The Fracture Risk Assessment Tool Probability and Trabecular Bone Score Mediate the Relationship between Sphingosine 1-phosphate Levels and Fracture Risk.

BACKGROUND: The sphingosine 1-phosphate (S1P) concentration is a potential biomarker of osteoporotic fracture and is associated with both the fracture risk assessment tool (FRAX) probability and trabecular bone score (TBS), which are well-known predictors of fracture. We sought to estimate the effect of the S1P concentration on fracture risk using the FRAX probability and TBS as mediators. METHODS: Plasma S1P concentrations, FRAX variables, and TBSs were measured in 66 postmenopausal women with fractures and 273 postmenopausal women without fractures. Associations between S1P concentration, FRAX probability, TBS, and fracture risk were analyzed using correlation, logistic regression, and mediation analyses. RESULTS: Subjects in the highest S1P concentration tertile had a higher fracture risk (odds ratio [OR], 5.09; 95% confidence interval [CI], 2.22-11.67) than those in the lowest S1P concentration tertile before adjustment. Subjects in the highest FRAX probability tertile had a higher fracture risk (OR, 14.59; 95% CI, 5.01-42.53) than those in the lowest FRAX probability tertile before adjustment. Subjects in the lowest TBS tertile had a higher fracture risk (OR, 4.76; 95% CI, 2.28-9.93) than those in the highest TBS tertile before adjustment. After adjustment for FRAX probability and TBS, the highest S1P concentration tertile was still associated with a higher fracture risk (OR, 3.13; 95% CI, 1.28-7.66). The FRAX probability and TBS accounted for 32.6% and 21.7%, respectively, of the relationship between the S1P concentration and fracture risk. CONCLUSIONS: The relationship between the circulating S1P concentration and fracture risk was partly mediated by the FRAX probability, bone microarchitecture, and other factors.

High Circulating Sphingosine 1-Phosphate is a Risk Factor for Osteoporotic Fracture Independent of Fracture Risk Assessment Tool.

Circulating sphingosine 1-phosphate (S1P) levels may be a biomarker for osteoporotic fracture (OF). This study assessed whether the addition of S1P levels to the fracture risk assessment tool (FRAX) could improve predictability of OF risk. Plasma S1P concentrations and FRAX variables were measured in 81 subjects with and 341 subjects without OF. S1P levels were higher in subjects with than those without OF (3.11 ± 0.13 µmol/L vs. 2.65 ± 0.61 µmol/L, P = 0.001). Higher S1P levels were associated with a higher likelihood of OF (odds ratio [OR] = 1.33, 95% confidence interval [CI] = 1.05-1.68), even after adjusting for FRAX probabilities. Compared with the lowest S1P tertile, subjects in the middle (OR = 3.37, 95% CI = 1.58-7.22) and highest (OR = 3.65, 95% CI = 1.66-8.03) S1P tertiles had higher rates of OF after adjustment. The addition of S1P levels to FRAX probabilities improved the area under the receiver-operating characteristics curve (AUC) for OF, from 0.708 to 0.769 (P = 0.013), as well as enhancing category-free net reclassification improvement (NRI = 0.504, 95% CI = 0.271-0.737, P < 0.001) and integrated discrimination improvement (IDI = 0.044, 95% CI = 0.022-0.065, P < 0.001). Adding S1P levels to FRAX probabilities especially in 222 subjects with osteopenia having a FRAX probability of 3.66-20.0% markedly improved the AUC for OF from 0.630 to 0.741 (P = 0.012), as well as significantly enhancing category-free NRI (0.571, 95% CI = 0.221-0.922, P = 0.001) and IDI (0.060, 95% CI = 0.023-0.097, P = 0.002). S1P is a consistent and significant risk factor of OF independent of FRAX, especially in subjects with osteopenia and low FRAX probability.

Assessment of patient-reported outcomes (PROs): treatment satisfaction, medication adherence, and quality of life (QoL) and the associated factors in postmenopausal osteoporosis (PMO) patients in Korea.

Patient-reported outcomes (PROs) provide practical guides for treatment; however, studies that have evaluated PROs of women in Korea with postmenopausal osteoporosis (PMO) are lacking. This cross-sectional, multi-center (29 nationwide hospitals) study, performed from March 2013 to July 2014, aimed to assess PROs related to treatment satisfaction, medication adherence, and quality of life (QoL) in Korean PMO women using osteoporosis medication for prevention/treatment. Patient demographics, clinical characteristics, treatment patterns, PROs, and experience using medication were collected. The 14-item Treatment Satisfaction Questionnaire for Medication (TSQM) (score-range, 0-100; domains: effectiveness, side effects, convenience, global satisfaction), Osteoporosis-Specific Morisky Medication Adherence Scale (OS-MMAS) (score-range, 0-8), and EuroQol-5 dimensions questionnaire (index score range, - 0.22 to 1.0; EuroQol visual analog scale score range, 0-100) were used. To investigate factors associated with PROs, linear (treatment satisfaction/QoL) or logistic (medication adherence) regression analyses were conducted. A total of 1804 patients (age, 62 years) were investigated; 60.1% used bisphosphonate, with the majority (67.2%) using weekly medication, 27.8% used daily hormone replacement therapy, and 12.1% used daily selective estrogen receptor modulator. Several patients reported gastrointestinal (GI) events (31.6%) and dental visits due to problems (24.1%) while using medication. Factors associated with the highest OS-MMAS domain scores were convenience and global satisfaction. GI events were associated with non-adherence. TSQM scores for effectiveness, side effects, and GI risk factors were significantly associated with QoL. Our study elaborately assessed the factors associated with PROs of Korean PMO women. Based on our findings, appropriate treatment-related adjustments such as frequency/choice of medications and GI risk management may improve PROs.

Assessment of Denosumab in Korean Postmenopausal Women with Osteoporosis: Randomized, Double-Blind, Placebo-Controlled Trial with Open-Label Extension.

PURPOSE: The efficacy and safety of denosumab was compared with placebo in Korean postmenopausal women with osteoporosis in this phase III study. MATERIALS AND METHODS: Women aged 60 to 90 years with a T-score of <-2.5 and ≥-4.0 at the lumbar spine or total hip were randomized to a single 60 mg subcutaneous dose of denosumab or placebo for the 6-month double-blind phase. Eligible subjects entered the 6-month open-label extension phase and received a single dose of denosumab 60 mg. RESULTS: Baseline demographics were similar in the 62 denosumab- and 64 placebo-treated subjects who completed the double-blind phase. Treatment favored denosumab over placebo for the primary endpoint {mean percent change from baseline in lumbar spine bone mineral density (BMD) at Month 6 [3.2% (95% confidence interval 2.1%, 4.4%; p<0.0001)]}; and secondary endpoints (mean percent change from baseline in lumbar spine BMD at Month 1, total hip, femoral neck, and trochanter BMD at Months 1 and 6, and median percent change from baseline in bone turnover markers at Months 1, 3, and 6). Endpoint improvements were sustained over 12 months in the open-label extension (n=119). There were no new or unexpected safety signals. CONCLUSION: Denosumab was well tolerated and effective in increasing BMD and decreasing bone turnover markers over a 12-month period in Korean postmenopausal women. The findings of this study demonstrate that denosumab has beneficial effects on the measures of osteoporosis in Korean postmenopausal women.

Clinical impact and cost-effectiveness of coronary computed tomography angiography or exercise electrocardiogram in individuals without known cardiovascular disease.

It is not clear whether screening by coronary computed tomographic angiography (CCTA) and/or exercise electrocardiogram (ECG) can improve clinical outcomes and reduce costs in individuals without known cardiovascular disease (CVD). In total, 71,811 consecutive individuals without known CVD who underwent general health examinations were enrolled. Using propensity-score matching according to screening tests, 1-year clinical outcomes and 6-month total and coronary artery disease-related medical costs were analyzed in separate groups: group 1 (CCTA [n = 2578] vs no screening [n = 5146]), group 2 (exercise ECG [n = 2898] vs no screening [n = 5796]), and group 3 (CCTA and exercise ECG [n = 2003] vs no screening [n = 4006]). There were no significant differences in the composite outcome of death, myocardial infarction, and stroke in each matched group: group 1 (0.35% vs 0.45%, P = 0.501), group 2 (0.14% vs 0.28%, P = 0.157), and group 3 (0.25% vs 0.27%, P = 0.858). However, revascularization was more frequent in the CCTA screening groups: group 1 (2.02% vs 0.45%, P < 0.001) and group 3 (1.40% vs 0.45%, P < 0.001). Matched screening groups had higher 6-month total and coronary artery disease-related medical costs: group 1 ($777 vs $603, P < 0.001 and $177 vs $39, P < 0.001), group 2 ($544 vs $492, P = 0.045 and $12 vs $15, P = 0.611), and group 3 ($705 vs $627, P = 0.090 and $135 vs $35, P < 0.001). In individuals without known CVD, CCTA screening with or without exercise ECG led to more frequent revascularization at the expense of higher medical costs, but did not decrease the 1-year risk of death, myocardial infarction, and stroke.