Improve Bone Mineral Density Research Articles

A systematic review and meta-analysis of the effects of probiotics on bone outcomes in rodent models.

Emerging evidence demonstrates an opportunity for using probiotics to support bone health but findings in humans are limited. This systematic review investigated if probiotic supplementation improves bone mineral density and bone structure in rodent models compared to no supplementation. Studies (n = 71) examining the effect of oral consumption of any probiotic strain on bone mineral density or bone structure in rodents were included. Meta-analyses were conducted separately by study model (intact, ovariectomized) and bone site (femur, tibia, spine) to determine the probiotic effect (standardized mean difference, SMD) on volumetric bone mineral density (vBMD), bone volume fraction (BV/TV) and cortical thickness (Ct.Th). Reasons for heterogeneity were explored (probiotic genus, sex, type of rodent). In intact rodents, probiotics resulted in greater vBMD (SMD = 0.43, 95% CI [0.13, 0.74], I2 = 3%, P<.05) and higher BV/TV (SMD = 0.63, 95% CI [0.25, 1.02], I2 = 57%, P<.05) at the femur without changes in cortical bone structure. In ovariectomized models, probiotic supplementation resulted in greater vBMD (femur: SMD = 1.28, 95% CI [1.01, 1.55], I2 = 3%, P<.05; tibia: SMD = 1.29, 95% CI [0.52, 2.05], I2 = 67%, P<.05; and spine: SMD = 1.47, 95% CI [0.97, 1.97], I2 = 26%, P<.05) as well as higher BV/TV (femur: SMD = 1.16, 95% CI [0.80, 1.52], I2 = 56%, P<.05; tibia: SMD = 2.13; 95% CI [1.09, 3.17], I2 = 79%, P<.05; spine: SMD = 2.04, 95% CI [1.17, 2.90], I2 = 76%, P<.05) and Ct.Th at the tibia (SMD = 2.35; 95% CI [0.72, 3.97], I2 = 82%, P<.05) but not at the femur versus control. The syntheses support probiotics as a strategy to improve bone outcomes in rodent models.

Modern approach to bone comorbidity in prolactinoma.

Prolactinomas account for more than half of pituitary adenomas, and besides their clinical impact on fertility and gonadal function, they lead to detrimental effects on bone. Patients with prolactinoma are prone to deterioration of bone structure caused not only by prolactin (PRL) induced hypogonadism but also by its direct actions on bone cells and calcium metabolism. However, clinical studies have shown inconsistent evidence regarding whether PRL could have a deleterious effect independently from gonadal insufficiency on skeletal integrity. Seminal studies from our group reported an increased prevalence of vertebral fractures (VFs) in both female and male patients with prolactinoma. Treatment of prolactinoma with dopamine agonists can restore gonadal function and improve bone mineral density. Since the presence of VFs may be related to more aggressive disease, bone comorbidities in prolactinoma should be managed by a multidisciplinary team in line with the recent concept of 'pituitary tumors centers of excellence'. The review aims to evaluate the mechanism of PRL actions on bone, as well as to provide practical indications for a modern approach to the management of skeletal complications of patients with prolactin-secreting adenoma considering different clinical characteristics and outcomes.

Denosumab for osteoporosis in older adults in long-term care: A randomized trial.

In long-term care (LTC), the incidence of hip or vertebral fractures are eight times that in the community. Despite the wide availability of osteoporosis therapy, LTC residents are omitted from pivotal trials and not treated. Denosumab is a relatively new, monoclonal antibody therapy for osteoporosis treatment. Via a randomized trial, we sought to determine the safety and efficacy of denosumab in LTC residents. We conducted a 2-year, double-blind, placebo-controlled, randomized clinical trial in 201 osteoporotic men and women aged ≥ 65 years, living in LTC communities. Participants with multimorbidity, dysmobility, and cognitive impairment were not excluded. The intervention was denosumab 60 mg subcutaneous every 6 months or placebo. Our primary outcome measures were hip and spine bone mineral density (BMD) improvement at 24 months. Secondary outcomes included BMD at other skeletal sites, function, and safety. We included 123 women and 78 men with a mean ± standard error age of 81.5 ± 0.6. Overall, 83% and 71% completed 12 and 24 months, respectively. Compared with placebo, the women receiving denosumab had a greater 24-month percent increase in spine (7.41 ± 0.93 vs. 2.15 + 0.56; p = 0.014), and total hip BMD (4.62 ± 0.62 vs. -0.19 ± 0.79; p = 0.007); and men in spine (7.91 ± 0.96 vs. 1.12 ± 1.13; p = 0.002) and total hip (3.74 ± 0.55 vs. 0.48 ± 0.74; p = 0.018). There were no significant differences in safety metrics. Denosumab was a safe and effective therapy for improving BMD in osteoporotic older men and women with multiple comorbidities in LTC.

Yigu decoction regulates plasma miRNA in postmenopausal osteoporosis patients: a randomized controlled trial

BackgroundPostmenopausal osteoporosis (PMOP) is a serious condition that affects elderly individuals. Our previous study revealed that Yigu decoction (YGD) effectively improved bone mineral density (BMD) in elderly individuals, but the mechanism underlying this effect remains unclear. In this study, we investigated the relationships among YGD, microRNAs (miRNAs), and bone metabolism by assessing the effects of YGD on the miRNA levels in patient plasma to provide a scientific basis for treating PMOP with YGD.MethodsIn this clinical trial, 60 patients were randomly assigned to the YGD group or the control group (ratio of 1:1) and treated for 3 months. The primary outcome measure was BMD, and the secondary outcome measures included plasma miRNA levels, visual analogue scale (VAS) scores, alkaline phosphatase (ALP) levels, anti-tartrate acid phosphatase (TRACP-5b) levels and traditional Chinese medicine (TCM) syndrome scores. We assessed the regulatory roles of miRNAs in PMOP patients by analysing publicly available data from the Gene Expression Omnibus (GEO) database. Bioinformatics methods were also used to explore the mechanism by which YGD regulates miRNAs that are involved in bone metabolism.ResultsCompared with those before treatment, the BMD, ALP levels, TRACP-5b levels, TCM syndrome scores and VAS scores improved in both groups after 3 months of treatment (P &amp;lt; 0.05). A total of 82 miRNAs differed between the groups. After analysing data from the GEO database, we confirmed that miR-133a-3p is the key molecule that mediates the effects of YGD intervention on PMOP. GO analysis of key genes suggested that gene enrichment was more pronounced in response to hormones, cellular response to growth factor stimulation, and positive regulation of physiological and metabolic processes. KEGG analysis revealed that these genes were enriched mainly in the PI3K-Akt, FOXO, and JAK-STAT pathways and other pathways. The results of the protein‒protein interaction (PPI) network analysis revealed that epidermal growth factor receptor (EGFR), Insulin-like growth factor 1 (IGF-1), Caveolin-1 (Cav-1) and others were core proteins.ConclusionThis study demonstrated that YGD is beneficial in the treatment of PMOP, ameliorating clinical symptoms and bone turnover indices. Moreover, the inhibition of miR-133a-3p expression may be the key mechanisms by which YGD regulates bone metabolism in the treatment of PMOP, although YGD regulates bone metabolism in a multitarget and multipathway manner.

Romosozumab following denosumab improves lumbar spine bone mineral density and trabecular bone score greater than denosumab continuation in postmenopausal women.

Romosozumab following anti-resorptive can be an effective sequential treatment strategy to improve bone strength. However, whether the transition to romosozumab after denosumab is associated with greater improvement in bone mineral density (BMD) and trabecular bone score (TBS) 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. Individuals who were transited to 12months of romosozumab after denosumab were 1:1 matched to those who continued an additional 12months of denosumab (n = 86 for each group; denosumab-romosozumab [DR] and denosumab-denosumab [DD]). Mean BMD gain by denosumab treatment in matched DR and DD groups from denosumab initiation to transition (median 4 times [range 2 to 8]) was +4.8% and + 2.0% in the lumbar spine and total hip. DR group showed greater LS BMD gain compared to the DD group (+6.8 vs. +3.3% point, P<.001) for 12months post-transition independent of the duration of prior denosumab treatment, yielding greater overall LS BMD gain in DR compared to DD (+11.6% vs. +8.0%, P<.001). DD group showed continued improvement of hip BMD, whereas hip BMD was maintained but not improved in the DR group. DR group was associated with greater TBS improvement than the DD group (2.9% vs 1.0%, P=.042). One month after the transition to romosozumab from denosumab, P1NP immediately increased above the level of denosumab initiation with relatively suppressed CTx, creating a transient anabolic window. For 12months follow-up, one incident morphometric vertebral fracture and one patella fracture were observed in DD, whereas one ankle fracture was observed in the DR group. Romosozumab following denosumab improved lumbar spine BMD and TBS greater than denosumab continuation in postmenopausal women.

Pregnancy and lactation associated osteoporotic vertebral fracture: the neurosurgical perspective through a multicentric study.

Pregnancy and lactation-associated osteoporosis is a rare form of osteoporosis occurring during late pregnancy and early lactation, featuring fragility fractures, primarily involving the vertebral bodies and leading to back pain. Its management involves osteoporosis treatment, complicated by potential drug-related dangerous effects on the fetus. Nevertheless, many controversies remain regarding diagnosis, prognosis, and treatment options. Herein, we propose a multicentric case series to provide a comprehensive neurosurgical, gynecological, and endocrinological perspective on the management of pregnancy and lactation-associated osteoporotic vertebral fractures.A multicenter retrospective study was conducted at the Neurosurgical Department of Università degli Studi di Napoli Federico II, the Neurosurgical Unit of Hopitaux Universitaires de Genève, and the Spine and Spinal Cord Surgery Unit of the University Hospital of Udine, collecting data from January 2014 to December 2022. The study has been approved by the ethical committee of each hospital.N = 11 patients with an overall number of 31 fractures were eligible, with a mean age of 36. N = 5 (16%) fractures in 4 patients (36%) developed during pregnancy, and N = 26 (84%) fractures in 7 (64%) patients occurred during lactation. The mean number of fractures per patient was 2,81. In 10 (90%) patients, fractures occurred at the first pregnancy, and 5 (45%) patients had uneventful subsequent pregnancies. The mean clinical signs and symptoms were back pain (92%), followed by loss of height (75%) and kyphosis (4 patients, 35%). One (9,09%) patient underwent in vitro fertilization (IVF), and one patient (9,09%) was receiving hormonal therapy (ethinylestradiol/drosiprenone). 10 out of 11 (90%) patients were treated conservatively, and 6 of them (60%) were managed with an orthosis. One (9,1%) patient underwent surgery for 5-level kyphoplasty. The mean average reduction of pain after one year of follow-up was 6,7 on the visual analogue scale (p-value 0,04).Pregnancy-related osteoporotic vertebral fractures are an emerging issue in developing countries, for which a conservative strategy ensures the best outcomes. The main goal is to improve bone mineral density through calcium and vitamin D supplementation and bone-active drugs as bisphosphonates or teriparatide. Surgery is warranted only in cases of a risk of severe deterioration of neurological functions.

Cost-effectiveness analysis of denosumab versus alendronate for improving bone mineral density in renal transplant recipients: a comparative study

BackgroundDenosumab and alendronate had a positive impact on bone mineral density (BMD) preservation after kidney transplantation. However, the cost-effectiveness of these agents in the context of kidney transplantation remains largely unexplored. We have conducted a cost-effectiveness analysis to compare the cost and the clinical outcomes of adding subcutaneous (SC) 60 mg denosumab every 6 months vs. oral weekly 70 mg Alendronate, to the standard care therapy (vitamin D and calcium) in renal transplant recipients (RTRs). The impact of both drugs on BMD t-score improvement and fracture prevention was investigated. A decision-analysis model from a health care payer perspective was applied.ResultsThe cost-effectiveness analysis has shown that alendronate add-on to the standard therapy was the most cost-effective regimen, in terms of BMD improvement and fracture prevention with an incremental cost-effectiveness ratio (ICER) of $154/patient/year. The one-way sensitivity analyses have delineated the change in cost-effectiveness when alendronate retail unit price was increased by 25% and 50%, or when denosumab retail unit price was decreased by 25% and 50%. The model was sensitive to the uncertainties (95% confidence interval) in the probabilities of fracture prevention and the probabilities of attaining the desired outcome.ConclusionThe model suggests that oral once weekly alendronate add-on regimen to standard therapy seems to be substantially more cost effective than twice yearly SC denosumab in terms of BMD improvement and fracture prevention in RTRs. Longer time horizon models with longer follow-up periods for fracture risks and adverse events are warranted to validate these data.

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

8810 Improvement in bone mineral density in tertiary hyperparathyroidism after renal transplant treated with parathyroidectomy

Abstract Disclosure: M. Zakher: None. 55 year old man with past medical history of end-stage renal disease (ESRD) and alcoholic cirrhosis who underwent simultaneous liver-kidney transplant (SLKT) seven months prior to presentation to endocrinology who was referred for management of hypophosphatemia as low as 1.0 mg/dl. Prior to the transplant, he had hyperphosphatemia and hyperparathyroidism with phosphate and parathyroid hormone (PTH) levels as high as 8.2 mg/dL and 682 pg/mL, respectively. PTH remained elevated at 244 pg/mL and vitamin D was 35 ng/mL the week of the initial endocrinology visit. Initial DXA scan six months after SLKT showed osteoporosis of the lumbar spine, total left proximal femur, and left femoral neck with T-scores of -3.4, -4.9, -5.6, respectively. Alendronate was started three weeks prior to the initial visit. Urine studies confirmed phosphate wasting with urinary phosphate excretion significantly higher than 100 mg/24h, FEPO4 greater than 70%, and TmP/GFR less than 2 mg/dL. Increased urinary excretion of phosphate was consistent with hyperparathyroidism. The extremely low urinary calcium in the setting of normocalcemia and the history of renal transplant suggested a tertiary hyperparathyroidism. Alendronate was discontinued eight months after the initial visit to reduce the risk of post-parathyroidectomy hypocalcemia and post-parathyroidectomy bone remodeling inhibition.One year after the initial visit, the patient had a bilateral neck exploration with total parathyroidectomy and auto transplantation of the parathyroid. Pathology showed hypercellular parathyroid tissue. He was hospitalized one week after surgery for symptomatic hypolcalcemia (calcium 5.8 mg/dL). He was taking one tablet of calcium carbonate three times daily at home instead of three tablets three times daily as prescribed. He was discharged on calcitriol 0.5 mcg once daily, magnesium oxide 800 mg twice daily, calcium carbonate 1 g three times daily, and cholecalciferol 5000 units once daily. He remained on these for eleven months as well as calcitriol for fifteen months with dose adjustments during visits. Calcitriol was discontinued when calcium was found to be 8.9 mg/dL and the patient was asymptomatic. Repeat DXA scan two years after the baseline DXA showed osteoporosis of the left femoral neck with a T score of -2.5. There was a tremendous improvement from the baseline DXA scan from +20% in the total lumbar spine to +170% in the left femoral neck. DXA scan four years after the baseline DXA scan showed osteopenia of the lumbar spine, total left proximal femur, and left femoral neck with T-scores of -1.7, -2.4, -1.9.This is a 55 year old man who underwent SLKT seven months prior to presentation to endocrinology who was referred for management of hypophosphatemia as low as 1.0 mg/dL found with tertiary hyperparathyroidism who underwent a parathyroidectomy that resulted in significant improvement in bone mineral density test. Presentation: 6/2/2024

6820 Assessing The Efficacy And Safety Of Setrusumab For Osteogenesis Imperfecta: Updated Phase 2 Data From The Phase 2/3 Orbit Study

Abstract Disclosure: G.S. Gottesman: Advisory Board Member; Self; Ultragenyx, Kyowa Kirin, Inc. Consulting Fee; Self; Ultragenyx. Research Investigator; Self; Alexion Pharmaceuticals, Inc., Ultragenyx. T.O. Carpenter: Advisory Board Member; Self; Ultragenyx. Consulting Fee; Self; Ultragenyx. Research Investigator; Self; Ultragenyx. M. Wallace: Advisory Board Member; Self; Ultragenyx. Consulting Fee; Self; Novosteo. P. Smith: Grant Recipient; Self; Ultragenyx. Research Investigator; Self; Ultragenyx. E.A. Imel: Consulting Fee; Self; Ultragenyx. Grant Recipient; Self; Ultragenyx. Research Investigator; Self; Ultragenyx. H. Wang: Employee; Self; Ultragenyx. Stock Owner; Self; Ultragenyx. H.M. Byers: Employee; Self; Ultragenyx. Stock Owner; Self; Ultragenyx. S. Krolczyk: Employee; Self; Ultragenyx. Stock Owner; Self; Ultragenyx. E.M. Lewiecki: Consulting Fee; Self; Amgen Inc, Radius Health, Inc. Grant Recipient; Self; Amgen Inc, Radius Health, Inc, Ultragenyx. Research Investigator; Self; Amgen Inc, Radius Health, Inc, Ultragenyx. Speaker; Self; Amgen Inc, Kyowa Kirin, Inc. Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by bone fragility and low bone mass with no universally accepted treatment. Setrusumab is a fully human anti-sclerostin monoclonal antibody that improved bone mineral density (BMD), bone strength, and bone turnover markers in adults with OI (ASTEROID; NCT03118570). In the ongoing Phase 2/3 Orbit study (NCT05125809), Phase 2 evaluated the efficacy and safety of setrusumab in pediatric and young-adult cohorts with OI based on PK/PD, safety, and BMD data, to determine the dosing strategy for the Phase 3 portion. Subjects with OI Types I, III, or IV, ages 5 to &amp;lt;26 years, were randomized 1:1 to receive 20 or 40 mg/kg setrusumab intravenously monthly. Six-month data as of August 2023 are presented. Twenty-four subjects (50% female, 75% &amp;lt;18 years of age) with OI Type I (n=17/24, 71%) or III/IV (n=7/24, 29%) were enrolled and randomized to receive 20 mg/kg (n=14/24) or 40 mg/kg (n=10/24) of setrusumab. The mean (SD) baseline-corrected area under the effect curve (AUEC) for serum P1NP in the 20 mg/kg setrusumab group was 4153 (4407) µg/(L*day) over month one of treatment, and 5256 (5521) µg/(L*day) in the 40 mg/kg group. Mean (SE) change from baseline in lumbar spine BMD in the 20 mg/kg group was 9.1% (1.8%) and 12.8% (2.5%) at M3 and M6, respectively (all p&amp;lt;0.05 vs baseline) and 9.3% (2.4%) and 16.1% (3.9%) in the 40 mg/kg group (M6 p&amp;lt;0.05 vs baseline). Mean (SE) baseline BMD Z-score in the 20 mg/kg group of 2.1 (0.8) improved by 0.6 (0.8) at M3 and 0.9 (0.8) at M6, and improved from 1.1 (0.4) at baseline by 0.5 (0.4) and 0.9 (0.4) at M3 and M6, respectively, in the 40 mg/kg group (all p&amp;lt;0.05 vs baseline). The median annualized fracture rate (excluding fingers, toes, face, and skull) was reduced significantly from 0.7 to 0 (p=0.042) after setrusumab initiation (calculated reduction of 67%). No new radiographically confirmed fractures excluding fingers, toes, face, and skull were reported in 20/24 (83%) subjects after starting setrusumab, while only 4/24 (17%) reported fractures (precipitating events: one subject: slipped on ice, stubbed toe, one subject each: fell off of tricycle, bending over in bed, tripped and fell). Setrusumab treatment resulted in no unexpected adverse events. Treatment-related adverse events included infusion-related reaction (7/24, 29%), headache (3/24, 13%) infusion site pain, bone pain, and upper respiratory tract infection (each 1/24, 4%). In Orbit Phase 2, we observed significant improvements from baseline in lumbar spine BMD at M3 and M6 at both 20 and 40 mg/kg doses, with no marked differences between dose groups. Fracture rates significantly decreased with setrusumab initiation, with 83% of subjects reporting no new fractures. Presentation: 6/1/2024

Osteogenic effect of alogliptin in chemical-induced bone loss: a tri-modal in silico, in vitro, and in vivo analysis.

To investigate the effects of Alogliptin in chemical-induced post-menopausal osteoporosis. The binding affinity of alogliptin with osteogenic proteins was analysed in silico. The effect of alogliptin on osteogenic proteins and mineralization of osteoblastic cells was evaluated in UMR-106 cells. Further, in vivo anti-osteoporotic activity of alogliptin was evaluated in postmenopausal osteoporosis. Various bone turnover markers were assayed in serum. This followed the analysis of microarchitecture of bone, histology, and immunohistochemistry (IHC) of bone tissue. Docking scores showed that alogliptin has binding affinity for bone alkaline phosphatase (BALP), osteocalcin, and bone morphogenic protein (BMP-2). Alogliptin also enhanced mineralization of osteoblast cells, evidenced with increased ALP, osteocalcin, and BMP-2. Animal studies revealed significant elevation of bone formation markers, bone ALP, osteocalcin and BMP-2, and decreased bone resorption markers, receptor activator of NF-κβ (RANKL), cathepsin K (CTSK), tartrate resistant acid phosphatase (TRAcP5b) in VCD-induced post-menopausal osteoporosis. Micro computed tomography (μCT) analysis and histology of femur bone and lumbar vertebrae demonstrated decrease in trabecular separation and improved bone density. IHC of femur showed reduced DPP4 enzyme. Alogliptin increased mineralization in osteoblast cells. It had beneficial effects also altered bone turnover markers, repaired the trabecular microstructure, improved bone mineral density, and exhibited bone forming capacity targeting DPP-4 enzyme in postmenopausal osteoporosis.

Role and mechanism of Actein on condylar bone metabolism in APOE deletion-induced osteoporotic mice

AimsTo investigate the effects of Actein from Cimicifugae Rhizoma on condylar bone and cartilage in APOE deletion-induced osteoporotic mice, and to preliminarily explore the underlying mechanism. MethodsSixty 8-week-old female mice were used, which underwent APOE−/− and ovariectomy procedures, followed by oral administration of Actein (15 mg/kg) and Atorvastatin Calcium (AC, 3 mg/kg) for eight weeks. Body weight, uterine weight, and systemic indexes related to bone metabolism and lipid metabolism were assessed in each group. Changes in condylar bone histomorphometric parameters were evaluated using Micro-CT. Morphological changes in the condyle were observed with Hematoxylin-Eosin (H&E), Safranin O/Fast Green, and Alcian Blue Hematoxylin/Orange G (ABH/OG) staining, with OARSI pathology scoring performed. Sirius red staining and immunofluorescence were used to determine the expression levels of Collagen I (Col I) and Collagen III (Col III) in bone matrix, and Col II in cartilage matrix. Immunohistochemistry assessed the relative expression levels of ALP and proteins associated with the Wnt/β-catenin/RUNX2 signaling pathway. ResultsAPOE−/− exacerbates ovariectomy -induced osteoporosis (OP) in condylar of mice. Actein and AC significantly reversed OP, improved bone mineral density (BMD), increased bone microarchitecture, and restored abnormal calcium and phosphorus metabolism in the blood and urine. Morphologically, APOE−/− and ovariectomy reduced condylar cartilage thickness, disrupted chondrocyte arrangement, chondrocyte cleavage, and clustered aggregation, resembling osteoarthritis (OA)-like changes. Actein and AC partially restored the disrupted chondrocyte arrangement, smoothed chondrocyte cleavage, and up-regulated the levels of chondrocyte matrix (Col II, aggrecan) and bone matrix (Col III, ALP). Actein reversed the OA process, potentially through the Wnt/β-catenin/RUNX2 signaling pathway. ConclusionAPOE−/− and ovariectomy induced OP, leading to OA-like lesions in condylar of mice. Actein promoted cartilage repair and trabecular bone recovery by increasing extracellular matrix synthesis (Col II, Col III, aggrecan), reversing the OA process, possibly through the Wnt/β-catenin/RUNX2 signaling pathway.

6795 Romosozumab improves bone mineral density and markers of bone resorption in a patient with osteogenesis imperfecta

6795 Romosozumab improves bone mineral density and markers of bone resorption in a patient with osteogenesis imperfecta

OS EFEITOS DE EXERCÍCIO DE IMPACTO EM PACIENTES COM OSTEOPOROSE PÓS MENOPAUSA

Introduction: Osteoporosis is a disease characterized by the loss of bone mineral density, which increases the risk of fractures, especially in women. It affects women more due to hormonal changes, and in postmenopause, due to the drop in estrogen levels, which aggravates bone loss. Objective: This was to investigate the effects of impact exercises in patients diagnosed with postmenopausal osteoporosis. Methods: This is an integrative review of the literature, where the PICO strategy was adopted, thus the guiding question of the study was “What are the effects of impact exercises on the bone mineral density of patients with postmenopausal osteoporosis?”. The data search took place between July and August 2024, in the PUBMED, PEDro and LILACS databases, using the descriptors: “impact exercises”, “osteoporosis” and “postmenopause”. A total of 76 articles were found and after applying the eligibility criteria, 8 were used in this review. Results: Impact exercises, such as resistance, aerobic and Pilates exercises, were shown to be effective in improving bone mineral density, muscle strength and balance in postmenopausal women, reducing the risk of fractures and improving quality of life. Conclusion: It is concluded that high-impact exercises offer several benefits for women with osteoporosis in the postmenopausal period, including increased muscle strength, improved balance, lipid profile, calcium absorption, quality of life and bone mineral density.

Efficacy of a single 5mg zoledronic acid infusion in preventing bone loss and fracture in postmenopausal women with breast cancer.

Chemotherapy-induced bone loss (CTIBL) is common among breast cancer patients, requiring comprehensive assessment and intervention. Zoledronic acid, a strong inhibitor of bone resorption, is effective in CTIBL management, though information on dosing and intervals, particularly the efficacy of the 5mg annual dose for osteoporosis in breast cancer patients, is limited. In this 12-month prospective observational study, 85 breast cancer patients were divided into three groups: 17 received no treatment, 17 received tamoxifen, and 51 received anastrozole or letrozole (AI). Post-surgery, patients were administered a single 5mg dose of zoledronic acid and monitored over 12months for changes in bone mineral density (BMD), fracture rates, and biochemical markers. Initially, the AI group was the oldest, averaging 59.1 ± 8.7years. At baseline, no significant differences in variables, except age, were observed. After 12months, BMD increased in all groups following a single zoledronic acid dose, with the smallest increase in the AI group at the lumbar spine: no treatment (2.4% ± 6.1%), tamoxifen (2.6% ± 3.4%), AI (0.6% ± 14.5%) (p = 0.778). CTx and P1NP levels were consistently suppressed up to 12months post-treatment, with smaller reductions in the AI group. There were no significant differences in fracture or bone metastasis rates among groups. A single infusion of 5mg zoledronic acid was effective in increasing bone density in breast cancer patients. However, AI-treated patients showed less improvement in vertebral bone mineral density and biochemical markers. Further long-term studies with larger cohorts are needed.

Minimal Impact of Age on Adaptive Bone Formation in the Distal Tibia of US Army Basic Combat Trainees: The ARMI Study

ABSTRACT Introduction Although bone formation has been observed in the distal tibia of trainees during Basic Combat Training (BCT), some animal studies have demonstrated greater mechanosensitivity in the juvenile compared to the mature skeleton. How age affects skeletal adaptations to military training is unknown. The purpose of this study was to determine if skeletal adaptations to US Army BCT differ by age. Methods We enrolled 2085 trainees (1303 males, 782 females). High-resolution peripheral quantitative computed tomography was used to assess total, cortical, and trabecular bone mineral density (BMD) and the microarchitecture of the distal tibia before and after 8 wk of BCT. Generalized linear models were used to compare mean percent change (95% confidence interval (CI)) in each bone parameter by age group (&lt;20, 20–25, 26–29, and ≥30 yr) and to evaluate differences in bone parameter changes between age groups (effect estimates (95% CI)). Models were stratified by sex with multivariable adjustment. Results Male and female trainees in all age groups had increases in total BMD, trabecular BMD, and trabecular bone volume fraction from baseline (P &lt; 0.01 for all). Male and female trainees also had increases in trabecular thickness from baseline in all groups (P &lt; 0.05) except females ≥30 yr old. Female trainees 20–25 yr old had a significantly larger increase in trabecular thickness than those &lt;20 yr old (effect estimate (95% CI), 0.33% (0.02%–0.64%); P &lt; 0.05). Trabecular microarchitecture was largely not otherwise different between age groups for either sex. Male and female trainees &lt;20 yr old had greater changes in cortical BMD compared to older age groups (males, P &lt; 0.01; females, P &lt; 0.05 for all). Conclusion Trainees &lt;20 yr old experience the greatest improvements in cortical BMD at the distal tibia during US Army BCT, suggesting that adaptive bone formation in cortical bone may be attenuated with skeletal maturity. However, the mechanosensitivity of trabecular bone to exercise training remains intact regardless of age.

Treatment of glucocorticoid-induced osteoporosis with concurrent denosumab and romosozumab: a case report.

Osteoporosis is a metabolic bone disorder for which treatment options include antiresorptive therapies (e.g., bisphosphonates, denosumab); anabolics (e.g., teriparatide, abaloparatide); and dual mechanisms (e.g., romosozumab). Management of osteoporosis with concurrent antiresorptive and anabolic agents may be superior to monotherapy, as demonstrated in the DATA trial with the combination of denosumab and teriparatide. However, there is limited experience with the combination of denosumab and romosozumab, which may be an alternative antiresorptive/anabolic regimen for individuals who are not candidates for PTH receptor agonists. In this case, we present a young man with glucocorticoid-induced osteoporosis who could not tolerate a daily injectable anabolic and who experienced improvement in bone mineral density with concurrent denosumab and off-label romosozumab administration.

Extending the Therapeutic Potential: Romosozumab in Osteoporosis Management

Abstract Current therapeutic approaches for osteoporosis predominantly involve anti-resorptive agents, but the emergence of bone anabolic therapy, such as romosozumab, presents a promising alternative. Romosozumab, a monoclonal antibody targeting sclerostin, exhibits both bone anabolic and antiresorptive effects, offering the potential to enhance bone mineral density and mitigate fracture risk. Evidence from several studies demonstrating the efficacy of romosozumab is now established in improving bone mineral density and reducing fracture rates in postmenopausal women and men. This review critically evaluates the role of romosozumab in osteoporosis management, emphasizing findings from real-world studies to facilitate its practical application in clinical settings. Adverse effects, comparative effectiveness with other osteoporotic agents, and challenges in sequential therapy are also discussed, providing insights for informed decision-making by physicians, particularly in the context of pre-treatment considerations. Additionally, the review examines global prescribing guidelines and highlights challenges associated with romosozumab utilization in special patient subgroups, aiming to optimize its clinical use.

Effects of total flavonoids of Rhizoma Drynariae on biochemical indicators of bone metabolism: a systematic review and meta-analysis.

Evidence shows that the total flavonoids of Rhizoma Drynariae (TFRD) can improve bone mineral density (BMD). However, there is no evidence to summarize the improvement of biochemical indicators of bone metabolism (BIBM). The PubMed, Web of Science, Cochrane Library, Embase, Chinese National Knowledge Infrastructure (CNKI), Wanfang Database, Chongqing VIP Information Database (VIP) and SinoMed were searched from inception to 6 May 2024. The final included studies performed meta-analyses using RevMan 5.3. Nine randomized controlled trials (RCTs) were ultimately included. The TFRD group had higher bone gla protein (BGP) and type I procollagen-N-propeptide (PINP) compared to the Other therapies (WMD: 5.11; 95% CI: 3.37, 6.84; p < 0.00001; WMD: 13.89; 95% CI: 11.81, 15.97; p < 0.00001). The tartrate-resistant acid phosphatase (TRACP) decreased significantly (WMD: -1.34; 95% CI: -1.62, -1.06; p < 0.00001). The alkaline phosphatase (ALP) increased significantly (WMD: 7.47; 95% CI: 6.29, 8.66; p < 0.00001). There were no significant differences in serum calcium (SC) or serum phosphorus (SP) levels between the TFRD and control groups (WMD: 0.08; 95% CI: -0.04, 0.20; p = 0.17; WMD: 0.02; 95% CI: -0.02, 0.05; p = 0.36). TFRD can stimulate bone formation and prevent bone resorption in osteoporosis (OP) patients, but it has no effect on SC and SP. https://www.crd.york.ac.uk/PROSPERO/.

Efficacy and Safety of Testosterone Replacement in Testicular Cancer Survivors With Treatment-Influenced Hypogonadism: A Systematic Review.

The objective is to evaluate the efficacy and safety of testosterone supplementation in testicular cancer survivors with treatment-related hypogonadism. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards and used Embase, PubMed/MEDLINE, Cochrane Central, Web of Science Core Collection, Korean Journal Index, SciELO, and Global Index Medicus to obtain data in June of 2024. Analyses evaluating testosterone supplementation in testicular cancer survivors with treatment-induced hypogonadism were included. Any analyses not assessing supplementation in this population or deemed unretrievable were excluded. Ten analyses were included for analysis. A total of 332 bilateral or unilateral testicular cancer survivors with treatment-influenced hypogonadism were reviewed, with 238 patients receiving testosterone replacement. Eight of the 10 analyses assessed participants without poor quality-of-life (QOL) metrics, metabolic factors, and bone mineral density (BMD) at baseline and only found a significant benefit in fat distribution metrics with testosterone supplementation. Two analyses evaluated participants with poor QOL metrics or BMD at baseline and showed improvements in QOL or BMD with testosterone supplementation. There is robust evidence regarding the efficacy and safety of testosterone replacement in hypogonadal individuals but limited evidence specifically evaluating supplementation in testicular cancer survivors with treatment-influenced hypogonadism. The results suggest testosterone replacement may be beneficial in patients with impaired QOL metrics, metabolic factors, and BMD at baseline; the results also suggest that routine supplementation for all individuals in this patient population lacks efficacy.