Background In this comprehensive retrospective nationwide cohort study, we examined the relationships between various asthma medications and bone health, utilizing data from the National Health Insurance Service database of South Korea.
Methods From 2015 to 2019, the relevant dataset included 168,611 individuals aged 66 years, among whom 8,747 were diagnosed with asthma. We focused on a subset of 6,173 patients, all 66-year-old women. Participants were categorized into four groups: nonusers of asthma medication (n=2,868), leukotriene antagonist users (n=2,281), inhaled corticosteroid (ICS) users (n=517), and those using a combination of ICS and long-acting beta-agonist (ICS+LABA) medication (n=507). The primary outcomes measured were the incidences of major osteoporotic fractures and hip fractures during the follow-up period.
Results Over 2.7 years of follow-up, 615 cases of major osteoporotic fractures and 96 cases of hip fractures were recorded. ICS users exhibited a heightened risk of both injuries, with hazard ratios of 1.38 (95% confidence interval [CI], 1.18 to 1.63; P<0.001) for major osteoporotic fractures and 1.56 (95% CI, 1.33 to 1.83; P<0.001) for hip fractures. Similarly elevated risks were observed in the ICS+LABA group. Notably, the risk associated with ICS was particularly pronounced among patients with osteopenia for both fracture types. Overall, the use of ICS, alone or in combination with LABA, in patients with asthma is associated with significantly increased risks of osteoporotic fractures, especially among those with osteopenia.
Conclusion These findings underscore the importance of considering bone health when managing asthma, especially in older patients and those with existing bone density issues.
So Young Park, Sung Hye Kong, Kyoung Jin Kim, Seong Hee Ahn, Namki Hong, Jeonghoon Ha, Sihoon Lee, Han Seok Choi, Ki-Hyun Baek, Jung-Eun Kim, Sang Wan Kim, on Behalf of Metabolic Bone Disease Study Group of Korean Endocrine Society
Endocrinol Metab. 2024;39(4):539-551. Published online July 17, 2024
This comprehensive review critically examines the detrimental impacts of endocrine-disrupting chemicals (EDCs) on bone health, with a specific focus on substances such as bisphenol A (BPA), per- and polyfluoroalkyl substances (PFASs), phthalates, and dioxins. These EDCs, by interfering with the endocrine system’s normal functioning, pose a significant risk to bone metabolism, potentially leading to a heightened susceptibility to bone-related disorders and diseases. Notably, BPA has been shown to inhibit the differentiation of osteoblasts and promote the apoptosis of osteoblasts, which results in altered bone turnover status. PFASs, known for their environmental persistence and ability to bioaccumulate in the human body, have been linked to an increased osteoporosis risk. Similarly, phthalates, which are widely used in the production of plastics, have been associated with adverse bone health outcomes, showing an inverse relationship between phthalate exposure and bone mineral density. Dioxins present a more complex picture, with research findings suggesting both potential benefits and adverse effects on bone structure and density, depending on factors such as the timing and level of exposure. This review underscores the urgent need for further research to better understand the specific pathways through which EDCs affect bone health and to develop targeted strategies for mitigating their potentially harmful impacts.
Background Osteoporosis is the most common metabolic bone disease and can cause fragility fractures. Despite this, screening utilization rates for osteoporosis remain low among populations at risk. Automated bone mineral density (BMD) estimation using computed tomography (CT) can help bridge this gap and serve as an alternative screening method to dual-energy X-ray absorptiometry (DXA).
Methods The feasibility of an opportunistic and population agnostic screening method for osteoporosis using abdominal CT scans without bone densitometry phantom-based calibration was investigated in this retrospective study. A total of 268 abdominal CT-DXA pairs and 99 abdominal CT studies without DXA scores were obtained from an oncology specialty clinic in the Republic of Korea. The center axial CT slices from the L1, L2, L3, and L4 lumbar vertebrae were annotated with the CT slice level and spine segmentation labels for each subject. Deep learning models were trained to localize the center axial slice from the CT scan of the torso, segment the vertebral bone, and estimate BMD for the top four lumbar vertebrae.
Results Automated vertebra-level DXA measurements showed a mean absolute error (MAE) of 0.079, Pearson’s r of 0.852 (P<0.001), and R2 of 0.714. Subject-level predictions on the held-out test set had a MAE of 0.066, Pearson’s r of 0.907 (P<0.001), and R2 of 0.781.
Conclusion CT scans collected during routine examinations without bone densitometry calibration can be used to generate DXA BMD predictions.
Kyoung Jin Kim, Jeonghoon Ha, Sang Wan Kim, Jung-Eun Kim, Sihoon Lee, Han Seok Choi, Namki Hong, Sung Hye Kong, Seong Hee Ahn, So Young Park, Ki-Hyun Baek, on Behalf of Metabolic Bone Disease Study Group of Korean Endocrine Society
Endocrinol Metab. 2024;39(2):267-282. Published online April 25, 2024
This review article investigates solid organ transplantation-induced osteoporosis, a critical yet often overlooked issue, emphasizing its significance in post-transplant care. The initial sections provide a comprehensive understanding of the prevalence and multifactorial pathogenesis of transplantation osteoporosis, including factors such as deteriorating post-transplantation health, hormonal changes, and the impact of immunosuppressive medications. Furthermore, the review is dedicated to organ-specific considerations in transplantation osteoporosis, with separate analyses for kidney, liver, heart, and lung transplantations. Each section elucidates the unique challenges and management strategies pertinent to transplantation osteoporosis in relation to each organ type, highlighting the necessity of an organ-specific approach to fully understand the diverse manifestations and implications of transplantation osteoporosis. This review underscores the importance of this topic in transplant medicine, aiming to enhance awareness and knowledge among clinicians and researchers. By comprehensively examining transplantation osteoporosis, this study contributes to the development of improved management and care strategies, ultimately leading to improved patient outcomes in this vulnerable group. This detailed review serves as an essential resource for those involved in the complex multidisciplinary care of transplant recipients.
Background In individuals with spinal cord injury (SCI), bone loss progresses rapidly to the area below the level of injury, leading to an increased risk of fracture. However, there are limited data regarding SCI-relevant characteristics for bone loss and the degree of bone loss in individuals with SCI compared with that in non-SCI community-dwelling adults.
Methods Data from men with SCI who underwent dual-energy X-ray absorptiometry at the National Rehabilitation Center (2008 to 2020) between 12 and 36 months after injury were collected and analyzed. Community-dwelling men were matched 1:1 for age, height, and weight as the control group, using data from the Korea National Health and Nutrition Examination Survey (KNHANES, 2008 to 2011).
Results A comparison of the SCI and the matched control group revealed significantly lower hip region T-scores in the SCI group, whereas the lumbar spine T-score did not differ between groups. Among the 113 men with SCI, the paraplegia group exhibited significantly higher Z-scores of the hip region than the tetraplegia group. Participants with motor-incomplete SCI showed relatively preserved Z-scores of the hip region compared to those of the lumbar region. Moreover, in participants with SCI, the percentage of skeletal muscle displayed a moderate positive correlation with femoral neck Z-scores.
Conclusion Men with SCI exhibited significantly lower bone mineral density of the hip region than community-dwelling men. Paraplegia rather than tetraplegia, and motor incompleteness rather than motor completeness were protective factors in the hip region. Caution for loss of skeletal muscle mass or increased adiposity is also required.
Maintenance of skeletal integrity requires the coordinated activity of multinucleated bone-resorbing osteoclasts and bone-forming osteoblasts. Osteoclasts form resorption lacunae on bone surfaces in response to cytokines by fusion of precursor cells. Osteoblasts are derived from mesenchymal precursors and lay down new bone in resorption lacunae during bone remodeling. Nuclear factorkappa B (NF-κB) signaling regulates osteoclast and osteoblast formation and is activated in osteoclast precursors in response to the essential osteoclastogenic cytokine, receptor activator of NF-κB ligand (RANKL), which can also control osteoblast formation through RANK-RANKL reverse signaling in osteoblast precursors. RANKL and some pro-inflammatory cytokines, including tumor necrosis factor (TNF), activate NF-κB signaling to positively regulate osteoclast formation and functions. However, these cytokines also limit osteoclast and osteoblast formation through NF-κB signaling molecules, including TNF receptor-associated factors (TRAFs). TRAF6 mediates RANKL-induced osteoclast formation through canonical NF-κB signaling. In contrast, TRAF3 limits RANKL- and TNF-induced osteoclast formation, and it restricts transforming growth factor β (TGFβ)-induced inhibition of osteoblast formation in young and adult mice. During aging, neutrophils expressing TGFβ and C-C chemokine receptor type 5 (CCR5) increase in bone marrow of mice in response to increased NF-κB-induced CC motif chemokine ligand 5 (CCL5) expression by mesenchymal progenitor cells and injection of these neutrophils into young mice decreased bone mass. TGFβ causes degradation of TRAF3, resulting in decreased glycogen synthase kinase-3β/β-catenin-mediated osteoblast formation and age-related osteoporosis in mice. The CCR5 inhibitor, maraviroc, prevented accumulation of TGFβ+/CCR5+ neutrophils in bone marrow and increased bone mass by inhibiting bone resorption and increasing bone formation in aged mice. This paper updates current understanding of how NF-κB signaling is involved in the positive and negative regulation of cytokine-mediated osteoclast and osteoblast formation and activation with a focus on the role of TRAF3 signaling, which can be targeted therapeutically to enhance bone mass.
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Background Persistence with denosumab in male patients has not been adequately investigated, although poor denosumab persistence is associated with a significant risk of rebound vertebral fractures.
Methods We retrospectively evaluated 294 Korean male osteoporosis patients treated with denosumab at three medical centers and examined their persistence with four doses of denosumab injection over 24 months of treatment. Persistence was defined as the extent to which a patient adhered to denosumab treatment in terms of the prescribed interval and dose, with a permissible gap of 8 weeks. For patients who missed their scheduled treatment appointment(s) during the follow-up period (i.e., no-shows), Cox proportional regression analysis was conducted to explore the factors associated with poor adherence. Several factors were considered, such as age, prior anti-osteoporotic drug use, the treatment provider’s medical specialty, the proximity to the medical center, and financial burdens of treatment.
Results Out of 294 male patients, 77 (26.2%) completed all four sequential rounds of the denosumab treatment. Out of 217 patients who did not complete the denosumab treatment, 138 (63.6%) missed the scheduled treatment(s). Missing treatment was significantly associated with age (odds ratio [OR], 1.03), prior bisphosphonate use (OR, 0.76), and prescription by non-endocrinologists (OR, 2.24). Denosumab was stopped in 44 (20.3%) patients due to medical errors, in 24 (11.1%) patients due to a T-score improvement over –2.5, and in five (2.3%) patients due to expected dental procedures.
Conclusion Our study showed that only one-fourth of Korean male osteoporosis patients were fully adherent to 24 months of denosumab treatment.
Calcium and vitamin D play an important role in mineral homeostasis and the maintenance of skeletal health. Calcium and vitamin D supplements have been widely used for fracture prevention in elderly populations. Many trials have studied the effectiveness and cardiovascular safety of calcium and vitamin D supplementation, with disparate results. In this review, we summarize the most important trials and systematic reviews. There is significant heterogeneity in clinical trial design, differences in the nature of trial outcomes (self-reported vs. verified), prior calcium intake, and trial size. Inconsistent results have been reported concerning the effects of calcium and vitamin D supplementation on cardiovascular outcomes. Most current guidelines recommend calcium intake of up to 1,200 mg daily, preferably from the diet, without concern for cardiovascular risk. Recommendations regarding vitamin D supplementation vary widely. There is compelling evidence from well-conducted randomized trials that modest vitamin D supplementation is safe but does not confer cardiovascular benefit or cardiovascular harm.
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Background Evidence has revealed the involvement of microRNAs (miRNAs) in modulating osteogenic differentiation, implying the promise of miRNA-based therapies for treating osteoporosis. This study investigated whether miR-181a-5p influences osteogenic differentiation and bone formation and aimed to establish the mechanisms in depth.
Methods Clinical serum samples were obtained from osteoporosis patients, and MC3T3-E1 cells were treated with osteogenic induction medium (OIM) to induce osteogenic differentiation. miR-181a-5p-, Runt-related transcription factor 1 (Runx1)-, and/or allograft inflammatory factor-1 (AIF-1)-associated oligonucleotides or vectors were transfected into MC3T3-E1 cells to explore their function in relation to the number of calcified nodules, alkaline phosphatase (ALP) staining and activity, expression levels of osteogenesis-related proteins, and apoptosis. Luciferase activity, RNA immunoprecipitation, and chromatin immunoprecipitation assays were employed to validate the binding relationship between miR-181a-5p and Runx1, and the transcriptional regulatory relationship between Runx1 and AIF-1. Ovariectomy (OVX)-induced mice were injected with a miR-181a-5p antagonist for in vivo verification.
Results miR-181a-5p was highly expressed in the serum of osteoporosis patients. OIM treatment decreased miR-181a-5p and AIF-1 expression, but promoted Runx1 expression in MC3T-E1 cells. Meanwhile, upregulated miR-181a-5p suppressed OIM-induced increases in calcified nodules, ALP content, and osteogenesis-related protein expression. Mechanically, miR-181a-5p targeted Runx1, which acted as a transcription factor to negatively modulate AIF-1 expression. Downregulated Runx1 suppressed the miR-181a-5p inhibitor-mediated promotion of osteogenic differentiation, and downregulated AIF-1 reversed the miR-181a-5p mimic-induced inhibition of osteogenic differentiation. Tail vein injection of a miR-181a-5p antagonist induced bone formation in OVX-induced osteoporotic mice.
Conclusion In conclusion, miR-181a-5p affects osteogenic differentiation and bone formation partially via the modulation of the Runx1/AIF-1 axis.
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To do one and to get more: Part I. Diabetes and bone Wen-Ling Lee, Peng-Hui Wang, Szu-Ting Yang, Chia-Hao Liu, Wen-Hsun Chang, Fa-Kung Lee Journal of the Chinese Medical Association.2022; 85(10): 965. CrossRef
Background Bone mineral density (BMD) testing is indicated for women aged 65 years, but screening strategies for osteoporosis are controversial. Currently, there is no study focusing on the BMD testing interval in Asian populations. The current study aimed to evaluate the estimated time interval for screening osteoporosis.
Methods We conducted a study of 6,385 subjects aged 50 years and older who underwent dual-energy X-ray absorptiometry screening more than twice at Samsung Medical Center as participants in a routine health checkup. Subjects were divided based on baseline T-score into mild osteopenia (T-score, <–1.0 to >–1.5), moderate osteopenia (T-score, ≤–1.5 to >–2.0), and severe osteopenia (T-score, ≤–2.0 to >–2.5). Information about personal medical and social history was collected by a structured questionnaire.
Results The adjusted estimated BMD testing interval for 10% of the subjects to develop osteoporosis was 13.2 years in mild osteopenia, 5.0 years in moderate osteopenia, and 1.5 years in severe osteopenia.
Conclusion Our study provides extended information about BMD screening intervals in Asian female population. Baseline T-score was important for predicting BMD screening interval, and repeat BMD testing within 5 years might not be necessary in mild osteopenia subjects.
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