High Risk Of Fracture Research Articles

Fracture risk prediction in postmenopausal women from GO Study: the comparison between FRAX, Garvan, and POL-RISK algorithms.

The aim of the longitudinal, retrospective study was to compare three tools designed to assess fracture risk: FRAX, Garvan, and POL-RISK in their prediction of fracture incidence. The study group consisted of 457 postmenopausal women with a mean age of 64.21 ± 5.94years from the Gliwice Osteoporosis (GO) Study. Comprehensive data on clinical factors related to fractures were collected for all participants. Bone densitometry was performed at the proximal femur using the Prodigy device (GE, USA). Fracture risk was established using the FRAX, Garvan, and POL-RISK algorithms. Data on the incidence of osteoporotic fractures were collected over the last 10years. During the period of observation 72, osteoporotic fractures occurred in 63 subjects. For a preliminary comparison of the predictive value of analyzed diagnostic tools, the fracture risk threshold of 10% was used. For FRAX, the fracture probability exceeding 10% was observed only in 11 subjects who experienced fractures; thus, the fracture was properly predicted only in 22.9% of women. For Garvan, the respective value was 90.5%, and for POL-RISK, it was 98.4%. That gave a very low true positive value for FRAX and a very high false positive value for Garvan and POL-RISK. Based on ROC curves, new thresholds for high risk of fractures were established for each calculator separately: 6.3% for FRAX major fracture, 20.0% for Garvan any fracture, and 18.0% for POL-RISK any fracture. Such thresholds improve the diagnostic accuracy of all compared fracture prediction tools. The current study showed that different fracture risk assessment tools, although having similar clinical purposes, require different cut-off thresholds for making therapeutic decisions. Better identification of patients requiring therapy based on such an approach may help reduce the number of new fractures.

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.

Diagnosis and treatment of osteoporosis: a paradigm shift

The main clinical manifestation of osteoporosis is a low-energy fracture. Fracture is associated with a high risk of disability and mortality. Therefore, the aim of osteoporosis treatment is to reduce the risk of fractures. Therefore, experts from the UK in 2019 developed and put into practice a fracture risk stratification system, on the basis of which a decision is made on the treatment of patients with osteoporosis. So patients with a very high risk of fractures need to prescribe anabolic therapy, followed by the appointment of antiresorptive drugs. Patients at high risk – the appointment of antiresorptive therapy, and if it is ineffective, the appointment of anabolic therapy. Patients with low and intermediate risk are recommended dynamic monitoring with constant reassessment of the risk of fractures. This conclusion completely changes the existing paradigm of osteoporosis treatment.

Chinese expert consensus on treatment of osteoporotic fractures with teriparatide (2024 edition)

Osteoporotic fracture is the most serious complication of osteoporosis, which is a special type of pathologic fracture of the skeleton that occurs because of osteoporosis. It is characterized by delayed fracture healing, high risk of re-fracture, high rate of disability and death, difficulty in treatment and long treatment time, and re-fracture has a"cascade effect". Guidelines in different countries recommend that patients with osteoporotic fractures and those at very high risk of fracture should consider anabolic agents as first treatment choice. Teriparatide is the only anabolic agent approved by National Medical Products Administration (NMPA), and it has the clinical efficacy of improving fracture healing, reducing the risk of re-fracture, and improving bone microstructure in the treatment of osteoporotic fracture. Due to deficiencies in the current standardization of clinical use of teriparatide, Committee of Accelerated Rehabilitation After Osteoporotic Fractures of China Association of Rehabilitation Technology Transformation and Promotion, Bone and Joint Group of Chinese Society of Osteoporosis and Bone Mineral Research and Osteoporosis Working Committee of Chinese Association of Orthopedic Surgeons developed this consensus. The development of this consensus follows the modified Delphi method and forms 8 evidence-based medical recommendations, aiming to propose methods and precautions for standardizing the application of teriparatide, and to emphasize the importance of teriparatide application for the treatment of patients with osteoporotic fracture.

Corticosteroid Injections and Risk of Fracture

Corticosteroid injections (CSIs) are an important tool for pain relief in many musculoskeletal conditions, but the longitudinal effects of these treatments on bone health and fracture risk are unknown. To determine whether cumulative doses of corticosteroid injections are associated with higher risk of subsequent osteoporotic and nonosteoporotic fractures. This cohort study included adult patients receiving any CSI from May 1, 2018, through July 1, 2022. Eligible patients resided in Olmsted County, Minnesota, and were empaneled to receive primary care within the Mayo Clinic. Cox proportional hazards regression models were used to evaluate risk of fracture based on cumulative injected corticosteroid dose. Receipt of any CSI during the study period. The primary outcome was risk of fracture by total triamcinolone equivalents received. Secondary outcomes consisted of risks of fracture based on triamcinolone equivalents received in subgroups of patients not at high risk for fracture and patients with osteoporosis. A total of 7197 patients were included in the study (mean [SD] age, 64.4 [14.6] years; 4435 [61.6%] women; 183 [2.5%] Black and 6667 [92.6%] White), and 346 (4.8%) had a new fracture during the study period. Of these fractures, 149 (43.1%) were considered osteoporotic. In the adjusted Cox proportional hazards regression model, there was no association of higher fracture risk based on cumulative CSI dose (adjusted hazard ratio [HR], 1.04 [95% CI, 0.96-1.11]). There was also no associated higher risk of fracture in the non-high-risk (adjusted HR, 1.11 [95% CI, 0.98-1.26]) or osteoporosis (adjusted HR, 1.01 [95% CI, 0.90-1.11]) subgroups. Age, Charleson Comorbidity Index, and previous fracture were the only factors that were associated with higher fracture risk. In this cohort study of cumulative injected corticosteroid dose and risk of subsequent fracture, no association was observed, including in patients with a preexisting diagnosis of osteoporosis. Treatment of painful conditions with CSI should not be withheld or delayed owing to concern about fracture risk.

Shared genetic architecture highlights the bidirectional association between major depressive disorder and fracture risk

BackgroundThere is limited evidence suggesting that osteoporosis might exacerbate depressive symptoms, while more studies demonstrate that depression negatively affects bone density and increases fracture risk.AimsTo explore the relationship between major...

The comprehensive incidence and risk factors of fracture in kidney transplant recipients: A meta-analysis.

Kidney transplant recipients are at high risk of fracture due to many factors such as nutritional status, hyperparathyroidism, acidosis and steroid administration. The current meta-analysis aimed to comprehensively analyse the incidence and risk factors of fracture in kidney transplant recipients. A systematic search on Embase, Web of Science, PubMed and Cochrane Library until November 2023 was performed. RStudio software was used to analyse data. Twenty-eight eligible studies containing 310 530 kidney transplant recipients were included in the analysis. The pooled incidence of fracture was 10% (95% confidence interval [CI]: 7%-13%) generally. When divided by regions, it was further observed that the pooled incidence of fracture was 13% (95% CI: 9%-17%) in Europe, 11% (95% CI: 6%-16%) in North America, 7% (95% CI: 3%-11%) in Asia. Regarding the risk factors, pooled analysis revealed that age of recipient (hazard ratio [HR] = 1.50, 95% CI: 1.17-1.91), female sex (HR = 1.45, 95% CI: 1.36-1.53), pretransplantation diabetes (HR = 1.76, 95% CI: 1.58-1.97), pretransplantation fracture history (HR = 2.28, 95% CI: 1.86-2.78), dialysis duration (HR = 1.09, 95% CI: 1.01-1.17) and deceased donor (HR = 1.21, 95% CI: 1.05-1.39) related to higher risk of fracture. The general quality of included studies was acceptable, and no publication bias existed except for the analysis between age of recipient and fracture incidence; further trim and fill method indicated age of recipient showed a correlation trend with the fracture incidence without the statistical significance. The pooled incidence of fracture reaches 10% in kidney transplant recipients, which relates to age of recipient, female sex, pretransplantation diabetes or fracture history, dialysis duration and decease donor.

The role of LncRNAs and CircRNAs in osteoporosis: a focus on osteogenesis and osteoclastogenesis signaling pathways

Abstract Background Osteoporosis is a crucial health concern interconnected with physical disabilities as well as financial burdens. It arises from an imbalance between osteoblasts and osteoclasts, provoking the reduction of bone mass and the disturbances in bone structure with high fracture risk. Considerable efforts were done to prevent and mitigate this public health issue. Nonetheless, further understanding of the etiopathology of osteoporosis and the underlying genetic and epigenetic pathways is required. Main body Emerging evidence indicates that noncoding RNAs, including long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), play crucial roles as epigenetic regulators in various pathological processes, including osteoporosis. LncRNAs are RNA transcripts with higher structural complexity that are developed owing to their secondary and tertiary structures, which allow them to create different binding sites for other biomolecules, such as DNA, RNA, and proteins. Another class of noncoding RNAs is circRNAs, which have a covalently closed loop structure without the 5′ cap and 3′ polyA tail and are formed by back-splicing of pre-mRNAs. Because of their closed structure, circRNAs are largely stable, resistant to RNA-degrading nucleases, and possess substantially longer circulatory half-lives than linear RNAs. Interestingly, both lncRNAs and circRNAs serve as competing endogenous RNAs by sponging multiple miRNA binding sites as well as interact with RNA-binding proteins (RBPs), thereby controlling the expression of their target genes. Several studies indicated that altered expression of these regulators could influence many biological processes in bone cells. Conclusion The current review provides current opinions on the role and the underlying mechanisms by which lncRNAs and circRNAs affect osteoblastic and osteoclastic activities. The deep understanding of these noncoding RNAs in osteoporosis offers distinctive avenues for innovative treatment strategies.

Effectiveness and Satisfaction with Telemedicine in Geriatric Patients at High Risk of Fragility Fractures.

Background: Telemedicine has increasingly widespread to improve the monitoring of patients with chronic diseases. Secondary prevention of fragility fractures is an urgent matter to be addressed by means of available technology, although supported by little evidence so far. We investigated the feasibility, efficacy, and satisfaction of managing older adults at high risk of fragility fractures during the COVID-19 lockdown. Methods: During the period January to July 2021, a prospective observational study for safety and adherence purposes was conducted among older adults (n = 407) with ongoing treatments for secondary prevention of fragility fractures. The study procedures comply with national and regional resolutions related to telemedicine service (TS), including equipment, staff behaviors, and patient reports. Results: A majority (86.48% [n = 352]) of the eligible patients joined the remote visits, mainly women (88.2%), 81.4 ± 8.8 years of age, 49.6% independent in 5 out of 6 BADL, despite high comorbidity (4.9 ± 1.5), and polypharmacy (4.9 ± 3.1). Almost all were on second-line antifracture treatments (95.58%) due to previous major (84.03%) and minor (42.5%) fragility fractures. About 58% reported good and very good reliability of the internet network, allowing easy access to the TS platform, and 54% declared the degree of satisfaction with TS as good and very good. About 75% of clinicians acknowledged the efficacy of TS and expressed willingness to recommend the use of TS to colleagues. Ultimately, 68% of specialists defined the time allocated for patients' remote visits as acceptable. Conclusion: TS may be an opportunity to improve the availability of appropriate health care services to satisfy patients' needs and optimize health care resource allocation.

P076 Exploring the correlation between body mass index and fracture risk in men

Abstract Background/Aims There has been an increase in interest in identifying patients with high risk of fracture, due to the high mortality. In De Laet et al. (2005) meta-analysis on 60000 women and men, which analysed the effect of body mass index (BMI), bone mineral density (BMD), age and gender on risk of any fracture; low BMI is linked to significantly higher fracture risk (two-fold at BMI of 20) when compared with a BMI 25. On the same comparison, high BMI (30) reduced risk of fractures by 17% (RR 0.83). This was significant in women, but not in men. No newer large-scale study focused on the correlation between BMI and fracture risks in men. Therefore, we set out to investigate the relationship between BMI and different fractures in male patients. Methods 5388 male patients referred for DEXA scan in the North West of England between 2004 and 2019 were included in the analysis. Logistic regression is performed for age, BMI, and BMD using R-4.3.1 for Windows. Results Prior to adjusting for BMD, low BMI is a significant risk factor for femur fracture. On the other hand, low BMI is a protective factor against tibia-fibula fractures. There was no significant correlation detected in spine, rib, humerus, forearm and elbow fractures. After adjusting for BMD, higher BMI is associated with significantly higher odds of humerus, tibia-fibula and wrist fractures, but no statistically significant association with spine, ribs and femur fractures. Conclusion Our results show the correlation between BMI, adjusted for BMD, and different fracture site. Our findings corroborated with previous literature, suggesting that BMI is likely a risk factor that is dependent on BMD. Furthermore, we highlighted that higher BMI is a protective factor for some fractures whilst being a risk factor for others. It is unclear whether the difference between the fracture types are due to the mechanism of fracture or the difference in disease progression at the different fracture sites - this is a potential area for future research. Disclosure M.H. Nguyen: None. M. Bukhari: None.

Treatment patterns in women with postmenopausal osteoporosis using abaloparatide: a real-world observational study

SummaryReview of medical records from 173 women with osteoporosis who received abaloparatide treatment revealed that 96.0% had at least one visit for osteoporosis management and 55.5% had medication support group access. The most common reasons for discontinuing treatment were financial (31.2%) and tolerability (22.8%). Most patients (64.8%) completed treatment as prescribed.PurposeAbaloparatide is approved for the treatment of women with postmenopausal osteoporosis at high risk for fracture. This study evaluated real-world treatment patterns for patients new to abaloparatide, regardless of osteoporosis treatment history.MethodsData for patients with ≥ 1 prescription for abaloparatide were collected retrospectively from six academic and clinical practice settings across the US.ResultsA total of 173 patients were enrolled (mean [SD] age, 69.8 [7.4] years). At the time of abaloparatide treatment initiation, 78.6% had received other osteoporosis medications. Mean (SD) time from discontinuation of osteoporosis medications prior to initiation of abaloparatide was 1.7 (3.2) years. Twenty-four months of follow-up data from the initiation date of abaloparatide was collected from 94.0% of patients and 6.0% of patients had 12–24 months of follow-up. During the follow-up period, 96.0% of patients had at least one visit for osteoporosis management and 55.5% had access to a medication support program. The median duration of therapy was 18.6 months and 105/162 (64.8%) completed abaloparatide treatment as prescribed. The most common reasons for treatment discontinuation were financial (31.2%) and tolerability (22.8%). Following completion of a course of treatment with abaloparatide, 82/162 (50.6%) patients transitioned to another osteoporosis medication. The median time between abaloparatide treatment course completion and the initiation of follow-on medication was 21 days.ConclusionMost patients completed treatment with abaloparatide as prescribed, and over half continued with an antiresorptive agent. This favorable conduct may be the result of regular follow-up visits and accessibility to both medication and patient support services.

Tuberculosis and osteoporotic fracture risk: development of individualized fracture risk estimation prediction model using a nationwide cohort study.

Tuberculosis (TB) is linked to sustained inflammation even after treatment, and fracture risk is higher in TB survivors than in the general population. However, no individualized fracture risk prediction model exists for TB survivors. We aimed to estimate fracture risk, identify fracture-related factors, and develop an individualized risk prediction model for TB survivors. TB survivors (n = 44,453) between 2010 and 2017 and 1:1 age- and sex-matched controls were enrolled. One year after TB diagnosis, the participants were followed-up until the date of fracture, death, or end of the study period (December 2018). Cox proportional hazard regression analyses were performed to compare the fracture risk between TB survivors and controls and to identify fracture-related factors among TB survivors. During median 3.4 (interquartile range, 1.6-5.3) follow-up years, the incident fracture rate was significantly higher in TB survivors than in the matched controls (19.3 vs. 14.6 per 1,000 person-years, p < 0.001). Even after adjusting for potential confounders, TB survivors had a higher risk for all fractures (adjusted hazard ratio 1.27 [95% confidence interval 1.20-1.34]), including hip (1.65 [1.39-1.96]) and vertebral (1.35 [1.25-1.46]) fractures, than matched controls. Fracture-related factors included pulmonary TB, female sex, older age, heavy alcohol consumption, reduced exercise, and a higher Charlson Comorbidity Index (p < 0.05). The individualized fracture risk model showed good discrimination (concordance statistic = 0.678). TB survivors have a higher fracture risk than matched controls. An individualized prediction model may help prevent fractures in TB survivors, especially in high-risk groups.

Acute Total Hip Arthroplasty Following Acetabular Fracture is Associated With a High Risk of Revision, Dislocation, and Periprosthetic Fracture

BackgroundThe aim of this study was to compare outcomes between acute, subacute, and delayed arthroplasty for acetabular fractures occurring within 1 week, from 1 week to 6 months, or more than 6 months before the index total hip arthroplasty (THA), versus THA without a history of acetabular fracture as a control. MethodsWe analyzed the records of patients undergoing primary THA who were enrolled in a national database for at least 2 years before and after the index procedure. Patients who had an initial diagnostic code for acetabular fracture occurring less than 1 week, from 1 week to 6 months, or at least more than 6 months before the THA were classified as acute THA (aTHA), subacute THA (saTHA), or delayed THA (dTHA), respectively. The control group was patients undergoing THA who did not have a history of acetabular fracture. There were 430,349 control primary THAs, 462 aTHAs, 675 saTHAs, and 1,162 dTHAs. ResultsAfter adjusting for age, sex, region, and comorbidities, patients who had an aTHA and saTHA experienced statistically significant increased odds of revision, dislocation, and periprosthetic fracture compared to primary THA without a history of acetabular fracture. Similarly, dTHA was associated with increased odds of revision, dislocation, and periprosthetic fractures compared to primary THA. In the multivariate analysis, aTHA had statistically significant higher rates of dislocation when compared to dTHA. ConclusionsPatients who had a history of acetabular fractures undergoing aTHA, saTHA, or dTHA have significantly increased rates of revision, periprosthetic fracture, and dislocation compared to primary THA in those who did not have a history of acetabular fractures.

Facile fabrication of phosphazene-quercetin-alendronate composites as pH-responsive bone-targeted nanomedicine for osteoporosis treatment

Osteoporosis, closely related to age, is characterized by impaired bone mass and bone strength, damage of bone microstructure, resulting in a higher risk of fractures with minimal trauma, especially in the hip and spine. Quercetin (Que), a natural compound, has previously demonstrated its potential anti-osteoporosis effects via promoting bone formation and anti-bone resorption. However, Que is poor water solubility, lack of bone targeting, and requires high concentration to exert its therapeutic effects. In this work, a pH-responsive and bone-targeted nanomedicine HCCP-Que-PEG-ALN (HQPA) was developed via using hexachlorocyclotriphosphazene(HCCP) as the cross-linkage, Que, alendronate (ALN), and amino-polyethylene glycol (NH2-PEG) as other building blocks. We demonstrated that HQPA can form spherical nanoparticles in aqueous solution with average size of 158.3 ± 59.8 nm with high drug loading capacity of Que (31.4 w/w%) and obvious bone-targeting capability. in vitro experimental results indicated that HQPA NPs have dual anti-osteoporosis effects of promoting osteoblasts and inhibiting osteoclasts. Furthermore, HQPA NPs can effectively reduce the bone loss in OVX mice with low toxicity to major organs. We believe that this method should be a general and useful route for fabrication of bone-targeted natural-compounds-based nanomedicines for treatment different bone-related diseases.

Review of recommendations for bisphosphonate treatment interruption-discontinuation

Bisphosphonates are the main medications in the treatment of osteoporosis, which are effective in reducing the risk of fractures in patients with osteoporosis. It is known that after treatment with bisphosphonates, bone mineral density remains quite stable for a certain time, as well as markers of bone metabolism remain reduced, which, along with the side effects of long-term bisphosphonate therapy, determines the possibility of “Drug holidays”. At the same time, during a break in bisphosphonate treatment, the risk of fractures begins to increase, which is a reason to resume therapy.Currently, there is no uniform worldwide data of starting a “drug holidays” on bisphosphonates. The duration of the “drug holidays” also differs in clinical recommendations from different countries. When to conduct a risk assessment of fractures during a “drug holidays”? To answer these questions, we assessed existing clinical recommendations for treatment interruption/discontinuation of bisphosphonates. A literature search was conducted using the following resources: PubMed®, the Cochrane Library, websites of major international osteoporosis associations, and other targeted Internet searches. The main search terms were “Clinical Guideline of Osteoporosis”, “Bisphosphonates”, “Drug holidays in osteoporosis”, “Discontinuation of bisphosphonates”. Тhe search was carried out using articles in Russian and English published between January 1, 2016 and September 15, 2023. 17 clinical guidelines from different countries (Russian, American, European, Asian and Australian) were found and analyzed in which was information about the break in the treatment and withdrawal of bisphosphonates.The majority of clinical recommendations have the same opinion on the issue of starting “drug holidays”: with a moderate risk of fractures, you can take a break from treatment with tableted bisphosphonates after 5 years, after zoledronic acid — after 3 years of therapy. At high and very high risk of fractures, the duration of treatment is 10 and 6 years, respectively. The duration of “drug holidays” vary in the recommendations, but in most cases the decision-making is based not on the duration, but on the assessment of the risk of fractures with their regular reassessment, which includes previous and new low-energy fractures, the emergence of new risk factors, a decrease in BMD, the dynamics of bone markers, re-evalua­tion of FRAX®.

Fractured cervical spine, dissected vertebral artery, and life-threatening stroke: A challenging case report and literature review

IntroductionVertebral artery injury (VAI) following blunt trauma can lead to acute or delayed life-threatening posterior fossa ischemic stroke. Its management raises controversial issues and is still open to debate. Material & methodWe report the case of a 48-year-old male who presented a life-threatening posterior circulation ischemic stroke, secondary to a vertebral artery dissection caused by a cervical spine fracture. This case was successfully managed through intravenous thrombolysis and endovascular thrombectomy followed by antiplatelet therapy and an anterior cervical discectomy and fusion. At the one-year follow-up, the patient had no persisting deficit and was back working as a policeman. ConclusionRapid management of patients with dramatic clinical presentation can lead to full recovery. Implications include a systematic screening of blunt trauma VAI through computed tomography angiography when dealing with high-risk cervical spine fractures; patients harboring both a cervical spine fracture and a VAI must be transferred to a tertiary referral hospital able to deal both with strokes and cervical spine surgery to ensure responsiveness in case of stroke.

An emergency department-based system intervention to improve osteoporosis screening for older adults at high-risk of fracture

Abstract Falls and osteoporosis are risk factors for fragility fractures. Bone mineral density (BMD) assessment is associated with better preventative osteoporosis care, but it is underutilized by those at high fracture risk. We created a novel electronic medical record (EMR) alert-driven protocol to screen patients in the emergency department (ED) for fracture risk and tested its feasibility and effectiveness in generating and completing referrals for outpatient BMD testing after discharge. The EMR alert was configured in two tertiary-care EDs and triggered by the term “fall” in the chief complaint, age (≥65 years for women, ≥70 years for men), and high fall risk (Morse score ≥ 45). The alert electronically notified ED study staff of potentially eligible patients. Participants received osteoporosis screening education and had BMD testing ordered. From November 15, 2020 to December 4, 2021, there were 2608 EMR alerts among 2509 patients. We identified 558 patients at high-risk of fracture who were screened for BMD testing referral. Participants were excluded for: serious illness (N = 141), no documented health insurance to cover BMD testing (N = 97), prior BMD testing/recent osteoporosis care (N = 58), research assistant unavailable to enroll (N = 53), concomitant fracture (N = 43), bedridden status (N = 38), chief complaint of fall documented in error (N = 38), long-term care residence (N = 34), participation refusal (N = 32), or hospitalization (N = 3). Of the 16 participants who had BMD testing ordered, 7 scheduled and 5 completed BMD testing. EMR alerts can help identify subpopulations who may benefit from osteoporosis screening, but there are significant barriers to identifying eligible and willing patients for screening in the ED. In our study targeting an innovative venue for osteoporosis care delivery, only about 1% of patients at high-risk of fracture scheduled BMD testing after an ED visit. Adequate resources during and after an ED visit are needed to ensure that older adults participate in preventative osteoporosis care.

Bone canonical Wnt signaling is downregulated in type 2 diabetes and associates with higher advanced glycation end-products (AGEs) content and reduced bone strength.

Type 2 diabetes (T2D) is associated with higher fracture risk, despite normal or high bone mineral density. We reported that bone formation genes (SOST and RUNX2) and advanced glycation end-products (AGEs) were impaired in T2D. We investigated Wnt signaling regulation and its association with AGEs accumulation and bone strength in T2D from bone tissue of 15 T2D and 21 non-diabetic postmenopausal women undergoing hip arthroplasty. Bone histomorphometry revealed a trend of low mineralized volume in T2D (T2D 0.249% [0.156-0.366]) vs non-diabetic subjects 0.352% [0.269-0.454]; p=0.053, as well as reduced bone strength (T2D 21.60 MPa [13.46-30.10] vs non-diabetic subjects 76.24 MPa [26.81-132.9]; p=0.002). We also showed that gene expression of Wnt agonists LEF-1 (p=0.0136) and WNT10B (p=0.0302) were lower in T2D. Conversely, gene expression of WNT5A (p=0.0232), SOST (p<0.0001), and GSK3B (p=0.0456) were higher, while collagen (COL1A1) was lower in T2D (p=0.0482). AGEs content was associated with SOST and WNT5A (r=0.9231, p<0.0001; r=0.6751, p=0.0322), but inversely correlated with LEF-1 and COL1A1 (r=-0.7500, p=0.0255; r=-0.9762, p=0.0004). SOST was associated with glycemic control and disease duration (r=0.4846, p=0.0043; r=0.7107, p=0.00174), whereas WNT5A and GSK3B were only correlated with glycemic control (r=0.5589, p=0.0037; r=0.4901, p=0.0051). Finally, Young's modulus was negatively correlated with SOST (r=-0.5675, p=0.0011), AXIN2 (r=-0.5523, p=0.0042), and SFRP5 (r=-0.4442, p=0.0437), while positively correlated with LEF-1 (r=0.4116, p=0.0295) and WNT10B (r=0.6697, p=0.0001). These findings suggest that Wnt signaling and AGEs could be the main determinants of bone fragility in T2D.

Bone canonical Wnt signaling is downregulated in type 2 diabetes and associates with higher advanced glycation end-products (AGEs) content and reduced bone strength

Type 2 diabetes (T2D) is associated with higher fracture risk, despite normal or high bone mineral density. We reported that bone formation genes (SOST and RUNX2) and advanced glycation end-products (AGEs) were impaired in T2D. We investigated Wnt signaling regulation and its association with AGEs accumulation and bone strength in T2D from bone tissue of 15 T2D and 21 non-diabetic postmenopausal women undergoing hip arthroplasty. Bone histomorphometry revealed a trend of low mineralized volume in T2D (T2D 0.249% [0.156–0.366]) vs non-diabetic subjects 0.352% [0.269–0.454]; p=0.053, as well as reduced bone strength (T2D 21.60 MPa [13.46–30.10] vs non-diabetic subjects 76.24 MPa [26.81–132.9]; p=0.002). We also showed that gene expression of Wnt agonists LEF-1 (p=0.0136) and WNT10B (p=0.0302) were lower in T2D. Conversely, gene expression of WNT5A (p=0.0232), SOST (p&lt;0.0001), and GSK3B (p=0.0456) were higher, while collagen (COL1A1) was lower in T2D (p=0.0482). AGEs content was associated with SOST and WNT5A (r=0.9231, p&lt;0.0001; r=0.6751, p=0.0322), but inversely correlated with LEF-1 and COL1A1 (r=–0.7500, p=0.0255; r=–0.9762, p=0.0004). SOST was associated with glycemic control and disease duration (r=0.4846, p=0.0043; r=0.7107, p=0.00174), whereas WNT5A and GSK3B were only correlated with glycemic control (r=0.5589, p=0.0037; r=0.4901, p=0.0051). Finally, Young’s modulus was negatively correlated with SOST (r=−0.5675, p=0.0011), AXIN2 (r=−0.5523, p=0.0042), and SFRP5 (r=−0.4442, p=0.0437), while positively correlated with LEF-1 (r=0.4116, p=0.0295) and WNT10B (r=0.6697, p=0.0001). These findings suggest that Wnt signaling and AGEs could be the main determinants of bone fragility in T2D.

Deciphering the complex relationship between type 2 diabetes and fracture risk with both genetic and observational evidence.

The 'diabetic bone paradox' suggested that type 2 diabetes (T2D) patients would have higher areal bone mineral density (BMD) but higher fracture risk than individuals without T2D. In this study, we found that the genetically predicted T2D was associated with higher BMD and lower risk of fracture in both weighted genetic risk score (wGRS) and two-sample Mendelian randomization (MR) analyses. We also identified ten genomic loci shared between T2D and fracture, with the top signal at SNP rs4580892 in the intron of gene RSPO3. And the higher expression in adipose subcutaneous and higher protein level in plasma of RSPO3 were associated with increased risk of T2D, but decreased risk of fracture. In the prospective study, T2D was observed to be associated with higher risk of fracture, but BMI mediated 30.2% of the protective effect. However, when stratified by the T2D-related risk factors for fracture, we observed that the effect of T2D on the risk of fracture decreased when the number of T2D-related risk factors decreased, and the association became non-significant if the T2D patients carried none of the risk factors. In conclusion, the genetically determined T2D might not be associated with higher risk of fracture. And the shared genetic architecture between T2D and fracture suggested a top signal around RSPO3 gene. The observed effect size of T2D on fracture risk decreased if the T2D-related risk factors could be eliminated. Therefore, it is important to manage the complications of T2D to prevent the risk of fracture.