Risk Factors For Osteoporosis Research Articles

OSTEO18, a novel urinary proteomic signature, associated with osteoporosis in heart transplant recipients

Abstract Background Immunosuppressive treatment in heart transplant (HTx) recipient causes osteoporosis. The urinary proteomic profile (UPP) includes peptide fragments derived from the bone extracellular matrix. Purpose Study aims were to develop and validate a multidimensional UPP biomarker for osteoporosis in HTx patients from single sequenced urinary peptides identifying the parent proteins. Methods A single-center HTx cohort was analyzed. Urine samples were measured by capillary electrophoresis coupled with mass spectrometry. Cases with osteoporosis and matching controls were randomly selected from all available 389 patients. In derivation case-control dataset, 1576 sequenced peptides detectable in ≥30% of patients. Applying statistical analysis on these, an 18-peptide multidimensional osteoporosis UPP biomarker (OSTEO18) was generated by support vector modeling. The 2 replication datasets included 118 and 94 patients. For further validation, the whole cohort was analyzed. Statistical methods included logistic regression and receiver operating characteristic curve (ROC) analysis. Results In derivation dataset, the AUC, sensitivity and specificity of OSTEO18 were 0.83 (95% CI: 0.76-0.90), 74.3% and 87.1%, respectively. In replication datasets, results were confirmatory. In the whole cohort (154 osteoporotic patients [39.6%]), the ORs for osteoporosis increased (p < 0.0001) across OSTEO18 quartiles from 0.39 (95% CI: 0.25-0.61) to 3.14 (2.08-4.75). With full adjustment for known osteoporosis risk factors, OSTEO18 improved AUC from 0.708 to 0.786 (p = 0.0003) for OSTEO18 categorized (optimized threshold: 0.095) and to 0.784 (p = 0.0004) for OSTEO18 as continuously distributed classifier. Conclusion OSTEO18 is a clinically meaningful novel biomarker indicative of osteoporosis in HTx recipients and is being certified as in-vitro diagnostic.

Low geriatric nutritional risk index is associated with osteoporosis and fracture risk in patients with chronic liver disease: a cross-sectional study

BackgroundPatients with chronic liver disease (CLD) frequently suffer from malnutrition and bone diseases, both of which heighten the risk of poor clinical outcomes. This study investigated the relationship between geriatric nutritional risk index (GNRI) and osteoporosis or fracture risk using the fracture risk assessment tool (FRAX) in patients with CLD.MethodsThis cross-sectional study included 209 consecutive patients with CLD. The participants were divided into two groups: the all-risk group (GNRI ≤ 98.0) with nutrition-related risk and the no-risk group (GNRI > 98.0) without nutrition-related risk. Osteoporosis was diagnosed according to the World Health Organization criteria. The FRAX was used to estimate the 10-year probabilities of hip fracture (FRAX-HF) and major osteoporotic fracture (FRAX-MOF).ResultsOf the 209 patients, 72 (34.4%) had osteoporosis. The all-risk group had a significantly higher prevalence of osteoporosis than the no-risk group (p < 0.001). Conversely, patients with osteoporosis had significantly lower GNRI than those without osteoporosis (p < 0.001). Multivariate analysis found lower GNRI to be a significant and independent risk factor for osteoporosis (odds ratio [OR], 0.927; p < 0.001) and high fracture risk derived from FRAX (without BMD) (OR, 0.904; p = 0.009). GNRI had a positive correlation with bone mineral density (BMD) at the lumbar spine, femoral neck, and total hip, but a negative correlation with FRAX-HF and FRAX-MOF in the FRAX with and without BMD (p < 0.001 for all). The cutoff value of GNRI for predicting osteoporosis was 104.9, with sensitivity of 0.667 and specificity of 0.657.ConclusionsThe GNRI was significantly associated with osteoporosis and FRAX-derived fracture risk in patients with CLD, suggesting that it could be a simple and useful indicator for the management of bone diseases.

Anticonvulsants impacting bone metabolism: interim results from a cross-sectional study

Background. Despite a wide range of antiepileptic drugs (AEDs) with an improved pharmacological profile, patients often experience a variety of side effects during long-trem anticonvulsant therapy, among which are osteoporotic disorders. Currently, the mechanisms of AED effect on bone metabolism remain poorly understood, which creates certain difficulties in prevention and treatment of AED-induced osteoporosis.Objective: to study bone mineral density and laboratory parameters of bone metabolism in patients with epilepsy and longterm AED administration.Material and methods. A cross-sectional study included two comparison groups: 100 adult patients with epilepsy receiving AEDs for more than 12 months and 58 healthy volunteers without taking AEDs. All participants underwent general clinical examination, computed tomography (CT) densitometry at three time points (L1, L2 and femoral neck) and laboratory tests of mineral metabolism.Results. According to CT-densitometry results, a decrease in bone mineral density was detected in the majority of participants from both study groups. While assessing an impact of osteoporosis risk factors on bone tissue in epileptic patients, low motor activity and duration of AED therapy were the most significant, which was associated with lower bone mineral density indices. The study of laboratory mineral metabolism indicators revealed significant inter-group differences in indicators such as ionized calcium, 25-hydroxy-calciferol, free thyroxine and prolactin (p(U)=0.044, p(U)=0.040, p(U)=0.001, p(U)=0.003, respectively).Conclusion. The intermediate study results showed that long-term anticonvulsant use negatively affected bone metabolism in patients suffering from epilepsy. The data obtained point at need for further in-depth study of AED therapy effect on mineral metabolism.

Sclerostin as a Genetic Determinant of Trabecular Bone Score in Postmenopausal Women: The Bushehr Elderly Health (BEH) Program.

Sclerostin, a protein encoded by the SOST gene, is an important genetic risk factor for osteoporosis in postmenopausal women. This study was conducted on the Iranian postmenopausal women, to investigate the association between this gene and the Trabecular Bone Score (TBS) as a novel index used for assessing osteoporosis. The present study, conducted in 2024, was performed on 1071 women aged 60 years and older who participated in the Bushehr Elderly Health (BEH) program. The associations between seven independent Single Nucleotide Polymorphisms (SNPs) within the SOST gene and mean TBS of L1 to L4 were examined using the additive, dominant, and recessive models. Genetic risk scores (GRS) were calculated for each postmenopausal woman based on the coefficient regressions derived from the additive and dominant models. The relationship between the GRS quartiles and TBS was evaluated using a linear regression model. After adjusting for age and Body Mass Index (BMI), the associations between the rs2023794-C and TBS were significant in the additive (β = 0.03, P= 4.7×10-5, PFDR= 0.0003) and dominant (β = 0.032, P= 5×10-5, PFDR= 0.0003) models. The GRS derived from both additive and dominant models were related to TBS (P<0.05). For the additive model GRS, TBS showed an average increase of 0.022 score for the fourth quartile in comparison with the first quartile, adjusted for age, BMI, type 2 diabetes mellitus (T2DM), and smoking status (P=0.001). SOST gene is associated with TBS and may have implications for personalized medicine. Targeting sclerostin through SOST could offer a therapeutic approach in managing osteoporosis in high-risk postmenopausal women.

The effect of body mass index on bone density by age distribution in women.

Osteoporosis significantly affects public health, especially among postmenopausal women, by reducing bone mass and increasing the risk of fractures. While the influence of body mass index (BMI) on Bone Mineral Density (BMD) is acknowledged, the specific age range in which BMI most significantly affects bone density remains unclear. This study aims to explore the relationship between BMI and BMD in different age groups to identify potential age-specific risk factors for osteoporosis. In a retrospective cohort study at the University of Health Sciences Turkey, X Hospital, DXA scans of 240 postmenopausal women aged 40 to 80 were analyzed between February 2018 and February 2020. The study used statistical analyses, including ANCOVA and Pearson correlation, to investigate the effects of BMI on BMD, adjusting for age and other variables. Analysis revealed a complex interaction between BMI and BMD. Controlling for BMI showed a statistically significant difference in measurements of lumbar T, neck T, and trochanter T between age groups (P < .05). Specifically, bone density in the 40 to 49 age range was found to be lower when adjusted for BMI, suggesting that the protective effect of higher BMI is less pronounced in younger postmenopausal ages but decreases less negatively in older groups. The impact of BMI on trochanter T measurements was markedly different, increasing in the 40 to 49 age group, while decreasing in others. BMI, along with body weight and age, are important determinants of BMD, but not the sole factors influencing bone loss. The study highlights the need for a personalized approach to osteoporosis risk, considering a broader spectrum of genetic, hormonal and lifestyle factors. It recommends further evaluation of other risk factors in larger cohorts and emphasizes the importance of future longitudinal research to elucidate the dynamic relationship between BMI and BMD over time.

Increased prevalence of osteopenia and osteoporosis in systemic sclerosis patients, including in men and young women- a case-control study.

To investigate bone mineral density (BMD), osteoporosis prevalence and systemic sclerosis (SSc) specific associations of BMD in SSc patients compared with background population. In total, 211 SSc patients (182 women, 29 men; mean age 61.3 and 62.2 respectively) and 505 age and sex matched controls from the same geographic area participated. BMD and T-score at total hip and lumbar spine was measured by Dual-energy X-ray absorptiometry. Osteopenia was defined as T-score -1.0 to -2.5; osteoporosis as T-score ≤-2.5. Associates of low BMD were identified by multiple regression analysis. Women with SSc had lower BMD for total hip (p< 0.001) and spine (p= 0.011), equivalent to ΔT-score -0.56 and -0.35 compared with controls. Osteopenia was present in 51.6% and 16.5% had osteoporosis (p= 0.001, compared with controls). Already in women below age 45, differences in hip BMD were apparent (ΔT-score -0.93, p= 0.005). In addition to expected risk factors for osteoporosis (older age, lower BMI and menopause), finger ulcers (p= 0.009) and diffuse skin involvement (p= 0.027) were associated with lower hip BMD in women. In men with SSc, more than half displayed osteopenia or osteoporosis and had numerically lower hip BMD than their age matched counterparts. SSc patients, including men and younger women, have lower BMD than the background population. Finger ulcers and diffuse skin involvement, in addition to older age, lower BMI and being post-menopausal, are associated with lower BMD in women. The data emphasizes the importance of performing bone health assessment of all SSc patients, including men and young subjects.

6967 Simple Prediction Model for Vitamin D Deficiency in Women with Osteoporosis or Risk Factors for Osteoporosis

Abstract Disclosure: T. Mullikapipat: None. N. Dumrongwongsuwinai: None. O. Vallibhakara: None. S. Rattanasiri: None. S. Vallibhakara: None. W. Wajanavisit: None. B. Ongphiphadhanakul: None. H. Nimitphong: None. Background: People at high risk of vitamin D deficiency, such as those at risk of osteoporosis, should have their 25-hydroxyvitamin D [25(OH)D] levels assessed. The availability and cost of 25(OH)D measurement in Thailand are both restricted. The objective of this study was to create a model for predicting vitamin D deficiency in women with osteoporosis or risk factors for osteoporosis. Methods: This was a cross-sectional study of women with or at risk of osteoporosis who visited Ramathibodi Hospital's outpatient clinics (medicine, obstetrics and gynecology, and orthopedic) between August 2016 and August 2019. All participants were assessed their 25(OH)D using a chemiluminescent assay (Liaison, DiaSorin Inc.; Stillwater, MN). Each participant completed a questionnaire to determine vitamin D intake through supplementation and sun exposure, as well as the existence of factors impacting vitamin D status. Vitamin D deficiency was defined as 25(OH)D levels less than 30 ng/mL. Logistic regression analyses were used to examine the predictors of vitamin D deficiency. In the vitamin D deficiency prediction model, odds ratios (OR) were converted into simple scores. The sensitivity, specificity, and positive and negative predictive values of the different cutoffs in the total risk score were calculated and used to establish the optimum cutoff for those at high risk of vitamin D deficiency. Internal validation on this model was carried out using a bootstrap resampling method of 1000. Results: Sixty percent of participants had vitamin D deficiency. The final model (n=488) for the prediction of vitamin D deficiency consisted of BMI ≥ 25 kg/m2 [OR 1.15, 95% confidence interval(CI) 0.99-2.30), no exercise (OR 1.59, 95% CI 1.02-2.49), exercise 1-2 times/week (OR 1.40, 95% CI 0.79-2.46), sunlight exposure &amp;lt; 15 minutes/day (OR 1.70, 95% CI 1.04-2.78), no vitamin D supplementation (OR 8.76, 95% CI 5.02-15.28), and vitamin D supplementation ≤ 20,000 IU/day (OR 2.31, 95% CI 1.34-3.96). The area under the curve was 0.747. At a cutoff of 6.6 in total risk score (range 4-13.6), the model predicted vitamin D deficiency with a sensitivity of 71.9 and a specificity of 65.3. The internal validation by Bootstrap revealed a ROC of 0.752 (95%CI 0.751-0.754). Conclusions: In women at risk of osteoporosis, a simple questionnaire can uncover variables related to vitamin D deficiency. The risk score might be used in clinical practice to identify individuals who could benefit from vitamin D supplementation without requiring 25(OH)D levels to be measured. However, external validation in a different cohort is required before implementation. Presentation: 6/2/2024

7635 Severe Osteoporosis in a Patient with Heterotopic Calcification: A Case Report

Abstract Disclosure: D. Salih Bacha: None. L.Z. Khan: None. Background: While osteoporosis and heterotopic ossification (HO) are distinct conditions affecting bone health, their coexistence poses intriguing clinical challenges. Osteoporosis, characterized by increased bone fragility, typically results from various factors such as aging, steroid use, or malabsorption. HO is a condition where bone forms abnormally in soft tissues. Risk factors that predispose to HO include male sex, spinal cord injury, trauma, surgery, and genetic factors. Treatment of HO is typically surgical resection and NSAIDs. Initial evidence supported the use of bisphosphonates for preventing ectopic bone formation post-trauma, but recent data failed to show significant benefit in HO prevention. This case presents a patient with unique challenges of both HO and bone fragility with multiple severe vertebral fractures. Case: A 44-year-old male patient had a major motor vehicle accident necessitating multiple recurrent abdominal surgeries. During one exploratory laparotomy, diffuse mesenteric calcifications were noted, indicative of HO. A baseline Dual X-ray Absorptiometry (DXA) scan revealed bone density of 1.003 g/cm2 and 0.788 g/cm2 at the spine and femoral neck, respectively, concerning for osteopenia. He was started on zoledronic acid in preparation for upcoming intestinal transplant. Few months after the transplant, he was started on daily tacrolimus and hydrocortisone for immunosuppression. Within months, he experienced sudden back pain while riding an elevator, and was found to have acute fractures in T8 and T9 vertebrae. A repeat DXA scan showed a further decline in bone density to 0.909 g/cm2 and 0.748 g/cm2 at the spine and femoral neck, respectively. Within a year, additional fractures occurred in the thoracic and lumbar spine (T10, T11, T12, L1, L2, L3, and L4), requiring multiple kyphoplasty interventions. Over time, worsening kyphosis, back pain, and height loss occurred, significantly affecting the patient's quality of life. He continued receiving yearly zoledronic acid infusions and underwent regular DXA scans, which revealed mild improvement in his bone density. Currently, there are no established guidelines specifying the optimal duration for bisphosphonate treatment in such cases. Therefore, our individualized treatment plan involves a tentative 10-year course of bisphosphonate treatment with yearly assessment of bone mineral density. Conclusion: Although the patient had some risk factors for osteoporosis, including daily steroid and tacrolimus use, the severity and frequency of his fractures suggested a potential synergy between osteoporosis and HO, where the formation of heterotopic calcifications may have been exacerbating his bone loss. The coexistence of osteoporosis and HO in this patient underscores the need for individualized care and establishment of treatment guidelines in patients with multiple bone disorders. Presentation: 6/3/2024

12453 Osteoporosis Screening In A Primary Care Clinic: Barriers And Solutions

Abstract Disclosure: B.M. Laquidara: None. S. Mistry: None. L. Guo: None. Purpose/Objective: Osteoporosis is a prevalent bone disorder that affects over 10 million people in the United States. The US Preventive Services Task Force (USPSTF) recommends screening females aged 65 and older with a baseline DEXA scan and to screen postmenopausal females younger than age 65 who have an increased risk of osteoporosis. Despite these guidelines, the screening rate for osteoporosis remains very low. Our quality improvement project seeks to first identify at what rate eligible patients in our residency primary care clinic are being screened for osteoporosis and what barriers (patient, provider, or clinical factors) to screening may decrease this rate. Methods: We reviewed a random sample medical records of 300 female patients aged &amp;gt;/= 50 years who visited our clinic within the last two years. We collected patient demographics, insurance status, presence of ≥1 risk factor of osteoporosis (fracture, heavy alcohol use, tobacco use, steroid use, BMI&amp;lt;19), MyChart activity, provider training level, diagnosis code, and whether a baseline DEXA was ordered and/or completed. We compared patient characteristics by DEXA order status using descriptive statistics, and used multivariable regression models to determine odds of DEXA order and completion. Results: The patients who were at high risk for osteoporosis were more likely to have an order without completion (OR 6.11, p &amp;lt;0.001). Increased age was associated with increased odds of having an order (OR 1.09, p&amp;lt;0.001). Increasing BMI was associated with decreased odds of having an order. Black patients and current smokers were less likely to have a DEXA scan ordered and completed after controlling for age and other confounding factors (p= 0.002 and 0.001 respectively). Among the 96 patients who had a completed DEXA scan, 74 had osteoporosis. The only significant predictor for having osteoporosis was low BMI (OR 0.87%, p&amp;lt;0.001). Conclusion: The results of this study suggest that while patients with a clinically high risk for osteoporosis are more likely to have an order placed for a DEXA scan, these patients often do not have a completed scan. Patients who have an ICD-10 diagnosis of high-risk for osteoporosis or osteoporosis in their electronic medical record are more likely to have both an ordered and completed scan. Utilizing this data, we will develop a variety of interventions such as a clinical didactic case for osteoporosis, a flow-sheet summary of proper osteoporosis screening and treatment initiation to be distributed in the clinic setting, and a short presentation during noon didactics where we review the proper screening method for osteoporosis. Following our intervention, we will re-examine the screening rate in our residency clinic to evaluate the effect of our intervention. Presentation: 6/3/2024

6483 Diaphyseal Medullary Stenosis With Malignant Fibrous Histiocytoma: A Rare Skeletal Dysplasia/Sarcoma Syndrome

Abstract Disclosure: A. Grover: None. C.R. Ferreira: None. R.I. Gafni: None. S. Jumani: None. M.T. Collins: None. K.L. Roszko: None. I.R. Hartley: None. Introduction: Diaphyseal medullary stenosis with malignant fibrous histiocytoma (DMS-MFH) is a rare autosomal dominant syndrome associated with pathologic fractures, myopathy, premature hair graying, and aggressive osteosarcomas. DMS-MFH has been linked to genetic variants in the methylthioadenosine phosphorylase (MTAP) gene, which encodes an enzyme in the methionine salvage and polyamine synthesis pathway. This pathway is implicated in other skeletal fragility disorders, such as Snyder-Robinson syndrome, suggesting a still undefined role of this pathway in bone biology. We describe a kindred with DMS-MFH and identify diagnostic challenges. Case: A 53-year-old perimenopausal woman presented with four fragility fractures over one year. Relevant history included premature hair graying, esophageal strictures, and nephrolithiasis. The patient’s bone formation markers were slightly elevated; bone resorption markers were within reference range. Her only osteoporosis risk factor was perimenopausal status. Bone series showed a diffuse heterogeneous appearance of the long bones with a mixed lytic/sclerotic appearance. DEXA scan revealed osteopenia. Family history was significant for 2 sons with aggressive osteosarcomas diagnosed in their late teens; one died at age 20. The other son is currently 39-years-old with recurrent osteosarcomas in three different limbs. The family also has a multigenerational history of severe bone fragility, muscle weakness, and premature hair graying. The patient, her living son, and his father underwent genome sequencing that identified a variant in MTAP (c.885A&amp;gt;G; p.(R295=)) in the patient and son. This variant was previously reported in three other families with DMS-MFH and has been shown to alter splicing. Notably, commercial genetic testing did not report this as a relevant variant, and diagnosis required independent analysis of the raw sequence data. Based on these findings, the patient and her son were diagnosed with DMS-MFH. Given the bone fragility with elevated bone turnover markers we treated the patient with yearly zoledronic acid infusions with no subsequent fractures. Surveillance for osteosarcoma is also being performed with annual whole-body MRI. Conclusion: DMS-MFH has been reported in only five families to date. The sixth family described here has clinical characteristics similar to the other kindreds. Due to high risk of aggressive osteosarcoma, timely diagnosis is imperative to decrease morbidity and mortality. Commercial genome sequencing may miss this diagnosis, so targeted genetic testing should be pursued. As more cases are identified, characterization of affected families may enhance our understanding of the natural history of the disease and guide surveillance and treatment strategies. Presentation: 6/2/2024

6374 Prevalence and risk factor of complications in patients with adult growth hormone deficiency: A retrospective database study

Abstract Disclosure: H. Fukuoka: None. S. Fujio: None. T. Endo: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. S. Tsuboi: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. Though adult growth hormone deficiency (AGHD) is known to lead to increased prevalence of complications, large database studies on AGHD have not been conducted. We investigated the clinical characteristics and prevalence of AGHD-related complications in Japanese patients. We identified 8,809 GH-untreated patients with AGHD from Medical Data Vision claims database between April 2008 and September 2022. In 2020, 3,420 AGHD patients were identified, and their prevalence of complications adjusted for sex and age was higher than that of Japanese general population, 9.3% vs 3.6% for diabetes mellitus (DM), 4.8% vs 1.3% for osteoporosis, and especially 22.0% vs 3.9% for dyslipidemia. We explored the risk factors for the onset of complications using Cox proportional hazard model. Age was significant risk factor for most complications and being female was significant risk factor for osteoporosis. DM was a significant risk factor for dyslipidemia, ischemic heart disease, cerebrovascular disease, and all cause death. AGHD increases the overall risk of metabolic complications, risk factors of these complications were similar to those in general population. Comprehensive treatment approach needs to be considered to alleviate the risk of complications. Presentation: 6/3/2024

6536 National Trends in Prevalence of Prediabetes and Diabetes Among Women With Low Bone Mineral Density: 2009-2018

Abstract Disclosure: A. Atri: None. C. Anastasopoulou: None. Introduction: In recent years, bone fragility has emerged as a complication of prediabetes (preDM) and diabetes mellitus (DM), resulting in reduced bone mass and increased fracture risk, and is an important, though under-studied risk factor for osteoporosis. However, the converse relationship, trends in prevalence of preDM and DM in women with low bone mineral density (BMD) in the United States, are not well established. Methods: We used data from the National Health and Nutrition Examination Survey (NHANES) for the years 2009-10, 2013–14 and 2017–18 to include U.S. women aged ≥ 50 years with T-score ≤ -1. Osteoporosis assessment in NHANES was not completed in 2011–12 and 2015–16, and therefore not included in the analysis. Osteopenia and osteoporosis were defined by a femoral neck BMD ≤1 to 2.5, and ≤2.5 standard deviations (SDs) below the BMD of a young female adult mean (T-score). Femur neck BMD was measured by dual energy x-ray absorptiometry (DEXA). PreDM and DM were defined using HbA1c values of 5.7 - 6.4% and ≥ 6.5% respectively. Participants with missing HbA1c and BMD data were excluded. Descriptive statistics were used for comparing means and medians. The Cochran-Armitage test was utilized for trend analysis. Results: In this nationally representative sample of US women with low BMD, the median (IQR) T-score at femoral neck worsened from -1.74 (-1.4 to -2.17) in 2009-10 to -1.87 (-1.43 to -2.32) in 2017-18 (trend p = 0.001). Similarly, the prevalence of osteoporosis increased from 13.7% to 16.9% (trend p = 0.001). Overall, in this cohort, the national prevalence of both preDM and DM decreased from 40% to 32.9% and 9.6% to 9%, respectively (trend p = 0.001). Along with a reduction in the overall prevalence of osteopenia (86.3% to 83.1%, p=0.001), the prevalence of both preDM and DM decreased from 39.2% to 32.6% and 10% to 9% (p = 0.001). In those with osteoporosis, the prevalence of preDM decreased from 45.2% to 34.4% (p trend=0.001), however, the prevalence of DM increased from 7.5% to 8.7% (p trend =0.001). Overall rates of uncontrolled DM (HbA1c &amp;gt; 7%) in women with osteoporosis showed significant improvement (5.8% to 3.5%, p = 0.001). Discussion Despite worsening trend in femoral neck BMD among US women age ≥ 50 years from 2009-10 to 2017-18, the overall prevalence of preDM and DM improved by 7.1% and 0.6% respectively. However, this favorable trend was not observed among women with osteoporosis, where the overall prevalence of DM increased by 1.2%, though the rate of uncontrolled DM significantly decreased by 2.3%. Targeted interventions to improve blood glucose control among women with low BMD, especially those with osteoporosis are warranted, to improve bone health, as well as reduce fall and fracture risk. Presentation: 6/2/2024

Excess dietary salt is associated with an altered bone strain index, degraded bone microarchitecture, vertebral fractures, and increased prevalence of osteoporosis in postmenopausal women-A study from a teaching hospital in southern India.

Excess dietary salt causes increased urinary calcium and this may lead to bone loss. We proposed to study the association between dietary salt intake and bone health in postmenopausal women from southern India. An observational study in which community-dwelling postmenopausal women were recruited. Daily salt intake and urine calcium/creatinine ratio were assessed. Bone biochemistry and densitometric parameters such as bone mineral density (BMD), trabecular bone score (TBS) vertebral fractures, and bone strain index (BSI) were assessed using Dual Energy X-Ray Absorptiometry (DXA). A total of 383 postmenopausal women with a mean ± SD age of 59.8 ± 7.2 years and BMI of 25.2 ± 4.6 kg/m2 were recruited. Among the participants, 165/383(43.1%) had osteoporosis at any site and 21% had moderate-severe vertebral fractures. The BMD at lumbar spine and femoral neck, TBS and BSI were significantly (p < 0.001) lower and the CTx was significantly (p = 0.008) higher among women with high salt intake (7.2 g/day) as compared to those with salt intake of <7.2 g/day. The prevalence of osteoporosis, low TBS, high BSI, and moderate-severe vertebral fractures significantly increased across low to high salt-intake categories. An ROC analysis showed that excess dietary salt was significantly associated with osteoporosis at any site with an AUC of 0.870 (95% CI: 0.832-0.907). On a multivariate analysis, excess salt intake conferred the highest odds of osteoporosis (OR: 2.296; 95% CI: 1.909-2.761). Excess dietary salt is associated with high urinary calcium and compromised bone health among postmenopausal women from southern India. This may be a modifiable risk factor in osteoporosis and warrants further research.

Risk Factors for Osteoporosis in Patients with Hodgkin’s Lymphoma. Literature Review

Risk Factors for Osteoporosis in Patients with Hodgkin’s Lymphoma. Literature Review

Utility of Radiographic Parameter in Assessing Bone Density and Subsequent Fractures in Patients With Osteoporotic Vertebral Compression Fracture.

To investigate the ability of radiological parameter canal bone ratio (CBR) to assess bone mineral density and to differentiate between patients with primary and multiple osteoporotic vertebral compression fracture (OVCF). A retrospective analysis was conducted on OVCF patients treated at our hospital. CBR was measured through full-spine x-rays. Patients were categorized into primary and multiple fracture groups. Receiver operating characteristic curve analysis and area under the curve (AUC) calculation were used to assess the ability of parameters to predict osteoporosis and multiple fractures. Predictors of T values were analyzed by multiple linear regression, and independent risk factors for multiple fractures were determined by multiple logistic regression analysis. CBR showed a moderate negative correlation with dual-energy x-ray absorptiometry T values (r = -0.642, p < 0.01). Higher CBR (odds ratio [OR], -6.483; 95% confidence interval [CI], -8.234 to -4.732; p < 0.01) and lower body mass index (OR, 0.054; 95% CI, 0.023-0.086; p < 0.01) were independent risk factors for osteoporosis. Patients with multiple fractures had lower T values (mean ± standard deviation [SD]: -3.76 ± 0.73 vs. -2.83 ± 0.75, p < 0.01) and higher CBR (mean ± SD: 0.54 ± 0.07 vs. 0.46 ± 0.06, p < 0.01). CBR had an AUC of 0.819 in predicting multiple fractures with a threshold of 0.53. T values prediction had an AUC of 0.816 with a threshold of -3.45. CBR > 0.53 was an independent risk factor for multiple fractures (OR, 14.66; 95% CI, 4.97-43.22; p < 0.01). CBR is negatively correlated with bone mineral density (BMD) and can be a novel opportunistic BMD assessment method. It is a simple and effective measurement index for predicting multiple fractures, with predictive performance not inferior to T values.

Serum proinflammatory cytokines, receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin (OPG) and RANKL/OPG ratio in mild and severe COVID-19

IntroductionOsteoporosis, a systemic skeletal disease, is characterized by a quantitative and qualitative, and progressive decrease in bone mass, which is related to inflammation. Since a cytokine storm is triggered in Coronavirus disease 2019 (COVID-19), this study aims to evaluate pro-inflammatory cytokines (TNF-α, IL-1β), Receptor activator of nuclear factor-κB ligand (RANKL)/serum osteoprotegerin (OPG) ratio, and their relationship in mild and severe COVID-19.MethodsThis study was performed on 48 adult patients (18 mild, 18 severe COVID-19, and 12 healthy subjects as a control group). Serum OPG, RANKL, TNF-α, IL-1β, 25-OH vitamin D, and ALKp were measured by ELISA and colorimetric assay.ResultsCOVID-19 patients had a significant increase in RANKL, and RANKL/OPG in mild and severe form (p < 0.001) while OPG decreased significantly in severe form compared to healthy controls (p < 0.05). Inflammatory cytokines (TNF-α and IL-1β) increased in both groups of patients whereas Alkaline phosphatase (ALKp) increased only in severe patients (p < 0.001). Both groups had 25-OH vitamin D deficiency in comparison to healthy ones (p < 0.001). Pearson’s correlation coefficient was performed to determine the relationship between RANKL, OPG, ALKp, and 25-OH vitamin D with TNF-α and IL-1β in mild and severe COVID-19, which was statistically significant.ConclusionSerum RANKL/OPG ratio was elevated in COVID-19 individuals and is assumed to be a risk factor for BMD reduction and osteoporosis in these patients. Correlations between IL-1β, TNF-α, ALKp, 25-OH vitamin D, OPG, RANKL, and RANKL/OPG ratio offered the potential role of these proinflammatory markers in the mechanism of osteoporosis in COVID-19 patients.

Long-term changes in bone mineral density and associated risk factors in individuals with spinal cord injury: A retrospective study.

Individuals with spinal cord injury (SCI) experience a notable decrease in bone mass below the level of injury. While studies have primarily focused on the acute phase with a small cohort, this study aimed to provide comprehensive insights into bone loss patterns over time. A total of 427 individuals with SCI who underwent dual-energy X-ray absorptiometry (DXA) testing at the Korea National Rehabilitation Center (2010-2021) were included and analyzed by categorizing the DXA results into 1-year intervals based on postinjury duration. Demographic characteristics (age, sex, body mass index, and alcohol/smoking history) and SCI-related factors (etiology, severity, extent of injury, motor score, and Korean Spinal Cord Independence Measure 3rd edition) were collected and analyzed. Linear mixed models and Bonferroni post hoc tests were performed to assess temporal changes in bone mass and linear regression analysis to assess the associations between possible risk factors and bone loss. DXA results revealed that substantial annual bone loss occurred in the total hip site up to 3 years postinjury and in the femoral neck site up to 2 years postinjury. Old age, women, and low body mass index were significant risk factors for bone loss in the SCI population. Additionally, during the chronic phase, lower Korean Spinal Cord Independence Measure 3rd edition scores were associated with low bone mass. Significant annual bone loss in the hip region persists for up to 3 years postinjury in individuals with SCI. While prioritizing the risk factors for osteoporosis commonly used in the general population, applying the SCIM score in the chronic phase may provide additional information on bone loss risk.

Clinical characteristics and risk factors of osteoporosis among older Asian men with type-2 diabetes mellitus, hypertension, or hyperlipidaemia

SummaryThis study investigated osteoporosis risk factors among older Asian men with type-2 diabetes mellitus, hypertension, or hyperlipidaemia in primary care. Advanced age, dementia, depression, and polypharmacy were associated with higher risks for osteoporosis. Screening strategies targeting these factors are crucial for improving bone health as part of comprehensive preventive care.PurposeAsian patients with type-2 diabetes mellitus (T2DM), hypertension, or hyperlipidaemia (DHL) are predominantly managed in primary care. They are also at risk of osteoporosis, but men are often under-screened and under-treated for this preventable bone disorder. This study aimed to identify the clinical characteristics and risk factors of osteoporosis among older men with DHL in primary care for early intervention.MethodsThis retrospective study included men aged 65 years and older managed in public primary care clinics for their DHL between 1st July 2017 and 30th June 2018. Demographic, clinical, laboratory, and imaging data were extracted from their electronic medical records based on their International Classification of Diseases-10 (ICD-10) diagnosis codes. Descriptive statistical analyses, with statistical significance set at p < 0.05, were conducted, followed by generalized estimating equation (GEE) modelling.ResultsMedical records of 17,644 men (83.1% Chinese, 16.9% minority ethnic groups, median age 71 years) were analysed. 2.3% of them had diagnosis of osteoporosis, 0.15% had fragility fracture, and 26.0% of those diagnosed with osteoporosis were treated with bisphosphonates. Their mean HbA1c was 6.9%; mean systolic and diastolic blood pressure were 133 and 69 mmHg. The GEE model showed that age (OR = 1.07, 95%CI = 1.05–1.09, p < 0.001), dementia (OR = 2.24, 95%CI = 1.33–3.77, p = 0.002), depression (OR = 2.38, 95%CI = 1.03–5.50, p = 0.043), and polypharmacy (OR = 6.85, 95%CI = 3.07–15.26, p < 0.001) were significantly associated with higher risks for osteoporosis.ConclusionAge, dementia, depression, and polypharmacy are associated with osteoporosis risks in men with DHL. Strategies to incorporate osteoporosis screening among older men with these risk factors are needed to improve their bone health.

Management of bone health in idiopathic inflammatory myopathies: A two-center audit in the United Kingdom and Hong Kong.

Patients with inflammatory idiopathic myopathies (IIM) face elevated risks of osteoporosis and fragility fracture. To evaluate current practice relating to bone health in adult patients with IIM in the United Kingdom and Hong Kong (HK). Patients were identified from IIM patient lists. Demographics, osteoporosis risk factors, DXA scans, and bone protection treatment were recorded. Adherence to regional standards was evaluated for each center. Following this, in the United Kingdom, up-to-date DXA scans were performed. Of 136 patients identified, 51 met selection criteria (UK, n = 20, HK, n = 31). Mean age in the United Kingdom was 59 (IQR 54-66); in Hong Kong, 65 (IQR 52.5-70). Most were female (UK 70%; HK 77%), current or previous steroid treatment was common (UK 90%; HK 100%) and some had experienced fragility fracture (UK 15%; HK 9%). The mean daily dose of prednisolone that patients were prescribed during the study was 12.5 mg (UK) and 14.3 mg (HK). Some patients had had a DXA scan (UK 50%; HK 35%) though several were outdated. Among those with BMD measured (UK, n = 20; HK, n = 11), osteopenia prevalence was 35% (UK) and 36% (HK) while osteoporosis was 5% (UK) and 36% (HK). Notably, 25% (UK) and 64% (HK) exceeded treatment thresholds. Treatments included anti-osteoporotic agents (UK 55%; HK 15%), Vitamin D/calcium supplements (UK 95%; HK 52%), or no treatment (UK 5%, HK 15%). Poor compliance with guidelines exists in both centers, particularly around investigation and monitoring of bone health for IIM patients. Integrated care models and increased resource allocation to bone health are imperative to improve management of this aspect of IIM.

Dysregulated myeloid differentiation in colitis is induced by inflammatory osteoclasts in a TNFα-dependent manner

Inflammatory bowel disease (IBD) is characterized by very severe intestinal inflammation associated with extra-intestinal manifestations. One of the most critical ones is bone destruction, which remains a major cause of morbidity and a risk factor for osteopenia and osteoporosis in IBD patients. In various mouse models of IBD, we and other have demonstrated concomitant bone loss due to a significant increase in osteoclast activity. Besides bone resorption, osteoclasts are known to control hematopoietic niches in vivo and modulate inflammatory responses in vitro, suggesting they may participate in chronic inflammation in vivo. Here, using different models of colitis, we showed that osteoclast inhibition significantly reduced disease severity and that induction of osteoclast differentiation by RANKL contributed to disease worsening. Our results demonstrate a direct link between osteoclast activity and myeloid cell accumulation in the intestine during colitis. RNAseq analysis of osteoclasts from colitic mice revealed overexpression of genes involved in the remodeling of hematopoietic stem cell niches. We also demonstrated that osteoclasts induced hematopoietic progenitor proliferation accompanied by a myeloid skewing in the early phases of colitis, which was confirmed in a model of RANKL-induced osteoclastogenesis. Mechanistically, inhibition of TNF-α reduced the induction of myeloid skewing by OCL both in vitro and in vivo. Lastly, we observed that osteoclastic activity and the proportion of myeloid cells in the blood are positively correlated in patients with Crohn’s disease. Collectively, our results shed light on a new role of osteoclasts in colitis in vivo, demonstrating they exert their colitogenic activity through an early action on hematopoiesis, leading to an increase in myelopoiesis sustaining gut inflammation.