Decreased Bone Mineral Density Research Articles

Zoledronate Sequential Therapy After Denosumab Discontinuation to Prevent Bone Mineral Density Reduction

ImportanceDiscontinuation of denosumab without transitioning to another antiresorptive agent results in rapid bone loss and an increased risk of fracture. Previous randomized studies reported inconsistent results regarding the efficacy of zoledronate as sequential therapy.ObjectiveTo investigate the use of sequential therapy with zoledronate to prevent bone loss and decreased bone mineral density (BMD) after denosumab discontinuation in the first year.Design, Setting, and ParticipantsThe Denosumab Sequential Therapy prospective, open-label, parallel-group randomized clinical trial was conducted at a referral center and 2 affiliated hospitals in Taiwan. Recruitment was conducted from April 1, 2019, to May 31, 2021, and a 2-year follow-up was planned. The trial included postmenopausal women and men aged 50 years or older who received regular denosumab treatment for at least 2 years and did not have previous exposure to other antiosteoporosis medication or meet other exclusion criteria.InterventionParticipants were assigned via stratified randomization to 1 of 2 groups: group A received continuous denosumab treatment (60 mg twice yearly) as the positive control, whereas group ZOL received 1 dose of zoledronate (5 mg) in the first year.Main Outcomes and MeasuresThe coprimary outcomes were BMD percentage changes in the lumbar spine (LS-BMD), total hip (TH-BMD), and femoral neck (FN-BMD), respectively. An intention-to-treat analysis was performed.ResultsThis study included 101 patients (95 women [94.1%]; median age, 72.0 [IQR, 67.0-76.0] years). There were 25 patients in group A (23 women [92.0%]; median age, 74.0 [IQR, 70.0 to 78.0] years) and 76 in group ZOL (72 women [94.7%]; median age, 71.0 [IQR, 65.7 to 76.0] years). In the first year, group ZOL had a significant median decrease in LS-BMD (−0.68% [IQR, −3.22% to 2.75%]) compared with group A (1.30% [IQR, −0.68% to 5.24%]) (P = .03). No significant differences between groups A and ZOL were observed for TH-BMD (median, 1.12% [IQR, −0.06% to 2.25%] vs 0% [−1.47% to 2.15%]) (P = .24) and FN-BMD (median, 0.17% [IQR, −2.29% to 2.90%] vs 0.18% [−2.73% to 3.88%]) (P = .71). We observed a significant difference in the median LS-BMD percentage change for the ZOL subgroup with 3 or more years of denosumab treatment before enrollment (−3.20% [IQR, −7.89% to 0.68%]) compared with group A (1.30% [IQR, −0.68% to 5.24%]) (P = .003).Conclusions and RelevanceIn this randomized trial of sequential therapy after denosumab discontinuation, bone loss was observed in LS-BMD in the first year among patients receiving zoledronate. A longer duration of denosumab treatment was associated with a further decrease in LS-BMD after zoledronate sequential therapy. Further randomized clinical trials and large-scale studies that investigate the strategies of sequential therapy after long-term denosumab treatment are needed.Trial RegistrationClinicalTrials.gov Identifier: NCT03868033

F2-Isoprostanes Are Associated With Increased Fracture Risk in Type 2 Diabetes.

Fracture risk is higher in type 2 diabetes (T2D) for a given bone mineral density (BMD) level. Increased oxidative stress in T2D induces diabetic complications and may affect T2D bone fragility. To investigate whether the levels of plasma F2-isoprostanes, a reliable oxidative stress marker, are associated with incident clinical fracture risk in older adults with diabetes. An observational cohort study was conducted in a well-characterized cohort from Health, Aging, and Body Composition study. Older black and white ambulatory adults with baseline plasma F2-isoprostanes measurements (baseline age 70-79 years, T2D: N=132; non-diabetes: N=571) were selected from the study cohort of 3075 individuals. Incident clinical fractures. In the Cox proportional hazard model with multivariate adjustments (including BMD, medications, and other risk factors), a 93% increase in incident clinical fracture risk was significantly associated with each SD increase in log plasma F2-isoprostanes in the T2D group (HR: 1.93, 95% CI 1.26-2.95, p=0.002), but there was no evidence of an association in the non-diabetes group (HR: 0.98, 95% CI 0.81-1.18, p=0.79, p for interaction < 0.001). Log plasma F2-isoprostanes were moderately correlated with a decline in baseline total hip BMD (r=-0.25, p=0.003), and with a 4-year decrease in total hip BMD (r=-0.28, p=0.008) in T2D. There was no evidence of correlation between log plasma F2-isoprostanes and circulating glycoxidation markers or bone turnover markers in either group. Plasma F2-isoprostanes levels in individuals with diabetes are associated with increased incident clinical fracture risk independently of baseline BMD.

Early signs of osteoarthritis in differing rat osteochondral defects.

Preclinical models of osteochondral defects (OCDs) are fundamental test beds to evaluate treatment modalities before clinical translation. To increase the rigor and reproducibility of translational science for a robust "go or no-go," we evaluated disease progression and pain phenotypes within the whole joint for two OCD rat models with same defect size (1.5x 0.8 mm) placed either in the trochlea or medial condyle of femur. Remarkably, we only found subtle transitory changes to gaits of rats with trochlear defect without any discernible effect to allodynia. At 8-weeks post-surgery, anatomical evaluations of joint showed early signs of osteoarthritis with EPIC-microCT. For the trochlear defect, cartilage attenuation was increased in trochlear, medial, and lateral compartments of the femur. For condylar defect, increased cartilage attenuation was isolated to the medial condyle of the femur. Further, the medial ossicle showed signs of deterioration as indicated with decreased bone mineral density and increased bone surface area to volume ratio. Thus, OCD in a weight-bearing region of the femur gave rise to more advanced osteoarthritis phenotype within a unilateral joint compartment. Subchondral bone remodeling was evident in both models without any indication of closure of the articular cartilage surface. We conclude that rat OCD, placed in the trochlear or condylar region of the femur, leads to differing severity of osteoarthritis progression. As found herein, repair of the defect with fibrous tissue and subchondral bone is insufficient to alleviate onset of osteoarthritis. Future therapies using rat OCD model should address joint osteoarthritis in addition to repair itself.

Biometric Changes Up to 2 Years After Hip Arthroscopy in National Collegiate Athletic Association Division I Athletes.

Patients who undergo hip arthroscopy for femoroacetabular impingement (FAI) require lower extremity immobilization for an extended period of time. Periods of immobilization combined with surgery have been associated with decreased muscle mass and bone mineral density (BMD). The purpose of this study was to characterize postoperative body composition and BMD changes after arthroscopy for FAI. It was hypothesized that both lean mass and BMD would decrease postoperatively and then normalize over time. Case series; Level of evidence, 4. This was a retrospective review of 23 National Collegiate Athletic Association Division I athletes who underwent hip arthroscopy between 2017 and 2019 and had a dual-energy x-ray absorptiometry scan preoperatively and at 3, 6, 12, or 24 months postoperatively. Linear mixed-effects models were used to compare pre- with postoperative lean and fat mass values for the total body and total leg (both operative and nonoperative sides) as well as trunk, pelvic, and spinal BMD. For total-leg, femur, and femoral BMD, linear mixed-effects models were used to evaluate the influence of time, side (operative vs nonoperative), and their interaction on each outcome measure. Regarding pelvic BMD, compared with baseline (mean, 1.41 g/cm2 [95% CI, 1.33-1.49]), significant decreases were seen at postoperative 3 months (mean, 1.36 g/cm2 [95% CI, 1.28-1.45 g/cm2]; P < .001) and 6 months (mean, 1.39 g/cm2 [95% CI, 1.27-1.52 g/cm2]; P < .01) but not at 12 months (mean, 1.42 g/cm2 [95% CI, 1.33-1.51 g/cm2]; P = .319). Total-leg BMD for the operative side increased significantly from baseline (mean, 1.52 g/cm2 [95% CI, 1.43-1.61 g/cm2]) to ≥2 years postoperatively (mean, 1.56 g/cm2 [95% CI, 1.47-1.65 g/cm2]) (P = .005). Combined leg fat mass was increased from baseline (mean, 6427 g [95% CI, 4855-7999 g]) to ≥2 years (mean, 11645 g [95% CI, 7845-15,446 g]) (P < .01). There were no significant differences in total-body fat or lean mass or combined-leg lean mass. In this patient population, a postoperative decrease in pelvic BMD that resolved by 12 months and an increase in total-leg BMD on the operative side at ≥2 years were observed. While hip arthroscopy for FAI may have significant benefits for long-term body composition and bone mass, clinicians should be aware of the potential implications of decreased bone mass for up to 12 months postoperatively.

Optimized surveillance frequency for low bone mineral density (BMD) screening using dual energy X-ray absorptiometry (DXA) in patients after lung transplant

BackgroundApproximately 2700 lung transplants are performed annually in the United States. These patients are at increased risk of developing low bone mineral density (osteopenia/osteoporosis) and subsequent osteoporosis-related fractures. Dual energy x-ray absorptiometry (DXA) is the most common method used for screening for low BMD, however, the optimal surveillance frequency for low BMD using DXA is unknown. MethodsWe evaluated the change in femoral neck, total femur, L1, L2, L3 and L4 BMD after lung transplant in a retrospective cohort of 259 patients (69.9% male) who were followed with serial DXA scans for a median of 725 (interquartile range (IQR) (361-1116)) days after transplant. Generalized linear mixed effects models allowing for random intercepts and random slopes adjusting for sex, time, time-squared, baseline osteopenia/osteoporosis, active rejection, and their interaction terms were used to model the rate of change of BMD at each site. The final multivariable models for the femoral neck, L1, and L4 BMD measurements had random slopes and intercepts, and the models for the total hip, L2, and L3 measurements had random slopes. Results65% of the patients undergoing lung transplants had osteopenia or osteoporosis before transplant. Men exhibited higher baseline BMD levels compared to women at all sites (P<0.001 for all). After transplant, the greatest rate of BMD decrease was at the femoral neck. Although patients with low BMD (osteopenia/osteoporosis) had significantly lower baseline BMDs (P<0.001 for all), they experienced a slower rate of BMD decrease at all sites compared to patients with normal BMD at baseline (P<0.001 for all). All patients received corticosteroids. 25% of patients had a history of active rejection. Patients with low BMD at baseline had significantly higher odds of receiving bisphosphonate therapy (odds ratio (OR) = 3.95, 95% CI (1.44, 13.51), P=0.003). We estimated that a significant change in the femoral neck BMD would be expected to occur within 409 days (95% CI (131, 708)) and again at 867 days (95% CI (551, 1216)) after lung transplant. ConclusionsOn average, patients undergoing lung transplant should be screened annually with DXA for the first two years after transplant, consistent with the current International Society for Heart and Lung Transplantation (ISHLT) guidelines.

Beta thalassemia minor: a potential risk factor for osteopenia and osteoporosis

A 74-year-old male patient with beta thalassemia minor presented in 2022 for a follow-up of osteoporosis diagnosed prior to 2004. At the time of presentation, his medical history included: radiation exposure to his head and neck, goiter, prostate cancer status post resection in 2019 without a history of anti-androgen therapy, and atrial fibrillation, for which he had been prescribed apixaban since 2021. Treatment with risedronate occurred from approximately 2004 to about 2011, with improvement in bone density to osteopenia. He had also taken vitamin D and calcium supplementation and engaged in regular weight-bearing exercise. The patient had no other known risk factors for decreased bone mineral density preceding the onset of his osteoporosis, and a previous workup for secondary causes of his osteoporosis etiology proved negative. We propose that beta thalassemia minor is potentially a risk factor for osteopenia and osteoporosis, and that bisphosphonates can be considered for management when therapeutic intervention is indicated. Even in the absence of other known risk factors, clinicians should consider periodically screening beta thalassemia minor patients with DXA for evaluation of bone health.

Fine particulate matter induces osteoclast-mediated bone loss in mice.

Fine particulate matter (FPM) is a major component of air pollution and has emerged as a significant global health concern owing to its adverse health effects. Previous studies have investigated the correlation between bone health and FPM through cohort or review studies. However, the effects of FPM exposure on bone health are poorly understood. This study aimed to investigate the effects of FPM on bone health and elucidate these effects in vitro and in vivo using mice. Micro-CT analysis in vivo revealed FPM exposure decreased bone mineral density, trabecular bone volume/total volume ratio, and trabecular number in the femurs of mice, while increasing trabecular separation. Histological analysis showed that the FPM-treated group had a reduced trabecular area and an increased number of osteoclasts in the bone tissue. Moreover, in vitro studies revealed that low concentrations of FPM significantly enhanced osteoclast differentiation. These findings further support the notion that short-term FPM exposure negatively impacts bone health, providing a foundation for further research on this topic.

Female Athlete Triad: Understanding the Interrelationship between Energy Availability, Menstrual Function, and Bone Health

The Female Athlete Triad (FAT) is a complex medical condition characterized by three interrelated components: low energy availability (EA) with or without disordered eating, menstrual dysfunction, and decreased bone mineral density (BMD). This syndrome is particularly prevalent among female athletes who engage in sports that prioritize leanness, endurance, and aesthetic performance, such as gymnastics, dance, and long-distance running. Prolonged exposure to inadequate caloric intake relative to energy expenditure can disrupt hormonal regulation, leading to irregular or absent menstrual cycles (amenorrhea) and compromising bone health. This cross-sectional study aims to investigate the prevalence and impact of low EA on menstrual function and BMD among 180 female athletes aged 18-30 years. Participants were divided into three menstrual status categories: eumenorrhea, oligomenorrhea, and amenorrhea. The study also categorized athletes into sports groups (aesthetic, endurance, and power sports) to identify patterns across different disciplines. Data collection included dietary intake records, exercise logs, menstrual history questionnaires, and DEXA scans to measure BMD at the lumbar spine and hip. Results indicate that 67% of participants exhibited low EA (&lt; 30 kcal/kgFFM/day), which was significantly associated with menstrual dysfunction (p &lt; 0.001). Among participants, 25% reported oligomenorrhea (irregular cycles), and another 25% experienced amenorrhea (absence of menstruation for more than three months). BMD analysis revealed that 30% of the athletes had osteopenia, while 5% were diagnosed with osteoporosis, highlighting the long-term risks associated with chronic low EA and menstrual irregularities. Notably, athletes engaged in aesthetic sports had the highest prevalence of low EA (80%) and menstrual dysfunction (45%), followed closely by those in endurance sports. These findings underscore the urgent need for targeted interventions to promote energy balance, safeguard reproductive health, and prevent bone deterioration among female athletes. Educational programs focusing on nutritional counseling, regular monitoring of menstrual health, and multidisciplinary care involving coaches, sports dietitians, and healthcare providers are essential to mitigate the risks of the Female Athlete Triad. Future research should further explore psychological factors influencing energy availability, including body image concerns and disordered eating patterns, to develop comprehensive prevention strategies.

Association between urine creatinine excretion and bone mineral density in chronic kidney disease: Results from the KNOW-CKD study.

Decreased lean body mass or muscle mass is associated with decreased bone mineral density in individuals with preserved renal function. However, the association between muscle mass and bone mineral density in chronic kidney disease (CKD) patients is not well known. The aim of this study was to assess the relationship between muscle mass estimated from urine creatinine (UCr) and bone mineral density in Korean CKD patients. This cross-sectional study analyzed 1872 participants from the Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD) cohort. Participants underwent UCr (g/day) and bone mineral density measurements, which were measured at the lumbar spine, total hip, and femoral neck by dual-energy X-ray absorptiometry. Patients were divided into three groups according to the tertiles of 24h UCr (T1-T3). The mean values for 24h urine creatinine of T1, T2, and T3 were 0.83 ± 0.23g, 1.18 ± 0.24g, and 1.55 ± 0.38g, respectively. A total of 172 patients were diagnosed withosteoporosis. The number of patients in each group was 92 (14.4%) in T1, 45 (7.3%) in T2, and 35 (5.7%) in T3. The odds ratio (95% confidence interval) for osteoporosis was 0.37 (0.20-0.69) for 1g/day increase of UCr. Compared with T1, the odds ratios (95% confidence interval) for osteoporosis were 0.58 (0.39-0.87) for T2 and 0.51 (0.32-0.80) for T3. Low 24-h UCr was associated with low bone mineral density. Low 24h UCr was significantly and independently associated with osteoporosis in Korean pre-dialysis CKD patients. Further research is warranted to verify the influence of muscle mass on bone health in CKD.

Оценка нутритивного статуса и рисков его нарушения у детей с болезнью Крона: одномоментное исследование

Children with Crohn's disease (CD) are at high risk for developing nutritional deficiencies. According to studies in adult patients with CD, loss of lean and skeletal muscle mass and decreased bone mineral density (BMD) are unfavorable prognostic factors for the course of the disease; among children, the prevalence of these changes has not been sufficiently studied as yet. The purpose of this research was to study the frequency and correlation between disorders of body composition and decreased bone mineral density in children with CD. Materials and methods used: medical records of 163 aged 5 to 17 y/o with a confirmed CD diagnosis were assessed for the risk of nutritional deficiency using STRONGkids screening tool, anthropometric parameters, body composition with bioimpedance measurements as well as the disease activity index with PCDAI and endoscopic activity with SES-CD. BMD was assessed in 145 using densitometry. Results: depending on the degree of risk of malnutrition, children were divided into 2 groups as follows: G1 with high and G2 with moderate risks for malnutrition. G1 patients had significantly lower values of both anthropometric indices (Z-scores BMI/age, mid-upper arm circumference/age) and lean and skeletal muscle mass (p&lt;0.001) along with more severe course of CD according to PCDAI (p&lt;0.001). According to bioimpedansometry data, a significant increase in catabolic processes was found in G1 children as a decrease in Z-scores for both the phase angle (p&lt;0.001) and the active cell mass (p&lt;0.001). A decrease in BMD was detected in 9 (37%) of G1 and 26 (21.4%) of G2. A correlation was found between Z-scores lean body mass/age and BMD/age (p&lt;0.001, Rs=0.612). Among children with reduced BMD values, the indicators for BMI, lean, skeletal muscle and active cell mass according to bioimpedance measurements were significantly lower (p&lt;0.001). Conclusion: the data obtained during the study proposes high incidence of decreased bone mineral density along with pathological changes in body composition in children with CD. The use of STRONGkids tool to identify children at high risk of developing malnutrition, especially in the absence of the technical ability to conduct a detailed assessment of nutritional status with determination of body composition and BMD indicators, makes it possible to timely identify patients requiring individual nutritional support aiming to optimizing diets and, if necessary, prescribing addition of specialized food supplements.

Oral Health Status among Postmenopausal Women Attending Tertiary Hospital of Bharatpur, Nepal

Introduction: Menopause is a biological process occurring in middle aged women causing changes in the level of circulating hormones. Changes in the oral flora, oral mucosa and decrease in bone mineral density leads to many menopauses related oral findings. Objective: This study was conducted with the objective to assess the oral health status of postmenopausal women visiting tertiary health care centre in Bharatpur, Chitwan. Methods: Analytical cross-sectional study was conducted among 224 postmenopausal women attending dental OPD in a tertiary health care centre. Comprehensive oral examination was done where CPITN index was used to record periodontal health and DMFT index was used to record caries experience of the patient. Data entry was done in Microsoft Excel and statistical analysis was done using SPSS version 20. Results: Total 224 patients were examined with age range of 45 to 78 years and the mean age of 56.71 years. 113 study participants comprising 50.4%, showed supra or subgingival calculus followed by gingival bleeding in 54 (24.1%). Mean decayed score among study participants was found to be 2.71±2.85, mean missing score was found to be 4.29±7.83. Conclusion: Mean score for missing teeth suggestive of sequel of dental caries and periodontitis was found higher among the post-menopausal women followed by mean decayed score. Dental caries score was high probably due to dryness of mouth and other predisposing factors.

A Study on the Rationality of Baicalein in the Treatment of Osteoporosis: A Narrative Review.

Baicalein (BN) is an active ingredient naturally present in Chinese herbs, such as Scutellaria baicalein, Coptis chinensis, and Dendrobium officinale. It has a variety of pharmacological activities, including antioxidant, anti-inflammatory and antibacterial effects. Therefore, Baicalein (BN) is widely used in the field of medicine and is considered a potential natural medicine. Osteoporosis (OP) is a bone metabolic disease characterized by decreased bone mineral density and bone structure destruction, which is mainly caused by decreased bone formation and increased bone resorption. With the continuous development of molecular biology, the signaling pathways and gene targets of bone metabolism are also expanding. Recent studies have shown that baicalein may affect the function of osteoblasts, osteoclasts, and bone marrow mesenchymal stem cells through MAPK/ERK and MAPKs/NF-κB signaling pathways, so as to have a therapeutic effect on OP. However, the specific mechanism of baicalein in the treatment of OP is still unclear. This article reviews the literature, analyzes and summarizes the mechanism of action of baicalein, and discusses its potential in the prevention and treatment of OP, so as to provide a basis for the clinical application of baicalein.

Risk factors for a decrease in bone mineral density in patients with Hodgkin's lymphoma.

BACKGROUND: Osteoporosis is characterized by a discharge of bone mass, which contributes to the development of pathological fractures. Hodgkin's lymphoma can cause a violation of bone microarchitectonics. The development of Hodgkin's lymphoma is characteristic of young people, on average from 16 to 35 years old. Early diagnosis of osteoporosis in young patients with Hodgkin's lymphoma is an urgent issue due to a prolonged asymptomatic decrease in bone mineral density, with the development of pathological fractures. AIMS: to study the risk factors for a decrease in bone mineral density in patients with Hodgkin's lymphoma who received pathogenetic therapy. MATERIALS AND METHODS: the study included 63 patients with Hodgkin's lymphoma and 30 volunteers from the control group. All patients answered the questionnaire questions in order to identify risk factors for osteoporosis. Common risk factors included: gender, age, body mass index; fractures in the history of the patient and his immediate family; taking hormone replacement therapy, proton pump inhibitors, glucocorticosteroids; the presence of concomitant diseases; the presence of amenorrhea in women; physical activity level and calcium intake. Specific factors include the use of chemotherapy drugs for the treatment of Hodgkin's lymphoma. The data obtained were subjected to statistical analysis in order to identify the most significant risk factors. RESULTS: osteopenia and osteoporosis are a serious complication of antitumor therapy of Hodgkin's lymphoma in young people. Unfortunately, today a small number of researchers are engaged in the problem of identifying predictors of osteoporosis in young patients with Hodgkin's lymphoma. Because of this study, the most significant risk factors for the development of osteoporosis were identified, namely low physical activity, taking proton pump inhibitors and glucocorticosteroids, as well as the development of secondary postcytostatic amenorrhea in women. CONCLUSIONS: timely diagnosis and prevention of osteoporosis in young patients will prevent a decrease in bone mineral density and reduce the risks of early disability in this category of patients.

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.

From Genomics to Metabolomics: Molecular Insights into Osteoporosis for Enhanced Diagnostic and Therapeutic Approaches.

Osteoporosis (OP) is a prevalent skeletal disorder characterized by decreased bone mineral density (BMD) and increased fracture risk. The advancements in omics technologies-genomics, transcriptomics, proteomics, and metabolomics-have provided significant insights into the molecular mechanisms driving OP. These technologies offer critical perspectives on genetic predispositions, gene expression regulation, protein signatures, and metabolic alterations, enabling the identification of novel biomarkers for diagnosis and therapeutic targets. This review underscores the potential of these multi-omics approaches to bridge the gap between basic research and clinical applications, paving the way for precision medicine in OP management. By integrating these technologies, researchers can contribute to improved diagnostics, preventative strategies, and treatments for patients suffering from OP and related conditions.

7465 Impact Of Geography And Insurance On Healthcare Utilization Preferences Of Individuals With Congenital Adrenal Hyperplasia In The United States

Abstract Disclosure: P.N. Surampudi: Research Investigator; Self; Spruce Biosciences. A.H. Hamrahian: Consulting Fee; Self; Spruce Biosciences. Research Investigator; Self; Spruce Biosciences. R. Charlton: Employee; Self; Spruce Biosciences. P. Ramtin: Employee; Self; Spruce Biosciences. M.E. Geffner: Consulting Fee; Self; Spruce Biosciences, Ferring Pharmaceuticals, Adrenas, Neurocrine Biosciences, Novo Nordisk, Eton, Pfizer, Inc., Nutritional Growth Solutions, Nutritional Growth Solutions. Research Investigator; Self; Novo Nordisk. Background: Relative to the general population, patients with classic congenital adrenal hyperplasia (CAH) have increased risks for morbidity and mortality which require specialized management across life stages[1]. Endocrine care, particularly as part of multi-disciplinary teams, can help mitigate risks of developing adrenal crises as well as the impact of glucocorticoid under- or overexposure, including adrenal insufficiency; cardiometabolic risk associated with insulin resistance and excess weight gain; fertility issues associated with irregular menses and gonadal adrenal rest tumors; diminished quality of life; increased mental health issues, including anxiety, depression, and sleep disturbance; and increased fracture risk associated with decreased bone mineral density. Study Objectives and Design: We hypothesized that the utilization of endocrine and multi-disciplinary care by patients with CAH in the United States (U.S.) could be adversely affected by non-therapeutic factors related to geographic location and access to health care. In this cross-sectional study, we utilized the Definitive Healthcare database (Nov. 2020-Nov. 2022) to gain insight into these factors in adults with CAH. Study Findings: Analysis of healthcare provider utilization revealed that only ∼30% of U.S. adults with CAH received care from endocrinologists. The rest utilized primary-care providers (PCPs: IM, FP, NP, PA, and Ob-Gyn) to obtain care. A review of insurance coverage of U.S. adults with CAH suggests that ∼70% had access to commercial insurance and over 50% resided in states with the largest populations (California, Texas, New York, Florida, Ohio, Michigan, and Illinois), both factors which should ordinarily increase accessibility of subspecialty endocrine and multi-disciplinary care. Conclusions: In our study, only 30% of U.S. CAH adults received care from an endocrinologist. Limited utilization of specialty care does not appear to be due to either diverse geographical distribution or access to healthcare. The gap in expert care may adversely affect the management of CAH and contribute to associated comorbidities. Increased partnership between PCPs and endocrinologists, and increased awareness and education regarding specialty care among patients with CAH are needed to improve health outcomes and thereby reduce the risk of morbidity and mortality in adults with CAH.

5071 Impact of Estrogen Replacement Therapy on Bone Health in a Novel Non-human Primate Model of Postmenopausal Women Living with HIV

Abstract Disclosure: K. Sauter: None. D.L. Takahashi: None. G. Webb: None. H. Hofmeister: None. O. Varlamov: None. J. Sacha: None. P. Kievit: None. Current antiretroviral therapy (ART) regimens have rendered HIV a manageable chronic condition rather than a fatal disease, with people who initiate ART soon after infection achieving nearly normal life expectancy. As a consequence of increased survival, more women living with HIV (WLWH) will now undergo menopause and be subject to a disease burden that reflects age along with adverse skeletal consequences of postmenopausal estrogen deficiency. In addition to known bone loss and increased fracture risk in postmenopausal women, ART also causes decreased bone mineral density. Therefore ART-suppressed WLWH may have a compounded detrimental effect on bone due to long-term ART treatment combined with menopause that may be attenuated with estrogen replacement. Eleven rhesus macaques were infected intravenously with SIVmac239M and received ART two weeks post-infection (PI). All animals were ovariectomized (OVX) at 35 weeks PI and received estrogen implants (n=6) or cholesterol implants (n=5). Weekly blood samples were collected and animals were monitored longitudinally for body composition including bone mineral content (BMC) via dual x-ray absorptiometry (DEXA). Infection with SIV caused a significant decrease, -8.2%, in pelvis BMC after 14 days of peak viremia with SIV. These changes were not observed in the BMC of spine or extremities. BMC remained suppressed by ∼7% for an additional 25 weeks PI during ART treatment. Measurement of circulating bone turnover markers (BTMs), osteocalcin and C-terminal telopeptide of type 1 collagen (CTX), decreased post infection without significant improvement after ART suppression. Induction of menopause via OVX and loss of estrogen induced a drastic increase in BTMs with a much larger increase in CTX, indicating potential global bone loss due to OVX. Post-implant, the control animals’ pelvis BMC continued to decrease to -20.9% and pelvis BMD to -9.3% indicating that OVX further exacerbated the effect of SIV and ART. However, animals that received estrogen implants demonstrated marked improvement in both measures to greater than baseline. SIV and subsequent long-term ART negatively impact pelvic BMC and BMD and this effect is compounded by menopause in our model of post-menopausal WLWH. However, estrogen replacement post-menopause may attenuate these detrimental bone effects despite long-term ART treatment. Presentation: 6/1/2024

12455 Bone Mineral Density Improvement After Resolution Of Endogenous Cushing Syndrome

Abstract Disclosure: C. Plessias: None. N. Charoenngam: None. T. Rittiphairoj: None. T. Suenghataiphorn: None. T. Srikulmontri: None. P. Wattanachayakul: None. M. Kurt: None. Bone Mineral Density Improvement After Resolution of Endogenous Cushing Syndrome: a Meta-analysis and meta-regression Patients with endogenous Cushing syndrome (eCS) are known to have decreased bone mineral density (BMD) and are prone to fragility fractures. Treatment of eCS have been shown in multiple studies to result in improvement in BMD. However, the degree of BMD improvement after resolution of eCS remains inadequately explored due to limited sample sizes in existing studies. Through systematic review, meta-analysis, and meta-regression techniques, we aimed to identify all available evidence to evaluate BMD improvement after resolution of eCS. Potentially eligible studies were identified from the PubMed and EMBASE databases from inception to February 2024, utilizing a search strategy incorporating terms related to "Bone mineral density" and "Cushing syndrome". Eligible studies must include adult or pediatric patients diagnosed with any form of eCS, encompassing Cushing disease (CD), adrenal adenoma, mild autonomous cortisol secretion or ectopic ACTH-secreting tumors, who received treatment resulting in CS resolution. These studies must either present lumbar spine (LS) or femoral neck (FN) BMD measurements in the form of T-score, Z-score or actual BMD values before and after CS resolution, or report mean differences (MD) of BMD, or provide individual BMD data. Point estimates with corresponding standard errors were extracted from each study and combined using the generic inverse variance method. Meta-regression analysis was utilized to explore the impact of time after resolution of eCS on BMD improvement.A total of 5,085 records were identified from the databases. After systematic review, 14 studies, including a total of 386 patients, were deemed eligible for analysis. The meta-analysis demonstrated that resolution of eCS resulted in statistically significantly improvement of LS BMD (pooled MD: Z-score: +0.76, 95%CI 0.50 – 1.02, I2 76%; T-score: +0.87, 95%CI 0.55 – 1.19, I2 78%; actual BMD: +0.092 g/cm2, 95%CI 0.060 – 0.124, I2 74%) and FN BMD (pooled MD: Z-score: +0.54, 95%CI 0.32 – 0.76, I2 75%; T-score: +0.38, 95%CI 0.25 – 0.51, I2 0%; actual BMD: +0.041 g/cm2, 95%CI 0.021 – 0.062, I2 0%). The meta-regression analysis revealed a statistically significant association between follow-up time and improvements in LS T-score BMD (predicted LS T-score improvement = 0.42 + 0.062 × year, p = 0.027) and FN Z-score BMD (predicted FN Z-score improvement = 0.35 + 0.037 × year, p = 0.003), but not with LS Z-score and FN T-score.In summary, our study presents the extent of improvement in LS and FN BMD following the resolution of eCS based on all available data in the literature. These findings have clinical significance as they offer guidance for management of osteoporosis following the resolution of eCS. Presentation: 6/3/2024

8711 The Effect of Testosterone Therapy Upon Bone Remodelling in Testosterone Deficient APOE-/- Mice Fed a High Fat Diet

Abstract Disclosure: A. Williamson: None. L. Bateman: None. C. LeMaitre: None. T.H. Jones: None. N. Aberdein: None. D.M. Kelly: None. Introduction: Low testosterone can lead to bone loss in males, but the mechanisms are not fully characterised. This study investigates the effects of testosterone depletion, and subsequent testosterone treatment on parameters of bone remodeling in a murine model of cardiometabolic disease. Methods: At 8 weeks of age, high-fat diet-fed ApoE-/- mice were randomised into three groups: sham surgery + placebo treatment (control, n=9), orchidectomy + placebo treatment (n =8), and orchidectomy + testosterone treatment (n=10). 25 week old mice were sacrificed and tissues collected for analysis. Left tibiae were decalcified, paraffin embedded and sectioned prior to immunostaining of bone turnover markers including receptor activator of nuclear factor κB ligand (RANKL), Osteoprotegerin (OPG), runx2, Alkaline Phosphatase (ALP), adiponectin and marrow lipid content. Right tibiae underwent mechanical 3-point bend testing at 0.05mm/s using a CellScale Univert. Results: µCT demonstrated a significant decrease in trabecular bone volume, number, and bone mineral density (BMD) and increased trabecular thickness in orchidectomised mice compared to controls. These parameters returned to control levels in testosterone treated orchiectomised mice. No significant differences were observed in cortical bone. Lipid deposition within the bone marrow was significantly increased in testosterone deficient mice compared to testosterone replete mice. No significant differences in ALP immunopositivity were detected between groups, and runx2 was significantly decreased in orchiectomised mice treated with testosterone compared to controls. The ratio of RANKL/OPG immunopositivity was significantly increased in testosterone deficient mice compared to testosterone replete mice. 3-point bending demonstrated no significant differences in maximal force between groups despite a downward trend in orchiectomised groups compared to controls. Osteoclast number quantified from TRAP-stained sections was not different between groups. Discussion: Testosterone depletion accelerates trabecular bone loss, mediated by increased osteoclastogenesis via the RANKL/OPG pathway and increased bone marrow adiposity, an effect reversed by testosterone treatment. While this study highlights the benefits of testosterone upon trabecular bone health in male mice these changes may not alter fracture risk as 3-point-bend maximal force was not affected. Presentation: 6/2/2024

Bone loss after bariatric surgery is observed mainly in the hip trabecular compartment and after hypoabsorptive techniques

We evaluated the impact of bariatric surgery on bone mineral density (BMD) and microarchitecture over one year using dual-energy X-ray absorptiometry (DXA), the trabecular bone score (TBS), and 3D-DXA to assess changes after different surgical techniques. This prospective, single-center study of 153 patients with severe obesity contrasts the effects on bone health of sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), and duodenal switch/single anastomosis duodeno-ileostomy with sleeve gastrectomy (DS/SADIS). To our knowledge, this is the first study to evaluate patients undergoing DS/SADIS and to incorporate 3D-DXA analysis in the assessment of bone loss.Patients were 81 % female with a mean age of 50 ± 9 years. Fifty-four per cent underwent SG; 16 %, RYGB; and 30 %, DS/SADIS. Our findings revealed a significant decrease in areal BMD at the LS (−3.49 ± 5.44 %), FN (−5.24 ± 5.86 %), and TH (−8.06 ± 5.14 %) one year after bariatric surgery. Bone microarchitecture at the LS assessed by TBS was degraded in 30 % of patients. Proximal femur 3D-DXA analysis showed that surgery-induced bone loss predominantly affects the trabecular compartment (Trabecular volumetric (v) BMD: −8.00 ± 6.57 %) rather than the cortical compartment (Cortical vBMD: −1.37 ± 2.79 %).These results suggest hypoabsorptive and mixed techniques (DS/SADIS and RYGB) were associated with greater BMD loss and deterioration of microarchitecture than restrictive techniques (SG).The primary determinants of bone density and impairment of microarchitecture were the extent of weight loss and the type of surgical procedure. Despite overall bone loss, Z-score assessments indicated that post-surgical bone status remained within or above the average ranges compared to a healthy population, except for TH following DS/SADIS.In conclusion, our research shows differences in the impact of bariatric surgery techniques on bone density and microarchitecture, emphasizing the need for careful postoperative monitoring of bone health, particularly in patients undergoing hypoabsorptive and mixed procedures.