OBJECTIVE: Evaluate effectiveness/safety of tacrolimus in patients in Korea with active rheumatoid arthritis (RA) and unsuccessful response to disease-modifying anti-rheumatic drugs (DMARDs). METHODS: Open-label, single-arm, non-comparative, 24-week, Phase-IV study in patients with active RA who had taken DMARDs for >6 months. Following a washout period, tacrolimus was initiated (baseline-12 weeks; dose 2 mg/day and 1.5 mg/day in patients aged ≤65 and >65 years, respectively). After 12 weeks, dose could be adjusted (remaining between 1~3 mg); treatment continued to 24 weeks. Primary endpoint was American College of Rheumatology 20% improvement (ACR20) (baseline-Week 24). Secondary endpoints included ACR50/ACR70 response, disease-activity score in 28 joints (DAS28) erythrocyte sedimentation rate (ESR), number of tender/swollen joints, and bone mineral density (BMD) loss. Adverse events (AEs) were recorded. RESULTS: Overall, 121 patients were analysed. Mean±standard deviation tacrolimus dose baseline-Week 24 was 1.81±0.47 mg/day. After 24 weeks, 64.5%, 39.7%, and 19.0% of patients were ACR20, ACR50, and ACR70 responders, respectively. DAS28-ESR score decreased from 5.5±0.8 (baseline) to 3.7±1.5 (Week 24; p < 0.0001); number of tender/swollen joints decreased. Between screening and Week 24, change in BMD-T score in lumbar and femur regions was −0.06±0.38 (p=0.1550) and −0.04±0.28 (p=0.0936), respectively, with no significant change in International Society for Clinical Densitometry classification. Fifty-six (46.3%) patients experienced 93 AEs; 75.3% were mild. No unexpected safety signals identified. CONCLUSION: Tacrolimus therapy was associated with a high proportion of ACR responders, and improved DAS28-ESR score and physical joint function during the study. Tacrolimus may be a suitable therapy for DMARD-resistant patients with RA.
Antirheumatic Agents* ; Arthritis, Rheumatoid* ; Blood Sedimentation ; Bone Density ; Classification ; Densitometry ; Femur ; Humans ; Joints ; Korea ; Mass Screening ; Osteoporosis ; Rheumatology ; Tacrolimus*

Globally, the elderly population is increasing rapidly, which means that the number of deformity correction operations for elderly spine deformity patient has increased. On the other hand, for aged patients with deformity correction operation, preoperative considerations to reduce the complications and predict a good clinical outcome are not completely understood. First, medical comorbidity needs to be evaluated preoperatively with the Cumulative Illness Rating Scale for Geriatrics or the Charlson Comorbidity Index scores. Medical comorbidities are associated with the postoperative complication rate. Managing these comorbidities preoperatively decreases the complications after a spine deformity correction operation. Second, bone densitometry need to be checked for osteoporosis. Many surgical techniques have been introduced to prevent the complications associated with posterior instrumentation for osteoporosis patients. The preoperative use of an osteogenesis inducing agent
Aged ; Comorbidity ; Compensation and Redress ; Congenital Abnormalities ; Densitometry ; Geriatrics ; Hand ; Humans ; Lower Extremity ; Osteogenesis ; Osteoporosis ; Pelvis ; Postoperative Complications ; Posture ; Spine ; Teriparatide

BACKGROUND/AIMS: Bone mineral density (BMD) is often low in patients with Crohn's disease (CD). This study aimed to evaluate the association between nutritional factors and BMD in a group of CD patients. METHODS: CD patients 18 years of age or older were included. The body mass index (BMI), waist circumference (WC) and dietary intake were evaluated during two 24-hour recalls. Bone densitometry was performed by dual-energy X-ray absorptiometry of the full body to assess body composition and of the lumbar vertebrae and femoral neck to assess BMD. RESULTS: In the 60 patients evaluated, there was no association between BMD and disease activity or between BMD and disease duration. We observed moderate correlations between BMD in at least one of the evaluated sites and BMI, lean mass, WC, and protein, calcium, phosphorus and magnesium dietary intakes (P < 0.05). In the linear regression analysis for spinal BMD, only BMI and calcium dietary intake remained associated (P < 0.05). In the linear regression analysis for femoral BMD, WC and phosphorus intake continued to be significant in the final model, although they had low explanatory power for BMD (P < 0.05). CONCLUSIONS: The prevalence of low BMD was high in CD patients. BMI, WC, calcium and phosphorus dietary intake were positively correlated with BMD.
Absorptiometry, Photon ; Body Composition ; Body Mass Index ; Bone Density* ; Calcium ; Crohn Disease* ; Densitometry ; Femur Neck ; Humans ; Linear Models ; Lumbar Vertebrae ; Magnesium ; Phosphorus ; Prevalence ; Waist Circumference

BACKGROUND: We determined the prevalence of sarcopenia according to fracture site and evaluated the associated risk factors in female patients with osteoporotic fractures. METHODS: A total of 108 patients aged 50 years or older with an osteoporotic fracture (hip, spine, or wrist) were enrolled in this retrospective observational study. A diagnosis of sarcopenia was confirmed using whole-body densitometry for skeletal muscle mass measurement. Logistic regression analysis was used to analyze the risk factors for sarcopenia. RESULTS: Of 108 female patients treated for osteoporotic fractures between January 2016 and June 2017, sarcopenia was diagnosed in 39 (36.1%). Of these, 41.5% (17/41) had hip fractures, 35% (14/40) had spine fractures, and 29.6% (8/27) had distal radius fractures. Body mass index (BMI; P=0.036) and prevalence of chronic kidney disease (CKD; P=0.046) and rheumatoid arthritis (P=0.051) were significantly different between the groups. In multivariable analysis, BMI (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.55–1.05, P=0.098) and CKD (OR 2.51; 95% CI, 0.38–16.2; P=0.233) were associated with an increased risk of sarcopenia; however, this was not statistically significant. CONCLUSIONS: This study evaluated the prevalence of sarcopenia according to the fracture site and identified associated risk factors in patients with osteoporotic fractures. A longterm, observational study with a larger population is needed to validate our results.
Arthritis, Rheumatoid ; Body Mass Index ; Densitometry ; Diagnosis ; Female ; Hip Fractures ; Humans ; Logistic Models ; Muscle, Skeletal ; Observational Study ; Osteoporosis ; Osteoporotic Fractures ; Prevalence ; Radius Fractures ; Renal Insufficiency, Chronic ; Retrospective Studies ; Risk Factors ; Sarcopenia ; Spine

BACKGROUND: Procollagen type I N-terminal propeptide (PINP) is one of the most clinically useful bone formation biomarkers. Therefore, the purpose of this study was to independently evaluate the performance of automated total PINP assay and established age- and gender-specific reference intervals for PINP in healthy Korean population. METHODS: The imprecision, linearity, and detection capability of Elecsys total PINP assay was determined and reference interval was established using 599 serums from Korean population with normal bone mineral densities based on bone densitometry. Age groups were divided into 20s, 30s, 40s, 50s, 60s and over. RESULTS: Elecsys total PINP had excellent performance in imprecision, linearity, and detection capability. When partitioning age groups in Korean male and female populations, there was significant difference in total PINP between different age groups. In male populations, PINP level was decreased with increasing age, then it remained steady after middle-age. In female populations, there was a decreasing tendency similar to that in the male population with a sharp increase in the 50 to 59 age group. CONCLUSIONS: Elecsys total PINP assay showed precise and reliable performance in our study. We established age-related PINP reference intervals for Korean male and female population with normal bone mineral densities.
Biomarkers ; Bone Density ; Collagen Type I ; Densitometry ; Female ; Humans ; Male ; Osteogenesis ; Peptide Fragments ; Procollagen ; Reference Values

BACKGROUND: This study evaluated the prevalence of osteosarcopenia, as well as the relationship between one-year mortality and osteosarcopenia, as defined by criteria of the Asian Working Group on Sarcopenia in patients age 60 or older with hip fracture. METHODS: A total of 324 patients age 60 years or older with hip fracture were enrolled in this retrospective observational study. The main outcome measure was the prevalence of osteosarcopenia, as well as the relationship between osteosarcopenia and 1-year mortality. The diagnosis of sarcopenia was carried out according to the Asian Working Group on Sarcopenia. Whole body densitometry analysis was used for skeletal muscle mass measurement and muscle strength were evaluated by handgrip testing. Mortality was assessed at the end of 1-year. Cox regression analysis was utilized to analyze the risk factor of osteosarcopenia. RESULTS: Of 324 patients with hip fracture, 93 (28.7%) were diagnosed with osteosarcopenia. In total, 9.0% died during the one-year follow-up. A one-year mortality of osteosarcopenia (15.1%) was higher than that of other groups (normal: 7.8%, osteoporosis only: 5.1%, sarcopenia only: 10.3%). Osteosarcopenia had a 1.8 times higher mortality rate than non-osteosarcopenia. CONCLUSION: The present study demonstrates that the prevalence of osteosarcopenia is not rare, and has a higher mortality rate than the non-osteosarcopenia group at the 1-year follow-up period. This is the first study evaluating the relationship between mortality and osteosarcopenia in patients with hip fracture.
Asian Continental Ancestry Group ; Densitometry ; Diagnosis ; Follow-Up Studies ; Hip ; Humans ; Mortality ; Muscle Strength ; Muscle, Skeletal ; Observational Study ; Osteoporosis ; Outcome Assessment (Health Care) ; Prevalence ; Retrospective Studies ; Risk Factors ; Sarcopenia

OBJECTIVE: The purpose of this study was to investigate the effects of estradiol on the expression of hypoxia-inducible factor (HIF)-1α and the differentiation of trophoblasts in human first trimester villous explant cultures. METHODS: Villous explant cultures were established from first trimester human placentas (6–8 weeks of gestation, n=3). Normal villous tissues were explanted on Matrigel and incubated under 3% O2 tension for 5 days. To evaluate the effects of estradiol on the villous explant cultures, 1 ng/mL of estradiol was added to the culture medium. The morphological integrities and viabilities of the villous explants were monitored. Immunohistochemistry for α5 and α1 integrin was performed to assess differentiation of extravillous trophoblasts (EVTs). Expression of HIF-1α in villous explant cultures was evaluated by western blotting and densitometry. RESULTS: EVTs emerging from first trimester villous explant cultures formed outgrowths of cells from the distal ends and invaded the surrounding Matrigel. Exposure of villous explants to estradiol resulted in the decreased outgrowth of cells from the distal end and decreased expression of α5 integrin. However, estradiol treatment increased the invasion of villous explants into the surrounding Matrigel, concomitant with the increased expression of α1 integrin, indicating differentiation of EVTs into more invasive EVTs. On western blots, the expression of HIF-1α decreased significantly after treatment with estradiol under 3% O2 tension. CONCLUSION: Our findings suggest that estradiol may downregulate expression of HIF-1α in placenta, which in turn promote trophoblast differentiation into invasive phenotype.
Blotting, Western ; Densitometry ; Estradiol ; Female ; Humans ; Immunohistochemistry ; Phenotype ; Placenta ; Pregnancy ; Pregnancy Trimester, First ; Trophoblasts

OBJECTIVES: As clinics that treat patients with osteoporosis do not usually have central dual-energy X-ray absorptiometry (DXA), bone density is often measured with radial DXA. However, no long-term evidence exists for radius bone density outcomes following treatment with once-weekly teriparatide in actual medical treatment. METHODS: We evaluated changes in bone density at 6-, 12-, and 18-month intervals using radial DXA in patients treated with once-weekly teriparatide for more than 6 months. RESULTS: A significant increase in bone mineral density (BMD) was observed at the 1/3 and 1/10 radius sites 12 months after the initiation of once-weekly teriparatide. We also observed that the rate of change in BMD was greater at the distal 1/10 radius than at the 1/3 radius. CONCLUSIONS: Considering these points, the effect of once-weekly teriparatide therapy can be observed at the radius. In clinics that do not have central DXA, but instead have radial DXA, these findings can help to evaluate the effect of once-weekly teriparatide treatment on osteoporosis.
Absorptiometry, Photon ; Bone Density ; Densitometry ; Humans ; Osteoporosis ; Radius ; Teriparatide

STUDY DESIGN: In vitro cell culture model. PURPOSE: To investigate the effect of small interfering RNA (siRNA) on Fas expression, apoptosis, and proliferation in serum-deprived rat disc cells. OVERVIEW OF LITERATURE: Synthetic siRNA can trigger an RNA interference (RNAi) response in mammalian cells and precipitate the inhibition of specific gene expression. However, the potential utility of siRNA technology in downregulation of specific genes associated with disc cell apoptosis remains unclear. METHODS: Rat disc cells were isolated and cultured in the presence of either 10% fetal bovine serum (FBS) (normal control) or 0% FBS (serum deprivation to induce apoptosis) for 48 hours. Fas expression, apoptosis, and proliferation were determined. Additionally, siRNA oligonucleotides against Fas (Fas siRNA) were transfected into rat disc cells to suppress Fas expression. Changes in Fas expression were assessed by reverse transcription-polymerase chain reaction and semiquantitatively analyzed using densitometry. The effect of Fas siRNA on apoptosis and proliferation of rat disc cells were also determined. Negative siRNA and transfection agent alone (Mock) were used as controls. RESULTS: Serum deprivation increased apoptosis by 40.3% (p<0.001), decreased proliferation by 45.3% (p<0.001), and upregulated Fas expression. Additionally, Fas siRNA suppressed Fas expression in serum-deprived cultures, with 68.5% reduction at the mRNA level compared to the control cultures (p<0.001). Finally, Fas siRNA–mediated suppression of Fas expression significantly inhibited apoptosis by 9.3% and increased proliferation by 21% in serum-deprived cultures (p<0.05 for both). CONCLUSIONS: The observed dual positive effect of Fas siRNA might be a powerful therapeutic approach for disc degeneration by suppression of harmful gene expression.
Animals ; Apoptosis* ; Cell Culture Techniques ; Cell Proliferation ; Densitometry ; Down-Regulation ; Gene Expression ; In Vitro Techniques ; Intervertebral Disc Degeneration ; Intervertebral Disc* ; Oligonucleotides ; Rats* ; RNA Interference ; RNA, Messenger ; RNA, Small Interfering ; Transfection

This prospective intervention study was undertaken to estimate the prevalence and treatment rate of osteoporosis following osteoporosis screening tests in the same cohort. From November 1, 2014 to August 31, 2015, participants received screening tests for osteoporosis using ultrasound bone densitometry and education concerning osteoporosis and related conditions. The participants were interviewed using a questionnaire on the diagnosis and initiation of osteoporosis treatment during the follow-up period. Of 960 potential participants, 595 people (68.8%; 150 men and 445 women) were given bone densitometry measurements and completed the questionnaire. The mean age of the participants was 74.0 years. Of the 595 participants, 393 people (66.1%; 67 men and 326 woman) were diagnosed with osteoporosis (T score <−2.5). The prevalence of osteoporosis showed an increasing trend, from 48.1% in 2004 to 66.1% in 2015. Of the 393 participants diagnosed with osteoporosis, 65 participants received additional bone densitometry measurements while hospitalized and osteoporosis management was re-initiated in 44 patients. The osteoporosis management rate in the study cohort increased from 21.6% to 32.8%, with osteoporosis diagnosed in 66.2% of participants at the latest follow-up. This prospective intervention study demonstrated that a screening test and an educational brochure increased the treatment rate from 21.6% to 32.8%.
Cohort Studies ; Densitometry* ; Diagnosis ; Education* ; Follow-Up Studies ; Humans ; Male ; Mass Screening* ; Osteoporosis* ; Pamphlets ; Prevalence* ; Prospective Studies ; Ultrasonography*