Journal of Bone Metabolism最新文献

{"title":"Association between Bone Mineral Density and Coronary Atherosclerotic Plaque According to Plaque Composition: Registry for the Women Health Cohort for Bone, Breast, and Coronary Artery Disease Study.","authors":"Kyoung Min Kim,&nbsp;Yeonyee E Yoon,&nbsp;Bo La Yun,&nbsp;Jung-Won Suh","doi":"10.11005/jbm.2022.29.2.123","DOIUrl":"https://doi.org/10.11005/jbm.2022.29.2.123","url":null,"abstract":"<p><strong>Background: </strong>Although biological links are unclear, low bone density and atherosclerosis are inversely associated. This study evaluated the association between bone mineral density (BMD) and coronary computed tomographic angiography (CCTA) findings, including coronary artery calcification (CAC) score and the presence, extent, and composition of coronary atherosclerotic plaque (CAP) in asymptomatic women.</p><p><strong>Methods: </strong>A symptomatic women aged ≥40 years (N=2, 100; median age, 52 years; range, 40-80 years) were selected from a retrospective observational cohort and stratified into normal, osteopenia, and osteoporosis groups according to BMD T-score grades. We evaluated CAC score and assessed the presence, extent, and stenosis severity of CAP on CCTA. Additionally, CAP was categorized as calcified, mixed, or non-calcified according to calcified component valiums (>130 Hounsfield units).</p><p><strong>Results: </strong>Osteopenia and osteoporosis were found in 28.8% and 5.3% of participants, respectively. CAC score and CAC severity significantly increased with decreased BMD grades (from normal to osteoporosis). The presence of CAP (overall, 15.6%; normal, 12.6%; osteopenia, 20.2%; osteoporosis, 28.8%; P<0.001) and number of segments with CAP significantly increased with decreased BMD grades. Furthermore, the number of segments with calcified or mixed plaques, excluding non-calcified plaques, increased with decreased BMD grades. Although most associations were attenuated or disappeared after adjusting for age and other covariates, calcified plaques showed a strong and age-independent association with BMD grades.</p><p><strong>Conclusions: </strong>The presence and severity of CAC and CAP were significantly associated with BMD severity in asymptomatic women, particularly for the presence of calcified plaques. Further studies are required to determine the association between vascular calcification and bone health status.</p>","PeriodicalId":15070,"journal":{"name":"Journal of Bone Metabolism","volume":"29 2","pages":"123-131"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/91/ab/jbm-2022-29-2-123.PMC9208904.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39999042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osteoporotic Fractures among Selective Estrogen Receptor Modulator Users in South Korea: Analysis Using National Claims Database.","authors":"Jung-Wee Park,&nbsp;Young-Kyun Lee,&nbsp;Yangseon Choi,&nbsp;Yong-Chan Ha","doi":"10.11005/jbm.2022.29.2.75","DOIUrl":"https://doi.org/10.11005/jbm.2022.29.2.75","url":null,"abstract":"<p><strong>Background: </strong>We evaluated (1) compliance with selective estrogen receptor modulator (SERM) use in postmenopausal women; and (2) the risk of osteoporotic fractures according to compliance and other patient characteristics.</p><p><strong>Methods: </strong>National claims data of postmenopausal women from January 2013 to December 2014 were reviewed. Demographics, comorbidities, type of medical institution, and patient compliance were investigated. Compliance was measured according to medication possession ratio (MPR) and the patients were classified into compliant (MPR ≥80%) or non-compliant (MPR <80%) groups. Osteoporotic fractures were followed up for 2 years after prescription.</p><p><strong>Results: </strong>Among 15,166 postmenopausal women, 4,130 were categorized as compliant. Osteoporotic fractures were confirmed in 669 patients. The hip fracture rate in the non-compliant group (0.39%) was marginally higher than that in the compliant group (0.36%; P=0.06). Compared to age 50 to 54 years, age 55 to 59 years showed protection against fractures (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.379-0.857; P=0.007), while those over 70 years showed a higher risk of fractures (HR, 2.035; 95% CI, 1.485-2.789; P<0.0001 for age 70-74 years; HR, 2.197; 94% CI, 1.588-3.041; P<0.0001 for age 75-79 years; and HR, 3.53; 95% CI, 2.493-4.999; P<0.0001 for age ≥80 years). Patients with mild (HR, 1.29; 95% CI, 1.088-1.530; P=0.0034) and moderate (HR, 1.286; 95% CI, 1.002-1.652; P=0.0486) comorbidities were associated with higher risks of fractures compared to those without comorbidities.</p><p><strong>Conclusions: </strong>Among postmenopausal women with osteoporosis, only 27.2% complied with SERM therapy. A marginal difference in hip fracture rate was observed between the compliant and non-compliant groups. Older age and severe comorbidities were associated with higher risks of osteoporotic fractures.</p>","PeriodicalId":15070,"journal":{"name":"Journal of Bone Metabolism","volume":"29 2","pages":"75-82"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e7/f8/jbm-2022-29-2-75.PMC9208906.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39999134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Extracellular Signal-Regulated Kinase Mitogen-Activated Protein Kinase Pathway in Osteoblasts.","authors":"Matthew B Greenblatt,&nbsp;Jae-Hyuck Shim,&nbsp;Seoyeon Bok,&nbsp;Jung-Min Kim","doi":"10.11005/jbm.2022.29.1.1","DOIUrl":"https://doi.org/10.11005/jbm.2022.29.1.1","url":null,"abstract":"<p><p>Extracellular signal-regulated kinases (ERKs) are evolutionarily ancient signal transducers of the mitogen-activated protein kinase (MAPK) family that have long been linked to the regulation of osteoblast differentiation and bone formation. Here, we review the physiological functions, biochemistry, upstream activators, and downstream substrates of the ERK pathway. ERK is activated in skeletal progenitors and regulates osteoblast differentiation and skeletal mineralization, with ERK serving as a key regulator of Runt-related transcription factor 2, a critical transcription factor for osteoblast differentiation. However, new evidence highlights context-dependent changes in ERK MAPK pathway wiring and function, indicating a broader set of physiological roles associated with changes in ERK pathway components or substrates. Consistent with this importance, several human skeletal dysplasias are associated with dysregulation of the ERK MAPK pathway, including neurofibromatosis type 1 and Noonan syndrome. The continually broadening array of drugs targeting the ERK pathway for the treatment of cancer and other disorders makes it increasingly important to understand how interference with this pathway impacts bone metabolism, highlighting the importance of mouse studies to model the role of the ERK MAPK pathway in bone formation.</p>","PeriodicalId":15070,"journal":{"name":"Journal of Bone Metabolism","volume":"29 1","pages":"1-15"},"PeriodicalIF":0.0,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e8/6d/jbm-2022-29-1-1.PMC8948490.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40318216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Food Security Moderates the Relationships of Muscle Mass with Metabolic Syndrome and Insulin Resistance.","authors":"Kayoung Lee","doi":"10.11005/jbm.2022.29.1.23","DOIUrl":"https://doi.org/10.11005/jbm.2022.29.1.23","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to determine whether food security moderates the relationship of skeletal muscle mass with metabolic syndrome (MetS) and insulin resistance (IR).</p><p><strong>Methods: </strong>This study analyzed the data of 10,680 adults using the Korea National Health and Nutrition Examination Survey from 2008 to 2011. The food security reported by households, appendicular skeletal muscle mass (ASM) divided by body mass index (BMI) (ASM/BMI), weight (ASM/weight), or height squared (ASM/height2) as muscle mass indicators, MetS (defined as presence of at least 3 components of MetS), and IR (defined as sex-specific highest quintile of homeostatic model assessment for IR) were assessed. The association between the muscle mass indicators and food security as well as their interaction with MetS and IR was analyzed for all participants and each sex using complex sample logistic regression and general linear model analyses.</p><p><strong>Results: </strong>When the ASM/BMI increased by 0.1 kg/BMI, the odds for MetS and IR decreased by 36% and 29%, respectively, after adjusting for age, sex, education, economic level, smoking, alcohol consumption, physical activity, chronic diseases, and intake of fats and protein. There was a significant interaction between ASM/BMI and food security in their relationship with MetS and its components. In the low food security group, the inverse relationship of ASM/BMI with MetS and IR was stronger than in the food security group. These findings were more pronounced in men than in women, and similar findings were observed in the association with ASM/weight.</p><p><strong>Conclusions: </strong>The associations of skeletal muscle mass with MetS and IR may be influenced by household food security in Korean adults.</p>","PeriodicalId":15070,"journal":{"name":"Journal of Bone Metabolism","volume":"29 1","pages":"23-33"},"PeriodicalIF":0.0,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/88/06/jbm-2022-29-1-23.PMC8948495.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40318217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of a New Food Frequency Questionnaire for Protein Intake Assessment in Korean.","authors":"Eunseo Heu, Yunjung Lee, Donghyun Kim, Yong-Chan Ha, Yongsoon Park","doi":"10.11005/jbm.2022.29.1.35","DOIUrl":"10.11005/jbm.2022.29.1.35","url":null,"abstract":"<p><strong>Background: </strong>Protein intake is a modifiable factor associated with sarcopenia prevention; however, no appropriate methods exist to assess dietary protein intake in Koreans. This study developed and validated a simple and convenient food frequency questionnaire (FFQ) to determine protein intake in Koreans.</p><p><strong>Methods: </strong>A total of 120 participants aged >19 years were asked to complete both the FFQ used by the Korean National Health and Nutrition Examination Survey (KNHANES) and the newly developed Korean Protein Assessment Tool (KPAT). Protein intakes measured using the FFQ and the KPAT were compared using Pearson correlation coefficients, Bland-Altman plots, and intraclass correlation coefficients.</p><p><strong>Results: </strong>Protein intakes from the FFQ (62.06±25.56 g/day) and KPAT (61.12±24.26 g/day) did not differ significantly (P=0.144). Pearson's correlation coefficient values ranging from 0.92 to 0.96 indicated a positive correlation, while the intraclass correlation coefficient of 0.979 indicated excellent reliability in protein intake of the FFQ and the KPAT. The Bland-Altman plot also showed high agreement in the mean differences in protein intakes estimated by the FFQ and the KPAT.</p><p><strong>Conclusions: </strong>KPAT, a newly developed and simplified method, showed an acceptable correlation compared to previous FFQ tools. Thus, the KPAT may be useful to assess dietary protein intake in the Korean population.</p>","PeriodicalId":15070,"journal":{"name":"Journal of Bone Metabolism","volume":"29 1","pages":"35-42"},"PeriodicalIF":0.0,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/53/74/jbm-2022-29-1-35.PMC8948491.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40318218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence, Clinical Implication, and Cause of Spine Hip Discordance in Elderly Patients with Fragility Hip Fracture.","authors":"Kyung-Hag Lee,&nbsp;Jung-Wee Park,&nbsp;Sujin Kim,&nbsp;Guen Young Lee,&nbsp;Sung Bin Park,&nbsp;Du-Bin Yang,&nbsp;Yong-Chan Ha","doi":"10.11005/jbm.2022.29.1.51","DOIUrl":"https://doi.org/10.11005/jbm.2022.29.1.51","url":null,"abstract":"<p><strong>Background: </strong>Spine-hip discordance (SHD) increases fracture risk. However, its prevalence and clinical implications have not been investigated in patients with hip fractures. This study determined the prevalence and association of SHD with mortality and investigated the cause of SHD in patients with hip fractures.</p><p><strong>Methods: </strong>This study included patients admitted for fragility hip fractures between 2011 and 2020. All patients underwent dual energy X-ray absorptiometry and anteroposterior and lateral views of the lumbosacral spine during admission. Data on demographics, diagnosis, American Society of Anesthesiologists score, and mortality were collected. A T-score difference of more than 1.5 between L1-4 and the femur neck was considered discordant, and 3 groups (lumbar low [LL] discordance, no discordance [ND], and femur neck low [FL] discordance) were compared. In the discordance group, lumbar radiographs were reviewed to determine the cause of discordance.</p><p><strong>Results: </strong>Among 1,220 eligible patients, 130 were excluded due to patient refusal or bilateral hip implantation; therefore, this study included 1,090 patients (271 male and 819 female). The prevalence of LL, ND, and FL was 4.4%, 66.4% and 29.2% in men and 3.9%, 76.1%, and 20.0% women. Mortality was not associated with discordance. The most common causes of discordance were physiological in the LL group and pathological in the FL group for both sexes.</p><p><strong>Conclusions: </strong>Patients with hip fractures showed lower rates of ND and higher rates of FL compared to the general population. True discordance should be carefully judged for pathological and artifact reasons. The clinical implications of SHD require further investigation.</p>","PeriodicalId":15070,"journal":{"name":"Journal of Bone Metabolism","volume":"29 1","pages":"51-57"},"PeriodicalIF":0.0,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/55/34/jbm-2022-29-1-51.PMC8948489.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40318220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationship between Low Muscle Strength, and Protein Intake: A Preliminary Study of Elderly Patients with Hip Fracture.","authors":"Kyung-A Choi,&nbsp;Eunseo Heu,&nbsp;Hyun-Cheul Nam,&nbsp;Yongsoon Park,&nbsp;Donghyun Kim,&nbsp;Yong-Chan Ha","doi":"10.11005/jbm.2022.29.1.17","DOIUrl":"https://doi.org/10.11005/jbm.2022.29.1.17","url":null,"abstract":"<p><strong>Background: </strong>The purpose of the present study was to assess the daily protein uptake and its relationship with sarcopenia, as defined by the Asian Working Group for Sarcopenia (AWGS), among elderly patients with hip fractures.</p><p><strong>Methods: </strong>Forty-seven elderly patients with hip fractures were enrolled in this retrospective observational study. The main outcome measures included protein uptake, muscle mass, and grip strength for sarcopenia in elderly patients. Sarcopenia was diagnosed according to AWGS. Wholebody densitometry was used to measure skeletal muscle mass, and muscle strength was evaluated using handgrip testing.</p><p><strong>Results: </strong>Of 47 patients with hip fractures (12 men and 35 women), 37 (79%) patients exhibited insufficient protein intake (range, 0.01-0.588 g/kg/day), and 10 (21%) patients exhibited excessive protein intake (range, 1.215-2.121 g/kg/day). The mean daily protein intake was 56.5 g (range, 7.2-136.0 g). Prevalence of low muscle strength (handgrip strength <18 kg in women and <26 kg in men) was detected in 13 (37%) women and 8 (67%) men (P=0.076). Sarcopenia (lower muscle mass and lower muscle strength) was detected in 9 (26%) women and 6 (50%) men (P=0.119). Although lower protein intake was marginally associated with sarcopenia (P=0.189), it was significantly associated with lower grip strength (P=0.042).</p><p><strong>Conclusions: </strong>The present study demonstrated that insufficient protein intake in elderly patients with hip fractures was common, and lower protein intake was significantly associated with lower muscle strength.</p>","PeriodicalId":15070,"journal":{"name":"Journal of Bone Metabolism","volume":"29 1","pages":"17-21"},"PeriodicalIF":0.0,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/03/df/jbm-2022-29-1-17.PMC8948493.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40320290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and Risk Factors of T-Score Spine-Hip Discordance in Patients with Osteoporotic Vertebral Compression Fracture.","authors":"Byung-Ho Yoon,&nbsp;Ho Won Kang,&nbsp;Su Min Kim,&nbsp;Young Do Koh","doi":"10.11005/jbm.2022.29.1.43","DOIUrl":"https://doi.org/10.11005/jbm.2022.29.1.43","url":null,"abstract":"<p><strong>Background: </strong>T-score discordance between the spine and hip is commonly observed when dual energy X-ray absorptiometry (DXA) is used to diagnose osteoporosis. However, information is scarce regarding the prevalence and risk factors for this problem in Korea. This study evaluated the prevalence of major/minor discordance and associated risk factors in elderly Korean patients with osteoporotic vertebral compression fractures (OVCFs).</p><p><strong>Methods: </strong>This study included 200 patients (37 men, 163 women) treated for thoracic or lumbar compression fractures between January 2015 and August 2021. DXA was performed to examine T-scores and determine the prevalence of discordance, defined as a difference between the T-score categories of the femur and spine in the same individual. The t-tests, χ2 tests, and regression analyses were used to assess the associated risk factors of T-score discordance among the subjects.</p><p><strong>Results: </strong>T-score concordance, minor discordance, and major discordance were observed in 137 (68.5%), 59 (29.5%), and 4 (2%) patients with OVCFs, respectively. The spinal T-score was lower than the femoral T-score in all major discordance and 81.3% (48/59) of minor discordant cases. Overall, the only factor related to T-score discordance was the age at fracture (odds ratio, -0.01; P=0.014).</p><p><strong>Conclusions: </strong>The results of this study showed that a significant number of subjects (31.5%) showed spine-hip discordance, even with a mean age in their 80s. More attention should be paid to the appropriate evaluation and management of elderly patients with OVCFs. Moreover, a longitudinal study is necessary to verify the clinical importance of T-score discordance in this population.</p>","PeriodicalId":15070,"journal":{"name":"Journal of Bone Metabolism","volume":"29 1","pages":"43-49"},"PeriodicalIF":0.0,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/32/79/jbm-2022-29-1-43.PMC8948492.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40318219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cervical Fusion-Requiring Mineral and Bone Disorder Disguised as Osteoporosis in a Chronic Kidney Disease Patient on Hemodialysis: A Case Report.","authors":"Jong Weon Lee,&nbsp;Suhyun Cho,&nbsp;Kyung-Min Kim,&nbsp;Jung Hyun Park","doi":"10.11005/jbm.2022.29.1.59","DOIUrl":"https://doi.org/10.11005/jbm.2022.29.1.59","url":null,"abstract":"<p><p>Bony deformities and fragility fractures in end-stage renal disease (ESRD) patients on long-term hemodialysis can be caused by either osteoporosis or chronic kidney disease-mineral and bone disorder (CKD-MBD). Correct identification of the underlying mechanism is critical since the treatment methods differ, and one treatment approach could negatively affect the other. Cervical kyphosis, severe enough to require immediate surgical treatment, can be caused by uncontrolled CKD-MBD, albeit in limited cases. This report presents the case of a 61-year-old female with an 11-year history of hemodialysis treatment and severe cervical kyphosis with myelopathy, which required 2-stage spinal surgeries. Our report calls for a careful diagnostic approach in ESRD patients with skeletal disorders, the points to consider before calcium replacement, and early detection of fragility fractures in them. Moreover, early mobilization and weight-bearing after the surgical procedure may lead to better neurological and functional improvements.</p>","PeriodicalId":15070,"journal":{"name":"Journal of Bone Metabolism","volume":"29 1","pages":"59-62"},"PeriodicalIF":0.0,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d0/dd/jbm-2022-29-1-59.PMC8948494.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40318221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of the Lysine Methyltransferase Inhibitor AZ505 on Bone Metabolism.","authors":"Min-Kyoung Song,&nbsp;Suhan Jung,&nbsp;Seojin Hong,&nbsp;Jun-Oh Kwon,&nbsp;Min Kyung Kim,&nbsp;Hong-Hee Kim","doi":"10.11005/jbm.2021.28.4.297","DOIUrl":"https://doi.org/10.11005/jbm.2021.28.4.297","url":null,"abstract":"<p><strong>Background: </strong>Protein methylation has important role in regulating diverse cellular responses, including differentiation, by affecting protein activity, stability, and interactions. AZ505 is an inhibitor of the SET and MYND domain-containing protein 2 lysine methylase. In this study, we investigated the effect of AZ505 on osteoblast and osteoclast differentiation in vitro and evaluated the effect of AZ505 in vivo on the long bones in mice.</p><p><strong>Methods: </strong>Osteoblast differentiation was assessed by alkaline phosphatase (ALP) and Alizarin red staining after culturing calvarial preosteoblasts in an osteogenic medium. Osteoclast differentiation was analyzed by tartrate-resistant acid phosphatase (TRAP) staining in bone marrow-derived macrophages cultured with macrophage-colony stimulating factor and receptor activator of nuclear factor-κB ligand (RANKL). For in vivo experiments, mice were intraperitoneally injected with AZ505 and femurs were examined by micro-computed tomography.</p><p><strong>Results: </strong>AZ505 increased ALP and Alizarin red staining in cultured osteoblasts and the expression of osteoblast marker genes, including Runx2 and osteocalcin. AZ505 resulted in decreased TRAP-staining of osteoclasts and expression of c-Fos and nuclear factor of activated T cells transcription factors and osteoclast marker genes, including cathepsin K and dendritic cell-specific transmembrane protein. Unexpectedly, in vivo administration of AZ505 markedly decreased the trabecular bone mass of femurs. In support of this catabolic result, AZ505 strongly upregulated RANKL expression in osteoblasts.</p><p><strong>Conclusions: </strong>The results indicate that AZ505 has a catabolic effect on bone metabolism in vivo despite its anabolic effect in bone cell cultures. The findings indicate that cell culture data should be extrapolated cautiously to in vivo outcomes for studying bone metabolism.</p>","PeriodicalId":15070,"journal":{"name":"Journal of Bone Metabolism","volume":" ","pages":"297-305"},"PeriodicalIF":0.0,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cb/26/jbm-2021-28-4-297.PMC8671023.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39724574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}