Lumbar Spine Bone Mineral Density Research Articles

Associations between apolipoprotein B and bone mineral density: a population-based study

BackgroundLipids are critical in bone metabolism, and several studies have highlighted their importance. This study aimed to investigate the relationship between apolipoprotein B (apo B) and bone mineral density (BMD) at different skeletal sites (lumbar spine, femoral neck, and total femur) and to compare the influence of apo B with other traditional lipid markers.MethodsThe study included participants from the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2016 who had complete data for apo B and BMD at the three skeletal sites. We used weighted multivariate regression analysis, subgroup analysis, and interaction tests to examine associations. Restricted cubic spline (RCS) was used to examine the non-linear relationship.ResultsA total of 4,258 adults were included in the study. Multivariate linear regression analysis showed that the relationship between apo B and BMD varied by skeletal site: a negative association was found with lumbar spine BMD [β = -0.054, 95%CI: (-0.073, -0.035)]. In contrast, a positive association was found with femoral neck BMD [β = 0.031, 95%CI: (0.011, 0.051)] and no significant association between apo B and total femur BMD.ConclusionsOur findings suggest that apo B is associated with BMD in a site-specific manner.

Pilot Study: Short Term Impact of Radiation Therapy on Bone Mineral Density and Bone Metabolism

Despite the risk of complications, high dose radiation therapy is increasingly utilized in the management of selected bone malignancies. In this study, we investigate the impact of moderate to high dose radiation (over 50 Gy) on bone metabolism and structure. Between 2015 and 2018, patients with a primary malignant bone tumor of the sacrum that were either treated with high dose definitive radiation only or a combination of moderate to high dose radiation and surgery were prospectively enrolled at a single institution. Quantitative CTs were performed before and after radiation to determine changes in volumetric bone mineral density (BMD) of the irradiated and non-irradiated spine. Bone histomorphometry was performed on biopsies of the irradiated sacrum and the non-irradiated iliac crest of surgical patients using a quadruple tetracycline labeling protocol. In total, 9 patients were enrolled. Two patients received radiation only (median dose 78.3 Gy) and 7 patients received a combination of preoperative radiation (median dose 50.4 Gy), followed by surgery. Volumetric BMD of the non-irradiated lumbar spine did not change significantly after radiation, while the BMD of the irradiated sacrum did (pre-radiation median: 108.0 mg/cm3 (IQR 91.8–167.1); post-radiation median: 75.3 mg/cm3 (IQR 57.1–110.2); p = 0.010). The cancellous bone of the non-irradiated iliac crest had a stable bone formation rate, while the irradiated sacrum showed a significant decrease in bone formation rate [pre-radiation median: 0.005 mm3/mm2/year (IQR 0.003–0.009), post-radiation median: 0.001 mm3/mm2/year (IQR 0.001–0.001); p = 0.043]. Similar effects were seen in the cancellous and endocortical envelopes. This pilot study shows a decrease of volumetric BMD and bone formation rate after high-dose radiation therapy. Further studies with larger cohorts and other endpoints are needed to get more insight into the effect of radiation on bone. Level of evidence: IV.

Evaluation of the Effect of Sodium-Glucose Cotransporter 2 Inhibition on Fracture Risk: Evidence From Mendelian Randomization and Genetic Association Study.

This study aims to evaluate the causal effect of sodium-glucose cotransporter 2 (SGLT2) inhibition on bone mineral density (BMD), osteoporosis, and fracture risk using genetics. Two-sample Mendelian randomization (MR) analyses were performed utilizing two sets of genetic variants as instruments (six and two single-nucleotide polymorphisms [SNPs]) associated with SLC5A2 gene expression and glycated hemoglobin A1c levels. Summary statistics of BMD from the Genetic Factors for Osteoporosis consortium (BMD for total body, n = 66,628; femoral neck, n = 32,735; lumbar spine, n = 28,498; forearm, n = 8143) and osteoporosis (6303 cases, 325,717 controls) and 13 types of fracture (≤17,690 cases, ≤328,382 controls) data from the FinnGen study were obtained. One-sample MR and genetic association analyses were conducted in UK Biobank using the individual-level data of heel BMD (n = 256,286) and incident osteoporosis (13,677 cases, 430,262 controls) and fracture (25,806 cases, 407,081 controls). Using six SNPs as the instrument, genetically proxied SGLT2 inhibition showed little evidence of association with BMD of total body, femoral neck, lumbar spine, and forearm (all p ≥ 0.077). Similar results were observed using two SNPs as instruments. Little evidence was found for the SGLT2 inhibition effect on osteoporosis (all p ≥ 0.112) or any 11 major types of fracture (all p ≥ 0.094), except for a nominal significance for fracture of lower leg (p = 0.049) and shoulder and upper arm (p = 0.029). One-sample MR and genetic association analysis showed that both the weighted genetic risk scores constructed from the six and two SNPs were not causally associated with heel BMD, osteoporosis, and fracture (all p ≥ 0.387). Therefore, this study does not support an effect of genetically proxied SGLT2 inhibition on fracture risk. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Association between triglyceride-glucose index and bone mineral density in US adults: a cross sectional study

ObjectiveDisorders in glucose and lipid metabolism have been shown to exert an influence on bone metabolism. The TyG index, which combines measures of glucose and triglycerides, provides insights into the overall metabolic status. However, the investigation of concurrent disturbances in glucose and lipid metabolism and their specific implications for bone metabolism remains limited in the existing research literature. This study aimed to explore the correlation between the TyG index and bone mineral density (BMD) in US adults.MethodsIn the National Health and Nutrition Examination Survey (NHANES), subjects were classified based on the TyG index into four groups (< 7.97, 7.97–8.39, 8.39–8.85, > 8.86). Linear regression analysis was conducted to determine the β value and 95% confidence interval (CI). Four multivariable models were constructed. Restricted cubic spline analyses and piecewise linear regression were employed to identify the association between the BMD and TyG index. An analysis of subgroups was also conducted in this study.ResultsSignificant variations in related characteristics were found among the US adult population, who were distributed into four groups based on the quartiles of the TyG index. A negative correlation between the TyG index and lumbar spine BMD was observed. In the multi-adjusted models, compared to Q1 of the TyG index, the β for Q4 of the TyG index for lumbar spine BMD was [β = − 0.008, 95% CI (− 0.017, 0)] in US adults. The association between the TyG index and lumbar spine BMD was found to be nonlinear (all nonlinear p < 0.001), with a threshold value based on restricted cubic spline analyses. Above the threshold point, the β for lumbar spine BMD was − 0.042 (95% CI, − 0.059, − 0.024). Below the threshold points, no significant difference was observed (p > 0.05). No significant interactions were observed among subgroups based on age, gender, presence of diabetes, BMI, and use of antidiabetic and antihyperlipidemic agents. Similar patterns of association were observed in total and subtotal bone density.ConclusionsThis study identified a nonlinear association between the TyG index and BMD in the US population. Furthermore, an increased level of the TyG index may indicate a higher risk of osteoporosis among US adults. These findings highlight the importance of considering glucose and lipid metabolism disturbances in understanding bone health and the potential for developing preventive strategies for osteoporosis.

Bone Mineral Density in Transgender Adolescents Treated With Puberty Suppression and Subsequent Gender-Affirming Hormones

Bone mineral density (BMD) z scores in transgender adolescents decrease during puberty suppression with a gonadotropin-releasing hormone (GnRH) agonist. Previous research found that after short-term use of gender-affirming hormones (GAH), pretreatment z scores were not restored. Long-term follow-up studies are lacking. To assess BMD after long-term GAH treatment in transgender adults who used puberty suppression in adolescence. This single-center cohort study with follow-up duration of 15 years selected participants from a database containing all people visiting a gender identity clinic at an academic hospital in the Netherlands between 1972 and December 31, 2018. Recruitment occurred from March 1, 2020, to August 31, 2021. A total of 75 participants diagnosed with gender dysphoria who had used puberty suppression before age 18 years prior to receiving at least 9 years of long-term GAH were included. Puberty suppression with a GnRH agonist followed by GAH treatment. Lumbar spine, total hip, and femoral neck BMD and z scores before the start of puberty suppression, at start of GAH, and at short- and long-term follow-up. Among 75 participants, 25 were assigned male at birth, and 50 were assigned female at birth. At long-term follow-up, the median (IQR) age was 28.2 (27.0-30.8) years in participants assigned male at birth and 28.2 (26.6-30.6) years in participants assigned female at birth. The median (IQR) duration of GAH treatment was 11.6 (10.1-14.7) years among those assigned male at birth and 11.9 (10.2-13.8) years among those assigned female at birth. The z scores decreased during puberty suppression. In individuals assigned male at birth, the mean (SD) z score after long-term GAH use was -1.34 (1.16; change from start of GnRH agonist: -0.87; 95% CI, -1.15 to -0.59) at the lumbar spine, -0.66 (0.75; change from start of GnRH agonist: -0.12; 95% CI, -0.31 to 0.07) at the total hip, and -0.54 (0.84; change from start of GnRH agonist: 0.01; 95% CI, -0.20 to 0.22) at the femoral neck. In individuals assigned female at birth, after long-term GAH use, the mean (SD) z score was 0.20 (1.05; change from start of GnRH agonist: 0.09; 95% CI, -0.09 to 0.27) at the lumbar spine, 0.07 (0.91; change from start of GnRH agonist: 0.10; 95% CI, -0.06 to 0.26) at the total hip, and -0.19 (0.94; change from start of GnRH agonist: -0.20; 95% CI, -0.26 to 0.06) at the femoral neck. In this cohort study, after long-term use of GAH, z scores in individuals treated with puberty suppression caught up with pretreatment levels, except for the lumbar spine in participants assigned male at birth, which might have been due to low estradiol concentrations. These findings suggest that treatment with GnRH agonists followed by long-term GAH is safe with regard to bone health in transgender persons receiving testosterone, but bone health in transgender persons receiving estrogen requires extra attention and further study. Estrogen treatment should be optimized and lifestyle counseling provided to maximize bone development in individuals assigned male at birth.

Risk factors for the comorbidity of osteoporosis/osteopenia and kidney stones: a cross-sectional study.

To evaluate whether low femoral neck bone mineral density (BMD) was associated with a higher risk of kidney stones, and identify risk factors for the comorbidity of osteoporosis/osteopenia and kidney stones. We analyzed individuals aged ≥ 20 years from National Health and Nutrition Examination Survey 2007-2020 data. Osteoporosis/osteopenia is defined as any T-score < -1.0 of femoral neck, total femoral, and mean lumbar spine (L1-L4) BMD. Dietary intakes (sodium, potassium, magnesium, calcium, phosphorus, calcium/phosphorus, vitamin D (25OHD2+25OHD3)) and serum parameters (sodium, potassium, calcium, phosphorus, bicarbonate, vitamin D, alkaline phosphatase (ALP)) were screened for identifying risk factors for the comorbidity. The prevalence of comorbidity of osteoporosis/osteopenia and kidney stones was 4.82%. Femoral neck BMD T-score was negatively associated with the prevalence of kidney stones (n=11,864). Dietary magnesium intake, serum phosphorus, and bicarbonate were negatively associated with the comorbidity prevalence, and serum ALP was positively associated with the comorbidity prevalence (n=6978). Additionally, there remain significant associations of dietary magnesium intake, serum ALP, and bicarbonate with not only femoral neck BMD T-score (n=11331), but also the prevalence of kidney stones (n=23,111) in general population. Furthermore, dietary magnesium intake was positively correlated to femoral neck BMD T-score in stone formers (SFs), while serum ALP was negatively correlated to femoral neck BMD T-score in SFs (n=1163). Low femoral neck BMD was closely associated with an increased risk of kidney stones. Low magnesium intake and increased serum ALP were associated with the increased risk of the comorbidity, as well as indicative of low femoral neck BMD T-score in SFs, which offered a clue to further clarify the mechanism leading to paradoxical calcification of bone resorption and kidney stones, and had the potential to perform personalized diagnostic workup for low BMD in SFs.

Up-regulation of plasma miRNA-21 and miRNA-422a in postmenopausal osteoporosis.

Many researchers focused on diverse miRNAs in the progression of osteoporosis in postmenopausal women. This study aimed to evaluate the association between plasma miRNA-21-5p and miRNA-422a with osteoporosis in postmenopausal women. This cross-sectional comparative study was performed on 126 randomly selected postmenopausal women aged 50-65, including 65 osteoporotic and 61 normal-bone mineral density (BMD) women. miRNA-21 and miRNA-422a were identified using qRT-PCR in these women. BMD was evaluated by the dual-energy X-ray absorptiometry method. A binary logistic regression model adjusted for confounders was used to evaluate the associations between plasma miRNAs' expression levels and osteoporosis. The Area Under Curve (AUC) was calculated to differentiate low BMD in the postmenopausal period using Receiver-Operator Characteristic (ROC) curves. miRNA-21 and miRNA-422a were significantly up-regulated in osteoporotic compared to non-osteoporotic postmenopausal women. The expression levels of miRNA-21 and miRNA-422a indicated a significant reverse correlation with both lumbar spine and femoral neck density. After adjusting the confounders, the likelihood of osteoporosis in the postmenopausal women with under the median plasma levels of miRNA-21 (OR = 0.025; 95% CI: 0.003 to 0.198, p<0.001) and miRNA-422a (OR = 0.037; 95% CI: 0.007 to 0.211, p<0.001) was significantly less than the women with the levels above the median. There were significant inverse correlations between miRNA-21 (p<0.001, r = -0.511) and miRNA-422a (p<0.001, r = -0.682) with BMD-lumbar spine as well as an inverse correlation between miRNA-21(p<0.001, r = -0.374) and miRNA-422a (p<0.001, r = -0.602) with BMD-femoral neck. The AUC (95%CI) for miRNA-21 and miRNA-422a was 0.84 (0.77 to 0.91) and 0.98 (0.96 to 0.99), respectively. ROC analysis illustrated that sensitivity and specificity values were 83.1% and 74%, respectively, for miRNA-21 at the cut-off point of 3.38. Also, at the cut-off point of 2.86, a sensitivity of 94% as well as a specificity of 89% was determined for miRNA-422a. This study indicated that the odds of osteoporosis in postmenopausal women increased with the higher expression of plasma miRNA-21 and miRNA-422a.

Bone Health, Body Composition and Physiological Demands in 70-85-Year-Old Lifelong Male Football Players.

The effects of lifelong football training on bone health, body composition and physiological demands were evaluated. A total of 20 veteran football players (VPG; 73.4 ± 3.7 years) and 18 untrained age-matched men (CG; 75.6 ± 4.2 years) were enrolled. Whole-body and regional dual-energy X-ray absorptiometry scans of arms, legs, proximal femur and lower spine (L1-L4) were recorded in all participants. We observerd higher bone mineral density (BMD) in the whole-body, arms and femoral regions and higher bone mineral content (BMC) in the legs and lower spine compared to the CG (p < 0.05), also higher total lean body mass (p < 0.05) and lower total body fat percentage (p < 0.05), were found. No differences in food habits were evidenced between the VPG and the CG, as evaluated using 3-day food records. Resting heart rate (RHR), blood pressure (BP) and activity profile during a football match were recorded using a global positioning system only in the VPG. The mean heart rate (HR)of theoretical maximal HR (ThHRmax), and peak of ThHRmax were 83.9 ± 8.6% and 98.6 ± 10.2%, respectively; the mean of total distance covered was 3666 ± 721 m, and the means of accelerations and decelerations were 419 ± 61 and 428 ± 65, respectively. Lifelong participation in football training improves regional BMD and BMC in legs, femur and lumbar spine compared to the CG. A high number of intense actions in term of HR and accelerations and decelerations suggests an elevated energy expenditure that in turn correlates to the healthier body composition observed in the VPG compared to the CG.

Serum high sensitivity C-reactive protein poorly predicts bone mineral density: A NHANES 2017-2020 analysis.

A reliable, widely available method to detect osteoporosis prior to fracture is needed. Serum levels of C-reactive protein may independently predict low bone mineral density (BMD) and high fracture risk. Existing empirical data focus on sexually and/or racially homogenous populations. This study tests the hypotheses that: C-reactive protein (1) negatively correlates with BMD and (2) fracture history, and (3) independently predicts BMD and fracture history in a diverse population. NHANES 2017-2020 pre-pandemic cycle data were analyzed in R studio. Strength and direction of relationships (-1 to +1) between variables were determined using Kendall's rank correlation coefficient (τ). Linear models were optimized to predict femoral neck or lumbar spine BMD. C-reactive protein positively correlated with femoral (τ = 0.09, p<0.0001) and spine BMD (τ = 0.10, p<0.0001). Individuals identifying as female demonstrated more robust, but still weak, correlations between C-reactive protein and femoral neck (τ = 0.15, p<0.0001; male, τ = 0.06, p = 0.051) and spine BMD (τ = 0.16, p<0.0001; male, τ = 0.06, p = 0.04). C-reactive protein positively correlated with fracture history (τ = 0.083, p = 0.0009). C-reactive protein significantly predicted femoral neck (R2 = 0.022, p = 0.0001) and spine BMD (R2 = 0.028, p<0.0001) and fracture history (R2 = 0.015, p<0.0001). Exploratory analyses identified weight was the single best predictor for femoral neck (R2 = 0.24, p<0.0001) and spine BMD (R2 = 0.21, p<0.0001). In sum, C-reactive protein statistically correlates with and predicts femoral neck and spine BMD, but the magnitude is too low to be biologically meaningful. While weight is a more robust predictor, individuals who are overweight or obese account for nearly half of all osteoporotic fractures, limiting the predictive power of this variable at identifying individuals at risk for osteoporosis. Identification of a robust predictor of fracture risk in a diverse population and across of range of body weights and compositions is needed.

Trabecular bone score in adults with type 1 diabetes: a meta-analysis.

Fracture rates in type 1 diabetes mellitus (T1DM) are disproportionately high compared to the modestly low bone mineral density (BMD). Distortion of bone microarchitecture compromises bone quality in T1DM and is indirectly measured by trabecular bone score (TBS). TBS could potentially be used as a screening tool for skeletal assessment; however, there are inconsistencies in the studies evaluating TBS in T1DM. We performed this meta-analysis to address this knowledge gap. An electronic literature search was conducted using PubMed, Scopus, and Web of Science resources (all-year time span) to identify studies relating to TBS in T1DM. Cross-sectional and retrospective studies in adults with T1DM were included. TBS and BMD data were extracted for pooled analysis. Fracture risk could not be analyzed as there were insufficient studies reporting it. Data from six studies were included (T1DM: n = 378 and controls: n = 286). Pooled analysis showed a significantly lower TBS [standardized mean difference (SMD) = - 0.37, 95% CI - 0.52 to - 0.21; p < 0.00001] in T1DM compared to controls. There was no difference in the lumbar spine BMD (6 studies, SMD - 0.06, 95% CI - 0.22 to 0.09; p = 0.43) and total hip BMD (6 studies, SMD - 0.17, 95% CI - 0.35 to 0.01; p = 0.06) in the case and control groups. Adults with T1DM have a lower TBS but similar total hip and lumbar spine BMD compared to controls. The risk attributable to the significant but limited difference in TBS falls short of explaining the large excess propensity to fragility fracture in adults with T1DM. Further studies on clarification of the mechanism and whether TBS is suited to screen for fracture risk in adults with T1DM are necessary.

Bone marrow metabolism is affected by body weight and response to exercise training varies according to anatomical location.

High body weight is a protective factor against osteoporosis, but obesity also suppresses bone metabolism and whole-body insulin sensitivity. However, the impact of body weight and regular training on bone marrow (BM) glucose metabolism is unclear. We studied the effects of regular exercise training on bone and BM metabolism in monozygotic twin pairs discordant for body weight. We recruited 12 monozygotic twin pairs (mean ± SD age 40.4 ± 4.5 years; body mass index 32.9 ± 7.6, mean difference between co-twins 7.6 kg/m2 ; eight female pairs). Ten pairs completed the 6-month long training intervention. We measured lumbar vertebral and femoral BM insulin-stimulated glucose uptake (GU) using 18 F-FDG positron emission tomography, lumbar spine bone mineral density and bone turnover markers. At baseline, heavier co-twins had higher lumbar vertebral BM GU (p < .001) and lower bone turnover markers (all p < .01) compared with leaner co-twins but there was no significant difference in femoral BM GU, or bone mineral density. Training improved whole-body insulin sensitivity, aerobic capacity (both p < .05) and femoral BM GU (p = .008). The training response in lumbar vertebral BM GU was different between the groups (time × group, p = .02), as GU tended to decrease in heavier co-twins (p = .06) while there was no change in leaner co-twins. In this study, regular exercise training increases femoral BM GU regardless of weight and genetics. Interestingly, lumbar vertebral BM GU is higher in participants with higher body weight, and training counteracts this effect in heavier co-twins even without reduction in weight. These data suggest that BM metabolism is altered by physical activity.

Analysis of the predictive value of the Geriatric Nutritional Risk Index for osteoporosis in elderly patients with T2DM: a single-center retrospective study

BackgroundMalnutrition is recognized as a risk factor for osteoporosis and T2DM. Previous studies have demonstrated the relationship between nutritional assessment tools and BMD. However, few studies have compared the effects of three nutritional risk assessment tools (GNRI, CONUT, and PNI). This study aimed to investigate the correlation between three nutritional assessment tools and BMD and to compare their validity in predicting osteoporosis in type 2 diabetes mellitus in the elderly.MethodsThis retrospective study collected clinical data from 525 elderly patients with type 2 diabetes mellitus and categorized the patients into osteoporotic and non-osteoporotic groups. The correlation between the three nutritional assessment tools and BMD was analyzed using Spearman partial correlation. Binary logistics regression was used to analyze the relationship between GNRI and osteoporosis. ROC curves were used to compare the validity of GNRI, PNI, and CONUT in predicting osteoporosis.ResultsSpearman’s partial correlation showed a positive correlation between femoral neck BMD and lumbar spine BMD, but no correlation was observed between total hip BMD and GNRI. Logistic regression analyses showed no association between PNI, CONUT scores, and the development of osteoporosis. After adjusting for age, sex, smoking, alcohol consumption, BMI, ALB, Cr, UA, FBG, TG, and HDL, the correlation between GNRI and osteoporosis remained. ROC curve analysis showed that GNRI in combination with age and albumin had better predictive ability for osteoporosis than PNI and CONUT.ConclusionGNRI was an independent protective factor against osteoporosis in elderly patients with T2DM, and the predictive ability of GNRI for osteoporosis in elderly patients with T2DM was better than that of PNI and CONUT scores.

THU465 Significant Improvement In Bone Mineral Density Following Treatment For Tumor Induced Osteomalacia

Abstract Disclosure: L.C. McHan: None. M. Augustine: None. Background: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by renal phosphate wasting and impaired activation of vitamin D due to excess secretion of FGF23, often from phosphaturic mesenchymal tumors (PMTs). TIO typically presents with months to years of bone pain, muscle weakness, and fractures often leading to functional decline. Given these nonspecific symptoms, diagnosis of TIO can be delayed for years. Removal of the tumor is curative, though it can sometimes be a challenge to localize. For those whose tumors are unable to be localized or removed, medical management with phosphorus and vitamin D is recommended. Patients with TIO have low bone mineral density (BMD) at time of diagnosis. Case Reports: We are presenting two cases of TIO, one managed surgically and one managed medically. Patient 1 is a 45-year-old man with Fabry disease who presented with years of progressive pain, difficulty ambulating, and multiple fractures. Lab workup revealed low serum phosphorus, elevated urinary phosphorus, elevated FGF23, and negative genetic testing for heritable causes of hypophosphatemic osteomalacia. DOTATATE imaging identified a subcutaneous left flank mass, which was excised resulting in improvement in symptoms and resolution of biochemical abnormalities. Additionally, lumbar spine (LS) bone mineral density (BMD) nearly doubled; prior to diagnosis of TIO, LS BMD was 0.601 g/cm2 and 8 months after surgical excision of the tumor, LS BMD was 1.178 g/cm2. Patient 2 is a 55-year-old nonverbal man with autism and intellectual disability who presented with months of progressive difficulty ambulating, presumed pain, functional decline, and multiple fractures. Workup revealed low serum phosphorus, elevated urinary phosphorus, and elevated FGF23 concerning for TIO. He was initiated on phosphorus and vitamin D supplementation, but no culprit tumor has been identified despite multiple scans over the course of years. However, the patient has had a significant improvement in functioning with medical management in addition to a remarkable 48% improvement in LS BMD, from 0.855 g/cm2 prior to diagnosis of TIO and 1.264 g/cm2 following 3 years of medical management. Clinical Lessons: In our review of the literature, there are few case reports and case series documenting the significant improvements in BMD with treatment of TIO. In our experience, two patients who had months to years of debilitating symptoms exhibited remarkable improvements in symptoms and marked improvement in LS BMD following treatment. This emphasizes the importance of recognizing the diagnosis of TIO, as even when the causative tumor is not identified, treatment typically has a significant impact on patient functioning and quality of life. Presentation: Thursday, June 15, 2023

THU420 Analysis Of Factors Affecting Bone Mineral Density In Children And Adolescents With Systemic Lupus Erythematosus

Abstract Disclosure: M. Ahn: None. S. Park: None. B. Suh: None. Background: Children and adolescents with chronic disease are at risk of developing bone fragility. In particular, low bone mineral density(BMD) is increasingly recognized in pediatric patients with glucocorticoid treated rheumatic disease. The purpose of this study was to evaluate the clinical characteristics of children and adolescents with systemic lupus erythematosus(SLE), and to analyze the factors associated with a lower BMD in these patients. Methods: Children and adolescents diagnosed with SLE who had received GC treatment were included. Clinical and laboratory data including anthropometry, GC exposure, other anti-rheumatic drug treatment, biochemical markers related to bone metabolism, serologic markers of disease activity in SLE, lateral thoracolumbar(D-L) spine radiography, and BMD were collected. Lumbar spine bone mineral density (LSBMD) was measured by Dual-energy x-ray absorptiometry(DXA). The correlation between BMD and anthropometry, steroid and anti-rheumatic treatment, biochemical variables was investigated. Results: A total of 30 patients with median age of 17.5 years (range 12 -25years) were included. Of the 29 patients who had DXA done, 7 patients had LSBMD z score lower than −2.0, and diagnosed as osteoporosis. SLE patients with osteoporosis were compared with those with a z score higher than −2.0. These patients had longer GC exposure, higher cumulative GC dose, longer hydroxychloroquine exposure. The main factor correlated with a low BMD was duration of GC exposure. BMD was positively correlated with height at diagnosis. Bone metabolic markers and serologic markers of disease activity in SLE had no significant correlation with BMD. Conclusion: Children and adolescent SLE patients with OP had longer GC exposure, higher cumulative GC dose compared with those with LSBMD z score higher than −2.0. The main factor correlated with a low BMD was duration of GC exposure. Therefore, efforts should be made to reduce the duration of GC exposure and reduce medication to the lower possible maintenance dose. Since longer treatment duration affects BMD, close monitoring during the treatment period is recommended to prevent further loss of bone mass in pediatric SLE patients. Presentation: Thursday, June 15, 2023

FRI683 Every Dose Counts: Response To Half The Recommended Dose Of Romosozumab

Abstract Disclosure: B.P. Ramchandani: None. F.S. Mirza: None. Introduction: Romosozumab (RSB) is a monoclonal antibody that inhibits sclerostin, increases bone formation and decreases bone resorption. It was approved by FDA in 2019 at a dose of 210 mg monthly for 1 year, followed by an anti-resorptive medication. We present a case of a 76 y.o. female with severe osteoporosis and history of intolerance to multiple medications, who was given half the monthly recommended dose of Romo due to extreme concern about side effects. We hereby report the response of her bone density to the treatment. Case Description: A 76-year-old female with history of primary biliary cirrhosis, Sjogren’s syndrome, hemorrhagic duodenal ulcer, s/p subtotal gastrectomy in 1962 presented for evaluation of severe osteoporosis. Fracture history was significant for T11 compression fracture in 2020 requiring kyphoplasty, and a T10 inferior endplate compression fracture requiring vertebroplasty in 2022. Osteoporosis was first diagnosed in 2005. She was intolerant of teriparatide in 2005 (stopped after six months due to nausea, hypercalcemia, cramps, pain in extremities and fatigue). Zoledronic acid (ZA) was administered in 2006 and 2008. Baseline urine telopeptide cross-links (NTx) was low at 18 which decreased to 10 while on ZA and further infusions were held. She declined denosumab and teriparatide was tried again in 2013 that she did not tolerate. She received ZA again in 2016. BMD did not improve on ZA and she declined further infusions. She was physically active and walked daily and was taking calcium citrate, vitamin D and ursodiol during this time. On examination, she was frail and elderly, with BMI of 16.6 mg/kg2. She had mild kyphoscoliosis of the spine with no spinal or paraspinal tenderness. Remainder of the exam was unremarkable. Laboratory evaluation showed normal serum calcium (9.5 mg/dl), albumin (4.1g/dl), Vit D 25-OH (36 mg/ml), bone specific alkaline phosphatase of 22.7 U/L and urine NTx of 23 nm BCE/mm creatinine. Bone density (BMD) in January 2022 showed lumbar spine (LS) BMD of 0.613 g/cm2 (T-score −4.7) and a total hip BMD of 0.575 g/cm2 (T-score −3.4). She was reluctant to consider any medications due to concern about side effects, but finally agreed to a trial of RSB at half the recommended dose at 105 mg monthly for 12 months. DXA scan a year later showed 17% increase in LS BMD (0.715 g/cm2, T-score -3.9), with stable total hip BMD. She has been transitioned to denosumab, which she was now agreeable to take. Discussion: Our patient showed significant improvement in BMD with half the recommended dose of RSB, comparable to the increase in LS BMD reported in phase 3 trials. She was petite and her weight-based dose was just short of 3 mg/kg body weight. Phase 1 and 2 studies had tried weight based and smaller doses of Romo and showed improvement in BMD. This case highlights the need for additional studies with weight-based dosing of RSB, which may reduce the cost of treatment. Presentation: Friday, June 16, 2023

OR13-06 Romosozumab After Denosumab Improves Lumbar Spine Bone Mineral Density And Microarchitecture Greater Than Denosumab Continuation In Postmenopausal Women

Abstract Disclosure: N. Hong: None. S. Shin: None. H. Kim: None. Y. Rhee: None. Transitioning to romosozumab from antiresorptives can be an effective strategy to improve bone strength. A phase 2 trial and a few observational studies showed improvement of lumbar spine bone mineral density (BMD) with maintained hip bone density by romosozumab after denosumab. However, whether transition to romosozumab after denosumab is associated with greater improvement in BMD and microarchitecture compared to denosumab continuation remains unclear. In this propensity score-matched cohort study, we analyzed data from postmenopausal women who initiated denosumab between 2017 and 2020 (at least two injections; n=696). Individuals who were transited to 12 months of romosozumab after denosumab (n=105) were 1:1 matched to those who continued denosumab (n=591) by propensity score using age (69 years), body mass index, BMD, and numbers of denosumab injection at the time of transition, BMD improvement during denosumab treatment, prior fracture and bisphosphonate use (n=93 for each; denosumab-romosozumab [DR] and denosumab-denosumab [DD]). BMD gain by denosumab in DR and DD groups from denosumab initiation to transition time (to romosozumab or denosumab continuation; median 4 times [range 2 to 8] of denosumab injection) was +4.6% and +2.4% in the lumbar spine (LS, T-score −3.4 to −3.1) and total hip (TH, T-score −2.5 to −2.4), without statistical difference. DR group showed greater LSBMD gain compared to the DD (+7.0% vs. +2.5%, P&amp;lt;0.001) during 12 months after the transition time, yielding greater net LSBMD gain in DR (median 2 years of denosumab followed by 1-year romosozumab) compared to DD (median 3 years of denosumab; +11.6% vs. +7.0%, P&amp;lt;0.001). Differences in LSBMD gain between DR and DD groups remained robust (adjusted difference +4.7% point, P&amp;lt;0.001) after adjustment for covariates. Hip BMD changes did not differ between DR and DD (DR vs. DD; FN, +1.3% vs. +2.0%, p=0.409; TH, -0.9% vs. +0.2%, P=0.132). DR group showed significant improvement in the trabecular bone score during romosozumab use (1.288 to 1.311, p=0.005), whereas denosumab continuation in the DD group did not (1.297 to 1.309, p=0.103). During 12 months, one incident morphometric vertebral fracture (grade 1) and one nonvertebral fracture (patella) were observed in DD, whereas one ankle fracture was observed in the DR group. In summary, romosozumab after denosumab improved lumbar spine BMD and microarchitecture greater than denosumab continuation, with the maintenance of hip BMD. Presentation: Friday, June 16, 2023

FRI671 Association Of Insulin-like Growth Factor-1 (igf-1) With Bone Mineral Density (bmd) In Survivors Of Childhood Acute Leukemia

Abstract Disclosure: S. Kim: None. S. Park: None. S. Sim: None. S. Kim: None. M. Ahn: None. K. Shin Hee: None. W. Cho: None. C. Kyung Soon: None. M. Jung: None. B. Suh: None. Purpose: To investigate bone mineral deficit in children survivors of childhood acute leukemia and analyze the association of IGF-1 with BMD status Methods : A total 214 patients (aged 8.47±4.42 for girls and 8.31±4.09 for boys at diagnosis) who were treated for acute leukemia were retrospectively reviewed. Types of leukemia, transplantation, and radiation therapy were investigated. Standard deviation scores (SDSs) of height, weight, body mass index (BMI), and lumbar spine BMD were measured at the end of treatment. Lumbar spine BMD was measured using dual-energy x-ray absorptiometry (DXA). Its relationships with calcium, phosphorus, alkaline phosphatase, bone specific alkaline phosphatase, calcitriol, parathyroid hormone, growth hormone, IGF-1, and insulin-like growth factor-binding protein-3 (IGFBP-3) were analyzed. Low BMD was defined lumbar spine BMD SDS less than -2.0 according to International Society for Clinical Densitometry guideline. Results: The overall prevalence of low BMD was found to be 15% (32/214). Age at diagnosis, transplantation, and radiation therapy were not significantly different between low BMD and normal BMD groups, however, BMI SDS and IGF-1 SDS were different between those two groups (-0.84±1.94 vs. 0.17±2.09, P = 0.012; -1.23 ±0.82 vs. -0.72 ± 0.78, P = 0.001, respectively). Correlation analysis showed that IGF-1 SDS is associated with BMI SDS and lumbar spine BMD SDS (rho=0.19, P=0.006; rho=0.248, P=0.001, respectively). Lumbar spine BMD SDS was related to BMI SDS and IGF-1 SDS by multivariate linear regression analysis (β = 0.15, P = 0.003; β = 0.31, P = 0.021, respectively). Multivariate logistic regression analysis showed that higher IGF-1 SDS was associated with a decreased of prevalence of low BMD (odds ratio: 0.42, 95% confidence interval: 0.24-0.75, P = 0.003). Conclusion: IGF-1 SDS was related to BMD, especially lumbar spine BMD, and a risk of prevalence of low BMD in children and adolescents. IGF-1 SDS seems to be a good tool for evaluating and predicting osteoporosis in children and adolescents. Presentation: Friday, June 16, 2023

FRI673 REMS Technology For The Evaluation Of BMD In Hypothyroidism

Abstract Disclosure: F.A. Lombardi: None. P. Pisani*: None. A.P. Quezada*: None. M. Muratore*: None. M. Di Paola*: None. E. Casciaro*: None. F. Conversano*: None. S. Casciaro: None. *Equal contributors in alphabetical order Thyroid hormones play a crucial role in skeletal development, adult bone turnover, and bone maintenance, but they can also have detrimental effects on bone formation when there is thyroid dysfunction. Thyrotoxicosis (hyperthyroidism), including subclinical illness, can affect bone metabolism, resulting in decreased Bone Mineral Density (BMD) and increased fractures risk, and is a significant contributor to secondary osteoporosis, especially in postmenopausal women. On the other hand, little is known about the impact of overt or subclinical hypothyroidism on bone metabolism. However, hypothyroidism lessens bone turnover, reducing both osteoclastic bone resorption and osteoblastic activity. Such alterations in bone metabolism could potentially result in an increase in bone mineralization, although data on BMD and the risk of fracture in hypothyroidism are lacking and conflicting. Radiofrequency Echographic Multi-spectrometry (REMS) is a novel radiation-free technology for assessing BMD and fracture risk. In this context, the goal of this study was to assess BMD using REMS in patients with and without hypothyroidism, in order to look a possible correlation between the disease, BMD loss and fracture risk. Methods: A sample of 51 Caucasian females with hypothyroidism was compared to a reference group of healthy women who were matched for gender, ethnicity, age, and body mass index (BMI). Using REMS technology, the BMD was measurement at the lumbar spine in all participants at the study. To determine whether the two groups’ lumbar spine BMD value varied, a t-test was run. Results: Patients with and without hypothyroidism were matched in order to get similar anthropometric parameters. In patient with and without hypothyroidism mean ± standard deviation (SD) for age and BMI are (64.8 ± 10.2, 65.2 ± 9.8) and (25.1 ± 3.6, 25.0 ± 3.7), respectively. Patients with hypothyroidism were shown to have a significative lumbar spine BMD difference (0.801 g/cm2 ± 0.063 vs 0.831 g/cm2 ± 0.071, p=0.03) respect to the healthy subjects. Conclusions: Although just a small number of hypothyroidism patients are included in this investigation, without any indication of the drug therapy and its effect, it has been shown that, as compared to controls, women with hypothyroidism have a net decline in REMS-measured BMD values. Based on this thought, REMS technology, thanks to its precision and diagnostic accuracy, might improve the efficient care and follow-up programmes of these patients. Presentation: Friday, June 16, 2023

THU181 Evaluation Of Bone Mineral Density In A Cohort Of Children With ACH Participating In The PROPEL 2 Study Of Infigratinib

Abstract Disclosure: R. Savarirayan: Advisory Board Member; Self; Ascendis Pharma, BioMarin, QED Therapeutics, Sanofi, Sanofi. Consulting Fee; Self; BioMarin. Grant Recipient; Self; Ascendis Pharma, BioMarin, QED Therapeutics, Therachon. Research Investigator; Self; Ascendis Pharma, BioMarin, QED Therapeutics, Therachon. J. De Bergua: None. P. Arundel: None. J. Salles: None. A. Leiva-Gea: None. M. Irving: Advisory Board Member; Self; Ascendis Pharma, BioMarin, QED Therapeutics, Sanofi, Therachon/Pfizer. Speaker; Self; BioMarin, QED Therapeutics. V. Saraff: None. H. McDevitt: None. M. Salcedo: None. M.P. Nicolino: None. V. Cormier-Daire: Advisory Board Member; Self; BioMarin. P. Kannu: Advisory Board Member; Self; Novartis, Ipsen. Grant Recipient; Self; CIHR. M. Skae: None. M. Bober: Advisory Board Member; Self; Biomarin. Consulting Fee; Self; Ascendis Pharma, Biomarin, Pfizer, QED Therapeutics. Grant Recipient; Self; Ascendis Pharma, BioMarin, Pfizer, QED Therapeutics. Research Investigator; Self; Ascendis Pharma, BioMarin, Pfizer, QED Therapeutics. J. Phillips III: None. T. Candler: None. P. Harmatz: Consulting Fee; Self; Audentes, Aeglea, Homology, JCR, Denali, Inventiva, Paradigm, Capsida, Chiesi, Avrobio. Grant Recipient; Self; BioMarin, Inventiva. Research Investigator; Self; BioMarin, Shire/Takeda, QED Therapeutics, RegenXbio, Denali, Ascendis, Amicus, Allievex, JCR, Orphazyme, Idorsia, Sangamo. H. Saal: Advisory Board Member; Self; Alexion. Grant Recipient; Self; Alexion, BioMarin, Pfizer, QED Therapeutics. Research Investigator; Self; Alexion, BioMarin, Pfizer, QED Therapeutics. J. Hoover-Fong: Consulting Fee; Self; Pfizer/Therachon, BioMarin, QED Therapeutics, Sanofi, Ascendis Pharma. Grant Recipient; Self; Pfizer/Therachon, BioMarin, Ascendis Pharma. Research Investigator; Self; Pfizer/Therachon, BioMarin, Ascendis Pharma. E. Muslimova: Employee; Self; QED Therapeutics. Stock Owner; Self; QED Therapeutics. T. Cho: Employee; Self; QED Therapeutics. Stock Owner; Self; QED Therapeutics. R. Weng: Employee; Self; QED Therapeutics. Stock Owner; Self; QED Therapeutics. D. Rogoff: Employee; Self; QED Therapeutics. Stock Owner; Self; QED Therapeutics. Background: Achondroplasia (ACH) is the most common form of short-limbed skeletal dysplasias and is caused by an activating pathogenic variant of the fibroblast growth factor receptor 3 (FGFR3) gene. People with ACH are at risk for several significant co-morbidities, including foramen magnum stenosis, obstructive sleep apnea, chronic otitis media with conductive hearing loss, spinal stenosis, and a propensity towards obesity. Decreased bone mass has been observed previously in gain-of-function mutation Fgfr3 mice, and adults with ACH can have a decrease in bone mineral density (BMD). Here we describe baseline BMD of a cohort of children with ACH participating in PROPEL 2, a proof-of-concept study evaluating preliminary efficacy and safety of infigratinib, an oral FGFR-1-3 tyrosine kinase inhibitor in development for ACH. Methods: Dual energy X-ray absorptiometry (DXA) scans of the spine (L1-4) were collected at baseline in children participating in PROPEL 2 using a Hologic or GE Lunar scanner following a pre-specified image acquisition procedure. Images were evaluated by a single reviewer. Results are expressed as z-score for age and sex based on average-height children. Results: 52 children (mean±SD age: 7.97±1.9 years; 29 female; mean±SD height z-score: -5.4±1) were included in this analysis. BMD of the lumbar spine was -0.96±0.9 SDS (min -4.1; max 0.7 SDS). No statistical difference was found between males and females. 85% of children (n=44) had a BMD &amp;lt;0 SDS, from which 21 (40%) had a BMD between -2 and &amp;lt; -1 SDS, 18 (35%) presented a BMD between -1 and 0, and 5 (10%) presented a BMD &amp;lt; -2 SDS. Eight children (15%) had a BMD &amp;gt;0 SDS. No correlations were observed between BMD and age, height z-score or BMI. Conclusion: Our findings show that lumbar spine BMD is lower in children with ACH compared with normative data from children of average height. Low BMD in the context of short stature is difficult to interpret, raising the question of the degree to which low bone status can be attributed to smaller bone size relative to age. Even though our findings do not take into account children’s height, no correlation between BMD and baseline height z-score was identified in this cohort, suggesting that the findings may not be solely attributable to overall height. These findings reinforce the need to better understand how to circumvent this limitation in children with skeletal dysplasias in order to improve DXA interpretation and avoid misdiagnoses. Presentation: Thursday, June 15, 2023

FRI672 Bone Mineral Density In Neurofibromatosis Type 1: A Systematic Review And Meta-analysis

Abstract Disclosure: N. Charoenngam: None. P. Wattanachayakul: None. A. Jaroenlapnopparat: None. P. Ungprasert: None. J. Chenbhanich: None. Neurofibromatosis type 1 (NF1) is known to be associated with low bone mineral density (BMD) and fragility fractures. However, evidence supporting specific age of early BMD measurement is limited as data on the degree of bone loss in NF1 are lacking. Using systematic review and meta-analysis technique, we aimed to identify all available data to assess BMD in patients with NF1. Potentially eligible studies were identified from Medline and EMBASE databases from inception to February 2023 using search strategy that comprised of terms for “Bone mineral density” and "Neurofibromatosis type 1”. Eligible study must include adult or pediatric patients with NF1. The study must report mean Z-score with variance of total body, lumbar spine, femoral neck or total hip BMD of the studied patients. Point estimates with standard errors were retrieved from each study and were combined using the generic inverse variance method. A total of 1,165 articles were identified. After systematic review, 19 studies were included. The majority of participants in the included studies were children and younger adults with the mean age of participants lower than 50 years old in all but one study. The meta-analysis revealed that patients with NF1 had negative mean Z-scores for total body BMD (pooled mean Z-score -0.808; 95%CI, -1.025 - -0.591) and BMD at lumbar spine (pooled mean Z-score -1.104; 95%CI, -1.376 - -0.833), femoral neck (pooled mean Z-score -0.726; 95%CI, -0.893 - -0.560) and total hip (pooled mean Z-score -1.126; 95%CI, -2.078 - -0.173). The subgroup meta-analysis in pediatric patients aged &amp;lt;18 years revealed that patients with NF1 had negative mean Z-scores for lumbar spine BMD (pooled mean Z-score -0.938; 95%CI, -1.299 - -0.577) and femoral neck BMD (pooled mean Z-score -0.585; 95%CI, -0.872 - -0.298). Based on the results from the meta-analysis, patients with NF1 had low Z-scores. However, the lower limits of the 95% CIs for the pooled mean Z-score for total body and specific site BMD were all higher than the Z-score cut-off of -2 for “low BMD for chronological age” in children and adults aged &amp;lt;50 years old. Therefore, the degree of low BMD may not be of clinical significance. Our results do not support the role of early BMD screening in children and young adults with NF1. Presentation: Friday, June 16, 2023