Validation of the Updated Korean Calcium Assessment Tool

Background: We previously developed the Korean Calcium Assessment Tool (KCAT) for assessing the intake of calcium and vitamin D in Korean women. However, based on the Korea National Health and Nutrition Examination Survey (KNHANES) VI and VII (2013–2018), major food sources for calcium and vitamin D have changed, and the National Standard Food Composition database was updated. Therefore, the present study aimed to update the KCAT and validate the Updated KCAT.Methods: A total of 285 women aged >19 years were asked to complete questionnaires of the KCAT and the Updated KCAT.Results: Calcium intake did not differ significantly between the KCAT (566±245 mg/day) and the Updated KCAT (569±248 mg/day; P=0.343). A correlation coefficient of 0.99 indicated a positive correlation on calcium intake between the KCAT and the Updated KCAT, with an almost perfect agreement by Cohen’s κ coefficients (0.95). Vitamin D intake assessed by the Updated KCAT was significantly higher than that assessed by the KCAT, which was positively correlated with a moderate agreement measured by Cohen’s κ coefficients (0.41).Conclusions: The present study demonstrated that the Updated KCAT was a valid tool for the rapid evaluation of calcium and vitamin D intake for Korean women.

Effect of Intermittent Fasting on Glucose Homeostasis and Bone Remodeling in Glucocorticoid-Induced Osteoporosis Rat Model

Background: The present study examined the effect of intermittent fasting (IF) on bone mineral content (BMC) and bone mineral density (BMD) and the markers of bone remodeling in a glucocorticoid-induced osteoporosis (GIO) rat model.Methods: Forty male rats were allocated to 4 groups (N=10 per group): control group of normal rats; control+IF group (normal rats subjected to IF for 16-18 hr daily for 90 days); dexamethasone (DEX) group: (DEX [0.5 mg i.p.] for 90 days); and DEX+IF group (DEX and IF for 90 days). By the end of the experiment, BMD and BMC in the right tibia were measured. Serum levels of the following were measured: glucose; insulin; triglycerides (TGs); total cholesterol; parathyroid hormone (PTH); osteoprotegerin (OPG); receptor activator of nuclear factor-κB (RANK); bone-resorbing cytokines, including bone deoxypyridinoline (DPD), N-terminal telopeptide of collagen type I (NTX-1), and tartrate-resistant acid phosphatase 5b (TRAP-5b); and bone-forming cytokines, including alkaline phosphatase (ALP) and osteocalcin (OC).Results: DEX administration for 90 days resulted in significantly increased serum levels of glucose, insulin, TGs, cholesterol, PTH, OPG, DPD, NTX-1, and TRAP-5b and significantly decreased BMD, BMC, and serum levels of RANK, OC, and ALP (all P<0.05). IF for 90 days significantly improved all these parameters (all P<0.05).Conclusions: IF corrected GIO in rats by inhibiting osteoclastogenesis and PTH secretion and stimulating osteoblast activity.

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.

Effect of Romosozumab on Trabecular Bone Score Compared to Anti-Resorptive Agents in Postmenopausal Women with Osteoporosis

Background: Romosozumab has shown significant improvement in bone mineral density (BMD) in previously reported trials. However, BMD reflects only bone strength and does not offer insight into the bone microarchitecture. The trabecular bone score (TBS) is a non-invasive tool used to assess bone microarchitecture. Several previous studies have evaluated the efficacy of anti-osteoporotic agents using the TBS. However, data regarding the potency of romosozumab based on the TBS is lacking. This retrospective observational cohort study demonstrated the impact of romosozumab use on the TBS.Methods: The primary outcome was the percentage change in the TBS from baseline to post-treatment. Postmenopausal osteoporosis patients were followed up for 6 and 12 months after romosozumab (210 mg monthly, N =10) and denosumab (60 mg every 6 months, N=21) or ibandronate (150 mg monthly, N=24) treatments, respectively. Patients who had previously used osteoporosis medications were included, if any the washout period was sufficient.Results: The percentage change in TBS from baseline to post-treatment was 2.53±2.98% (6 months, N=10; P=0.04), 0.59%±3.26% (12 months, N=21; P=0.48), and -0.45±3.66% (12 months, N=24; P=0.51) in the romosozumab, denosumab, and ibandronate groups, respectively. Romosozumab demonstrated a noticeable increase in TBS, although it did not reach the least significant change (5.8%) in TBS.Conclusions: Romosozumab improved the TBS in postmenopausal women with osteoporosis. TBS may be potentially useful for monitoring romosozumab treatment.

The Potential Role of Exercise Training and Mechanical Loading on Bone-Associated Skeletal Nerves

The spatial distribution, innervation, and functional role of the bone-associated skeletal nerves have been previously reported in detail. However, studies examining exercise-induced associations between skeletal nerves and bone metabolism are limited. This review introduces a potential relationship between exercise and the skeletal nerves and discusses how it can contribute to exercise-induced bone anabolism. First, the background and current understanding of nerve fiber types and their functions in the skeleton are provided. Next, the influence of exercise and mechanical loading on the skeletal nervous system is elaborated. Effective synthesis of recent studies could serve as an established baseline for the novel discovery of the effects of exercise on skeletal nerve density and bone anabolic activity in the future. Therefore, this review overviews the existing evidence for the neural control of bone metabolism and the potential positive effects of exercise on the peripheral skeletal nervous system. The influence of exercise training models on the relationships of sensory nerve signals with osteoblast-mediated bone formation and the increased bone volume provides the first insight on the potential importance of exercise training in stimulating positive adaptations in the skeletal nerve-bone interaction and its downstream effect on bone metabolism, thereby highlighting its therapeutic potential in a variety of clinical populations.

Preoperative Vitamin D Deficiency is Associated with Postoperative Functional Recovery and Complications after Hip Fracture Surgery

Background: Low concentrations of vitamin D are considered one of the risk factors for hip fracture and are associated with worse outcomes. The purpose of this retrospective study was to compare vitamin D deficient group and vitamin D sufficient group and assess the association preoperative vitamin D deficiency and postoperative walking ability after hip fracture surgery.Methods: Between January 2014 and January 2020, 1,029 elderly patients with hip fracture (243 in men and 785 in women) were measured preoperative serum 25-hydroxy-vitamin D3 levels. Among 1,029 elderly patients, 702 patients were classified as Vitamin D deficient group (<20 ng/mL). Outcome parameters for functional recovery were the length of the hospital stay and KOVAL score, and those for complications were delirium, pneumonia, and thromboembolism.Results: The mean length of the hospital stay in the vitamin D deficient group was significantly longer than in the vitamin D sufficient group (27.7±17.8 vs. 2.9±11.8 days; odds ratio [OR], 1.03; 95% confidence interval [CI], 1.02-1.05; P=0.001). The mean postoperative KOVAL score in the deficient group was significantly higher than in the sufficient group (4.0±2.1 vs. 3.1±1.9 days; OR, 1.21; 95% CI, 1.11-1.32; P=0.001). Vitamin D deficiency was significantly associated with a higher risk of delirium and pneumonia in deficiency group.Conclusions: Preoperative vitamin D deficiency in hip fractures patients was associated with prolonged duration of hospital stay and decrease of postoperative ambulatory status, and may increase the risk of delirium and pneumonia. Therefore, it is necessary to evaluate the preoperative vitamin D level and recommend vitamin D supplementation in elderly patients with a high probability of hip fracture.

Effects of the Lysine Methyltransferase Inhibitor AZ505 on Bone Metabolism

Background: 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.Methods: 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.Results: 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.Conclusions: 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.

Effects of Different Types of Mechanical Loading on Trabecular Bone Microarchitecture in Rats

Mechanical loading is generally considered to have a positive impact on the skeleton; however, not all types of mechanical loading have the same beneficial effect. Many researchers have investigated which types of mechanical loading are more effective for improving bone mass and strength. Among the various mechanical loads, high-impact loading, such as jumping, appears to be more beneficial for bones than low-impact loadings such as walking, running, or swimming. Therefore, the different forms of mechanical loading exerted by running, swimming, and jumping exercises may have different effects on bone adaptations. However, little is known about the relationships between the types of mechanical loading and their effects on trabecular bone structure. The purpose of this article is to review the recent reports on the effects of treadmill running, jumping, and swimming on the trabecular bone microarchitecture in small animals. The effects of loading on trabecular bone architecture appear to differ among these different exercises, as several reports have shown that jumping increases the trabecular bone mass by thickening the trabeculae, whereas treadmill running and swimming add to the trabecular bone mass by increasing the trabecular number, rather than the thickness. This suggests that different types of exercise promote gains in trabecular bone mass through different architectural patterns in small animals.