bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Vitro Effect of CCL11 on Myogenic Differentiation and Its Relevance With Sarcopenia Parameters in Older Adults
Authors: Park So Jeong , Kim Da Ae , Lee Jin Young , Kim Beom-Jun 
Published: May 2021

Abstract
Background: The C-C motif chemokine ligand 11 (CCL11) has been receiving attention as a potential pro-aging factor and thus may be also involved in muscle metabolism and sarcopenia, a key component of aging phenotypes. To clarify this possibility, we investigated the effects of CCL11 on in vitro muscle biology and clinical relevance with sarcopenia parameters in older adults. Methods: Primary mouse myoblasts and C2C12 cells were used for experimental research. Blood samples were collected from 79 participants who underwent a functional assessment, and CCL11 level was measured using a quantikine ELISA kit. Sarcopenia was diagnosed using the Asian-specific cut-off points. Results: CCL11 treatment stimulated the differentiation of both primary myoblasts and C2C12 cells into mature myotubes, and consistently increased the expression of myogenic differentiation markers, such as myosin heavy chain and myogenin. Among C-C chemokine receptors (CCRs), CCR5, not CCR2 and CCR3, was predominantly expressed in muscle cells, and CCR5 inhibitor blocked CCL11-stimulated myogenesis. In a clinical study, after adjustment for sex, age, and body mass index, serum CCL11 level was not significantly different according to the status of sarcopenia, low muscle mass, low muscle strength, and low physical performance, and was not associated with any of skeletal muscle index, grip strength, gait speed, time to complete 5 chair stands, and short physical performance battery score. Conclusions: Contrary to expectations, CCL11 showed the beneficial effects on muscle metabolism at least in vitro system. However, the role of CCL11 on muscle health in humans was not evident, suggesting that circulating CCL11 level may not be a useful biomarker for sarcopenia risk assessment in older adults.
Oleanolic Acid Modulates 25-Hydroxyvitamin D3 1-alpha-hydroxylase in Osteoblasts and Human Mesenchymal Stem Cells
Authors: Yu Wen-Xuan , Poon Christina Chui-Wa , Lee Wayne Yuk-Wai , Wong Man-Sau 
Published: May 2021

Abstract
Objectives: 25-Hydroxyvitamin D3 1-alpha-hydroxylase (CYP27B1) catalyzes the hydroxylation of 25-hydroxyvitamin D3 (25(OH)D3) to 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3), the bioactive form of vitamin D3. Our previous studies suggested that oleanolic acid (OA), a pentacyclic triterpenoid presents in many food and herbs, can improve circulating 1,25(OH)2D3 in ovariectomized (OVX) mice and increase CYP27B1 expression in human renal proximal tubular cells (HKC-8). However, the role of OA in regulating CYP27B1 in bone is far from clear. The present study is designed to study the effects of OA on CYP27B1 expressions and 1,25(OH)2D3 production in bone cells. Methods: The mRNA and protein expressions of CYP27B1, as well as bone metabolism markers were determined in osteoblast-like UMR-106 cells in response to treatments of parathyroid hormone (PTH) (10–7 M) or OA (10–9 - 10–5 M) for 24 hours. By using excessive 25(OH)D3 (10–6 M) as substrate, cellular production of 1,25(OH)2D3 was measured to determine CYP27B1 activity. To mimic the physiological condition, human mesenchymal stem cells (hMSCs) were pre-treated with 25(OH)D3 (10–7 M) for 12 hours, followed by OA treatment (10–9 - 10–6 M) for another 24 hours, the osteogenic effects of OA on alkaline phosphatase (ALP) activity and CYP27B1 expression were evaluated. Results: PTH (10–7 M, p&lt;0.001) and OA (10–9 M, p&lt;0.05) significantly upregulated mRNA and protein expressions of CYP27B1 in UMR-106 cells. 4-hour treatments of PTH (10–7 M) and OA (10–9 M) also stimulated the 1,25(OH)2D3 production by 46.02 % (p&lt;0.001) and 17.60 % (p&lt;0.01), respectively. Moreover, the mRNA expressions of ALP and osteocalcin (OCN) involved in osteoblast differentiation, were upregulated in response to PTH and OA in UMR-106 cells (p&lt;0.05). The protein expression of CYP27B1 was upregulated by treatment with OA in hMSCs supplemented with 25(OH)D3 (10–8 M, p&lt;0.05 vs. supplement alone). Furthermore, OA (10–8 M) potentiated the effects of 25(OH)D3 on osteogenesis in hMSCs by enhancing ALP activity by 47.77 % (p&lt;0.01). Conclusions: Our results indicated that the bone anabolic effects of OA are associated with its actions to improve local bioactivation of vitamin D3 in osteoblasts and hMSCs, suggesting the involvement of paracrine or autocrine activities of 1,25(OH)2D3 in mediating the actions of OA in bone. Funding Sources: This work is supported by research studentship of Wen-Xuan Yu, The Hong Kong Polytechnic University.
The Effect of Dietary Vitamin D3 Level on Bone Osteometry and Mechanical Properties in Young Rats
Authors: Muszyński Siemowit , Świątkiewicz Małgorzata , Szymczyk Beata , Oczkowicz Maria , Furgał-Dzierżuk Iwona 
Published: May 2021

Abstract
Recent knowledge indicates that vitamin D3 not only regulates the calcium-phosphate metabolism, but also as a hormone with steroidal features, has significant remedial-homeostatic ability and has a pleiotropic function in the body. Medical observations confirm the beneficial effect of elevated levels of vitamin D3 in the prevention or alleviation of the course of many diseases of the cancer and autoimmune basis, diabetes and coronary diseases. The deficiencies of this vitamin in children, adolescents and young women are observed, causing the rickets or bone fragility. As the increasingly limited role of obtaining vitamin D3 from the sun exposure, supplementation of food sources becomes particularly important. The aim of the study was to evaluate the effect of the increased dietary vitamin D3 level on health status using rats as the model animals. The experiment was carried out on 36 weaned rat Wistar, half female and male, 5–6 weeks old. Animals were divided into 3 groups. All rats obtained ad libitum the same feed mixture but differed in the vitamin D3 level (0, 1000 or 5000 IU/kg). Bone length and weight, cross-section area and wall thickness were measured, cortical index was calculated. The mechanical properties were determined using the 3-point bending test performed on a universal testing machine (Zwick Z010). The supports were placed at 40% of the total bone length and the measuring head loaded bone samples with a constant speed of 10 mm/min until fracture. The bone mineral density was determined using the dual-energy X-ray absorptiometry (DEXA) method on a DiscoveryWHologic X-ray densitometer. We observed that, the vitamin D3 presence in feed did not significantly affect the bone geometrical traits in young rats. The vitamin D3 supplementation, regardless its level, increased the bone mineral density by 8–12% (P&lt;0.05) and some mechanical properties were improved (P&lt;0.05) in comparison to group without vitamin D3 supplementation. Also, the femur bone of rats supplemented with vitamin D3 characterised by the higher share force (11–14%), work needed for destruction (24–55%), ultimate strain, ultimate stress (5–7%). The bone elastic strength was the highest in group III, receiving the vitamin D3 in amount excessing the standard requirement of rats. Summerizing it can be concluded, contrary to the assumptions, we did not confirmed the significant effect of increased vitamin D3 level in feed on MBD and most of the mechanical traits. However, the maximal elastic strenght was the highest in group receiving 5000 IU/kg of vitamin D3, which reflects the highest elastic strength of midshaft cortical bone under reversible deformation and the maximum stress which a bone can withstand before fracture, but the difference was not statistically confirmed.
The Role of Thyroid Hormone 3,3 ‘, 5 - Triiodothyronine (T3) in the Expression of Osteocalcin and Lipocalin 2 (LCN2) in Osteoblasts
Authors: de Camargo Andrade Amanda Fantini , Pinto Thaís Silva , Feltran Geórgia Silva , Ferretti Renato , Zambuzzi Willian Fernando 
Published: May 2021

Abstract
Introduction: The thyroid hormone 3,3 ‘, 5 - triiodothyronine (T3) has an important role in bone physiology and metabolism, stimulating osteodifferentiation and bone homeostasis. Although there is this evidence, little is known about the synergistic events of T3 together with the endocrine role of other players that interfere with osteoblast metabolism, such as Lipocalin 2 (LCN2) and its hypothalamic-located MCR4 receptor. It is also known that LCN2 interferes at a physiological level with the parameters of food intake. Objective: To evaluate the role of the thyroid hormone 3,3 ‘, 5 - Triiodothyronine (T3) in the control of the expression of both Osteocalcin (OCN) and Lipocalin 2 (LCN2) in osteoblasts. Materials and Methods:. In order to understand the molecular and physiological mechanisms about that probable synergism, the experiments were as follows: Mouse pre-osteoblasts were challenged with T3 hormone treatments in three levels (1nM; 1.5nM; 2.0nM) and different times (0h; 24h; 72h). The samples were collected to perform gene expression of the main osteodifferentiation markers (RUNX2, OTX, BSP), matrix remodeling (MMPs, TIMPs, BMPII) and zymography assay for analysis of metalloproteinase activities (MMPs). Results and Discussion: Preliminarily, it was founded a synergism between the hormone T3 and LCN2 expression in osteoblasts, occurring the modulation of the marker genes of differentiation, extracellular matrix and hormonal synthesis. The T3 hormone acts in the modulation of RUNX2, OTX, BMP2, favoring osteodifferentiation and the remodeling of the matrix, probably activating the TIMP1-MMP9 and TIMP2-MMP2 complexes, mainly in hyperthyroid conditions. In addition, we note a direct influence of T3 on the both expression of both Osteocalcin (OCN) and Lipocalin 2 (LCN2). Final Considerations: Our preliminary data indicates that the hormone T3 acts on the metabolism of osteoblasts through the modulation of LCN2 and BMPII. These molecular findings need to be confronted with further analyzes in vivo for more conclusive physiological conclusions.
A Hospitalist-Led Fracture Liaison Service Improves Care of Hip Fracture Patients
Authors: Drabkin Anne , Rothman Micol Sara , Audrey Goold , Robin Yasui , Diana Mancini 
Published: May 2021

Abstract
Background: Osteoporosis care traditionally falls to outpatient primary care providers despite the fact that over 300,000 elderly patients are hospitalized yearly with hip fractures in the United States. Internal medicine hospitalists are often involved in the co-management of their care on surgical teams and are skillful in osteoporosis recognition and management. Objective: A hospitalist-led Fracture Liaison Service (FLS) was established to provide improved care of hospitalized patients with hip fractures. Methods: A retrospective evaluation of inpatient and post-discharge management of patients admitted with low-impact hip fractures was performed before (8/17-2/18) and after (8/19 - 2/20) launch of the hospitalist Fracture Liaison Service (H-FLS). Results: Eighty-nine patients were admitted with a hip fracture in post-launch period compared to 73 admitted prior. 74% vs 11% of eligible patients (based on adequate renal function and vitamin D stores) were discharged with anti-osteoporosis medications (p&lt;0.001), 82% vs 38% were discharged with vitamin D/calcium supplements (p&lt;0.001), 22% vs 5% underwent a DXA scan after discharge (p&lt;0.05) and 65% vs 0% were referred to outpatient osteoporosis-specific care at discharge (p&lt;0.001). Conclusion: A hospitalist-led FLS is a unique approach to osteoporosis care that significantly improved quality metrics for elderly patients with osteoporotic hip fractures including initiation of anti-osteoporosis medication and bone density imaging. Outpatient follow-up data are needed to evaluate adherence to this initial management over time.
Clinical Risk Factors for Osteoporotic Fractures in Men With Non-Metastatic Prostate Cancer on Androgen Deprivation Therapy With or Without Anti-Osteoporosis Treatment
Authors: Sonnabend Hajerah , Pulipati Vishnu Priya , Baim Sanford , Beck Todd , Simmons J Alan , Ritz Ethan M 
Published: May 2021

Abstract
Introduction: Androgen deprivation therapy (ADT) decreases bone mineral density and increases osteoporotic fracture (OsteoFx) risk.
Hypothesis: To assess OsteoFx clinical risk factors (CRF) most predictive of future OsteoFx among men with prostate cancer on ADT.
Methods: 4370 electronic medical records were reviewed of adult men with prostate cancer on cancer therapy +/- anti-osteoporosis therapy (Anti-OsteoRx) from 2011–2019. Cancer therapy included ADT (anti-androgens, GnRH agonists & antagonists, orchiectomy) and supplemental cancer therapy (SupplRx) (prostatectomy, brachytherapy, radiation, immunotherapy, and chemotherapy). Anti-OsteoRx included bisphosphonates, denosumab, and parathyroid hormone analogs. Patients with other cancers within 5 years of initial visit, metastasis, and traumatic fractures were excluded. Retrospective analysis was done to determine baseline characteristics, type and duration of ADT, Anti-OsteoRx, SupplRx, and osteoporosis CRF.
Results: 615 men on ADT +/- SupplRx +/- Anti-OsteoRx were included in the study. 10.08% had OsteoFx irrespective of SupplRx or Anti-OsteoRx. Comparing the OsteoFx group to the non-fracture group, the following CRF were found to be statistically significant (p &lt;0.05): age at prostate cancer diagnosis (75.10 +/- 11.80 vs 71.59 +/- 9.80 y), diabetes mellitus (DM) (33.9 vs 19%), pre-existing comorbidities affecting bone (PreCo) (41.9 vs 24.8%), steroid use (11.3 vs 4.0%), and anti-convulsant and proton-pump inhibitor (med) use (45.2 vs 26.8%).
9.89% of 374 men on ADT only without (wo) Anti-OsteoRx fractured. Statistically significant CRF for OsteoFx were age (76.86 +/- 10.55 vs 73.02 +/- 10.06 y), DM (40.5 vs 19.6%), PreCo (45.9 vs. 26.4%), and med use (48.6 vs. 25.5%).
In the following subgroups there were no statistically significant difference in CRF:•7.64% of 170 men on ADT + SupplRx wo Anti-OsteoRx •19.23% of 52 men on ADT only + Anti-OsteoRx •10.52% of 19 men on ADT + SupplRx + Anti-OsteoRx
To increase statistical power, patients on ADT +/- SupplRx were assessed:•Among 71 men on ADT +/- SupplRx + Anti-OsteoRx, there were no statistically significant differences in CRF•Among the 544 men on ADT +/- SupplRx wo Anti-OsteoRx, significant CRF for OsteoFx were age (75.16 + 11.70 vs 71.37 + 9.85 y), DM (38 vs 19.4%), PreCo (38 vs 24.1%), steroid use (12 vs 3.8%), and med use (48 vs 24.3%)
Discussion:
Men with prostate cancer requiring ADT have a higher incidence of osteoporosis defined by DXA prior to initiating ADT compared to age-matched cohorts (Hussain et al). Our study revealed ADT with CRF is associated with OsteoFx irrespective of SupplRx or Anti-OsteoRx. Limitations include inability to evaluate efficacy of Anti-OsteoRx due to insufficient power.
Conclusion: OsteoFx risk assessment utilizing CRF, FRAX, DXA with timely intervention may prevent OsteoFx in these high-risk patients.
Fracture Rates in Men With Non-Metastatic Prostate Cancer on Androgen Deprivation Therapy With or Without Anti-Osteoporosis Treatment
Authors: Sonnabend Hajerah , Pulipati Vishnu Priya , Baim Sanford , Beck Todd , Ritz Ethan M , Simmons J Alan 
Published: May 2021

Abstract
Introduction: Androgen deprivation therapy (ADT) decreases bone mineral density and increases osteoporotic fracture (OsteoFx) risk. Hypothesis: To assess OsteoFx incidence most predictive of future OsteoFx among men with prostate cancer on ADT. Methods: 4370 electronic medical records were reviewed of adult men with prostate cancer on cancer therapy +/- anti-osteoporotic therapy (Anti-OsteoRx) from 2011–2019. Cancer therapy included ADT (anti-androgens, GnRH agonists & antagonists, orchiectomy) and supplemental cancer therapy (SupplRx) (prostatectomy, brachytherapy, radiation, immunotherapy, and chemotherapy). Anti-OsteoRx included bisphosphonates, denosumab, and parathyroid hormone analogs. Patients with other cancers within 5 years of initial visit, metastasis or traumatic fractures were excluded. Retrospective analysis was done to determine baseline characteristics, type and duration of ADT, Anti-OsteoRx, SupplRx, and OsteoFx incidence. Results: Fracture rate subgroups: • ADT only - Anti-OsteoRx 37/ 374 fractured (9.89%) • ADT only + Anti-OsteoRx 10/52 fractured (19.23%) • ADT + SupplRx + Anti-OsteoRx 2/19 fractured (10.53%) • ADT + SupplRx + Anti-OsteoRx 13/170 fractured (7.65%) Comparing fracture rates between subgroups: • Comparing ADT only +/- Anti-OsteoRx, statistical significance was observed with higher fracture rate in patients taking Anti-OsteoRx (19.23% vs. 9.89%, p &lt; 0.044) • Comparing ADT + SupplRx +/- Anti-OsteoRx, no significant difference in fracture rates due to small number of fractures Comparing combined subgroups: • ADT +/- SupplRx + Anti-OsteoRx 12/71 (16.9%) fractured • ADT +/- SupplRx - Anti-OsteoRx 50/544 (9.19%) fractured • Statistically significant between groups fracture rates was observed (p= 0.042) in patients treated with Anti-OsteoRX. Discussion: Patients receiving Anti-OsteoRx, regardless of their prostate cancer therapies, had higher rates of fractures (16.9 vs. 9.19%, p= 0.042) due to their being selected for therapy based on greater clinical risks. The Anti-OsteoRx group had a higher percentage of glucocorticoid listed as a historical medication (26.8 vs.15.3% vs, p= 0.023), glucocorticoids administered (50.7 vs. 30.3% p=0.001), and anticonvulsants and proton-pump inhibitor use (45.1 vs. 26.5%, p= 0.002). Conclusion: Higher fracture rates were observed in patients on Anti-OsteoRx that could be related to their being selected for treatment based on risk factors known to be associated with osteoporosis. Limited Anti-OsteoRx use in our study is possibly related to lack of standardized guidelines for prevention of osteoporotic fractures in prostate cancer patients. OsteoFx risk assessment utilizing CRF, DXA, and FRAX may prevent fractures in these high-risk patients. Further long-term prospective studies to address these unresolved queries are warranted.
Methadone Maintenance Treatment, Sex Hormones and Low Bone Density in a Population of Injection Drug Users
Authors: Wehbeh Leen , Diaz Jenny Pena , Moseley Kendall Ford , Piggott Damani , Dobs Adrian Sandra , Brown Todd Tarquin 
Published: May 2021

Abstract
Background: Methadone maintenance treatment (MMT) is associated with low bone mineral density (BMD) in those treated for opioid addiction. However, it is unclear whether observed adverse effects on the skeleton are related to a direct effect of opioids on bone metabolism or mediated by other mechanisms including MMT-induced gonadal dysfunction. We hypothesized that MMT is associated with low BMD in persons with a history of injection drug use (PWID) and that this effect is explained by differences in sex hormones.
Methods: We recruited 280 participants from the AIDS Linked to the Intravenous Experience (ALIVE) study, a long-standing cohort of PWID. All participants had been exposed to hepatitis C virus (HCV antibody positive). In addition to a morning assessment of free testosterone (FT) and estradiol (E2), all participants underwent dual-energy x-ray absorptiometry (DXA) of the lumbar spine (LS) and hip (total hip (TH) and femoral neck (FN)). Multivariable linear regression was used to assess the relationship between MMT and T-score with and without inclusion of E2/FT concentrations. Models were stratified by sex and adjusted for age, BMI, HCV infection, HIV, current alcohol use, current smoking, vitamin D3 level, and current heroin use.
Results: All participants were African American and 37% female. The median (Q1, Q3) age was 57 years (51, 61), median (Q1, Q3) BMI was 26 kg/m2 (22, 30) and 107 (38%) were receiving MMT. FT and E2 were significantly lower in men receiving MMT vs not (p &lt; 0.01 for both). In women, there were no differences in sex hormones based on MMT use. The prevalence of low BMD (defined as LS, TH, or FN T-score ≤ -1) was 25% (23% in men and 29% in women; p = 0.3); 12 (4.3%, 2 men and 8 women; p = 0.09) had osteoporosis (T-score ≤ -2.5). In men, MMT was associated with -0.7 lower LS-T score (95% CI [-1.3, -0.1], p=0.046) in adjusted models compared to those not receiving MMT. The magnitude of this association was reduced after adjusting for E2 and FT (-0.2, 95% CI [-0.8, 0.5], p=0.665)). In women, MMT was not associated with LS-T score (MD -0.3, 95% CI [-1.3, 0.4], p=0.631). There were no associations between MMT and TH or FN BMD in either men or women.
Conclusion: In this study, MMT was associated with lower lumbar spine BMD in men with a history of IDU, which was potentially mediated by the effect of MMT on sex hormones. More rigorous screening for co-morbidities including hypogonadism and low BMD in men receiving MMT may be warranted.
Appropriate Cutoff for 25OHD Levels in the Diagnosis of Normocalcemic Primary Hyperparathyroidism (NPHPT): A Systematic Review
Authors: Yedla Niharika , Wang Xiangbing David 
Published: May 2021

Abstract
Introduction: The Fourth International Workshop in 2014 delineated guidelines for the diagnosis of NPHPT which include ruling out secondary causes of hyperparathyroidism, and recommended cutoffs for 25 vitamin D (25OHD) to be ≥20ng/mL. Keeping in mind that the exact levels to optimize 25OHD in hyperparathyroid states are unknown, we aim to review possible variation in the prevalence of NPHPT if 25OHD cutoffs were to be raised to rule out vitamin D deficiency with more specificity. Methods: A PubMed search was conducted with key words “normocalcemic primary hyperparathyroidism” to review studies about NPHPT and 25OHD status. 533 articles were found, and 127 articles were identified by title/abstract screening with year of publication between 2014 to 2020. Ten studies were identified for the systematic review based on full text review for relevance. Results: Studies have been conducted in various countries across all continents to characterize NPHPT further. 5/10 studies used 25OHD cutoff of ≥20ng/mL and 4 studies had a cutoff of ≥30ng/mL and 1 study looked into the difference in prevalence with both cutoffs. All 3 studies from Italy used the higher cutoff. Rosario et al from Brazil reported a decrease in prevalence of NPHPT from 6.8% (25OHD≥20ng/mL) to 0.74% by supplementing those subjects to 25OHD ≥30ng/mL without any increase in serum calcium or parathyroid hormone (PTH) levels.1 Wang et al found that when total 25OHD levels were kept between 30–40 ng/mL, free 25OHD levels were actually lower compared to normal subjects.2 Conclusion: The levels of 25OHD that would define deficiency in NPHPT remain undetermined and both &gt;20 ng/mL and &gt;30ng/mL have been studied as cutoffs. It is well known that vitamin D insufficiency (25D 20-30ng/mL) drives up PTH and supplementation to 30-40ng/mL is required to reduce such effects. Wang et al suggest that free 25OHD levels correlate better with PTH as compared to total 25OHD and maybe a more reliable marker of 25OHD status. We suggest that a diagnostic criterion of ≥30ng/mL would be more appropriate in ruling out 25OHD deficiency in this special population. The role of free 25OHD levels in PHPT needs further evaluation. References: 1. Rosário PW, Calsolari MR. Normocalcemic Primary Hyperparathyroidism in Adults Without a History of Nephrolithiasis or Fractures: A Prospective Study. Horm Metab Res. 2019 Apr;51(4):243–247. doi: 10.1055/a-0859-1020. Epub 2019 Mar 6. PMID: 30840998. 2. Wang X, Meng L, Su C, Shapses SA. LOW FREE (BUT NOT TOTAL) 25-HYDROXYVITAMIN D LEVELS IN SUBJECTS WITH NORMOCALCEMIC HYPERPARATHYROIDISM. Endocr Pract. 2020 Feb;26(2):174–178. doi: 10.4158/EP-2019-0325. Epub 2019 Sep 26. PMID: 31557077