Recent Update on the Prevalence of Sarcopenia in Koreans: Findings from the Korea National Health and Nutrition Examination Survey.

BACKGROUND: As recognized by the World Health Organization in 2016 with its inclusion in the International Classification of Diseases, Tenth Revision as M62.84, and by South Korea in 2021 as M62.5, the diagnostic guidelines for sarcopenia vary globally. Despite its prevalence in older populations, data on sarcopenia in Koreans aged 60 and above is scarce, highlighting the need for research on its prevalence in this demographic. METHODS: Utilizing the 2022 Korea National Health and Nutrition Examination Survey dataset, sarcopenia was assessed among 1,946 individuals aged 60 or older according to the Asian Working Group for Sarcopenia 2019 criteria, incorporating grip strength and bioelectrical impedance analysis measurements. Statistical analyses were performed to differentiate categorical and continuous variables using logistic regression and Student's t-tests, respectively. RESULTS: The prevalence of sarcopenia was found to increase with age, with the highest prevalence observed in the oldest age group (80 years and older). The overall prevalence of sarcopenia in our study population was 6.8%. Among men, the prevalence of sarcopenia was 5.5% in the 60 or older age group, 9.6% in the 70 or older age group, and 21.5% in the 80 or older age group. Among women, the prevalence of sarcopenia was 7.9%, 10.5%, and 25.9%, respectively. CONCLUSIONS: This study highlights the significant burden of sarcopenia in elderly Koreans, particularly among the oldest individuals. These findings call for targeted interventions to manage and prevent sarcopenia, along with further research on its risk factors, consequences, and effective mitigation strategies.

Effectiveness and Usefulness of Bone Turnover Marker in Osteoporosis Patients: A Multicenter Study in Korea.

BACKGROUND: This study aimed to investigate real-world data of C-terminal telopeptide (CTX), propeptide of type I collagen (P1NP), and osteocalcin through present multicenter clinical study, and retrospectively analyze the usefulness of bone turnover markers (BTMs) in Koreans. METHODS: The study focused on pre- and post-menopausal patients diagnosed with osteoporosis and excluded patients without certain test results or with test intervals of over 1 year. The demographic data and 3 BTMs (CTX, P1NP, and osteocalcin) were collected. The patients were classified by demographic characteristics and the BTM concentrations were analyzed by the group. RESULTS: Among women with no history of fractures, the levels of P1NP (N=2,100) were 43.544±36.902, CTX (N=1,855) were 0.373 ±0.927, and osteocalcin (N=219) were 10.81 ±20.631. Among men with no history of fractures, the levels of P1NP (N=221) were 48.498±52.892, CTX (N=201) were 0.370±0.351, and osteocalcin (N=15) were 7.868 ±10.674. Treatment with teriparatide increased the P1NP levels after 3 months in both men and women, with a 50% increase observed in women. Similarly, treatment with denosumab decreased the CTX levels after 3 months in both men and women, with a reduction of 50% observed in women. CONCLUSIONS: The results of this study can contribute to the accurate assessment of bone replacement status in Koreans. We also provide the P1NP level in the Korean population for future comparative studies with other populations.

Association between the dietary inflammatory index and bone markers in postmenopausal women.

INTRODUCTION: The health problem of postmenopausal women is emerging as an important problem due to the increased aging population. This study investigated the association between dietary inflammatory index (DII) and bone markers in postmenopausal women. METHODS: A cross-sectional study was conducted on 132 postmenopausal women aged 45-70 years. The DII score was calculated using the 3-day food records and divided into tertiles according to the DII score. The lifestyle factors that could affect bone mineral density (BMD) in postmenopausal women were investigated and included the EuroQol- 5 Dimension (EQ-5D), physical activity, and eating habits. Skeletal muscle index-weight (SMIw) was used to evaluate skeletal muscle mass, and alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BSALP), and phosphorus (P) measured as bone biomarkers. The BMD was measured using dual-energy X-ray absorptiometry, and the association between anthropometric, biochemistry, BMD, and DII was assessed. RESULTS: In the anti-inflammatory group, a high intake of fiber, vitamins, and minerals was observed. After adjusting for confound factors, with higher DII score, percent body fat increased (ß = 0.168, p = 0.012), and SMIw decreased linear regression analysis (ß = -0.329, p = 0.037, respectively). For biochemistry, confound factors were adjusted, with higher DII score, ALP, BSALP and P decreased and DII score increased (ß = -0.057, p = 0.002, ß = -0.167, p = 0.004, ß = -1.799, p = 0.026, respectively). The relationship between DII and BMD was not significant, but osteopenia increased as DII score increased. CONCLUSION: The low DII score is positively associated with low body fat, high muscle mass, elevated bone markers, and low risk of osteopenia.

Medication Related Osteonecrosis of the Jaw: 2021 Position Statement of the Korean Society for Bone and Mineral Research and the Korean Association of Oral and Maxillofacial Surgeons.

Antiresorptives are the most widely prescribed drugs for the treatment of osteoporosis. They are also used in malignant bone metastases, multiple myeloma, and Paget's disease, and provide therapeutic efficacy on those diseases. However, it was reported that the occurrence of osteonecrosis of the jaw (ONJ) could be related to antiresorptive exposures, and there have been many cases regarding this issue. Therefore, a clearer definition and treatment guidelines were needed for this disease. The American Society for Bone and Mineral Research and the Amnerican Association of Oral and Maxillofacial Surgeons reported statements on bisphosphonate-related ONJ (BRONJ), and a revised version was recently presented. In the revised edition, the diagnosis BRONJ was changed to medication-related ONJ (MRONJ), which reflects consideration of the fact that ONJ also occurs for denosumab, a bone resorption inhibitor of the receptor activator of the nuclear factor-κB ligand antibody family, and bevacizumab, an anti-angiogenesis inhibitor. The Korean Society for Bone and Mineral Research and the Korean Association of Oral and Maxillofacial Surgeons had collectively formed a task force for the preparation of an official statement on MRONJ based on a previous position paper in 2015. The task force reviewed current knowledge and coordinated dental and medical opinions to propose the guideline customized for the local Korean situation.

Citation Analysis of the Journal of Bone Metabolism from Korean Citation Index, Web of Science, and Scopus.

BACKGROUND: Nine years have passed since the Journal of Bone Metabolism (JBM) was launched as an English journal in 2012; it was finally included in Scopus in January 2019. Therefore, this study aimed to provide evidence of increased international recognition based on journal metrics and reflect on its efforts to be recognized as a top-notch journal. METHODS: Databases, such as the Web of Science (WoS), Scopus, Korean Citation Index (KCI), and citation indicators, including the impact factor (IF) and SCImago journal rank (SJR) were reviewed and calculated according to years, and the results were drawn. Furthermore, country-wise contributions and top-cited articles were also investigated. RESULTS: The JBM 2020 IF was 2.17 in the WoS. The 2020 SJR in Scopus was 0.334, with a ranking of 165/219 (75.3%) in the Endocrinology, Diabetes, and Metabolism category. The 2020 KCI was 0.42. Of 263 articles, 260 were citable (98.9%), and of 176 original articles, 15 (8.5%) were supported by research grants. The total citation of JBM has increased from 16 in 2014 to 141 in 2020; however, its KCI remained stationary from 0.29 in 2015 to 0.42 in 2020. CONCLUSIONS: Currently, JBM is increasingly cited by international researchers than Korean researchers, indicating that the journal's content is valued at an international level. Its inclusion in PubMed Central appears to have increased its international relevance; however, publishing English-only articles may hinder its use domestically. Therefore, efforts should be made to increase citation rates and enhance domestic readership.

Application of the Trabecular Bone Score in Clinical Practice.

The trabecular bone score (TBS) was introduced as an indirect index of trabecular microarchitecture, complementary to bone mineral density (BMD), and is derived using the same dual energy X-ray absorptiometry images. Recently, it has been approved for clinical use in Korea. Therefore, we conducted a comprehensive review to optimize the use of TBS in clinical practice. The TBS is an independent predictor of osteoporotic fractures in postmenopausal women and men aged >50 years. The TBS is potentially useful in monitoring the skeletal effects of anabolic agents but not of antiresorptive agents. In postmenopausal women with type 2 diabetes mellitus, the TBS assesses osteoporotic fracture risk not captured by BMD. However, high body mass index and soft tissue thickness can cause underestimation of the TBS; however, this limitation has been improved in recent versions of the TBS software. However, a high precision error and low reproducibility limit the use of TBS. This review may provide information on the application of the TBS in clinical practice based on reliable evidence.

Comparisons of Muscle Quality and Muscle Growth Factor Between Sarcopenic and Non-Sarcopenic Older Women.

Sarcopenia, an age-related disease, is one of the important health problems in the elderly and the prevalence of sarcopenia is rapidly increased among the Korean population. This study examined the muscle quality and muscle growth factors of elderly women to identify the potential diagnostic tool for sarcopenia. One hundred and thirty-six elderly women, aged over 65 years old, initially enrolled, but only 59 participants who met the criteria (sarcopenic group, n = 27; non-sarcopenic group, n = 32) completed the study. Muscle quality assessment included thigh cross-sectional computed tomography scan and maximal isometric muscle strength. Muscle growth factors such as GDF-15, myostatin, activin A, and follistatin were analyzed, and a battery of Senior Fitness Test was used to examine functional fitness. The statistical significance level was set at 0.05. Elderly women with sarcopenia had a lower thigh muscle volume (-20.1%), and a higher thigh intermuscular adipose tissue (15.8%) than those of the non-sarcopenic group (p < 0.05). However, no significant differences in muscle growth factors were observed between the groups. Muscle quality variables including maximal voluntary isometric contraction (OR: 0.968, p < 0.001), relative maximal voluntary isometric contraction (OR: 0.989, p < 0.05), thigh muscle volume (OR: 0.836, p < 0.001), and thigh intermuscular adipose tissue (OR: 1.138, p < 0.05) were associated with a risk of sarcopenia. Our findings suggest that the sarcopenic group exhibits a poor thigh muscle quality in comparison with the non-sarcopenic group. Muscle quality assessment can be utilized for sarcopenia identification, but our study remains inconclusive for the causality of muscle growth factors in sarcopenia.

Early Prediction of Tumor Response to Neoadjuvant Chemotherapy and Clinical Outcome in Breast Cancer Using a Novel FDG-PET Parameter for Cancer Stem Cell Metabolism.

Cancer stem cells (CSCs) contribute to chemoresistance and tumor relapse. By using the distinct metabolic phenotype of CSC, we designed novel PET parameters for CSC metabolism and investigated their clinical values. Patients with breast cancer who underwent 18F-FDG PET/CT before neoadjuvant chemotherapy (NAC) were retrospectively included. We developed a method to measure CSC metabolism using standardized uptake value histogram data. The predictive value of novel CSC metabolic parameters for pathologic complete response (pCR) was assessed with multivariable logistic regression. The association between the CSC parameter and disease-free survival (DFS) was also determined. We identified 82 patients with HER2-positive/triple-negative subtypes and 38 patients with luminal tumors. After multivariable analysis, only metabolic tumor volume for CSC (MTVcsc) among metabolic parameters remained the independent predictor of pCR (OR, 0.12; p = 0.022). MTVcsc successfully predicted pathologic tumor response to NAC in HER2-positive/triple-negative subtypes (accuracy, 74%) but not in the luminal subtype (accuracy, 29%). MTVcsc was also predictive of DFS, with a 3-year DFS of 90% in the lower MTVcsc group (<1.75 cm3) versus 72% in the higher group (>1.75 cm3). A novel data-driven PET parameter for CSC metabolism provides early prediction of pCR after NAC and DFS in HER2-positive and triple-negative subtypes.

Presacral Anastomotic Sinus After Low Anterior Resection Mimicking Recurrent Rectal Cancer.

Presacral anastomotic sinus is recognized as a complication of anastomotic leakage in patients with rectal cancer. Active inflammation in the anastomotic sinus can masquerade as pelvic recurrence of rectal cancer. We present a case of progressive inflammation in anastomotic sinus demonstrated by serial FDG PET/CT scans. Despite its benign nature, increased FDG uptake in this nonnegligible condition, which could lead to further detrimental complications including secondary cancer, may have clinical implications.

Tetrabromobisphenol A Promotes the Osteoclastogenesis of RAW264.7 Cells Induced by Receptor Activator of NF-kappa B Ligand In Vitro.

BACKGROUND: Tetrabromobisphenol A (TBBPA), one of the most widely used brominated flame-retardants, is a representative persistent organic pollutants group. Studies on TBBPA toxicity have been conducted using various target cells; however, few studies have investigated TBBPA toxicity in bone cells. Therefore, this study investigated the in vitro effects of TBBPA on osteoclasts, a cell type involved in bone metabolism. METHODS: RAW264.7 cells were cultured in medium containing 50 ng/mL receptor activator of nuclear factor kappa B ligand (RANKL) and varying concentrations of TBBPA. To evaluate the effects of TBBPA on the differentiation and function of osteoclasts, osteoclast-specific gene expression, tartrate-resistant acid phosphatase (TRAP) activity, bone resorbing activity, mitochondrial membrane potential (MMP) and mitochondrial superoxide were measured. RESULTS: The presence of 20 µ TBBPA significantly increased TRAP activity in RANKL-stimulated RAW264.7 cells, the bone resorbing activity of osteoclasts, and the gene expression of Akt2, nuclear factor of activated T-cells cytoplasmic 1, and chloride channel voltage-sensitive 7. However, TBBPA treatment caused no change in the expression of carbonic anhydrase II, cathepsin K, osteopetrosis-associated transmembrane protein 1, Src, extracellular signal-related kinase, GAB2, c-Fos, or matrix metalloproteinase 9. Furthermore, 20 µ TBBPA caused a significant decrease in MMP and a significant increase in mitochondrial superoxide production. CONCLUSION: This study suggests that TBBPA promotes osteoclast differentiation and activity. The mechanism of TBBPA-stimulated osteoclastogenesis might include increased expression of several genes involved in osteoclast differentiation and reactive oxygen species production.

Vascular Parkinsonism by Infarctions at Different Locations on 18F-FP-CIT PET/CT.

Cerebral vascular lesions are integral to the diagnosis of vascular parkinsonism (VP). The VP, also referred to as lower body parkinsonism, is frequently caused by subcortical white matter lesions, but lesions at any levels of the nigro-striato-thalamo-cortical pathway can also cause VP, thus giving rise to various symptoms other than gait disturbance. Previous dopamine transporter imaging studies using SPECT showed heterogeneous patterns suggesting diverse contributing lesions to VP. Here we present 3 cases of VP demonstrated by F-FP-CIT PET/CT, visualizing vascular lesions at different levels between the midbrain and motor cortex. Distinctive clinical manifestations of them recapitulate the pathogenesis of VP.

High circulating follistatin-like protein 1 as a biomarker of a metabolically unhealthy state.

The inflammatory biomarkers that fully characterize the metabolically unhealthy (MU) state-which is a risk factor for cardiovascular disease (CVD)-remain unclear. Recent studies suggest follistatin-like protein 1 (FSTL1) could be used as a biomarker for inflammation and CVD, however there is little information on FSTL1 levels in the MU state. We aimed to evaluate the associations between FSTL1, the presence of MU state and subclinical coronary atherosclerosis. In a cross-sectional study, we evaluated FSTL1 levels and their relationship with the presence of MU state and coronary artery plaques in 230 Korean patients. Significant increase in FSTL1 levels was observed in subjects with MU state (p = 0.020), but not those with obesity state according to body mass index criteria (p = 0.790). After adjusting for confounders, the odd ratio (OR) for the MU state among patients in the highest FSTL1 tertile (T3) was higher in comparison with the lowest tertile (T1) (OR = 3.60, 95% confidence interval [95% CI] = 1.20-10.83). In a subgroup (n = 66), FSTL1 levels were also marginally higher in patients with plaques (p = 0.098). The OR for plaque presence in patients with T3 was significantly higher in comparison with T1 after adjusting for confounders (OR = 12.51, 95% CI = 1.15-135.73). Plasma FSTL1 may be a useful biomarker for the risk of MU state and CVD.

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.

Comparison of screening strategies for prevalent vertebral fractures in South Korea: vertebral fracture assessment vs. spine radiography.

BACKGROUND: Vertebral Fracture Assessment (VFA) is a useful tool to detect the vertebral fracture (VF) with low cost and radiation exposure. We aimed to compare screening strategies including VFA and spine radiography (X-ray) for detecting VF in terms of clinical effectiveness, cost and radiation exposure. METHODS: Three screening strategies: 1) X-ray following VFA, 2) VFA only, and 3) X-ray only were compared using a Markov model based on administrative data from South Korea in a population aged ≥50 years. We compared the incidence of new VFs, cost-effectiveness of reducing new VFs and radiation exposure in each strategy. RESULTS: The incidence of new VFs was reduced in all screening strategies compared to no screening: 29.4% for women and 12.5% for men in both X-ray following the VFA and VFA only strategies and 35% for women and 17.5% for men in the X-ray only strategy. The X-ray following VFA strategy had the lowest cost, followed by the X-ray only, and VFA only strategies. The radiation doses for X-ray only were 2,647-2,989 µSv and 3,253-3,398 µSv higher than in the X-ray following VFA and VFA only strategies. The new VF prevention effect was greater in women, and more prominent in older people (women ≥ 70, men ≥ 80) than people ≥ 50 years. CONCLUSIONS: The X-ray following VFA strategy is a cost-effective option for screening prevalent VF to prevent new VF in people aged ≥50 years due to its high effectiveness, lowest cost, and least radiation exposure.

Short-Term Teriparatide and Recombinant Human Bone Morphogenetic Protein-2 for Regenerative Approach to Medication-Related Osteonecrosis of the Jaw: A Preliminary Study.

Our objective was to examine whether adjunct teriparatide administration and local application of recombinant human bone morphogenetic protein-2 (rhBMP-2) is beneficial for the regeneration of jaw bone in patients with medication-related osteonecrosis of the jaw (MRONJ). This study enrolled 17 patients diagnosed with MRONJ. All patients received sequestrectomy under general or local anesthesia with suspension of bisphosphonate. The bone regeneration ratio was compared on cone beam computed tomography (CBCT) scans, acquired immediately post-operation and after 6 months. The patients were divided into groups, based on their treatment regimens: teriparatide combined with rhBMP-2 (parathyroid hormone [PTH]+BMP), rhBMP-2 (BMP), and the control. Biochemical markers were also evaluated at the baseline (T0), 1 month (T1), and 3 months (T2) after surgery. Significant increase was observed in the values of the biochemical markers, serum osteocalcin, and serum C-terminal telopeptide cross-link of type I collagen, within 3 months of surgery in the PTH+BMP group, whereas the mean value in the BMP group did not show a significant change. In all groups, the MRONJ lesions were healed and new bone formation was detected in the CBCT images. The regeneration ratio was significantly greater in the group PTH+BMP than in the BMP and control groups. Significantly greater amount of bone formation was observed in the group PTH+BMP than in the BMP and control groups. Local application of rhBMP-2 alone also had a beneficial effect on bone regeneration but was not more significant than control. Based on these findings, administration of short-term teriparatide with rhBMP-2 in MRONJ patients may maximize the regeneration of bone after surgery. © 2017 American Society for Bone and Mineral Research.

A retrospective study of osteomyelitis and osteonecrosis of the jaws and its etiologic implication of bisphosphonate in Asians.

OBJECTIVE: The objective of this study were to find the annual case trend of inflammatory jawbone diseases and to investigate the impact of medication-related osteonecrosis of the jaws (MRONJ). MATERIAL AND METHODS: A retrospective study of 372 patients diagnosed with inflammatory jawbone condition except for alveolar osteitis from 2007 to 2015 was initiated. History taking and investigation of etiologic factors MRONJ, osteoradionecrosis (ORN), odontogenic infection, foreign body, and trauma were investigated. A separate analysis showed the number of MRONJ cases in two age groups (under 70 years; 70 years and over) and serum C-terminal peptide (s-CTX) values that were found. RESULTS: The results showed that the number of MRONJ cases was significantly larger in the older age group (p < 0.05). Regarding gender and sites of lesions, MRONJ was significantly frequent in the female and the mandible (p < 0.05). The R 2 values for the regression analysis for MRONJ (R 2 = 0.9234) and odontogenic etiology (R 2 = 0.0427) signified linear increase in the number of MRONJ cases, whereas bone lesions due to traditional odontogenic etiology stayed stationary. CONCLUSION: The number of MRONJ has escalated, and most of the patients are elderly people. The current trend of inflammatory conditions of the jaw may have changed since the advent of MRONJ. CLINICAL RELEVANCE: Long-term bisphosphonate therapy became a major risk factor for the osteomyelitis and osteonecrosis of the jaws. Thorough medical history, taking would be essential and communication with prescribing physicians should be emphasized during the dental treatment planning.

Bisphosphonate related osteonecrosis of the jaws (BRONJ) in osteoporotic males.

BACKGROUND: The purpose of this study was to describe the clinical characteristics of bisphosphonate related osteonecrosis of the jaws (BRONJ) in osteoporotic males. METHODS: The medical records of BRONJ patients from 2007 to 2014 were reviewed. The data from only the male patients was extracted, and demographic data was collected and biochemical markers were measured. RESULTS: 11 Patients out of 210 (5 %) being males. Among the 11 patients, the indication of bisphosphonate (BP) was osteoporosis in 9 patients, and cancer in two. In one of the osteoporosis patients, osteoporosis was thought to be secondary to hypogonadism after testicular tumor resection. Serum c-terminal telopetide crosslink of type I collagen (s-CTX) values ranged from 60 to 165 pg/mL (mean: 84.6 ± 36.8, median: 70). Serum osteocalcin (s-OC) ranged from 0 to 5.06 ng/mL (mean: 1.83 ± 1.66, median: 1.5) and vitamin D ranged from 0 to 11.9 (mean: 5.02 ± 4.92, median: 3.5). CONCLUSION: BRONJ can be overlooked in male patients with osteoporosis. Although the incidence of BRONJ in males may be low, dentists should also check if their male patients are on osteoporosis treatment since osteoporosis in males can be manifested as a secondary disease to hypogonadism.

Decreased Plasma Levels of Sclerostin But Not Dickkopf-1 are Associated with an Increased Prevalence of Osteoporotic Fracture and Lower Bone Mineral Density in Postmenopausal Korean Women.

Although sclerostin (SOST) and Dickkopf-related protein 1 (DKK1) are major regulators in bone metabolism, their associations with osteoporotic fracture (OF) in Asians are inconclusive. Furthermore, there have been no clinical studies separately considering non-vertebral and vertebral fractures in terms of the blood levels of SOST and DKK1. Among 513 consecutive postmenopausal Korean women, we identified 103 cases defined as subjects with OF (i.e., non-vertebral and/or vertebral fractures). The controls were randomly selected from the remaining 410 subjects and matched 1:1 to cases according to both age and body mass index. Non-vertebral and morphological vertebral fractures were identified by an interviewer-assisted questionnaire and lateral thoracolumbar radiographs, respectively. Bone mineral density (BMD) and plasma levels of SOST and DKK1 were measured. Plasma SOST levels were lower in subjects with OF than in the control group. Each standard deviation decrement of plasma SOST concentration was associated with a multivariable-adjusted odds ratio of 1.77 for any prevalent OF type. The odds for OF was 2.97-fold higher in subjects in the lowest SOST tertile compared with subjects in the highest SOST tertile. These associations remained significant when the non-vertebral and vertebral fractures were analyzed separately. However, prevalent OF was not associated with plasma DKK1 levels, regardless of the type of fracture and the adjustment model employed. Consistently, plasma SOST levels were positively related with BMD values at all measured skeletal sites, although this was not observed for DKK1. Circulating SOST but not DKK1 may be a potential biomarker for predicting bone health in Asians.

Low Plasma Level of Leucine-Rich Repeat-Containing 17 (LRRc17) Is an Independent and Additive Risk Factor for Osteoporotic Fractures in Postmenopausal Women.

A novel role of leucine-rich repeat-containing 17 (LRRc17), an LRR protein secreted by osteoblasts, as a negative regulator of receptor activator of NF-κB ligand-induced osteoclast differentiation was found. However, the clinical association between LRRc17 and osteoporotic fracture (OF) has not yet been investigated. We hypothesized that low circulating plasma level of LRRc17 might serve as an independent and additive risk factor for OF, including vertebral fractures (VF) and non-vertebral fractures (non-VF). In this case-control study, 102 OF cases and 102 age- and body mass index-matched controls (mean age, 63.2 years) were analyzed among 532 postmenopausal women. VF (n = 49) and non-VF (n = 60) participants were identified using lateral thoracolumbar radiographs and an interviewer-assisted questionnaire, respectively. Median LRRc17 levels were significantly lower in participants with any OF (117.5 versus 197.3 pg/mL, p < 0.001), VF (93.2 versus 172.4 pg/mL, p = 0.002), and non-VF (124.5 versus 206.9 pg/mL, p = 0.008) compared with the respective controls without fractures. The prevalence of OF increased from the highest LRRc17 tertile (≥228.5 pg/mL, 33.8%) to the lowest (<95.6 pg/mL, 63.2%). Each log unit decrease of LRRc17 was associated with greater risk of OF (odds ratio [OR] = 1.46; 95% confidence interval [CI] 1.10-1.96; p = 0.009) and VF (OR = 2.42; 95% CI 1.39-4.23; p = 0.002). Plasma LRRc17 significantly improved discrimination of OF, particularly VF, when added to models including clinical risk factors and bone mineral density according to the area under receiver operating characteristics curves (AUC 0.71 to 0.81, p = 0.036), category-free net reclassification improvement (0.79; 95% CI 0.37-1.21; p < 0.001), and integrated discrimination improvement (0.13; 95% CI 0.06-0.20; p < 0.001). Low plasma LRRc17 was an independent risk factor for OF, which improved risk stratification, particularly in the spines of postmenopausal women. © 2016 American Society for Bone and Mineral Research.