Journal of Bone Metabolism最新文献

Background: Probiotics are live microorganisms that confer health benefits on the host. Many animal studies have shown that among the probiotics, lactobacilli exert favorable effects on bone metabolism. Herein, we report the results of a randomized controlled trial performed to investigate the effect of Lactobacillus fermentum (L. fermentum) SRK414 on bone health in postmenopausal women.

Methods: The bone turnover markers (BTMs) and bone mineral density (BMD) in participants in the study group (N=27; mean age, 58.4±3.4 years) and control group (N=26; mean age, 59.5±3.4 years) were compared during a 6-month trial. BTMs were measured at pretrial, 3 months post-trial, and 6 months post-trial, while BMD was measured at pre-trial and 6 months post-trial. Changes in the gut microorganisms were also evaluated.

Results: Femur neck BMD showed a significant increase at 6 months post-trial in the study group (P=0.030) but not in the control group. The control group showed a decrease in osteocalcin (OC) levels (P=0.028), whereas the levels in the study group were maintained during the trial period. The change in L. fermentum concentration was significantly correlated with that in OC levels (r=0.386, P=0.047) in the study group at 3 months post-trial.

Conclusions: Probiotic (L. fermentum SRK414) supplementation was found to maintain OC levels and increase femur neck BMD during a 6-month trial in postmenopausal women. Further studies with a larger number of participants and a longer study period are required to increase the utility of probiotics as an alternative to osteoporosis medication.

Background: This study compared the effects of hip fractures on mortality according to sex and age in a nationwide cohort of elderly patients with hip fractures and controls.

Methods: Patients with hip fractures and matched controls were selected from the National Health Insurance Service-Senior cohort. Time-dependent propensity score matching was estimated from a Cox proportional hazards model with January 1, 2005, as the baseline and hip fracture as an event. Patients were matched by age and sex to participants at risk of developing a hip fracture at time zero. The effect size is presented as hazard ratio (HR) using a Cox proportional hazards model with a robust variance estimator that accounts for clustering within the matched pairs.

Results: Altogether, 14,283 patients with incident hip fractures and 28,566 matched controls were identified. The HR of male sex in hip fractures was 1.31 (95% confidence interval [CI], 1.22-1.40; Pinteraction<0.01). Moreover, the HR of age group in hip fractures was 0.73 (95% CI, 0.66-0.80; Pinteraction<0.01) between the 65 to 74 and 75 to 84 years groups, 0.76 (95% CI, 0.71-0.81; Pinteraction<0.01) between the 75 to 84 and ≥85 years groups, and 0.55 (95% CI, 0.50-0.61; Pinteraction<0.01) between the 65 to 74 and ≥85 years groups.

Conclusions: Male sex increases the risk of death in elderly patients with hip fractures versus matched controls, but the increased risk of death with age in hip fractures was decreased compared to that in matched controls.

Background: The association between osteoporosis, a common metabolic bone disorder, and atherosclerosis has been reported in different studies. In this study, we aimed to investigate the association between the coronary artery calcium score (CACS) and bone mineral density (BMD) at different sites and bone biomarkers in postmenopausal women.

Methods: A total of 184 participants were enrolled in this study. The CACS and BMD at different sites, including the spinal, total hip, and femoral neck, were measured using computed tomography angiography and dual energy X-ray absorptiometry, respectively. Serum levels of osteocalcin, β-C-terminal telopeptide (β-CTX), parathyroid hormone, and 25-hydroxy-vitamin D were measured.

Results: A negative association between CACS and bone biomarker levels (osteocalcin, P=0.021; β-CTX, P=0.013) was noted. The univariable model showed an association between CACS and osteoporosis of the femoral neck (P=0.03). It was found that with an increase of 10 U in CACS, the odds of osteoporosis at the femoral neck escalates by 2% (odds ratio=1.02, 95% confidence interval, 1.002-1.03) using the multivariate logistic regression model, while such an association with osteoporosis could not be found at the spinal site. The best cutoff point of the calcium score was estimated to be 127.

Conclusions: The results suggest that in postmenopausal women, coronary atherosclerosis is independently associated with osteoporosis of the femoral neck, but such an association could not be detected with spinal osteoporosis. The importance of screening for osteoporosis in patients with cardiovascular disease and the implications of preventive measures in the primary care setting were highlighted considering the common risk factors.

Background: Cells have heterogeneous cellular diversity in size, morphology, cell cycle, metabolism, differentiation degree, and spatial distribution. The shift of specific cells towards the desired cells is crucial for maintaining uniform cellular function and can be represented by homogeneity and heterogeneity. Here, we developed a simple and direct method for evaluating the homogeneous distribution of desired cells in a constant region.

Methods: We differentiated osteoclast progenitors into bone-resorbing multinucleated giant osteoclasts in a 2-dimensional culture plate under 2 conditions. Cells were stained with tartrate-resistant acid phosphatase to assess osteoclast differentiation, images were taken using a microscope and divided into sectors, and the number of osteoclasts (≥3 nuclei) in each sector was counted. To assess the homogeneity of the spatial distribution of osteoclasts, the standard deviation (SD) was calculated from the mean number of osteoclasts within each sector.

Results: From the 2 groups, a value with a SD close to 0 indicates high spatial homogeneity while a relatively high SD represents low spatial homogeneity.

Conclusions: Our findings suggest that spatial homogeneity can be represented as SD.

Adequate vitamin D status is essential for bone health. New randomized controlled trials investigating the effect of vitamin D supplementation on bone health have recently been published. This position statement updates and expands on the previous 2015 position statement of the Korean Society for Bone and Mineral Research on the adequate vitamin D status for healthy older adults (age ≥ 70 years) and those at high risk of osteoporosis and fracture (adults on osteoporosis medications) to maintain serum 25-hydroxy-vitamin D (25[OH]D) levels ≥ 20 ng/mL but < 50 ng/mL. A serum 25(OH)D level of 30 ng/mL may be beneficial for those on anti-resorptives. Vitamin D can be obtained from ultraviolet light exposure and diet. To reach the target vitamin D status through intake, adults must consume at least 400 IU/day to reach 20 ng/mL and 800 to 1,000 IU/day to reach 30 ng/mL. Foods familiar to the Korean diet that are high in vitamin D content or consumed frequently enough to positively impact vitamin D status are introduced in addition to the amount required to help reach one's target vitamin D status.

Background: Osteolysis is one of the most common problems that occurs after total hip and knee arthroplasty and has recently become a significant problem after total ankle arthroplasty (TAA). In this study, we investigated the role of LIM homeobox transcription factor 1-β (Lmx1b) in osteoclast differentiation. By evaluating the expression profiles associated with osteolysis following TAA treatment, Lmx1b was found to be differentially expressed in patients with osteolysis after TAA.

Methods: To identify the important genes associated with osteolysis after TAA, RNA sequencing was performed by analyzing 8 patient samples: 5 primary TAA samples (control group) and 3 TAA samples revised for flexion instability (osteolysis group). By analyzing the differentially expressed genes and gene ontologies, Lmx1b expression was found to be upregulated in the osteolysis group compared to that in the control group. Focusing on the role of Lmx1b in bone cells, Lmx1b was overexpressed by a retrovirus in osteoclast precursor cells. The cultured cells were stained with tartrate-resistant acid phosphatase, and the expression of osteoclast-related genes was analyzed using real-time polymerase chain reaction.

Results: Lmx1b overexpression in osteoclast precursors suppresses osteoclast formation and resorptive activity. The expression of osteoclast marker genes was significantly reduced during osteoclast differentiation by Lmx1b overexpression. Furthermore, Lmx1b is associated with nuclear factor of activated T cells 1 (NFATc1) and inhibited NFATc1 translocation into the nucleus.

Conclusions: These results provide novel insights into the anti-bone resorptive effect of Lmx1b on osteolysis after TAA and may lead to the development of effective preventative and therapeutic strategies for peri-implant osteolysis.

Ectopic parathyroid adenomas of the retropharyngeal space are relatively rare. Herein, we report a case of primary hyperparathyroidism (PHPT) secondary to a retropharyngeal parathyroid adenoma. A 22-year-old woman presented with elevated serum calcium and parathyroid hormone (PTH) levels, revealed during a medical check-up. The patient had a history of ureteral stones and a confirmed low bone mass. Neck 99mTechnetium-sestamibi singlephoton emission computed tomography (CT) and ultrasonography did not reveal any suspicious lesions. There was no evidence of hereditary PHPT based on the results of targeted gene sequencing. Surgical exploration was unsuccessful, and the PHPT persisted after the first surgery. Approximately a year after the failed operation, 18F-fluorocholine (FCH) positron emission tomography/CT (PET-CT) became available, and when performed, it revealed increased uptake in the retropharyngeal space of the right side of the neck. The results of parathyroid venous sampling were concordant with a >2-fold elevation of PTH level in the veins on the right side of the neck compared to the peripheral veins. The 1.8 cm-diameter mass was successfully removed resulting in an 87% reduction in intraoperative PTH level (198.0-26.5 pg/mL). Subsequently, normalizations of calcium and PTH levels were achieved. In summary, ectopic parathyroid adenomas, including retropharyngeal lesions, should also be suspected when investigating an elusive case of PHPT. 18F-FCH PET-CT can be a useful complementary modality for detecting culprit lesions.

Background: The impact of osteopenia as a risk factor for fractures is underrecognized. Moreover, the efficacy of selective estrogen receptor modulators (SERMs) in postmenopausal women with osteopenia is limited. This study aimed to evaluate the efficacy of SERMs in postmenopausal women with osteopenia.

Methods: Thirty-two postmenopausal women with osteopenia were treated with 3 types of SERMs medication: raloxifene (group I, N=15), bazedoxifene (group II, N=8), and raloxifene with cholecalciferol (group III, N=9). Bone mineral density (BMD) was measured using dual energy X-ray absorptiometry scans before treatment to after 3 years of treatment once a year.

Results: Patients in group I showed significant increases in hip BMD, -1.93 to -1.73 and spine BMD, -1.85 to -1.67. In addition, patients in groups II and III showed significant increases in hip BMD, -1.93 to -1.69 and -2.22 to -1.86, respectively and spine BMD, -2.1 to -1.3 and -2.22 to -1.37, respectively. The BMD increased in the hip and spine by 9.7% and 10.3%, respectively in group I, 38.0% and 12.4%, respectively in group II, and 38.2% and 16.2%, respectively in group III.

Conclusions: In this study, we found that SERMs could improve spine and hip BMD. In conclusion, preemptive treatment using SERMs is necessary for postmenopausal women with osteopenia. None of the patients experienced fractures during the follow-up period.

Background: We compared the efficacy of a fixed dose combination of raloxifene 60 mg/vitamin D 800 IU to raloxifene 60 mg alone on vitamin D status, as indicated by change in serum 25-hydroxy-vitamin D (25[OH]D) levels.

Methods: In this 16-week, open-label, randomized, active controlled, multicenter clinical trial conducted in 4 university-affiliated hospitals in Korea, postmenopausal women aged 55 to 70 years with osteoporosis or osteopenia were randomly assigned in a 1:1 ratio to receive raloxifene 60 mg/cholecalciferol 800 IU combination therapy or raloxifene 60 mg monotherapy. Primary endpoint was change in serum 25(OH)D level from baseline to 16 weeks after the intervention.

Results: A total of 96 participants were randomly assigned to raloxifene/vitamin D combination therapy (N=49) and raloxifene monotherapy (N=47) groups. At week 16, serum 25(OH)D level increased from baseline, only in the raloxifene/vitamin D combination therapy group. Change in serum 25(OH)D level from baseline to week 16 was higher in the raloxifene/vitamin D combination therapy group (2.7±6.5 ng/mL) than in the raloxifene monotherapy (-1.7±6.2 ng/mL; P=0.0034) group. Proportions and number of adverse events (AEs) categorized by the System-Organ Class were not different between the groups. There was only one severe AE case (spondylolisthesis; raloxifene/vitamin D group), unlikely to be related to trial intervention.

Conclusions: Among postmenopausal women with osteoporosis or osteopenia, a fixed dose combination of raloxifene 60 mg/vitamin D 800 IU showed superior efficacy in elevating serum 25(OH)D levels compared with raloxifene 60 mg alone during 16 weeks of follow-up. The safety of raloxifene/vitamin D combination was comparable to raloxifene alone.