Endocrinology and Metabolism

Review Article

Thyroid
Evaluation and Management of Bone Health in Patients with Thyroid Diseases: A Position Statement of the Korean Thyroid Association: A Ram Hong, Ho-Cheol Kang; Endocrinol Metab. 2023;38(2):175-189. Published online April 27, 2023; DOI: https://doi.org/10.3803/EnM.2023.1701

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Thyroid hormones play an important physiological role in maintaining adult bone structure and strength. Consequently, thyroid dysfunction is related to skeletal outcomes. Overt hyperthyroidism is an established cause of high bone turnover with accelerated bone loss, leading to osteoporosis and increased fracture risk. Hyperthyroidism induced by thyroid-stimulating hormone-suppressive therapy in patients with differentiated thyroid cancer is a cause of secondary osteoporosis. In contrast, there is a lack of evidence on the negative impact of hypothyroidism on bone health. Considering the clinical updates on the importance of bone health in thyroid dysfunction, the Task Force from the Clinical Practice Guidelines Development Committee of the Korean Thyroid Association recently developed a position statement on the evaluation and management of bone health of patients with thyroid diseases, particularly focused on endogenous hyperthyroidism and thyroid-stimulating hormone-suppressive therapy-associated hyperthyroidism in patients with differentiated thyroid cancer. Herein, we review the Korean Thyroid Association’s position statement on the evaluation and management of bone health associated with thyroid diseases.

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Review on the protective activity of osthole against the pathogenesis of osteoporosis
Jincai Chen, Xiaofei Liao, Juwen Gan
Frontiers in Pharmacology.2023;[Epub] CrossRef

Original Articles

Calcium & bone metabolism
Persistence with Denosumab in Male Osteoporosis Patients: A Real-World, Non-Interventional Multicenter Study: Chaiho Jeong, Jeongmin Lee, Jinyoung Kim, Jeonghoon Ha, Kwanhoon Jo, Yejee Lim, Mee Kyoung Kim, Hyuk-Sang Kwon, Tae-Seo Sohn, Ki-Ho Song, Moo Il Kang, Ki-Hyun Baek; Endocrinol Metab. 2023;38(2):260-268. Published online April 27, 2023; DOI: https://doi.org/10.3803/EnM.2023.1663

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Background
Persistence with denosumab in male patients has not been adequately investigated, although poor denosumab persistence is associated with a significant risk of rebound vertebral fractures.
Methods
We retrospectively evaluated 294 Korean male osteoporosis patients treated with denosumab at three medical centers and examined their persistence with four doses of denosumab injection over 24 months of treatment. Persistence was defined as the extent to which a patient adhered to denosumab treatment in terms of the prescribed interval and dose, with a permissible gap of 8 weeks. For patients who missed their scheduled treatment appointment(s) during the follow-up period (i.e., no-shows), Cox proportional regression analysis was conducted to explore the factors associated with poor adherence. Several factors were considered, such as age, prior anti-osteoporotic drug use, the treatment provider’s medical specialty, the proximity to the medical center, and financial burdens of treatment.
Results
Out of 294 male patients, 77 (26.2%) completed all four sequential rounds of the denosumab treatment. Out of 217 patients who did not complete the denosumab treatment, 138 (63.6%) missed the scheduled treatment(s). Missing treatment was significantly associated with age (odds ratio [OR], 1.03), prior bisphosphonate use (OR, 0.76), and prescription by non-endocrinologists (OR, 2.24). Denosumab was stopped in 44 (20.3%) patients due to medical errors, in 24 (11.1%) patients due to a T-score improvement over –2.5, and in five (2.3%) patients due to expected dental procedures.
Conclusion
Our study showed that only one-fourth of Korean male osteoporosis patients were fully adherent to 24 months of denosumab treatment.

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Denosumab

Reactions Weekly.2023; 1963(1): 206. CrossRef

Calcium & Bone Metabolism
Bone Mineral Density Screening Interval and Transition to Osteoporosis in Asian Women: Hyunju Park, Heera Yang, Jung Heo, Hye Won Jang, Jae Hoon Chung, Tae Hyuk Kim, Yong-Ki Min, Sun Wook Kim; Endocrinol Metab. 2022;37(3):506-512. Published online June 9, 2022; DOI: https://doi.org/10.3803/EnM.2022.1429

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Background
Bone mineral density (BMD) testing is indicated for women aged 65 years, but screening strategies for osteoporosis are controversial. Currently, there is no study focusing on the BMD testing interval in Asian populations. The current study aimed to evaluate the estimated time interval for screening osteoporosis.
Methods
We conducted a study of 6,385 subjects aged 50 years and older who underwent dual-energy X-ray absorptiometry screening more than twice at Samsung Medical Center as participants in a routine health checkup. Subjects were divided based on baseline T-score into mild osteopenia (T-score, <–1.0 to >–1.5), moderate osteopenia (T-score, ≤–1.5 to >–2.0), and severe osteopenia (T-score, ≤–2.0 to >–2.5). Information about personal medical and social history was collected by a structured questionnaire.
Results
The adjusted estimated BMD testing interval for 10% of the subjects to develop osteoporosis was 13.2 years in mild osteopenia, 5.0 years in moderate osteopenia, and 1.5 years in severe osteopenia.
Conclusion
Our study provides extended information about BMD screening intervals in Asian female population. Baseline T-score was important for predicting BMD screening interval, and repeat BMD testing within 5 years might not be necessary in mild osteopenia subjects.

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Effects of Bazedoxifene/Vitamin D Combination Therapy on Serum Vitamin D Levels and Bone Turnover Markers in Postmenopausal Women with Osteopenia: A Randomized Controlled Trial
Chaiho Jeong, Jeonghoon Ha, Jun-Il Yoo, Young-Kyun Lee, Jung Hee Kim, Yong-Chan Ha, Yong-Ki Min, Dong-Won Byun, Ki-Hyun Baek, Ho Yeon Chung
Journal of Bone Metabolism.2023; 30(2): 189. CrossRef

Calcium & Bone Metabolism
Real-World Safety and Effectiveness of Denosumab in Patients with Osteoporosis: A Prospective, Observational Study in South Korea: Yumie Rhee, Dong-Gune Chang, Jeonghoon Ha, Sooa Kim, Yusun Lee, Euna Jo, Jung-Min Koh; Endocrinol Metab. 2022;37(3):497-505. Published online June 3, 2022; DOI: https://doi.org/10.3803/EnM.2022.1427

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Background
The efficacy and safety of denosumab have been established in a phase 3, randomized, placebo-controlled trial in Korean postmenopausal women with osteoporosis. This postmarketing surveillance study was aimed to investigate the safety and effectiveness of denosumab in Korean real-world clinical practice.
Methods
Patients with osteoporosis who had received denosumab per the Korean approved indications in the postmarketing setting between September 2014 and September 2019 were enrolled. The primary endpoint was the incidence of adverse events (AEs) and adverse drug reactions (ADRs). The secondary endpoint was the percent change from baseline in bone mineral density (BMD) of the lumbar spine, total hip, and femoral neck.
Results
Of the 3,221 patients enrolled, 3,185 were included in the safety analysis set; 2,973 (93.3%) were female, and the mean± standard deviation (SD) age was 68.9±9.9 years. The mean±SD study period was 350.0±71.4 days. AEs, fatal AEs, and ADRs occurred in 19.3%, 0.8%, and 1.6%, respectively. The most frequent AEs, occurring in >0.5% of patients, were dizziness (0.7%), arthralgia (0.7%), back pain (0.6%), and myalgia (0.6%). Hypocalcemia occurred in 0.3% of patients. There were no cases of osteonecrosis of the jaw and atypical femoral fracture. Mean±SD percent change from baseline in BMD of the lumbar spine, total hip, and femoral neck was 7.3%±23.6%, 3.6%±31.4%, and 3.2%±10.7%, respectively.
Conclusion
The safety and effectiveness of denosumab in Korean patients with osteoporosis in this study were comparable with those in the Korean randomized controlled trial, with no new safety findings.

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Adverse Effects of Denosumab in Kidney Transplant Recipients: A 20-Year Retrospective Single-Center Observation Study in Central Taiwan
Tsung-Yin Tsai, Zi-Hong You, Shang-Feng Tsai, Ming-Ju Wu, Tung-Min Yu, Ya-Wen Chuang, Yung-Chieh Lin, Ya-Lian Deng, Chiann-Yi Hsu, Cheng-Hsu Chen
Transplantation Proceedings.2023; 55(4): 837. CrossRef
Persistence with Denosumab in Male Osteoporosis Patients: A Real-World, Non-Interventional Multicenter Study
Chaiho Jeong, Jeongmin Lee, Jinyoung Kim, Jeonghoon Ha, Kwanhoon Jo, Yejee Lim, Mee Kyoung Kim, Hyuk-Sang Kwon, Tae-Seo Sohn, Ki-Ho Song, Moo Il Kang, Ki-Hyun Baek
Endocrinology and Metabolism.2023; 38(2): 260. CrossRef
Denosumab

Reactions Weekly.2022; 1919(1): 221. CrossRef
Denosumab, an effective osteoporosis treatment option for men
Sung Hye Kong
The Korean Journal of Internal Medicine.2022; 37(5): 947. CrossRef

Hypothalamus and Pituitary Gland
Metabolic Impacts of Discontinuation and Resumption of Recombinant Human Growth Hormone Treatment during the Transition Period in Patients with Childhood-Onset Growth Hormone Deficiency: Yun Jeong Lee, Yunha Choi, Han-Wook Yoo, Young Ah Lee, Choong Ho Shin, Han Saem Choi, Ho-Seong Kim, Jae Hyun Kim, Jung Eun Moon, Cheol Woo Ko, Moon Bae Ahn, Byung-Kyu Suh, Jin-Ho Choi; Endocrinol Metab. 2022;37(2):359-368. Published online April 25, 2022; DOI: https://doi.org/10.3803/EnM.2021.1384

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Background
Discontinuing growth hormone (GH) treatment during the transition to adulthood has been associated with adverse health outcomes in patients with childhood-onset growth hormone deficiency (CO-GHD). This study investigated the metabolic changes associated with interrupting GH treatment in adolescents with CO-GHD during the transition period.
Methods
This study included 187 patients with CO-GHD who were confirmed to have adult GHD and were treated at six academic centers in Korea. Data on clinical parameters, including anthropometric measurements, metabolic profiles, and bone mineral density (BMD) at the end of childhood GH treatment, were collected at the time of re-evaluation for GHD and 1 year after treatment resumption.
Results
Most patients (n=182, 97.3%) had organic GHD. The median age at treatment discontinuation and re-evaluation was 15.6 and 18.7 years, respectively. The median duration of treatment interruption was 2.8 years. During treatment discontinuation, body mass index Z-scores and total cholesterol, low-density lipoprotein, and non-high-density lipoprotein (HDL) cholesterol levels increased, whereas fasting glucose levels decreased. One year after GH treatment resumption, fasting glucose levels, HDL cholesterol levels, and femoral neck BMD increased significantly. Longer GH interruption (>2 years, 60.4%) resulted in worse lipid profiles at re-evaluation. The duration of interruption was positively correlated with fasting glucose and non-HDL cholesterol levels after adjusting for covariates.
Conclusion
GH treatment interruption during the transition period resulted in worse metabolic parameters, and a longer interruption period was correlated with poorer outcomes. GH treatment should be resumed early in patients with CO-GHD during the transition period.

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Relationship between the Stimulated Peak Growth Hormone Level and Metabolic Parameters in Children with Growth Hormone Deficiency
Seong Yong Lee
The Ewha Medical Journal.2023;[Epub] CrossRef

Review Article

Calcium & Bone Metabolism
Discontinuing Denosumab: Can It Be Done Safely? A Review of the Literature: Wei Lin Tay, Donovan Tay; Endocrinol Metab. 2022;37(2):183-194. Published online April 14, 2022; DOI: https://doi.org/10.3803/EnM.2021.1369

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Denosumab, which has been approved for the treatment of osteoporosis since 2010, is a fully humanised monoclonal antibody against a cytokine, receptor activator of nuclear factor kappa B ligand (RANKL), involved in bone resorption. Continued use of denosumab results in a potent and sustained decrease in bone turnover, an increase in bone mineral density (BMD), and a reduction in vertebral and hip fractures. The anti-resorptive effects of denosumab are reversible upon cessation, and this reversal is accompanied by a transient marked increase in bone turnover that is associated with bone loss, and of concern, an increased risk of multiple vertebral fractures. In this review, we outline the effects of denosumab withdrawal on bone turnover markers, BMD, histomorphometry, and fracture risk. We provide an update on recent clinical trials that sought to answer how clinicians can transition away from denosumab safely with follow-on therapy to mitigate bone loss and summarise the recommendations of various international guidelines.

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Loss of lower extremity bone mineral density 1 year after denosumab is discontinued in persons with subacute spinal cord injury
Christopher M. Cirnigliaro, Michael F. La Fountaine, J. Scott Parrott, Steven C. Kirshblum, Susan J. Sauer, Sue A. Shapses, Isa A. McClure, William A. Bauman
Osteoporosis International.2023; 34(4): 741. CrossRef
Persistence with Denosumab in Male Osteoporosis Patients: A Real-World, Non-Interventional Multicenter Study
Chaiho Jeong, Jeongmin Lee, Jinyoung Kim, Jeonghoon Ha, Kwanhoon Jo, Yejee Lim, Mee Kyoung Kim, Hyuk-Sang Kwon, Tae-Seo Sohn, Ki-Ho Song, Moo Il Kang, Ki-Hyun Baek
Endocrinology and Metabolism.2023; 38(2): 260. CrossRef

Original Articles

Calcium & Bone Metabolism Big Data Articles (National Health Insurance Service Database)
10-Year Fracture Risk in Postmenopausal Women with Osteopenia and Osteoporosis in South Korea: Yeon-Hee Baek, Sun Wook Cho, Han Eol Jeong, Ju Hwan Kim, Yunji Hwang, Jeffrey L. Lange, Ju-Young Shin; Endocrinol Metab. 2021;36(6):1178-1188. Published online December 16, 2021; DOI: https://doi.org/10.3803/EnM.2021.1215

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Background
In South Korea, women aged 66 years are eligible for complimentary bone mineral density (BMD) screening via the National Screening Program for Transitional Ages. We aimed to evaluate the 10-year fracture risk in women receiving BMD screening between January 2008 and December 2015.
Methods
BMD was classified as normal (T-score ≥–1.0 standard deviation [SD]), osteopenia (T-score <–1.0 SD and >–2.5 SD), and osteoporosis (T score ≤–2.5 SD) from dual-energy X-ray absorptiometry. Follow-up continued from the screening date until a diagnosis for clinical fragility fracture (including sites of the vertebrae, hip, pelvis, clavicle, humerus, forearm, wrist, lower leg, and ankle), censored at the earliest date of trauma, death, or December 2017; fracture was ascertained using diagnostic codes from the National Health Insurance Service database. A multivariable Cox proportional hazard model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of fracture in women with osteopenia or osteoporosis relative to women with normal BMD.
Results
Among the 271,197 women screened, 44.0% had osteopenia and 35.2% had osteoporosis. The 10 year cumulative incidence of fragility fractures was 31.1%, 37.5%, and 44.3% in women with normal BMD, osteopenia, and osteoporosis, respectively. Fracture risk was higher in women with osteopenia (HR, 1.31; 95% CI, 1.28 to 1.34) and osteoporosis (HR, 1.68; 95% CI, 1.64 to 1.72) than in women with normal BMD.
Conclusion
Women with osteopenia and women with osteoporosis, identified by the national BMD screening program, demonstrated a substantially elevated risk of fracture.

Citations

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Big Data Research in the Field of Endocrine Diseases Using the Korean National Health Information Database
Sun Wook Cho, Jung Hee Kim, Han Seok Choi, Hwa Young Ahn, Mee Kyoung Kim, Eun Jung Rhee
Endocrinology and Metabolism.2023; 38(1): 10. CrossRef
Chronic airway disease as a major risk factor for fractures in osteopenic women: Nationwide cohort study
Sung Hye Kong, Ae Jeong Jo, Chan Mi Park, Kyun Ik Park, Ji Eun Yun, Jung Hee Kim
Frontiers in Endocrinology.2023;[Epub] CrossRef
Biomimetic Porous Magnesium Alloy Scaffolds Promote the Repair of Osteoporotic Bone Defects in Rats through Activating the Wnt/β-Catenin Signaling Pathway
Yuanchao Zhu, Gaozhi Jia, Yifei Yang, Jian Weng, Su Liu, Mengwei Zhang, Geng Zhang, Haotian Qin, Yixiao Chen, Qi Yang, Guangyin Yuan, Fei Yu, Hui Zeng
ACS Biomaterials Science & Engineering.2023; 9(6): 3435. CrossRef
A Meaningful Journey to Predict Fractures with Deep Learning
Jeonghoon Ha
Endocrinology and Metabolism.2022; 37(4): 617. CrossRef
The Efficacy of Selective Estrogen Receptor Modulators Monotherapies in Postmenopausal Women with Osteopenia
Kyung Wook Kim, Young Il Kim, Ki-Choul Kim
Journal of Bone Metabolism.2022; 29(3): 185. CrossRef
Correlation of Psoas Muscle Index with Fragility Vertebral Fracture: A Retrospective Cross-Sectional Study of Middle-Aged and Elderly Women
Yihui Zhang, Yilihamu Dilixiati, Wei Jiang, Xiufeng Cao, Yuanyuan Chen, Hui Guo, Christian-Heinz Anderwald
International Journal of Endocrinology.2022; 2022: 1. CrossRef

Calcium & Bone Metabolism
Changes in Serum Dickkopf-1, RANK Ligand, Osteoprotegerin, and Bone Mineral Density after Allogeneic Hematopoietic Stem Cell Transplantation Treatment: Eunhee Jang, Jeonghoon Ha, Ki-Hyun Baek, Moo Il Kang; Endocrinol Metab. 2021;36(6):1211-1218. Published online December 8, 2021; DOI: https://doi.org/10.3803/EnM.2021.1248

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Background
Dickkopf-1 (DKK1) regulates bone formation by inhibiting canonical Wnt/β-catenin pathway signaling, and indirectly enhances osteoclastic activity by altering the expression ratio of receptor activator of nuclear factor-κB ligand (RANKL) relative to osteoprotegerin (OPG). However, it is difficult to explain continued bone loss after allogeneic stem cell transplantation (allo-SCT) in terms of changes in only RANKL and OPG. Few studies have evaluated changes in DKK1 after allo-SCT.
Methods
We prospectively enrolled 36 patients with hematologic malignancies who were scheduled for allo-SCT treatment. Serum DKK1, OPG, and RANKL levels were measured before (baseline), and at 1, 4, 12, 24, and 48 weeks after allo-SCT treatment. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry before (baseline) and 24 and 48 weeks after allo-SCT treatment.
Results
After allo-SCT treatment, the DKK1 level decreased rapidly, returned to baseline during the first 4 weeks, and remained elevated for 48 weeks (P<0.0001 for changes observed over time). The serum RANKL/OPG ratio peaked at 4 weeks and then declined (P<0.001 for changes observed over time). BMD decreased relative to the baseline at all timepoints during the study period, and the lumbar spine in female patients had the largest decline (–11.3%±1.6% relative to the baseline at 48 weeks, P<0.05).
Conclusion
Serum DKK1 levels rapidly decreased at 1 week and then continued to increase for 48 weeks; bone mass decreased for 48 weeks following engraftment in patients treated with allo-SCT, suggesting that DKK1-mediated inhibition of osteoblast differentiation plays a role in bone loss in patients undergoing allo-SCT.

Citations

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Fracture risk and assessment in adults with cancer
Carrie Ye, William D. Leslie
Osteoporosis International.2023; 34(3): 449. CrossRef
Short-Term Impact of Hematopoietic Stem Cell Transplantation in Leukemia Patients on Bone Bio Markers, Electrolytes and Blood Profile
Rhythm Joshi, Zehva Khan, Aakriti Garg, Dinesh Bhurani, Nidhi B Agarwal, Ubada Aqeel, Mohd Ashif Khan
OBM Transplantation.2023; 07(02): 1. CrossRef

Bone Metabolism
Comparison of the Effects of Various Antidiabetic Medication on Bone Mineral Density in Patients with Type 2 Diabetes Mellitus: Jeonghoon Ha, Yejee Lim, Mee Kyoung Kim, Hyuk-Sang Kwon, Ki-Ho Song, Seung Hyun Ko, Moo Il Kang, Sung Dae Moon, Ki-Hyun Baek; Endocrinol Metab. 2021;36(4):895-903. Published online August 9, 2021; DOI: https://doi.org/10.3803/EnM.2021.1026

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Background
Prospective comparative studies on the effects of various antidiabetic agents on bone metabolism are limited. This study aimed to assess changes in bone mass and biochemical bone markers in postmenopausal patients with type 2 diabetes mellitus (T2DM).
Methods
This prospective, multicenter, open-label, comparative trial included 264 patients with T2DM. Patients who had received a metformin, or sulfonylurea/metformin combination (Group 1); a thiazolidinedione combination (Group 2); a dipeptidyl peptidase-4 inhibitor (gemigliptin) combination (Group 3); or an sodium-glucose cotransporter 2 inhibitor (empagliflozin) combination (Group 4) were prospectively treated for 12 months; bone mineral density (BMD) and bone turnover marker (BTM) changes were evaluated.
Results
The femoral neck BMD percentage changes were −0.79%±2.86% (Group 1), −2.50%±3.08% (Group 2), −1.05%±2.74% (Group 3), and −1.24%±2.91% (Group 4) (P<0.05). The total hip BMD percentage changes were −0.57%±1.79% (Group 1), −1.74%±1.48% (Group 2), −0.75%±1.87% (Group 3), and −1.27%±1.72% (Group 4) (P<0.05). Mean serum BTM (C-terminal type 1 collagen telopeptide and procollagen type 1 amino-terminal propeptide) levels measured during the study period did not change over time or differ between groups.
Conclusion
Significant bone loss in the femoral neck and total hip was associated with thiazolidinedione combination regimens. However, bone loss was not significantly associated with combination regimens including gemigliptin or empagliflozin. Caution should be exercised during treatment with antidiabetic medications that adversely affect the bone in patients with diabetes at a high risk of bone loss.

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Association of Bone Turnover Markers with Type 2 Diabetes Mellitus and Microvascular Complications: A Matched Case-Control Study
Yilin Hou, Xiaoyu Hou, Qian Nie, Qiuyang Xia, Rui Hu, Xiaoyue Yang, Guangyao Song, Luping Ren
Diabetes, Metabolic Syndrome and Obesity.2023; Volume 16: 1177. CrossRef
Complementary effects of dapagliflozin and lobeglitazone on metabolism in a diet-induced obese mouse model
Yun Kyung Lee, Tae Jung Oh, Ji In Lee, Bo Yoon Choi, Hyen Chung Cho, Hak Chul Jang, Sung Hee Choi
European Journal of Pharmacology.2023; 957: 175946. CrossRef

Clinical Study
Romosozumab in Postmenopausal Korean Women with Osteoporosis: A Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study: Ki-Hyun Baek, Yoon-Sok Chung, Jung-Min Koh, In Joo Kim, Kyoung Min Kim, Yong-Ki Min, Ki Deok Park, Rajani Dinavahi, Judy Maddox, Wenjing Yang, Sooa Kim, Sang Jin Lee, Hyungjin Cho, Sung-Kil Lim; Endocrinol Metab. 2021;36(1):60-69. Published online February 24, 2021; DOI: https://doi.org/10.3803/EnM.2020.848

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Background
This phase 3 study evaluated the efficacy and safety of 6-month treatment with romosozumab in Korean postmenopausal women with osteoporosis.
Methods
Sixty-seven postmenopausal women with osteoporosis (bone mineral density [BMD] T-scores ≤–2.5 at the lumbar spine, total hip, or femoral neck) were randomized (1:1) to receive monthly subcutaneous injections of romosozumab (210 mg; n=34) or placebo (n=33) for 6 months.
Results
At month 6, the difference in the least square (LS) mean percent change from baseline in lumbar spine BMD (primary efficacy endpoint) between the romosozumab (9.5%) and placebo (–0.1%) groups was significant (9.6%; 95% confidence interval, 7.6 to 11.5; P<0.001). The difference in the LS mean percent change from baseline was also significant for total hip and femoral neck BMD (secondary efficacy endpoints). After treatment with romosozumab, the percent change from baseline in procollagen type 1 N-terminal propeptide transiently increased at months 1 and 3, while that in C-terminal telopeptide of type 1 collagen showed a sustained decrease. No events of cancer, hypocalcemia, injection site reaction, positively adjudicated atypical femoral fracture or osteonecrosis of the jaw, or positively adjudicated serious cardiovascular adverse events were observed. At month 9, 17.6% and 2.9% of patients in the romosozumab group developed binding and neutralizing antibodies, respectively.
Conclusion
Treatment with romosozumab for 6 months was well tolerated and significantly increased lumbar spine, total hip, and femoral neck BMD compared with placebo in Korean postmenopausal women with osteoporosis (ClinicalTrials.gov identifier NCT02791516).

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Zepeng Chen, Ming Li, Shuzhen Li, Yuxi Li, Junyan Wu, Kaifeng Qiu, Xiaoxia Yu, Lin Huang, Guanghui Chen
Expert Opinion on Drug Safety.2023; 22(4): 339. CrossRef
Evaluation of the efficacy and safety of romosozumab (evenity) for the treatment of osteoporotic vertebral compression fracture in postmenopausal women: A systematic review and meta‐analysis of randomized controlled trials (CDM‐J)
Wenbo Huang, Masashi Nagao, Naohiro Yonemoto, Sen Guo, Takeshi Tanigawa, Yuji Nishizaki
Pharmacoepidemiology and Drug Safety.2023; 32(6): 671. CrossRef
Efficacy and Cardiovascular Safety of Romosozumab: A Meta-analysis and Systematic Review
Seo-Yong Choi, Jeong-Min Kim, Sang-Hyeon Oh, Seunghyun Cheon, Jee-Eun Chung
Korean Journal of Clinical Pharmacy.2023; 33(2): 128. CrossRef
Efficacy and safety of anti-sclerostin antibodies in the treatment of osteoporosis: A meta-analysis and systematic review
Frideriki Poutoglidou, Efthimios Samoladas, Nikolaos Raikos, Dimitrios Kouvelas
Journal of Clinical Densitometry.2022; 25(3): 401. CrossRef
Benefits of lumican on human bone health: clinical evidence using bone marrow aspirates
Yun Sun Lee, So Jeong Park, Jin Young Lee, Eunah Choi, Beom-Jun Kim
The Korean Journal of Internal Medicine.2022; 37(4): 821. CrossRef
What is the risk of cardiovascular events in osteoporotic patients treated with romosozumab?
I. R. Reid
Expert Opinion on Drug Safety.2022; 21(12): 1441. CrossRef
Proxied Therapeutic Inhibition on Wnt Signaling Antagonists and Risk of Cardiovascular Diseases: Multi-Omics Analyses
Yu Qian, Cheng-Da Yuan, Saber Khederzadeh, Ming-Yu Han, Hai-Xia Liu, Mo-Chang Qiu, Jian-Hua Gao, Wei-Lin Wang, Yun-Piao Hou, Guo-Bo Chen, Ke-Qi Liu, Lin Xu, David Karasik, Shu-Yang Xie, Hou-Feng Zheng
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Multi-Omics Analyses Identify Pleiotropy and Causality Between Circulating Sclerostin and Atrial Fibrillation
Yu Qian, Peng-Lin Guan, Saber Khederzadeh, Ke-Qi Liu, Cheng-Da Yuan, Ming-Yu Han, Hai-Xia Liu, Mo-Chang Qiu, Jian-Hua Gao, Wei-Lin Wang, Yun-Piao Hou, Guo-Bo Chen, Lin Xu, David Karasik, Shu-Yang Xie, sheng zhifeng, Hou-Feng Zheng
SSRN Electronic Journal .2022;[Epub] CrossRef

Clinical Study
Low Predictive Value of FRAX Adjusted by Trabecular Bone Score for Osteoporotic Fractures in Korean Women: A Community-Based Cohort Study: Hana Kim, Jung Hee Kim, Min Joo Kim, A Ram Hong, HyungJin Choi, EuJeong Ku, Ji Hyun Lee, Chan Soo Shin, Nam H. Cho; Endocrinol Metab. 2020;35(2):359-366. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.359

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Background
The value of the Fracture Risk Assessment Tool (FRAX) and the trabecular bone score (TBS) for assessing osteoporotic fracture risk has not been fully elucidated in Koreans. We conducted this study to clarify the predictive value of FRAX adjusted by TBS for osteoporotic fractures in Korean women.
Methods
After screening 7,192 eligible subjects from the Ansung cohort, 1,165 women aged 45 to 76 years with available bone mineral density (BMD) and TBS data were enrolled in this study. We assessed their clinical risk factors for osteoporotic fractures and evaluated the predictive value of FRAX with or without BMD and TBS.
Results
During the mean follow-up period of 7.5 years, 99 (8.5%) women suffered major osteoporotic fractures (MOFs) and 28 (2.4%) experienced hip fractures. FRAX without BMD, BMD-adjusted FRAX, and TBS-adjusted FRAX were significantly associated with the risk of MOFs (hazard ratio [HR] per percent increase, 1.08; 95% confidence interval [CI], 1.03 to 1.14; HR, 1.09; 95% CI, 1.03 to 1.15; and HR, 1.07; 95% CI, 1.02 to 1.13, respectively). However, BMD-adjusted FRAX and TBS-adjusted FRAX did not predict MOFs better than FRAX without BMD based on the Harrell’s C statistic. FRAX probabilities showed limited value for predicting hip fractures. The cut-off values of FRAX without BMD, FRAX with BMD, and FRAX with BMD adjusted by TBS for predicting MOFs were 7.2%, 5.0%, and 6.7%, respectively.
Conclusion
FRAX with BMD and TBS adjustment did not show better predictive value for osteoporotic fractures in this study than FRAX without adjustment. Moreover, the cut-off values of FRAX probabilities for treatment might be lower in Korean women than in other countries.

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Review Articles

Bone Metabolism
Potential Biomarkers to Improve the Prediction of Osteoporotic Fractures: Beom-Jun Kim, Seung Hun Lee, Jung-Min Koh; Endocrinol Metab. 2020;35(1):55-63. Published online March 19, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.1.55

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Osteoporotic fracture (OF) is associated with high disability and morbidity rates. The burden of OF may be reduced by early identification of subjects who are vulnerable to fracture. Although the current fracture risk assessment model includes clinical risk factors (CRFs) and bone mineral density (BMD), its overall ability to identify individuals at high risk for fracture remains suboptimal. Efforts have therefore been made to identify potential biomarkers that can predict the risk of OF, independent of or combined with CRFs and BMD. This review highlights the emerging biomarkers of bone metabolism, including sphongosine-1-phosphate, leucine-rich repeat-containing 17, macrophage migration inhibitory factor, sclerostin, receptor activator of nuclear factor-κB ligand, and periostin, and the importance of biomarker risk score, generated by combining these markers, in enhancing the accuracy of fracture prediction.

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Bone Metabolism
Effects of Resistance Exercise on Bone Health: A Ram Hong, Sang Wan Kim; Endocrinol Metab. 2018;33(4):435-444. Published online November 30, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.4.435

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90 Citations

Abstract PDF PubReader ePub Crossref - TDM

The prevalence of chronic diseases including osteoporosis and sarcopenia increases as the population ages. Osteoporosis and sarcopenia are commonly associated with genetics, mechanical factors, and hormonal factors and primarily associated with aging. Many older populations, particularly those with frailty, are likely to have concurrent osteoporosis and sarcopenia, further increasing their risk of disease-related complications. Because bones and muscles are closely interconnected by anatomy, metabolic profile, and chemical components, a diagnosis should be considered for both sarcopenia and osteoporosis, which may be treated with optimal therapeutic interventions eliciting pleiotropic effects on both bones and muscles. Exercise training has been recommended as a promising therapeutic strategy to encounter the loss of bone and muscle mass due to osteosarcopenia. To stimulate the osteogenic effects for bone mass accretion, bone tissues must be exposed to mechanical load exceeding those experienced during daily living activities. Of the several exercise training programs, resistance exercise (RE) is known to be highly beneficial for the preservation of bone and muscle mass. This review summarizes the mechanisms of RE for the preservation of bone and muscle mass and supports the clinical evidences for the use of RE as a therapeutic option in osteosarcopenia.

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Original Articles

Bone Metabolism
Association between Serum Fibroblast Growth Factor 21 Levels and Bone Mineral Density in Postmenopausal Women: Hoon Sung Choi, Hyang Ah Lee, Sang-Wook Kim, Eun-Hee Cho; Endocrinol Metab. 2018;33(2):273-277. Published online June 21, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.2.273

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Abstract PDF PubReader ePub Crossref - TDM

Background

Despite the beneficial effect of fibroblast growth factor 21 (FGF21) on metabolic disease, there are concerns about adverse effects on bone metabolism, supported by animal studies. However, a recent human study showed the positive association between serum FGF21 level and bone mineral density (BMD) in healthy premenopausal women. We undertook this study to examine the association between FGF21 level and BMD in healthy postmenopausal Korean women who are susceptible to osteoporosis.

Methods

We used data of 115 participants from a cohort of healthy postmenopausal women (>50 years old) to examine the association between serum FGF21 level and BMD. The clinical characteristics were obtained from the participants, and blood testing and serum FGF21 testing were undertaken. BMD of the lumbar spine, femoral neck and total hip area, and bone markers were used in the analyses.

Results

The mean age of the participants was 60.2±7.2 years. Serum FGF21 levels showed negative correlation with BMD and T-scores in all three areas, but there were no statistically significant differences. Multivariate analyses with adjustment for age and body mass index also did not show significant association between serum FGF21 level and BMD. In addition, serum FGF21 level also showed no correlation with osteocalcin and C-telopeptide levels.

Conclusion

In our study, serum FGF21 level showed no significant correlation with BMD and T-scores.

Citations

Citations to this article as recorded by

Fibroblast growth factor 21 and bone homeostasis
Yan Tang, Mei Zhang
Biomedical Journal.2023; 46(4): 100548. CrossRef
FGF21 negatively affects long-term female fertility in mice
Beat Moeckli, Thuy-Vy Pham, Florence Slits, Samuel Latrille, Andrea Peloso, Vaihere Delaune, Graziano Oldani, Stéphanie Lacotte, Christian Toso
Heliyon.2022; 8(11): e11490. CrossRef
Potential role of fibroblast growth factor 21 in the deterioration of bone quality in impaired glucose tolerance
D. T. W. Lui, C. H. Lee, V. W. K. Chau, C. H. Y. Fong, K. M. Y. Yeung, J. K. Y. Lam, A. C. H. Lee, W. S. Chow, K. C. B. Tan, Y. C. Woo, K. S. L. Lam
Journal of Endocrinological Investigation.2021; 44(3): 523. CrossRef
Skeletal Muscle and Bone – Emerging Targets of Fibroblast Growth Factor-21
Hui Sun, Matthew Sherrier, Hongshuai Li
Frontiers in Physiology.2021;[Epub] CrossRef
Age‐related bone loss is associated with FGF21 but not IGFBP1 in healthy adults
Shuen Yee Lee, Kai Deng Fam, Kar Ling Chia, Margaret M. C. Yap, Jorming Goh, Kwee Poo Yeo, Eric P. H. Yap, Sanjay H. Chotirmall, Chin Leong Lim
Experimental Physiology.2020; 105(4): 622. CrossRef
Chronic Kidney Disease Is Associated with Increased Plasma Levels of Fibroblast Growth Factors 19 and 21
Małgorzata Marchelek-Myśliwiec, Violetta Dziedziejko, Monika Nowosiad-Magda, Katarzyna Dołęgowska, Barbara Dołęgowska, Andrzej Pawlik, Krzysztof Safranow, Magda Wiśniewska, Joanna Stępniewska, Maciej Domański, Kazimierz Ciechanowski
Kidney and Blood Pressure Research.2019; 44(5): 1207. CrossRef

Bone Metabolism
Association between Bone Mineral Density and Albuminuria: Cross-Sectional Analysis of Data from the 2011 Korea National Health and Nutrition Examination Survey V-2: Tae Yang Yu, Ha-Young Kim, Jeong Mi Lee, Dae Ho Lee, Chung Gu Cho; Endocrinol Metab. 2018;33(2):211-218. Published online May 4, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.2.211

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42 Download
4 Citations

Abstract PDF PubReader ePub Crossref - TDM

Background

Albuminuria is known to be independently associated with progression of renal and cardiovascular disease. However, little is known regarding the exact relationship between albuminuria and bone mineral density (BMD). The aim of this population-based study conducted in Korea was to identify the association between albuminuria and BMD.

Methods

We performed a cross-sectional analysis of data from the Korea National Health and Nutrition Examination Survey (KNHANES V-2) 2011. BMD was measured for total hip (TH), femur neck (FN), and lumbar spine (LS). Analysis of covariance was used to compare BMD levels between the groups at the TH, FN, and LS sites, after adjusting for age. Separate analyses were performed according to sex; women were divided into two groups according to menopausal status and each group was subdivided into three according to urine albumin-to-creatinine ratio (level 1, <30 mg/g; level 2, 30 to 299 mg/g; level 3, ≥300 mg/g).

Results

Data on a total of 1,831 adults (857 men and 974 women) were analyzed. In postmenopausal women, after adjusting for age, BMD of TH tended to decrease as levels of albuminuria increased (0.767±0.117, 0.757±0.129, 0.752±0.118, respectively; P=0.040). However, there was no significant difference in BMD according to albuminuria level in premenopausal women and men.

Conclusion

Level of albuminuria was closely related with BMD of TH in postmenopausal women, after adjusting for age, but there was no significant relationship between albuminuria and BMD in premenopausal women and men.

Citations

Citations to this article as recorded by

Association between urinary albumin creatinine ratio and cardiovascular disease
Yoo Jin Kim, Sang Won Hwang, Taesic Lee, Jun Young Lee, Young Uh, Gulali Aktas
PLOS ONE.2023; 18(3): e0283083. CrossRef
Association between urine albumin to creatinine ratio and bone mineral density: a cross-sectional study
Kemal Sherefa Oumer, Yawen Liu, Tesfaye Getachew Charkos, Shuman Yang
Irish Journal of Medical Science (1971 -).2022; 191(1): 427. CrossRef
Association between perfluoroalkyl substances concentration and bone mineral density in the US adolescents aged 12-19 years in NHANES 2005-2010
Xianmei Xiong, Baihang Chen, Zhongqing Wang, Liqiong Ma, Shijie Li, Yijia Gao
Frontiers in Endocrinology.2022;[Epub] CrossRef
Mood and Metabolic Health Status of Elderly Osteoporotic Patients in Korea: A Cross-Sectional Study of a Nationally Representative Sample
Hyen Chul Jo, Gu-Hee Jung, Seong-Ho Ok, Ji Eun Park, Jong Chul Baek
Healthcare.2021; 9(1): 77. CrossRef

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