Risk Of Osteoporotic Fractures Research Articles

Type 2 diabetes and bone mineral density: A meta-analysis and systematic review.

Type 2 diabetes (T2D), a widespread chronic metabolic disorder, presents frequently in clinical settings. The relationship between T2D and bone mineral density (BMD) has been subject to ongoing investigation, yielding inconclusive results. A systematic literature search was conducted across several databases, including CNKI, VIP, CBM, Wanfang, PubMed, Cochrane Library, and Embase, targeting observational studies that explored the impact of microangiopathy associated with T2D on BMD or bone metabolism. The search spanned from the inception of each database to July 1, 2023. The Newcastle-Ottawa Scale was employed for quality assessment, and RevMan 5.3 software was utilized for data analysis. Stata 14.0 was used for the quantitative evaluation of publication bias regarding outcome measures. The inclusion criteria were met by 30 observational studies, comprising 6470 participants-3121 with diabetes and 3349 without. The meta-analysis revealed no significant difference in overall BMD between the nondiabetic and T2D groups (mean difference [MD] = -0.07, 95% confidence interval [CI] [-0.17, 0.03], Z = 1.45, P = .15). However, BMD at the lumbar vertebrae was significantly higher in nondiabetic individuals compared with those with T2D (MD = -0.14, 95% CI [-0.22, -0.06], Z = 3.32, P = 0.0009), as was the case with femoral neck BMD (MD = -0.11, 95% CI [-0.18, -0.04], Z = 3.08, P = .002). A difference in femoral neck BMD between nondiabetics and individuals with T2D approached but did not reach statistical significance (MD = -0.14, 95% CI [-0.27, 0.00], Z = 1.94, P = .05). An inverted funnel plot analysis suggested possible publication bias, as evidenced by an asymmetrical distribution of studies around the axis of symmetry, with overlap observed in several cases. The findings indicate a significant association between T2D and reduced BMD at critical sites such as the lumbar vertebrae and femoral neck, highlighting an increased risk of osteoporosis or osteoporotic fractures in these regions.

The impact of novel hormonal agents on fracture risk in prostate cancer patients: a nationwide population-based cohort study

Prostate cancer (PC) treatment, particularly androgen deprivation therapy (ADT), remains pivotal, albeit linked to increased fracture risk due to osteoporosis. The advent of novel hormonal agents (NHAs) has spurred inquiries into their influence on bone health. This study aimed to evaluate the impact of NHAs on bone health in patients receiving combination therapy. We conducted a retrospective analysis using Taiwan’s National Health Insurance Research Database, encompassing men aged 45 and above diagnosed with PC without bone metastasis and undergoing ADT between 2000 and 2018. The study involved 25,949 patients, categorized into those receiving standard ADT (n = 25,166) and those on NHA combination therapy (n = 783). Our analysis delved into fracture risk, comorbidities, and osteoporosis treatments. Patients on NHA combination therapy faced significantly higher risks of any osteoporotic fracture and major osteoporotic fracture than those on ADT alone (HR = 1.29, 95% CI 1.04–1.61; HR = 1.37, 95% CI 1.06–1.75, respectively). Notably, age emerged as a critical factor, with the highest risk observed in those aged 90 or above. The 5-year overall survival rates were lower for patients who experienced any osteoporotic fracture, major osteoporotic fracture, and hospitalization due to osteoporotic fracture compared to those who did not experience these fractures (51.5% vs. 56.5%, 47.1% vs. 56.7%, and 48.2% vs. 56.3%, respectively, p < 0.001). Furthermore, patients not using any bone-modifying agents had the highest risk for all fracture types. In conclusion, NHA combination therapy in PC patients potentially escalates the risk of osteoporotic fractures, especially in older individuals. Our findings underscore the pivotal role of osteoporosis treatments in preventing fractures, emphasizing the importance of evaluating fracture risk in patients undergoing NHA combination therapy.

Ventricular and supraventricular ectopic beats burden is correlated with bone mineral density and osteoporotic fracture risk in postmenopausal females

Abstract Introduction Patients (pts) with osteoporosis (OP) have an increased 10-year cardiovascular death risk. Low bone mineral density (BMD) observed in OP may be associated with arrhythmic presentation of cardiovascular diseases (CVD). Few studies assessed the relationship between OP and arrhythmia. Aim Arrhythmias assessment in pts with OP. Methods A total of 103 postmenopausal female pts (mean age 69 +/- 7), consulted by endocrinologist, were divided into 2 groups according to BMD (assessed by dual energy X-ray absorptiometry). BMD measurements, expressed as T-score (T-sc), were taken from the femoral neck (T-sc Neck), entire total hip (T-sc TH) and/or spine (T-sc L2-L4, L1-L4). Arrhythmia was evaluated using 24-hour Holter-ECG monitoring (HM). Major osteoporotic and total hip fracture risks (MOFR and THFR, respectively) were assessed by the FRAX scale. We compared 51 pts with OP (T-sc ≤ -2.5), with 52 matched controls without OP, including 44 pts with osteopenia (T-sc &amp;gt; -2.5). There were no significant differences between the groups regarding the history of stroke, myocardial infarction, coronary artery disease or arterial hypertension. Exclusion criteria included heart failure NYHA &amp;gt;II and/or LVEF &amp;lt;36%, acute coronary syndrome within the last 6 months, severe valvular disease, cardiac implantable electronic device. Results There was a trend towards a greater number of supraventricular and ventricular arrhythmias in the OP group compared to the controls. Arrhythmic burden was significantly correlated with BMD measures: correlations were observed between 24-hour ventricular ectopic beats (VEB) count with T-sc Neck (r=-0.20, p=0.04), with T-sc TH (r=-0.22, p=0.03). The number of supraventricular ectopic beats (SVEB) in HM was also correlated with BMD parameters: T-sc Neck (r=-0.21, p=0.03), T-sc TH (r=-0.23, p=0.02). Multivariate analysis (linear regression model) revealed that age and T-sc TH were independently related with ectopy: age (0.07; CI: 0.01 - 0.13, p=0.03) and T-sc TH (-0.58; CI: -1.07 - -0.08, p=0.02) were predictors for VEB, and SVEB were related to age (0.07; CI: 0.03 - 0.12, p&amp;lt;0.01) and, with borderline significance with T-sc TH (-0.34; CI: -0.699 - 0.012, p=0.058). Ectopic beats count was also positively correlated with osteoporotic fracture risk: VEB with THFR (r=0.206, p=0.04) and SVEB with MOFR (r=0.21, p=0.04). Conclusions The study showed an increased arrhythmia burden as detected in HM in pts with OP. Beside the T-sc TH, age was identified as an independent factor of increased SVEB / VEB. The main significant negative correlations were observed between the number of VEB / SVEB and BMD in femur (T-sc Neck, T-sc TH). Ectopic beats count was also positively correlated with osteoporotic fracture risk: VEB with THFR and SVEB with MOFR.

Acute hyperlipidemia has transient effects on large-scale bone regeneration in male mice

Excessive dietary fat intake increases plasma lipid levels and has been associated with reduced bone mineral density (BMD) and increased risk of osteoporotic fracture, especially in older postmenopausal women. The objective of this study was to investigate whether there are sex-related differences in lipid metabolism that could have an impact on large-scale bone regeneration. Because ribs provide a unique exception as the only bones capable of completely regenerating large-scale defects, we used a rib resection mouse model in which human features are recapitulated. After 10 days of exposure to a low-fat diet or high-fat diet (HFD), we performed large-scale rib resection surgeries on male and female mice (6–7 weeks old) with deletion of the low-density lipoprotein (LDL) receptor (Ldlr−/−) and age- and sex-matched wild-type (WT) mice were used as controls. Plasma analysis showed that short-term exposure to HFD significantly increases total cholesterol, LDL cholesterol, and triglycerides levels in Ldlr−/− mice but not in WT, with no differences between males and females. However, under HFD, callus bone volume was significantly reduced exclusively in male Ldlr−/− mice when compared to WT, although these differences were no longer apparent by 21 days after resection. Regardless of diet or genotype, BMD of regenerated ribs did not differ significantly between groups, although male mice typically had lower average BMD values. Together, these results suggest that short-term hyperlipidemia has transient effects on large-scale bone regeneration exclusively in male mice.

Increased Risk of Osteoporotic Vertebral Compression Fractures Following Epidural Steroid Injections in Patients with Lumbar Degenerative Disease: A Retrospective Cohort Study.

Background/Objectives: Lumbar degenerative disease is a common age-related condition, with epidural steroid injection (ESI) being a widely employed conservative treatment approach. However, the potential effect of ESI on osteoporosis and fracture risk remains unclear. This study investigated the risk of osteoporotic vertebral compression fractures (OVCFs) in patients with lumbar degenerative disease who underwent ESI treatment. Methods: A cohort of 64 patients who received ESI treatment and a control group of 256 patients were included in this study. Demographic data, clinical characteristics, and follow-up information were collected. Cox proportional hazards models were used to analyze risk factors for OVCF, and subgroup analyses were conducted. Results: OVCF was more common in the ESI group than in the control group (hazard ratio [HR]: 3.49, 95% confidence interval [CI]: 1.06-11.43, p = 0.039). After confounding factors were adjusted for, ESI remained an independent risk factor for OVCF (HR: 4.60, 95% CI: 1.01-20.89, p = 0.048). In a subgroup analysis, lower socioeconomic status was associated with higher OVCF risk (HR: 11.82, 95% CI: 1.06-131.26, p = 0.044). The ESI group had improved short-term pain relief, with nonsignificant long-term effects. Conclusions: Patients with lumbar degenerative disease receiving ESI treatment are at an increased risk of OVCF, particularly those with lower socioeconomic status. These findings underscore the importance of regular bone density monitoring and fracture prevention following ESI treatment. Clinicians should carefully weigh the short-term benefits of ESI against the long-term risks and develop individualized follow-up plans for high-risk patients.

Risk of osteoporotic fractures in menopausal women with common mental health diagnoses prescribed SSRIs/SNRIs: cohort and self-controlled case series analyses

SummaryIn a population-based cohort study of menopausal women with common mental health diagnoses, SSRIs/SNRIs were associated with a 32% increased risk of osteoporotic fractures. The risk of osteoporotic fractures was particularly increased for longer periods of treatment with SSRIs/SNRIs (> 5 years) and in younger menopausal women (< 50 years old).PurposeTo investigate the association between selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) and the risk of osteoporotic fractures (OF) in menopausal women with common mental health diagnoses (CMHD).MethodsWe conducted the study with two designs (cohort and self-controlled case series [SCCS]), using the IQVIA Medical Research Database (IMRD) UK. The source population comprised women aged ≥ 50 years and women with a record indicating menopause (< 50 years). All women had a recorded CMHD. For the cohort analysis, the risk of OFs was estimated by comparing women prescribed SSRIs/SNRIs (exposed) to those not exposed. Cox regression was used to estimate hazard ratios (HR) with 95% confidence intervals (CIs). For the SCCS, women acted as their own controls; periods of exposure to SSRIs/SNRIs were compared to periods of non-exposure using conditional Poisson regression to estimate incidence rate ratios (IRR) with 95% CIs.ResultsWe identified 292,848 women, of whom 35,222 experienced OFs within a median follow-up of 6.01 years. We found strong evidence of an association between SSRIs/SNRIs and the risk of OFs (adjusted HR = 1.32, 95% CI:1.29–1.35). Compared to periods of no exposure, SSRIs/SNRIs increased the risk of OFs during the first 30 days (IRR = 1.38, 95% CI:1.26–1.51), during the first 90 days (IRR = 1.58, 95% CI: 1.48–1.69), and the remaining exposure (IRR = 1.42, 95% CI:1.37–1.48).ConclusionsIn a population of menopausal women with CMHDs, the prescribing of SSRIs/SNRIs antidepressants was associated with a higher risk of OFs. Careful assessment of osteoporosis risk needs to be considered when treating menopausal women with SSRIs/SNRIs antidepressants.

Segmentation methods for quantifying X-ray Computed Tomography based biomarkers to assess hip fracture risk: a systematic literature review.

The success of using bone mineral density and/or FRAX to predict femoral osteoporotic fracture risk is modest since they do not account for mechanical determinants that affect bone fracture risk. Computed Tomography (CT)-based geometric, densitometric, and finite element-derived biomarkers have been developed and used as parameters for assessing fracture risk. However, to quantify these biomarkers, segmentation of CT data is needed. Doing this manually or semi-automatically is labor-intensive, preventing the adoption of these biomarkers into clinical practice. In recent years, fully automated methods for segmenting CT data have started to emerge. Quantifying the accuracy, robustness, reproducibility, and repeatability of these segmentation tools is of major importance for research and the potential translation of CT-based biomarkers into clinical practice. A comprehensive literature search was performed in PubMed up to the end of July 2024. Only segmentation methods that were quantitatively validated on human femurs and/or pelvises and on both clinical and non-clinical CT were included. The accuracy, robustness, reproducibility, and repeatability of these segmentation methods were investigated, reporting quantitatively the metrics used to evaluate these aspects of segmentation. The studies included were evaluated for the risk of, and sources of bias, that may affect the results reported. A total of 54 studies fulfilled the inclusion criteria. The analysis of the included papers showed that automatic segmentation methods led to accurate results, however, there may exist a need to standardize reporting of accuracy across studies. Few works investigated robustness to allow for detailed conclusions on this aspect. Finally, it seems that the bone segmentation field has only addressed the concept of reproducibility and repeatability to a very limited extent, which entails that most of the studies are at high risk of bias. Based on the studies analyzed, some recommendations for future studies are made for advancing the development of a standardized segmentation protocol. Moreover, standardized metrics are proposed to evaluate accuracy, robustness, reproducibility, and repeatability of segmentation methods, to ease comparison between different approaches.

Feasibility study of opportunistic osteoporosis screening on chest CT using a multi-feature fusion DCNN model

SummaryA multi-feature fusion DCNN model for automated evaluation of lumbar vertebrae L1 on chest combined with clinical information and radiomics permits estimation of volumetric bone mineral density for evaluation of osteoporosis.PurposeTo develop a multi-feature deep learning model based on chest CT, combined with clinical information and radiomics to explore the feasibility in screening for osteoporosis based on estimation of volumetric bone mineral density.MethodsThe chest CT images of 1048 health check subjects were retrospectively collected as the master dataset, and the images of 637 subjects obtained from a different CT scanner were used for the external validation cohort. The subjects were divided into three categories according to the quantitative CT (QCT) examination, namely, normal group, osteopenia group, and osteoporosis group. Firstly, a deep learning–based segmentation model was constructed. Then, classification models were established and selected, and then, an optimal model to build bone density value prediction regression model was chosen.ResultsThe DSC value was 0.951 ± 0.030 in the testing dataset and 0.947 ± 0.060 in the external validation cohort. The multi-feature fusion model based on the lumbar 1 vertebra had the best performance in the diagnosis. The area under the curve (AUC) of diagnosing normal, osteopenia, and osteoporosis was 0.992, 0.973, and 0.989. The mean absolute errors (MAEs) of the bone density prediction regression model in the test set and external testing dataset are 8.20 mg/cm3 and 9.23 mg/cm3, respectively, and the root mean square errors (RMSEs) are 10.25 mg/cm3 and 11.91 mg/cm3, respectively. The R-squared values are 0.942 and 0.923, respectively. The Pearson correlation coefficients are 0.972 and 0.965.ConclusionThe multi-feature fusion DCNN model based on only the lumbar 1 vertebrae and clinical variables can perform bone density three-classification diagnosis and estimate volumetric bone mineral density. If confirmed in independent populations, this automated opportunistic chest CT evaluation can help clinical screening of large-sample populations to identify subjects at high risk of osteoporotic fracture.

9342 Managing Osteoporosis In Patients With Phocomelia: Challenges And Strategies

Abstract Disclosure: M. Renzu: None. C. Hubers: None. V. Mehta: None. A.M. Qazi: None. A.M. Satei: None. D.K. Yerasuri: None. Introduction: Phocomelia, a rare congenital limb malformation, often results from disruptions in limb bud formation during embryonic stage, due to genetic mutations, teratogens, or environmental factors like thalidomide embryopathy. These disruptions pose unique challenges in bone health management, including an increased risk of osteoporosis.We present a case report of a 52-year-old patient with phocomelia who developed an early onset severe osteoporosis. This case stresses the need for specific measures and care to tackle bone health in individuals with congenital limb anomalies. Case Presentation: A 52-year-old white female with phocomelia, had absence of the left forearm and hand, as well as a transverse tibial deficiency with a prosthetic left lower leg since the age of 1. Osteoporosis was diagnosed after follow-up, with initial osteopenia noted at age 49. DEXA scan showed lumbar osteopenia, radial osteoporosis, and bilateral femoral neck osteopenia. FRAX score showed an 11.9% risk of osteoporotic fracture and 3.1% risk of a hip fracture.Risk factors to her osteoporosis included late menarche, early menopause due to hysterectomy, and a history of hormone replacement therapy without pregnancies. Also, chronic colitis and diarrhea caused malabsorption issues. Her left hip bone mineral density was disproportionately low due to chronic prosthesis use, necessitating close monitoring and treatment initiation with Denosumab, along with vitamin D3 and calcium supplementation.As of the latest follow-up, the patient is closely monitored, and improvement is noted in her condition. She has incorporated daily gym sessions into her routine, indicating proactive engagement in her well-being. Discussion: Managing osteoporosis in patients with phocomelia needs a personalized approach, considering the patient's unique anatomical challenges and the limitations of traditional osteoporosis management strategies. Bone tissue adapts its structure based on mechanical loading, with reduced loading in deformed limbs leading to increased resorption and elevated osteoporosis risk. Tailored treatment plans, including Denosumab, which is known as an effective pharmacological option for managing osteoporosis, complemented by dietary adjustments to enhance vitamin D and calcium intake. Physical therapy programs play a vital role in muscle strengthening and balance improvement, reducing fracture risk.Another challenge that patients with phocomelia face is barriers to accessing healthcare services, like limited specialized care providers, financial constraints, and transportation difficulties, leading to increased morbidity. Hence early screening and intervention are essential to prevent osteoporotic complications. Overall, a comprehensive approach to osteoporosis management in phocomelia patients is crucial for optimizing outcomes and enhancing quality of life. Presentation: 6/3/2024

8455 Denosumab Is Associated With Decreased Mortality Compared To Zoledronic Acid In Diabetic Osteoporotic Patients: A Population-Based Cohort Study

Abstract Disclosure: V. Rouach: Consulting Fee; Self; Amgen Inc. H. Gortler: None. Y. Greenman: None. C. Gabriel: None. G. inbalL: None. Background: Anti-resorptive therapies are the mainstay of osteoporosis management, but evidence of their efficacy in the diabetic population is limited and comparison between treatments is lacking. A retrospective analysis, presented at the American Society for Bone and Mineral Research (ASBMR) 2023 Annual Meeting, suggests that denosumab leads to greater reduction in fracture risk than zoledronic acid among treatment-naive postmenopausal women with osteoporosis. However, a comparative study recently published suggests higher mortality with denosumab versus oral bisphosphonates. Aim: To assess the association between zoledronic acid or denosumab and the risk of major osteoporotic fracture and mortality in osteoporotic patients with diabetes type 2. Methods: The study population was identified by electronic records of a diabetes registry cross-linked with an osteoporosis registry of a large provider healthcare organization in Israel. Index date was at osteoporosis registry entry. Demographics, Comorbidity Index (CCI), diabetes complications, bone mineral density (BMD) T-scores, hemoglobin A1c levels, eGFR, purchase of statins, and anti-resorptive agents were collected. Propensity score matching was performed. Kaplan-Meier curves were generated to assess the time to outcomes. Multivariable Cox's proportional hazards survival model was performed. Results: A total of 27503 diabetic osteoporotic patients were identified, 13343 (48%) patients initiated treatment; 12214 (91.5%) started an oral bisphosphonate, 627 (4.7%) zoledronic acid and 502 (3.7%) denosumab. The median follow-up was 8.9 years. The denosumab treated patients were older (75.7 vs 71.9, p&amp;lt;0.01), had longer diabetes duration (8.4 vs 7.2, p&amp;lt;0.01), were more frequently treated with insulin (29.7 vs 23.9, p=0.02) and had a lower eGFR (59.4 vs 75.3, p&amp;lt;0.01). Male/Female ratio, BMI, CCI, smoking status, alcohol consumption, Hip BMD, HbA1c levels, microvascular complications, hypoglycemic events and statins prescriptions were similar. After propensity weighting, we observed a significant reduced risk of death among the denosumab treated patients (RR=0.72 [0.58-0.91]) without a significant difference in the risk of fracture (RR=0.9 [0.82-1.12]). Conclusions: In this cohort of diabetic osteoporotic patients, denosumab was associated with a significantly reduced mortality compared to zoledronic acid, without a significant difference in the risk of fractures. The effect of denosumab on mortality is yet to be explored. Presentation: 6/1/2024

9236 Denosumab Is Associated With Decreased Mortality Compared To Zoledronic Acid In Diabetic Osteoporotic Patients: A Population-Based Cohort Study

Abstract Disclosure: V. Rouach: Consulting Fee; Self; Amgen Inc. H. Gortler: None. Y. Greenman: None. C. Gabriel: None. G. inbalL: None. Background: Anti-resorptive therapies are the mainstay of osteoporosis management, but evidence of their efficacy in the diabetic population is limited and comparison between treatments is lacking. A retrospective analysis, presented at the American Society for Bone and Mineral Research (ASBMR) 2023 Annual Meeting, suggests that denosumab leads to greater reduction in fracture risk than zoledronic acid among treatment-naive postmenopausal women with osteoporosis. However, a comparative study recently published suggests higher mortality with denosumab versus oral bisphosphonates. Aim: To assess the association between zoledronic acid or denosumab and the risk of major osteoporotic fracture and mortality in osteoporotic patients with diabetes type 2. Methods: The study population was identified by electronic records of a diabetes registry cross-linked with an osteoporosis registry of a large provider healthcare organization in Israel. Index date was at osteoporosis registry entry. Demographics, Comorbidity Index (CCI), diabetes complications, bone mineral density (BMD) T-scores, hemoglobin A1c levels, eGFR, purchase of statins, and anti-resorptive agents were collected. Propensity score matching was performed. Kaplan-Meier curves were generated to assess the time to outcomes. Multivariable Cox's proportional hazards survival model was performed. Results: A total of 27503 diabetic osteoporotic patients were identified, 13343 (48%) patients initiated treatment; 12214 (91.5%) started an oral bisphosphonate, 627 (4.7%) zoledronic acid and 502 (3.7%) denosumab. The median follow-up was 8.9 years. The denosumab treated patients were older (75.7 vs 71.9, p&amp;lt;0.01), had longer diabetes duration (8.4 vs 7.2, p&amp;lt;0.01), were more frequently treated with insulin (29.7 vs 23.9, p=0.02) and had a lower eGFR (59.4 vs 75.3, p&amp;lt;0.01). Male/Female ratio, BMI, CCI, smoking status, alcohol consumption, Hip BMD, HbA1c levels, microvascular complications, hypoglycemic events and statins prescriptions were similar. After propensity weighting, we observed a significant reduced risk of death among the denosumab treated patients (RR=0.72 [0.58-0.91]) without a significant difference in the risk of fracture (RR=0.9 [0.82-1.12]). Conclusions: In this cohort of diabetic osteoporotic patients, denosumab was associated with a significantly reduced mortality compared to zoledronic acid, without a significant difference in the risk of fractures. The effect of denosumab on mortality is yet to be explored. Presentation: 6/1/2024

7281 Increased Incidence Of Fracture And Predicted Fracture Risk In Patients With Mild Autonomous Cortisol Secretion

Abstract Disclosure: R. Sagar: None. A. Saadulla: None. A. Abbas: None. Background: Mild autonomous cortisol secretion (MACS) is common in patients presenting with adrenal incidentalomas (AI) and has been associated with cardiovascular and metabolic co-morbidities. Whilst there is growing evidence to support the increased risk of cardiometabolic co-morbidity in this cohort, the bone health effects are less well characterised. Our study evaluated the prevalence of fragility fracture and fracture risk in patients with AI and MACS compared with a cohort of patients with benign, non-functional AI. Methods: Retrospective observational data were collected on 391 patients with MACS and an AI along with 626 patients with a benign, non-functional AI. Demographic, biochemical, radiological and bone health data were recorded. FRAX, a validated fracture risk stratifying tool, was used to calculated risk scores for all patients aged between 40 and 90 and risk category according to national guidance were also recorded. Results: MACS cohort (mean age 69±10 and 53% female) had a mean cortisol on overnight dexamethasone suppression test of 76.6±21nmol/l. Benign, non-functional patients had a mean age 61.4±12 and 57% female. Both cohorts had predominantly unilateral lesions (76% in MACS versus 84%). Patients with MACS had a significantly higher prevalence of all fragility fractures, 15.9% compared with 6.7% in the benign, non-functional group, p&amp;lt;0.0001. Patients with MACS had a significantly higher 10-year risk of major osteoporotic fracture (10.6±3.8% versus 7.1±5.4%, p&amp;lt;0.0001) and also hip fracture (7.2±4.1% versus 1.9±2.7%, p&amp;lt;0.0001). 17% of MACS cohort were classed as either high or very high fracture risk, with a further 28% classed as intermediate risk requiring further assessment of bone health compared with 3% high/very high risk in the non-functional group. Despite this only 31% of the MACS group had undergone DEXA scan to assess bone mineral density compared to 13% of the non-MACS group. Only 5% of MACS patients were on osteoporosis treatment (3% in non-MACS cohort). Conclusions: Patients with MACS make up a large proportion of those presenting with adrenal incidentaloma. Our study suggests an increased prevalence of fragility fractures along with increased fracture risk in patients with MACS compared to those with non-functional AI. However, we also demonstrate an unmet need, with less than 1/3 of patients with MACS undergoing formal bone health assessment and just 5% of the total cohort on treatment for osteoporosis despite a significant proportion meeting intervention thresholds. Presentation: 6/1/2024

7740 Adult-Onset Hypophosphatasia Presenting As Low Alkaline Phosphatase Level Following Denosumab Use For Osteoporosis

Abstract Disclosure: J. Ocampo Mascaro: None. P. Wax: None. M. Al Mukaddam: Grant Recipient; Self; Ipsen, Incyte Research Funding. Background: Hypophosphatasia (HPP) is a genetic disease characterized by low activity of the tissue non-specific alkaline phosphatase. It has a broad range of clinical phenotypes, with adults usually presenting with an incidental low alkaline phosphatase (ALP) finding. Differentiating this from other causes of low ALP is challenging, especially when treating osteoporosis, as antiresorptive therapy such as denosumab and bisphosphonates may cause low ALP and carry the potential of increasing risk of atypical femoral fractures in patients with undiagnosed HPP. Clinical Case: A 64-year-old woman with history of nephrolithiasis, hypercalciuria, and osteoporosis (screening DXA lowest T-score -3.3 in femoral neck (FN)) but no prior fractures or dental issues was seen in clinic. Initial bloodwork showed normal range calcium, 25-OH vitamin D, and intact PTH. Pre-treatment ALP was 42 IU/L (N 39-117). Work up for secondary causes of osteoporosis was negative. Three yearly doses of IV zoledronic acid resulted in +4.2% BMD increase in lumbar spine (LS) but no changes in FN. She had no side effects but was found to have a decrease in ALP to 33 IU/L. This normalized back to 42 IU/L during a three-year drug holiday. Follow up DXA noted significant decline in BMD, hence denosumab was initiated. ALP decreased back to the 30-35 IU/L range. Fasting Vitamin B6 level (off B6 supplements for 1 week) was 23.4 ng/ml (N 2.1-21). Urine phosphoethanolamine was mildly elevated at 5 mmol/mol creatinine (N ≤4). Genetic testing evidenced a pathogenic ALPL variant (Exon 6, c.575T&amp;gt;C (p.Met192Thr), heterozygous) compatible with HPP. She had tolerated three doses of denosumab by then with BMD improvement of 5.0% in LS but no changes in FN and no atypical femoral fracture. Denosumab was stopped. Abaloparatide was started for osteoporosis with close monitoring for worsening hypercalciuria. Conclusion: This case demonstrates that adult HPP patients may present with subtle findings and lower range of normal ALP and may tolerate short courses of antiresorptive agents. There is a need for better screening and diagnostic criteria for adult HPP patients whose ALP levels may not be initially low before initiating antiresorptive drugs for osteoporosis. The risk of adverse effects from therapy will likely vary significantly based on the clinical severity/presentation of HPP as some adults with lower ALP ranges might be more susceptible to developing atypical femur fractures (1). Balancing atypical femur fracture risk with the benefits of antiresorptive treatment in decreasing risk of osteoporotic fractures highlights the need for better risk stratification to prevent undertreatment of osteoporosis. Reference: 1. Warren AM, Ebeling PR, Grill V, Seeman E, Sztal-Mazer S. Bilateral atypical femoral fractures during denosumab therapy in a patient with adult-onset hypophosphatasia. Endocrinol Diabetes Metab Case Rep. 2021 Sep 1;2021:21-0096. Presentation: 6/2/2024

Imminent risk of the first and second recurrent osteoporotic fractures in South Korea

BackgroundA history of fractures increases the likelihood of experiencing subsequent and secondary fractures. To prevent further fractures, global guidelines recommend aggressive proactive treatment with medication for patients at an imminent risk of osteoporotic fracture (OF), which is defined as a high likelihood of experiencing subsequent fractures in the near future. However, there is a lack of research focusing on patients with imminent risk of OFs in South Korea. Hence, this study aimed to evaluate the imminent risk of the first and second recurrent OFs among patients with OF in South Korea. MethodsWe conducted a retrospective analysis using the comprehensive Health Insurance Review and Assessment database, which encompasses the entire population of Korea from 2012 to 2017. The study focused on eligible patients aged 55 years and older who experienced an OF in 2013, including fractures in the hip/femur, vertebral, humerus, radius, tibia/fibula, and ankle regions. The first OF occurring in 2013 was considered the index OF. To ensure that the index fracture was the index OFs, we excluded patients who had any OF within 1 year before their index OF. We assessed the incidence of the first recurrent OF within 2 years after the index OF, and the second recurrent OF within 2 years after the occurrence of the first recurrent OF. Additionally, we estimated the risks of experiencing the first and second recurrent OFs according to age and sex using multi-variable Cox proportional hazard regression analysis. ResultsApproximately 17 % of patients with an index OF had the first recurrent OF within 2 years after the index OF. Of those with a first recurrent OF, 28 % experienced a second recurrent OF within 2 years after the first recurrent OF. The two-year incidence rate of the first recurrent OF was 9.6 per 100 person-years (95 % confidence interval [CI], 9.6–9.7). The two-year incidence rate of the second recurrent OF was 22.0 per 100 person-years (95 % CI, 21.6–22.4), which is higher than that of the first recurrent OF. Females had a 31 % higher risk of the first recurrent OF (hazard ratio [HR] = 1.31; 95 % CI, 1.20–1.43) and a 43 % higher risk of the second recurrent OF than males (HR = 1.43; 95 % CI, 1.35–1.51). ConclusionsIn Korea, the imminent risk of a second recurrent OF was higher than that of a first recurrent OF. Consequently, given the elevated risk of subsequent fractures with the number of OFs experienced, a more targeted approach to treatment is recommended for patients with a first recurrent OF considering the risk of subsequent OF.

CAUSES, DIAGNOSTICS AND PSYCHOLOGICAL IMPACT OF PREMATURE OVARIAN INSUFFICIENCY- REVIEW OF LITERATURE

Premature ovarian insufficiency (POI) before the age of 35 occurs in 1 in 250 women. It can develop on a genetic basis, but also may be a consequence of iatrogenic interventions, such as surgery, radiation or chemotherapy. The patients with impaired ovarian endocrine function may experience disruptive menopausal symptoms. Estrogens deficiency consequences include increased risk of osteoporotic fractures and cardiovascular events. Lack of folliculogenesis and ovulation results in infertility. Detailed review of the literature was conducted to summarize current knowledge about causes, diagnostics, psychological impact and novel therapeutic methods in POI. Review of the literature was conducted by searching the PubMed database and Google Scholar. Checking the literature was carried out by the following keywords: ‘premature ovarian insufficiency’, ‘POI’, ‘etiology’, ‘symptomatology’, ‘treatment’, ‘pathogenesis’, ‘genes’, ‘mutations’, ‘psychological effects’, ‘oncofertility’. The multifactorial aetiology of POI, including genetic, autoimmune, iatrogenic, and environmental factors, highlights the complexity of this condition and the need for a multidisciplinary approach to diagnosis and treatment. Progress in molecular methods of genetic diagnostics, such as whole-genome sequencing, may help identify causative mutations in a larger proportion of idiopathic cases. Hormonal replacement therapy is the gold standard for alleviating menopausal symptoms, maintaining bone density, and reducing cardiovascular risk. The psychological impact of POI cannot be underestimated, with many patients experiencing significant emotional distress and dissatisfaction with the manner in which their diagnosis is delivered. Healthcare providers must prioritize sensitive and informative communication, while also referring patients to appropriate sources of emotional support.

Treating Osteoporosis in Patients with Atypical Femoral Fracture.

Patients who have suffered an atypical femoral fracture while on bisphosphonates or denosumab may continue to be at risk for typical osteoporotic fractures. There are no studies to provide guidance on safe treatment for such patients. Instead, using an illustrative case, 5 principles of management are provided that may lead to decreased osteoporotic fracture risk. The first principle is to discontinue the anti-resorptive medications, which may be challenging in the patient on denosumab because of rebound vertebral fractures reported in patients stopping denosumab. The second principle is to maximize non-pharmacologic management to reduce falls and fractures. Home safety, other methods of fall risk reduction, adequate nutrition, and an exercise prescription should help reduce fracture risk. Investigating potential secondary causes of osteoporosis, particularly if the original workup was not comprehensive, is the third principle because treatment of some specific causes may lower fracture risk. Reviewing the medication list is the fourth principle, with the goal of eliminating drugs that may increase fracture risk; and considering thiazides for some patients, which may lower fracture risk. Finally, some patients may benefit from anabolic therapy. One potential (but not FDA-approved) method is to use long-term cyclic teriparatide or abaloparatide on a three-months on, three-months off schedule. Tailoring the approach to each patient is important, based on the five clinical principles, in the absence of evidence-based management recommendations.

The Bone, Exercise, Alendronate, and Caloric Restriction (BEACON) trial design and methods

BackgroundAmong older adults living with obesity, intentional weight loss (WL) improves prognosis of many comorbidities. However, concomitant decline in bone mineral density (BMD) limits overall benefit of WL by increasing osteoporotic fracture risk. Identification of intervention strategies to maximize body fat loss, while minimizing harm to the musculoskeletal system, is an important area of clinical research. The main objective of the Bone, Exercise, Alendronate, and Caloric Restriction (BEACON) trial (NCT05764733) is to compare the independent and combined effects of a 12-month intervention of resistance training (RT) plus bone-loading exercises and bisphosphonate use on dietary WL-associated bone loss among 308 older (≥60 years) adults living with an indication for WL and bisphosphonate use. MethodsAll participants will receive the same group-mediated dietary intervention targeting 8–10 % WL and be randomized to one of four groups: no RT and placebo capsules (NoRT+PL); progressive RT plus bone-loading exercises and placebo capsules (RT++PL); no RT and oral bisphosphonate (70 mg weekly oral alendronate; NoRT+BIS); or progressive RT plus bone-loading exercises and oral bisphosphonate (RT++BIS). Total hip areal (a)BMD measured via dual-energy x-ray absorptiometry (DXA) is the primary, powered study outcome. Secondary skeletal outcome measures include femoral neck and lumbar spine aBMD, high resolution peripheral quantitative computed tomography (HRpQCT) bone assessments of the radius and tibia, and biomarkers of bone turnover. DiscussionBEACON will address an understudied, yet important, clinical research question by studying the independent and combined effects of two scalable intervention strategies aimed at optimizing skeletal integrity in older adults undergoing WL.Clinical Trials Registration: NCT05764733

Insulin resistance, bone health, and fracture risk.

The dramatic increase in obesity and metabolic syndrome (MetS) over the last half-century has led to a worldwide epidemic of type 2 diabetes mellitus (T2DM) as well as in the incidence of insulin resistance (IR). IR is defined as an impaired biological response to insulin stimulation in target tissues and is primarily related to the liver, muscle, and adipose tissue. The most frequent underlying cause is central obesity, and it is known that excess abdominal adipose tissue secretes increased amounts of free fatty acids, which directly affects insulin signalling, reduces glucose uptake in muscle, and triggers excessive triglyceride synthesis and gluconeogenesis in the liver. When pancreatic β cells are unable to secrete the higher levels of insulin needed, T2DM, the main complication of IR, occurs. Although obesity is generally associated with increased bone mass, recent data challenge this view and highlight the multifaceted nature of the obesity-bone relationship. Patients with T2DM are at significant risk for well-known complications of diabetes, including retinopathy, nephropathy, macrovascular disease, and neuropathy, but it is clear that they are also at high risk for fragility fractures. Moreover, recent data provide strong evidence that IR may key role in the increased fracture risk observed in both obesity and T2DM. In this concise review article, the role of IR in increased risk of osteoporotic fractures in MetS, obesity, and T2DM is discussed and summarised, including consideration of the need for fracture risk assessment as a 'preventive measure', especially in patients with T2DM and chronic MetS with abdominal obesity. Personalised and targeted diagnostic and therapeutic approaches to prevent osteoporotic fractures in IR-related diseases are needed and could make significant contributions to health outcomes.

Ukrainian guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis

Introduction. Glucocorticoid-induced osteoporosis (GIOP) is a bone metabolic disease that develops as a result of glucocorticoid (GC) use, is one of the most frequent causes of secondary osteoporosis, leads to an increase in the risk of low-energy fractures, disability and mortality of GC users. Despite the few stu­dies conducted in Ukraine on the epidemiology and treatment of GIOP, there have been no national recommendations for its ma­nagement until now, which has become the background for their creation. The purpose was to develop national guidelines for the diagnosis, prevention, and treatment of GIOP based on the analytical analysis of modern literary sources to improve the awareness of the medical community of Ukraine, improve management, and reduce the socio-economic burden of the disease. Materials and ­methods. A group of 18 experts, leading Ukrainian scientists in various fields, was created to develop the guideline. An analysis of current literary sources on epidemiology, risk factors, diagnosis, prevention and treatment of GIOP, and monitoring of the effectiveness and safety of its treatment was carried out. Evidence was synthesized ­using the GRADE system, and a critical assessment of the quality of the recommendations was carried out using the AGREE II tool. ­Results. The guideline consists of 12 provisions on screening, diagnosis, prevention, and treatment of GIOP. The authors emphasized the need to increase the awareness of the medical community of Ukraine regarding the problem, as well as patients regarding the possible side effects of GC. They presented the features of the clinical assessment of the osteoporotic fracture risk in GC users, as well as modern and available in Ukraine methods of diagnosis and treatment of GIOP. Conclusion. The first Ukrainian guideline for screening, diagnosis, prevention, and treatment of GIOP is an important national tool for its management, which is recommended by the Board of the Ukrainian Association of Osteoporosis for use in practical health care by doctors of various specialties.

Long-Term Bone Density Changes and Fracture Risk in Myasthenia Gravis: Implications for FRAX® Tool Application.

Myasthenia gravis (MG) patients often require long-term glucocorticoid therapy, which may affect bone health. This study aimed to assess long-term changes in bone mineral density (BMD), evaluate osteoporotic fracture incidence, and examine the relationship between MG-specific factors and bone health outcomes over a 10-year period. This single-center, prospective cohort study included 28 MG patients. BMD, T-scores, Z-scores, and bone turnover markers were measured at baseline. FRAX® scores were calculated and adjusted for glucocorticoid dose. Fracture occurrence was monitored for over 10 years. Five (17.9%) patients experienced major osteoporotic fractures during follow-up. The fracture group had significantly lower baseline BMD and T-scores than the no-fracture group. Baseline FRAX® scores for major osteoporotic fracture risk were significantly higher in the fracture group (median 19.0% vs. 5.7%, p = 0.001). The fracture group progressed from osteopenia at baseline to osteoporosis by the end of this study. This study highlights the importance of early and regular bone health assessments in MG patients, particularly those receiving long-term glucocorticoid therapy. The FRAX® tool may be valuable for fracture risk stratification in this population. These findings can inform clinical practice and improve long-term management strategies for MG patients who are at risk of osteoporotic fractures.