deformity.

Association between BMI and osteoporotic fractures at different sites in Chinese women: a case-control retrospective study in Changsha.

BACKGROUND: Osteoporotic fractures are a growing problem in an aging society. The association between body mass index (BMI) and osteoporotic fractures varies by fracture site and ethnicity. Limited knowledge exists regarding this association in native Chinese, particularly utilizing local databases as reference sources. OBJECTIVE: To investigate the association between BMI and osteoporotic fractures at different sites in Chinese women. METHODS: Three thousand ninety-eight female patients with radiographic fractures and 3098 age- and sex-matched healthy controls without fractures were included in the study. Both of them underwent assessment using dual-energy X-ray absorptiometry (DXA), with BMD measurements calculated using our own BMD reference database. Participants were classified into underweight (BMI < 18.5 kg/m2), normal weight (18.5 ≤ BMI < 24.0 kg/m2), overweight (24 ≤ BMI < 28 kg/m2) and obese (BMI ≥ 28 kg/m2) according to the Chinese BMI classification standard. RESULTS: There were 2296 (74.1%) vertebral fractures, 374 (12.1%) femoral neck fractures, and 428 (13.8%) other types of fractures in the case group. Bone mineral density (BMD) was almost lower in the fracture groups compared to the control groups (p = 0.048 to < 0.001). Compared with normal weight, underweight had a protective effect on total [odds ratio (OR) = 0.61; 95% confidence interval (CI), 0.49 -0.75; P< 0.001], and lumbar fractures (OR = 0.52; 95% CI, 0.41 - 0.67; P < 0.001), while obesity was associated with an increased risk for total (OR = 2.26; 95% CI, 1.85 - 2.76; P < 0.001), lumbar (OR = 2.17; 95% CI, 1.72 - 2.73; P < 0.001), and femoral neck fractures (OR = 4.08; 95% CI, 2.18 - 7.63; P < 0.001). Non-linear associations were observed between BMI and fractures: A J-curve for total, lumbar, and femoral neck fractures, and no statistical change for other types of fractures. Underweight was found to be a risk factor for other types of fracturess after adjusting for BMD (OR = 2.29; 95% CI, 1.09 - 4.80; P < 0.001). Osteoporosis and osteopenia were identified as risk factors for almost all sites of fracture when compared to normal bone mass. CONCLUSIONS: Underweight has a protective effect on total and lumbar spine fractures in Chinese women, while obesity poses a risk factor for total, lumbar, and femoral neck fractures. The effect of BMI on fractures may be mainly mediated by BMD.

Cost-consequence analysis of continuous denosumab therapy for osteoporosis treatment in South Korea.

BACKGROUND: Insurance reimbursement provisions in South Korea limit osteoporosis medication availability for patients with T-scores exceeding - 2.5. This study aimed to evaluate the financial impact and fracture prevention of continuous denosumab therapy until a T-score>-2.0 (Dmab-C strategy), versus discontinuation of denosumab after reaching T-score>-2.5 (Dmab-D strategy) in osteoporosis patients. METHODS: A cost-consequence analysis from a Korean healthcare system perspective was performed using a newly developed Markov model. The incidence of vertebral and non-vertebral fracture, fracture-related deaths, drug costs, and fracture-treatment costs were estimated and compared between Dmab-C and Dmab-D strategy over a lifetime in eligible patients aged 55 years. RESULTS: Base-case analysis revealed that Dmab-C prevented 32.21 vertebral fracture (VF) and 12.43 non-VF events per 100 patients over a lifetime, while reducing 1.29 fracture-related deaths. Lifetime direct healthcare cost saving per patient was KRW 1,354,655 if Dmab-C replaces Dmab-D. When productivity losses were considered, Dmab-C saved KRW 29,025,949 per patient compared to Dmab-D. The additional treatment costs of Dmab-C could be offset by the higher subsequent treatment costs and fracture treatment costs of Dmab-D. The sensitivity analysis showed consistent patterns with results of the base-case analysis. CONCLUSION: Continuous treatment using denosumab until osteoporosis patients achieve and maintain a T-score of -2.0 would provide greater clinical and economic benefits in terms of fracture prevention and reduced mortality risks compared to outcomes from discontinuing treatment at a T-score of -2.5 or above. This new treatment strategy would effectively lower the risk of fractures and fracture-related mortality, ultimately leading to lower medical expenses.

PKM2 is a Novel Osteoporosis-Associated Protein in Chinese.

Purpose:Osteoporosis is characterized by low bone mineral density (BMD) and high risk of osteoporotic fracture (OF). Peripheral blood monocytes (PBM) can differentiate into osteoclasts to resorb bone. This study was to identify PBM-expressed proteins significant for osteoporosis in Chinese Han elderly population (>65 years), and focused on two phenotypes of osteoporosis: low BMD and OF. METHODS: Label-free quantitative proteomics was employed to profile PBM proteome and to identify differentially expressed proteins (DEPs) between OF (N=27) vs. non-fractured (NF, N=24) subjects and between low BMD (N=12) vs. high BMD (N=12) subjects in women. Western blotting (WB) was conducted to validate differential expression, and ELISA to evaluate translational value for secretory protein of interest. RESULTS: We discovered 59 DEPs with fold change (FC)>1.3 (P<1×10-5), and validated the significant up-regulation of pyruvate kinase isozyme 2 (PKM2) with osteoporosis (P<0.001). PKM2 protein upregulation with OF was replicated with PBM in men (P=0.04). Plasma PKM2 protein level was significantly elevated with OF in an independent sample (N=100, FC=1.68, P=0.01). Pursuant functional assays showed that extracellular PKM2 protein supplement not only promoted monocyte trans-endothelial migration, growth, and osteoclast differentiation (marker gene expression), but also inhibited osteoblast growth, differentiation (ALP gene expression), and activity. CONCLUSION: The above findings suggest that PKM2 protein is a novel osteoporosis-associated functional protein in Chinese Han elderly population. It may serve as a risk biomarker and drug target for osteoporosis.