Search

Kenji Inoue, Taku Kawashima, Seiki Katakura, Kyoko Shidara, Takayuki Fujimoto, Hiromi Kohmoto, Minako Shiokawa, Ryo Moriyama, Ryoko Okayama Inouye Eye Hospital, Tokyo, Japan Purpose: To evaluate the efficacy and safety of tafluprost/timolol fixed combination (TTFC). Study design: A prospective clinical study. Methods: Twenty-eight patients (28 eyes) with primary open-angle glaucoma, who had used tafluprost and timolol gel for at least 3 months with good adherence, were enrolled. Concomitant administration of tafluprost and timolol was switched to TTFC without a washout period. The intraocular pressure (IOP), blood pressure, pulse rate, and ocular signs were compared between before switching (baseline), and 4 and 8 weeks after switching. A questionnaire survey was also performed 4 weeks after switching to investigate ocular comfort and patient preferences. Results: The IOP showed no significant change after switching to TTFC (14.8 ± 2.8, 14.6 ± 3.4, and 14.8 ± 3.7 mmHg at baseline, Week 4, and Week 8, respectively). The pulse rate and systolic blood pressure showed no changes, but diastolic blood pressure was significantly lower at Week 8. At baseline, fluorescein staining revealed corneal abnormalities in 3 patients, which resolved by Week 8 in 1 patient. Hyperemia was noted in 2 patients at baseline, and this also resolved by Week 8 in 1 patient. Three patients discontinued study treatment for the following reasons (1 patient each): blurred vision; ocular irritation, eyelid erythema, and asthenopia; and loss to follow-up from Week 8. The questionnaire survey revealed no significant differences between the 2 treatments, although more patients preferred TTFC. Conclusion: Among 28 patients enrolled, only 2 patients discontinued the study treatment due to adverse reactions. In patients whose adherence was considered relatively good to concomitant therapy, switching to TTFC achieved similar IOP control with good safety and a high level of patient acceptance. Keywords: tafluprost/timolol fixed combination, switching, intraocular pressure, adverse reactions

Michitaka Sugahara, Takayuki Fujimoto, Kyoko Shidara, Kenji Inoue, Masato Wakakura Inouye Eye Hospital, Tokyo, Japan Introduction: Here, we describe a patient who presented with anterior ischemic optic neuropathy (AION) and subsequently developed uveitis. Case: A 69-year-old man was referred to our hospital and initially presented with best-corrected visual acuities (BCVA) of 20/40 (right eye) and 20/1000 (left eye) and relative afferent pupillary defect. Slit-lamp examination revealed no signs of ocular inflammation in either eye. Fundus examination revealed left-eye swelling and a pale superior optic disc, and Goldmann perimetry revealed left-eye inferior hemianopia. The patient was diagnosed with nonarteritic AION in the left eye. One week later, the patient returned to the hospital because of vision loss. The BCVA of the left eye was so poor that the patient could only count fingers. Slit-lamp examination revealed 1+ cells in the anterior chamber and the anterior vitreous in both eyes. Funduscopic examination revealed vasculitis and exudates in both eyes. The patient was diagnosed with bilateral panuveitis, and treatment with topical betamethasone was started. No other physical findings resulting from other autoimmune or infectious diseases were found. No additional treatments were administered, and optic disc edema in the left eye improved, and the retinal exudates disappeared in 3 months. The patient's BCVA improved after cataract surgery was performed. Conclusion: Panuveitis most likely manifests after the development of AION. Keywords: anterior ischemic optic neuropathy, uveitis

ObjectiveTo determine the effect of an antibody to vascular endothelial growth factor (VEGF) on bone blood flow, bone strength, and bone mass in the young adult mouse.MethodsTen-week-old male BALB/cJ mice were body weight-randomized into either a rodent anti-VEGF monoclonal antibody (anti-VEGF, B20-4.1.1; 5 mg/kg 2×/wk.; n = 12) group or a vehicle (VEH; n = 12) group. After 42 days, mice were evaluated for bone blood flow at the distal femur by 18F-NaF-PET/CT and then necropsied. Samples from trabecular and cortical bone regions were evaluated for bone strength by mechanical testing, bone mass by peripheral quantitative computed tomography (pQCT), and micoarchitecture (MicroCT). Hydration of the whole femur was studied by proton nuclear magnetic resonance relaxometry (1H NMR).ResultsDistal femur blood flow was 43% lower in anti-VEGF mice than in VEH mice (p = 0.009). Ultimate load in the lumbar vertebral body was 25% lower in anti-VEGF than in VEH mice (p = 0.013). Bone mineral density (BMD) in the trabecular region of the proximal humeral metaphysis by pQCT, and bone volume fraction and volumetric BMD by MicroCT were the same in the two groups. Volume fraction of bound water (BW) of the whole femur was 14% lower in anti-VEGF than in VEH mice (p = 0.003). Finally, BW, but not cortical tissue mineral density, helped section modulus explain the variance in the ultimate moment experienced by the femur in three-point bending.ConclusionAnti-VEGF caused low bone blood flow and bone strength in trabecular bone regions without influencing BMD and microarchitecture. Low bone strength was also associated with low bone hydration. These data suggest that bone blood flow is a novel bone property that affects bone quality.

Both epidemiologic and clinical research continues to be performed in osteoarthritis (OA). While epidemiologic studies identify risk factors for incident and progressive disease, clinical studies explore the role of both non-pharmacologic and pharmacologic treatments, including oral and intra-articular therapies. We performed a systematic review of the literature using PubMed for the time period between April 1, 2015 to February 22, 2016. Selected publications in the areas of both epidemiology and treatment are reviewed in this article.

NHK led the world in developing a high-sensitivity Super-HARP pickup tube using the avalanche multiplication effect. The authors have now developed an improved version (2/3-inch, with electromagnetic focusing and electromagnetic deflection) which is eight times more sensitive and has much better lag characteristics. The handy New Super-HARP color camera which uses this newly-developed pickup tube has higher sensitivity than human vision (11 lux, F8), negligibly low lag, and a limiting resolution of over 700 TV lines. It will be a powerful tool in emergency news gathering at night, the production of scientific programs, and other applications.

Background: Cognitive behavioral therapy (CBT) is a valuable treatment for mood disorders and anxiety. CBT methods, such as cognitive restructuring, are employed to change automatic negative thoughts to more realistic ones., Objective: This study extends on previous research conducted by the authors, focused on the process of correcting automatic negative thoughts to realistic ones and reducing distress and anxiety via CBT with a virtual agent. It was aimed to investigate whether the previously applied virtual agent would achieve changes in automatic negative thoughts when modifications to the previous experimental paradigm are applied and when user motivation is taken into consideration. Furthermore, the potential effects of existing participant knowledge concerning CBT or automatic thoughts were explored., Methods: A single-group, 2-session experiment was conducted using a within-group design. The study recruited 35 participants from May 15, 2023, to June 2, 2023, via Inter Group Corporation, with data collection following from June 5 to June 20, 2023, at Nara Institute of Science and Technology, Japan. There were 19 male and 16 female participants (age range: 18-50 years; mean 33.66, SD 10.77 years). Participants answered multiple questionnaires covering depressive symptomatology and other cognitive variables before and after a CBT session. CBT was carried out using a virtual agent, who participants conversed with using a CBT dialogue scenario on the topic of automatic negative thoughts. Session 2 of the experiment took place 1 week after session 1. Changes in distress and state anxiety were analyzed using a Wilcoxon signed-rank test and t-test for paired samples. The relationships of motivation with cognitive changes and distress or anxiety changes were investigated via correlation analysis. Multiple linear regression was used to analyze the potential predictive qualities of previous knowledge of CBT and automatic negative thoughts regarding outcome measures., Results: Significant reductions in distress (all P<.001) and state anxiety (all P<.003) emerged throughout the first and second experimental sessions. The CBT intervention increased participants' recognition of their negative thinking and their intention to change it, namely their motivation to change it. However, no clear correlations of motivation with changes in distress or anxiety were found (all P>.04). Participants reported moderate subjective changes in their cognition, which were in part positively correlated with their motivation (all P<.007). Lastly, existing knowledge of CBT did not predict reductions in distress during the first session of the experiment (P=.02)., Conclusions: CBT using a virtual agent and a CBT dialogue scenario was successful in reducing distress and anxiety when talking about automatic negative thoughts. The promotion of client motivation needs to be critically considered when designing interventions using CBT with a virtual agent, and further experimental investigations on the causal influences between motivation and outcome measures need to be conducted., (©Katja Frischholz, Hiroki Tanaka, Kazuhiro Shidara, Kazuyo Onishi, Satoshi Nakamura. Originally published in JMIR Formative Research (https://formative.jmir.org), 15.10.2024.)

Background: The high prevalence of mental illness is a critical social problem. The limited availability of mental health services is a major factor that exacerbates this problem. One solution is to deliver cognitive behavioral therapy (CBT) using an embodied conversational agent (ECA). ECAs make it possible to provide health care without location or time constraints. One of the techniques used in CBT is Socratic questioning, which guides users to correct negative thoughts. The effectiveness of this approach depends on a therapist's skill to adapt to the user's mood or distress level. However, current ECAs do not possess this skill. Therefore, it is essential to implement this adaptation ability to the ECAs., Objective: This study aims to develop and evaluate a method that automatically adapts the number of Socratic questions based on the level of detected psychological distress during a CBT session with an ECA. We hypothesize that this adaptive approach to selecting the number of questions will lower psychological distress, reduce negative emotional states, and produce more substantial cognitive changes compared with a random number of questions., Methods: In this study, which envisions health care support in daily life, we recruited participants aged from 18 to 65 years for an experiment that involved 2 different conditions: an ECA that adapts a number of questions based on psychological distress detection or an ECA that only asked a random number of questions. The participants were assigned to 1 of the 2 conditions, experienced a single CBT session with an ECA, and completed questionnaires before and after the session., Results: The participants completed the experiment. There were slight differences in sex, age, and preexperimental psychological distress levels between the 2 conditions. The adapted number of questions condition showed significantly lower psychological distress than the random number of questions condition after the session. We also found a significant difference in the cognitive change when the number of questions was adapted based on the detected distress level, compared with when the number of questions was fewer than what was appropriate for the level of distress detected., Conclusions: The results show that an ECA adapting the number of Socratic questions based on detected distress levels increases the effectiveness of CBT. Participants who received an adaptive number of questions experienced greater reductions in distress than those who received a random number of questions. In addition, the participants showed a greater amount of cognitive change when the number of questions matched the detected distress level. This suggests that adapting the question quantity based on distress level detection can improve the results of CBT delivered by an ECA. These results illustrate the advantages of ECAs, paving the way for mental health care that is more tailored and effective., (©Kazuhiro Shidara, Hiroki Tanaka, Hiroyoshi Adachi, Daisuke Kanayama, Takashi Kudo, Satoshi Nakamura. Originally published in JMIR Formative Research (https://formative.jmir.org), 14.03.2024.)

An inter-laboratory study was performed in eight laboratories to evaluate the simultaneous quantification method for HT-2 toxin (HT-2), T-2 toxin (T-2), diacetoxyscirpenol (DAS), neosolaniol (NES), 3-acetyldeoxynivalenol (3-AcDON), 15-acetyldeoxynivalenol (15-AcDON), deoxynivalenol (DON), deoxynivalenol-3-glucoside (D3G), nivalenol (NIV), and fusarenon-X (FUS-X) in feed. The mycotoxins in the samples were extracted with hydrous acetonitrile, purified using a multifunctional column (InertSep ® VRA-3) and a phospholipid removal column (Hybrid SPE ® -Phospholipid), and then quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with atmospheric pressure chemical ionisation mode. The mean recovery, repeatability, reproducibility, and Horwitz ratio from the inter-laboratory validation study were 99.8-109%, 3.1-9.8%, 4.3-9.8%, and 0.19-0.45, respectively, for type A trichothecenes (HT-2, T-2, DAS, and NES). Those values for type B trichothecenes (3-AcDON, 15-AcDON, DON, NIV, and FUS-X) were 89.9-116%, 3.4-9.1%, 5.6-14%, and 0.25-0.70, and the values for modified mycotoxin (D3G) were 78.2-96.7%, 3.5-6.4%, and 13-22%, respectively., (© 2023. The Author(s) under exclusive licence to Society for Mycotoxin (Research Gesellschaft für Mykotoxinforschung e.V.) and Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Differences in the distribution of individual-level clinical risk factors across regions do not fully explain the observed global disparities in COVID-19 outcomes. We aimed to investigate the associations between environmental and societal factors and country-level variations in mortality attributed to COVID-19 among people with rheumatic disease globally., Methods: In this observational study, we derived individual-level data on adults (aged 18-99 years) with rheumatic disease and a confirmed status of their highest COVID-19 severity level from the COVID-19 Global Rheumatology Alliance (GRA) registry, collected between March 12, 2020, and Aug 27, 2021. Environmental and societal factors were obtained from publicly available sources. The primary endpoint was mortality attributed to COVID-19. We used a multivariable logistic regression to evaluate independent associations between environmental and societal factors and death, after controlling for individual-level risk factors. We used a series of nested mixed-effects models to establish whether environmental and societal factors sufficiently explained country-level variations in death., Findings: 14 044 patients from 23 countries were included in the analyses. 10 178 (72·5%) individuals were female and 3866 (27·5%) were male, with a mean age of 54·4 years (SD 15·6). Air pollution (odds ratio 1·10 per 10 μg/m 3 [95% CI 1·01-1·17]; p=0·0105), proportion of the population aged 65 years or older (1·19 per 1% increase [1·10-1·30]; p<0·0001), and population mobility (1·03 per 1% increase in number of visits to grocery and pharmacy stores [1·02-1·05]; p<0·0001 and 1·02 per 1% increase in number of visits to workplaces [1·00-1·03]; p=0·032) were independently associated with higher odds of mortality. Number of hospital beds (0·94 per 1-unit increase per 1000 people [0·88-1·00]; p=0·046), human development index (0·65 per 0·1-unit increase [0·44-0·96]; p=0·032), government response stringency (0·83 per 10-unit increase in containment index [0·74-0·93]; p=0·0018), as well as follow-up time (0·78 per month [0·69-0·88]; p<0·0001) were independently associated with lower odds of mortality. These factors sufficiently explained country-level variations in death attributable to COVID-19 (intraclass correlation coefficient 1·2% [0·1-9·5]; p=0·14)., Interpretation: Our findings highlight the importance of environmental and societal factors as potential explanations of the observed regional disparities in COVID-19 outcomes among people with rheumatic disease and lay foundation for a new research agenda to address these disparities., Funding: American College of Rheumatology and European Alliance of Associations for Rheumatology., Competing Interests: MID reports research support from Pfizer for unrelated work. AS reports grants from a consortium of 13 companies (AbbVie, Bristol Myers Squibb, Celltrion, Fresenius Kabi, Lilly, Mylan, Hexal, Merck, Pfizer, Roche, Samsung, Sanofi-Aventis, and UCB) supporting the German RABBIT register, and personal fees from lectures for AbbVie, Merck, Roche, Bristol Myers Squibb, and Pfizer, outside of the submitted work. EFM reports that the Portuguese League Against Rheumatic Diseases received support for specific activities: grants from Abbvie, Novartis, Janssen-Cilag, Lilly Portugal, Sanofi, Grünenthal SA, Merck, Celgene, Medac, Pharmakern, the Global Alliance for Patient Access; grants and non-financial support from Pfizer; and non-financial support from Grünenthal GmbH, outside of the submitted work. KLH reports receiving speaker fees from Abbvie and grant income from Bristol Myers Squibb, UCB, and Pfizer, unrelated to this work. KLH is also supported by the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre. LG reports research grants from Amgen, Galapagos, Janssen, Lilly, Pfizer, Sandoz, and Sanofi; and consulting fees from AbbVie, Amgen, Bristol Myers Squibb, Biogen, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, and UCB, all unrelated to this work. LC has not received fees or personal grants from any laboratory, but her institute works by contract for laboratories among other institutions, such as Abbvie Spain, Eisai, Gebro Pharma, Merck Sharp & Dohme España, SA Pharma, Novartis Farmaceutica, Pfizer, Roche Farma, Sanofi, Aventis, Astellas Pharma, Actelion Pharmaceuticals España, Grünenthal GmbH, and UCB Pharma. JAS has performed consultancy for AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Gilead, Inova Diagnostics, Janssen, and Optum, unrelated to this work. LW has received consulting or speaking fees from Aurinia Pharma, outside of the submitted work. MFU-G reports grant or research support from Jannsen and Pfizer, unrelated to this work. The Swedish Rheumatology Quality Register, with LL as register holder, has agreements with Abbvie, Amgen, Eli Lilly, Gilead, Novartis, Pfizer, Sanofi, Sobi, and UCB for register data analyses, unrelated to this work. CR has received consulting or speaker fees from Abbvie, Amgen, AstraZeneca, BMS, Biogen, Eli Lilly, Glenmark, GlaxoSmithKline, Merck, Mylan, and Pfizer; and grants from Biogen, Lilly, and Nordic Pharma, all unrelated to this work. MJS has received speaker fees from Abbvie, AstraZeneca, Novartis, and Pfizer. AR has received speaker fees from Janssen, Pfizer, and Novartis. GP-E reports reports personal consulting fees, speaking fees, or both from Pfizer, GlaxoSmithKline, Janssen, Sandoz, and Sanofi, outside of the submitted work. PCR reports personal consulting fees, speaking fees, or both from Abbvie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB; and travel assistance from Roche. PMM has received consulting fees, speaker fees, or both from Abbvie, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, and UCB, unrelated to this work. PMM is supported by the NIHR University College London Hospitals Biomedical Research Centre. ES is a Board Member of the Canadian Arthritis Patient Alliance, a patient-run, volunteer-based organisation whose activities are largely supported by independent grants from pharmaceutical companies. JWL has received research funding from Pfizer, outside of the submitted work. JSH is supported by grants from the Rheumatology Research Foundation and has salary support from the Childhood Arthritis and Rheumatology Research Alliance. JSH has performed consulting for Novartis, Sobi, and Biogen, unrelated to this work. PS reports honorarium for doing social media for American College of Rheumatology journals. RG reports personal fees, speaking fees, or both from Abbvie, Janssen, Novartis, Pfizer, and Cornerstones; and travel assistance from Pfizer. SB reports non-branded consulting fees for AbbVie, Horizon, and Novartis; and is employed by Pfizer. ZSW reports grant support from Bristol Myers Squibb and Principia–Sanofi; and performed consultancy for Viela Bio and MedPace, outside of the submitted work. ZSW's work is supported by grants from the National Institutes of Health. JY has performed consulting for Eli Lilly, Pfizer, Aurinia, and AstraZeneca, outside of the submitted work. All other authors declare no competing interests., (Published by Elsevier Ltd.)

Online counseling is essential for overcoming mobility restrictions, schedule limitations, and mental health stigma. However, government counseling offices are being inun-dated with consultations for which non-mental health supports are targeted. Therefore, we aim to create a classification model that classifies whether the clients have mental health issues or other issues. We expect to support counselors by presenting the classification results. We conducted the first automatic detection of clients who might be suffering from mental health issues and used almost 1000 actual counseling sessions for our machine learning framework. We achieved an F1-score of 0.646 by classifying dialogue sessions using features such as frequency-inverse, document frequency, document embedding of a large-scale language model, linguistic inquiry and word count, topic modeling, and statistics of dialogue sentences. In addition, we performed dimensionality reduction with principal component analysis. We also conducted evaluation experiments using dialogue sentences from the beginning to the middle of sessions as input and clarified the relationship between the number of messages in the dialogues and the transition in the classification performance. We also identified the words that contribute to detecting mental health issues for each client and counselor. Clinical relevance-This study makes it possible to detect the trends identified in a client's anxieties during counseling. Our findings are critical for designing systems that assist counselors.

Background and Objectives: Vitamin D receptor activators and calcimimetics (calcium-sensing receptor agonists) are two major options for medical treatment of secondary hyperparathyroidism. A higher serum calcification propensity (a shorter T 50 value) is a novel surrogate marker of calcification stress and mortality in patients with CKD. We tested a hypothesis that a calcimimetic agent etelcalcetide is more effective in increasing T 50 value than a vitamin D receptor activator maxacalcitol., Design, Setting, Participants, & Measurements: A randomized, multicenter, open-label, blinded end point trial with active control was conducted in patients with secondary hyperparathyroidism undergoing hemodialysis in Japan. Patients were randomly assigned to receive intravenous etelcalcetide 5 mg thrice weekly (etelcalcetide group) or intravenous maxacalcitol 5 or 10 µ g thrice weekly (maxacalcitol group). The primary, secondary, and tertiary outcomes were changes in T 50 value, handgrip strength, and score of the Dementia Assessment Sheet for Community-Based Integrated Care System from baseline to 12 months, respectively., Results: In total, 425 patients from 23 dialysis centers were screened for eligibility, 326 patients were randomized (etelcalcetide, n =167; control, n =159), and 321 were included in the intention-to-treat analysis (median age, 66 years; 113 women [35%]). The median (interquartile range) of T 50 value was changed from 116 minutes (interquartile range, 90-151) to 131 minutes (interquartile range, 102-176) in the maxacalcitol group, whereas it was changed from 123 minutes (interquartile range, 98-174) to 166 minutes (interquartile range, 127-218) in the etelcalcetide group. The increase in T 50 value was significantly greater in the etelcalcetide group (difference in change, 20 minutes; 95% confidence interval, 7 to 34 minutes; P =0.004). No significant between-group difference was found in the change in handgrip strength or in the Dementia Assessment Sheet for Community-Based Integrated Care System score., Conclusions: Etelcalcetide was more effective in increasing T 50 value than maxacalcitol among patients on hemodialysis with secondary hyperparathyroidism. There was no difference in handgrip strength or cognition between the two drugs., Clinical Trial Registry Name and Registration Number: VICTORY; UMIN000030636 and jRCTs051180156., (Copyright © 2021 by the American Society of Nephrology.)

An analytical method for the simultaneous quantitation of ten trichothecenes of type A (HT-2 toxin, T-2 toxin, diacetoxyscirpenol, and neosolaniol) and type B (3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol, deoxynivalenol, deoxynivalenol-3-glucoside, nivalenol, and fusarenon-X) in feed has been developed using liquid chromatography with tandem mass spectrometry. Mycotoxins extracted twice from samples using aqueous acetonitrile were purified using a multifunctional clean-up column, followed by a phospholipid removal column. Trichothecenes were analysed using liquid chromatography atmospheric pressure chemical ionization tandem mass spectrometry. The extraction efficiency of the mycotoxins and the repeatability of some were improved by repeated extractions. Ionization enhancement (signal enhancement) of some mycotoxins was improved by using the phospholipid removal column at the clean-up step. Spike and recovery tests of trichothecenes were conducted on maize, barley, soybean meal, rapeseed meal, and formula feeds (for starting broiler chicks, suckling pigs, and beef cattle). The mean recovery values were 70.6-119% with relative standard deviations < 17%. The limit of quantification and the limit of detection of our method were 20 and 6 μg/kg, respectively, for 3-acetyldeoxynivalenol and 15-acetyldeoxynivalenol; 10 and 3 μg/kg, respectively, for T-2 toxin, deoxynivalenol, and fusarenon-X; and 5 and 2 μg/kg, respectively, for nivalenol and the remaining mycotoxins.

Objective: Determine if LLP2A-Ale or PTH (1-34) affects the prevalence of glucocorticoid-induced osteonecrosis (ON) in a mouse model., Methods: Eight-week-old young adult male BALB/cJ mice were weight-randomized into Control (Con), glucocorticoid (GC)-only, or concurrent treatments with GC and LLP2A-Ale (250 μg/kg or 500 μg/kg, IV, Days 1, 14, 28) or parathyroid hormone hPTH (1-34) (40 μg/kg, 5×/week). Mice were necropsied after 45 days for qualitative evaluation of prevalent ON and quantitative evaluation of vascularity in the distal femoral epiphysis (DFE); and quantitative evaluation of bone mass, microarchitecture, and strength in the distal femoral metaphysis and lumbar vertebral body., Results: The prevalence of ON was 14% in the Con group and 36% in the GC-only group ( P  = 0.07). The prevalence of ON did not differ among GC-only, GC + LLP2A-Ale, and GC + PTH groups. GC-only mice had significantly lower trabecular and cortical bone strength than Con, while GC + LLP2A-Ale (500 μg/kg) and GC + PTH (1-34) groups had significantly greater trabecular bone strength than the GC-only group. GC + LLP2A-Ale (250 μg/kg and 500 μg/kg) and GC + PTH had significantly higher trabecular bone volume than GC-only mice at the vertebrae, distal femoral epiphyses and distal femoral metaphyses. DFE vascularity was lower in GC-only mice than in all other groups., Conclusion: Neither LLP2A-Ale nor hPTH (1-34) reduced the prevalence of GC-induced ON, compared to GC-only mice. However, GC-treated mice given LLP2A-Ale or hPTH (1-34) had better bone mass, microarchitecture, and strength in trabecular-rich regions, and higher levels of vascularity than GC-only mice.

Objective: Glucocorticoids (GCs) are commonly prescribed as treatment for chronic inflammatory diseases. Prolonged use of GCs is a common cause of atraumatic osteonecrosis (ON) and secondary osteoporosis. Currently, there is no effective treatment for this disease; therefore, a reliable animal model would be useful to study both the pathology and novel treatment strategies for patients with the disease. The aim of this study was to establish a validated, reproducible model of GC-induced ON and bone loss in two different mouse strains (BALB/c and C57BL/6)., Methods: Seven-week-old male BALB/c ( n  = 32) and male C57BL/6 mice ( n  = 32) were randomised into placebo or GC groups and treated with daily 4 mg/L oral dexamethasone in drinking water for 90 days. Study outcome measures included histologic assessment of ON of the distal femur, bone mass and mechanical strength of tibia and lumbar vertebral body, osteoclast number, biochemical measure of bone formation and bone marrow fat quantitation., Results: GC-induced ON lesions were observed in the distal femur in 47% of the male BALB/c mice and 25% of the male C57BL/6 mice. GC treatment decreased the trabecular bone volume and serum pro-collagen type 1N-protease (P1NP) in BALB/c mice compared with the placebo ( p  < 0.05) and reduced tibial bone strength in both BALB/c and C57BL/6 mice. GC-treated BALB/c mice had significantly greater marrow fat levels compared to the placebo group., Conclusion: GC-induced ON was more prevalent in the male BALB/c mice compared to the male C57BL/6 mice. GC treatment significantly reduced bone mass, bone formation measured by P1NP, bone strength and increased marrow fat levels in male BALB/c mice. Therefore, the use of male BALB/c mice strain is recommended for both diagnostic and therapeutic studies for the prevention and treatment of ON and bone loss following prolonged treatment with GCs., The Translational Potential of This Article: GCs are commonly used to treat patients with various chronic inflammatory diseases, and this is associated with both the development of ON and bone loss. Our study confirmed that the BALB/c mouse strain treated for 90 days with GC may be useful for developing novel treatments for ON.