Endocrinology and Metabolism

Original Article

End-to-End Semi-Supervised Opportunistic Osteoporosis Screening Using Computed Tomography: Jieun Oh, Boah Kim, Gyutaek Oh, Yul Hwangbo, Jong Chul Ye; Received October 20, 2023 Accepted March 5, 2024 Published online May 9, 2024; DOI: https://doi.org/10.3803/EnM.2023.1860 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Osteoporosis is the most common metabolic bone disease and can cause fragility fractures. Despite this, screening utilization rates for osteoporosis remain low among populations at risk. Automated bone mineral density (BMD) estimation using computed tomography (CT) can help bridge this gap and serve as an alternative screening method to dual-energy X-ray absorptiometry (DXA).
Methods
The feasibility of an opportunistic and population agnostic screening method for osteoporosis using abdominal CT scans without bone densitometry phantom-based calibration was investigated in this retrospective study. A total of 268 abdominal CT-DXA pairs and 99 abdominal CT studies without DXA scores were obtained from an oncology specialty clinic in the Republic of Korea. The center axial CT slices from the L1, L2, L3, and L4 lumbar vertebrae were annotated with the CT slice level and spine segmentation labels for each subject. Deep learning models were trained to localize the center axial slice from the CT scan of the torso, segment the vertebral bone, and estimate BMD for the top four lumbar vertebrae.
Results
Automated vertebra-level DXA measurements showed a mean absolute error (MAE) of 0.079, Pearson’s r of 0.852 (P<0.001), and R² of 0.714. Subject-level predictions on the held-out test set had a MAE of 0.066, Pearson’s r of 0.907 (P<0.001), and R² of 0.781.
Conclusion
CT scans collected during routine examinations without bone densitometry calibration can be used to generate DXA BMD predictions.

Review Article

Calcium & bone metabolism
Bone Loss after Solid Organ Transplantation: A Review of Organ-Specific Considerations: Kyoung Jin Kim, Jeonghoon Ha, Sang Wan Kim, Jung-Eun Kim, Sihoon Lee, Han Seok Choi, Namki Hong, Sung Hye Kong, Seong Hee Ahn, So Young Park, Ki-Hyun Baek, on Behalf of Metabolic Bone Disease Study Group of Korean Endocrine Society; Endocrinol Metab. 2024;39(2):267-282. Published online April 25, 2024; DOI: https://doi.org/10.3803/EnM.2024.1939

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Abstract PDF PubReader ePub: This review article investigates solid organ transplantation-induced osteoporosis, a critical yet often overlooked issue, emphasizing its significance in post-transplant care. The initial sections provide a comprehensive understanding of the prevalence and multifactorial pathogenesis of transplantation osteoporosis, including factors such as deteriorating post-transplantation health, hormonal changes, and the impact of immunosuppressive medications. Furthermore, the review is dedicated to organ-specific considerations in transplantation osteoporosis, with separate analyses for kidney, liver, heart, and lung transplantations. Each section elucidates the unique challenges and management strategies pertinent to transplantation osteoporosis in relation to each organ type, highlighting the necessity of an organ-specific approach to fully understand the diverse manifestations and implications of transplantation osteoporosis. This review underscores the importance of this topic in transplant medicine, aiming to enhance awareness and knowledge among clinicians and researchers. By comprehensively examining transplantation osteoporosis, this study contributes to the development of improved management and care strategies, ultimately leading to improved patient outcomes in this vulnerable group. This detailed review serves as an essential resource for those involved in the complex multidisciplinary care of transplant recipients.

Original Articles

Estrogen Replacement Therapy Continuously Combined with Progesterone; Effect on Bone Mineral Density and Lipid Metabolism.: Keun Yong Park; J Korean Endocr Soc. 1995;10(4):411-417. Published online November 7, 2019

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Abstract PDF: A study in 51 healthy postmenopausal women was performed to assess the effect of estrogen replacement therapy continuously combined with progesterone for 6 months on bone mineral density and lipid metabolism.Seventeen hysterectomized women were treated with conjugated estrogen(0.625mg/D), 33 nonhysterectomized women with conjugated estrogen(0.625mg/D) and medroxyprogesterone(2.5mg/D), and 1500mg/day calcium supplementation was given to all patients.After 6 month-treatment, serum total cholesterol and LDL-cholesterol levels were reduced significantly (p<0.01) between the two groups. But lumber BMD and other lipid profiles were not changed significantly between the two groups. Our data suggest that continuously applied progesterone in combined hormone replacement therapy dose not annihilate the beneficial effects on bone mineral density and lipid metabolism induced by estrogen.

Study on Restriction Fragment Length Polymorphisms of Vitamin - D Receptor Gene in relation to Bone Mineral Density and Bone Markers in Pre - and Postmenopausal Korean Women.: Myung Hee Yoo, Dong Won Byun, Kyo Il Suh, Guk Bae Kim, Sang Woo Kim, Ihn Gul Moon, In Kwon Han; J Korean Endocr Soc. 1994;10(3):249-261. Published online November 6, 2019

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Abstract PDF: Osteoporosis is now a major health problem because of the increasing elderly population and related osteoporosis fractures. Recently, it has been suggested that lower bone mass with/and high bone turnover rate is considered to be important in the developing of osteoporosis, and so there has been many efforts to identify the risk factors which is considered to cause lower bone mass and high bone turnover.Osteocalcin, the most abundant noncollagenous protein in bone, is a marker of bone turnover and its synthesis is induced by calcitriol(the active form of vitamine-D) through the vitamine-D receptor(VDR) and a specific vitamine D-responsive element in the osteocalcin gene promoter. Serum concentrations of osteocalcin are under the strong genetic influences and may reflect allelic variation in VDR gene. Therefore, the present study were designed to find the relationships among the polymorphisms of Vitamine-D receptor gene, bone mineral density and bone markers. We analysed the restriction fragment length polymorphisms of VDR gene with Bsm I endonuclease enzyme in relation to bone mineral density by using DEXA(dual energy X-ray absorptiometry, QDR-2000) and bone markers, especially serum osteocalcin concentrations in 356 pre- and postmenopausal Korean women.The frequence of RFLPs of VDR gene is 3.3% in BB type, 10.1% in Bb type, 86.6% in bb type. The concentrations of osteocalcin, alkaline phosphatase, procollagen-C and urinary deoxypyridinoline/creatinine were found to be higher in postmenopausal than premenopausal women and the levels of BMD were lower in postmenopausal than premenopausal women. The BB type, which is known to have a strong genetic determinant, is less frequently encountered in Korean women and does not correlate with levels of bone markers and bone mineral density. Even though the number of women with BB type is small, we noted the mean serum level of each bone marker was greater in postmenopausal women with BB type than in premenopausal women with the same genotype.In conclusion, this may suggest a partial agreement of our data with that of Australlian group and that we have to try to find out another genotype specifically related with lower bone density in Korean women.

Changes in Bone Mineral Density in Patients with Sheehan's Syndrome.: Jae Myung Yoo, Sang Jin Kim, Kyung Mook Choi, Sei Hyun Baik, Dong Seop Choi, Eun Jong Lee, Yong Hyun Kim; J Korean Endocr Soc. 1994;9(1):10-17. Published online November 6, 2019

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Abstract PDF: Osteoporosis is a common clinical problem with high risk of fractures in old age, especially postmenopausal women.Secondary causes of osteoporosis can be identified in 20% of women and 40% of men with vertebral fractures. One of the causes of secondary osteoporosis is endocrine disease such as hypogonadism, ovarian agenesis, hyperadrenocorticism, hyperthyroidism, hyperparathyroidism and diabetes mellitus. Patients with Sheehan's syndrome have deficiency of multiple hormones which may cause bone loss.To determine changes in the bone mineral density in women with Sheehan's syndrome and to compare clinical and biochemical characteristics between the patients with osteoporosis and the patients without osteoporosis, we measured the bone mineral density(BMD) of the lumber spine and midradius by dual energy X-ray absortiometry(DEXA) and the serum levels of estrogen and osteocalcin in 11 patients of Sheehan's syndrome.The results were as follows;1) The BMDs of the lumbar spine were significantly decreased in patients with Sheehan's syndrome when compared with those of age-matched control.2) The prevalence of osteoporosis in patients with Sheehan's syndromes was 55%. Between the patients with osteoporosis and the patients without osteoporosis, there were no difference in the onset age of amenorrhea, the duration of amenorrhea, and the serum levels of osteocalcin and alkaline phosphatase.3) Serum estradiol levels were decreased uniformly in the patients with Sheehan's syndrome except three patients with estrogen replacement, but the concentration of estradiol was not correlated with the degree of the decrease in bone mass.In conclusion, the patients with Sheehan's syndrome have an increased prevalence of osteoporosis. But the effect of each anterior pituitary hormone deficiency on bone loss should be clarified in the futher prospective study.

Clinical Study
High Levels of Serum DPP-4 Activity Are Associated with Low Bone Mineral Density in Obese Postmenopausal Women: Sang-Wook Kim, Eun-Hee Cho; Endocrinol Metab. 2016;31(1):93-99. Published online March 16, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.1.93

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Abstract PDF PubReader

Background

Dipeptidyl peptidase 4/CD26 (DPP-4) is a widely expressed cell surface serine protease. DPP-4 inhibitors, one of common anti-diabetic agents play a protective role in bone metabolism in recent studies. A soluble form of DPP-4 is found in serum, and exhibits DPP-4 enzymatic activity. However, the physiological role of serum or soluble DPP-4 and its relationship with DPP-4 enzymatic function remain poorly understood. The aims of current study were to determine the association between serum DPP-4 activity and bone mineral density (BMD) in postmenopausal women.

Methods

We recruited data and serum samples from 124 consecutive healthy postmenopausal women aged >50 years. We divided study subjects into obese (body mass index [BMI] ≥25 kg/m²) and non-obese (BMI <25 kg/m²) postmenopausal women and examined the correlation between serum DPP-4 activity and clinical variables in each groups.

Results

A total of 124 postmenopausal women was enrolled, with a mean age of 59.9±7.1 years. The mean BMI of the study patients was 24.4±2.8 kg/m². Regarding bone turnover markers, serum DPP-4 activity was positively correlated with serum calcium concentrations, intact parathyroid hormone, and serum C-telopeptide levels in all of the study subjects. However, there was no association between serum DPP-4 activity and BMD in the spine or femoral neck in all of the study subjects. Serum DPP-4 activity was negatively correlated (R=−0.288, P=0.038) with BMD of the spine in obese postmenopausal women.

Conclusion

This study demonstrated for the first time that serum soluble DPP-4 activity was negatively correlated with BMD in obese postmenopausal women.

Citations

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N. V. Timkina, A. V. Simanenkova, T. L. Karonova, T. D. Vlasov, N. Yu. Semenova, А. A. Bairamov, V. A. Timofeeva, A. A. Shimshilashvili, E. V. Shlyakhto
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Osteoporosis International.2017; 28(5): 1631. CrossRef
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Thomas H. Ambrosi, Antonio Scialdone, Antonia Graja, Sabrina Gohlke, Anne-Marie Jank, Carla Bocian, Lena Woelk, Hua Fan, Darren W. Logan, Annette Schürmann, Luis R. Saraiva, Tim J. Schulz
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Dipeptidyl Peptidase-4 and Adolescent Idiopathic Scoliosis: Expression in Osteoblasts
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Association of Coronary Artery Disease and Osteoporotic Vertebral Fracture in Korean Men and Women.: Sun Ok Song, Kyung Won Park, Seung Hoon Yoo, Won Jun Koh, Byung Soo Kang, Tae Ho Kim, Hyeong Jin Kim, Yun Hyeong Cho, Deok Kyu Cho, Se Hwa Kim; Endocrinol Metab. 2012;27(1):39-44. Published online March 1, 2012; DOI: https://doi.org/10.3803/EnM.2012.27.1.39

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Abstract PDF

BACKGROUND
The association of osteoporotic vertebral fracture or osteoporosis with coronary artery disease (CAD) was investigated in Korean men and women. METHODS: Four hundred consecutive postmenopausal women and men aged 50 years and older, undergoing coronary angiography, were enrolled for the evaluation of established or suspected coronary artery disease. CAD was diagnosed if there was narrowing of > 50% diameter in one or more major coronary artery. Morphometric vertebral fracture was assessed using lateral thoracic and lumbar spine radiographs. Bone mineral density was performed using dual-energy x-ray absorptiometry. RESULTS: Of the 400 subjects in the study (mean age of 61.9 +/- 11.6 years), 256 patients had CAD. Vertebral fracture was observed in 94 (23.5%) patients. There was no difference in vertebral fracture according to the presence or absence of CAD. In logistic regression analysis, vertebral fracture was not significantly associated with CAD after adjustment for multiple risk factors. Although women had lower BMD at any given site than men, BMD was not associated with the presence or absence of CAD among 191 patients. CONCLUSION: Our study demonstrated that osteoporotic vertebral fracture or osteoporosis was not associated with coronary artery disease in Korean men and women.

Citations

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Fundamental and practical aspects of coronary artery calcification
O. L. Barbarash, V. V. Kashtalap, I. A. Shibanova, A. N. Kokov
Russian Journal of Cardiology.2020; 25: 4005. CrossRef
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I. A. Skripnikova, M. A. Kolchina, O. V. Kosmatova, M. A. Myagkova, V. E. Novikov, O. Yu. Isaykina, O. M. Drapkina
Rational Pharmacotherapy in Cardiology.2020; 16(6): 868. CrossRef
Association factor analysis between osteoporosis with cerebral artery disease
Eun-Sun Jin, Je Hoon Jeong, Bora Lee, Soo Bin Im
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VASCULAR CALCIFICATION, ATHEROSCLEROSIS AND BONE LOSS (OSTEOPOROSIS): NEW PATHOPHYSIOLOGICAL MECHANISMS AND FUTURE PERSPECTIVES FOR PHARMACOLOGICAL THERAPY
A. Dolzhenko, T. Richter, S. Sagalovsky
Almanac of Clinical Medicine.2016; 44(4): 513. CrossRef
Aortic Calcification and Bone Metabolism: The Relationship between Aortic Calcification, BMD, Vertebral Fracture, 25-Hydroxyvitamin D, and Osteocalcin
Kwang Joon Kim, Kyoung Min Kim, Kyeong Hye Park, Han Seok Choi, Yumie Rhee, Yong Ho Lee, Bong Soo Cha, Myong Jin Kim, Sun Min Oh, J. Keenan Brown, Sung Kil Lim
Calcified Tissue International.2012; 91(6): 370. CrossRef

Case Reports

A Case of Primary Hyperparathyroidism with Rapid Regression of a Brown Tumor after Parathyroidectomy.: Ji Young Mok, Ha Yeon Kim, Hsing Chien Ter, Sang Ock Kim, Dong Kyun Kim, Ji Sun Han, So Young Park, Sa Rah Lee, Mi Kyoung Park, Duk Kyu Kim; J Korean Endocr Soc. 2010;25(1):50-55. Published online March 1, 2010; DOI: https://doi.org/10.3803/jkes.2010.25.1.50

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Abstract PDF: Primary hyperparathyroidism is mainly caused by parathyroid adenoma (85%) and is characterized by hypercalcemia, osteoporosis, renal stones, and gastrointestinal and neurological disorders. Because of improvements in blood analysis over the last two decades, primary hyperparathyroidism is typically diagnosed early and asymptomatically. A rare clinical manifestations of primary hyperparathyroidism, brown tumors (osteitis fibrosa cystica), are osteolytic lesions resulting from long-term hyperparathyroidism. Radiologically, it is difficult to distinguish a brown tumor from plasmacytoma, multiple myeloma, or bone metastasis. We report a case of a 44-year-old man with primary hyperparathyroidism that caused a large brown tumor (11 x 5 x 8 cm) that mimicked plasmacytoma or cancer metastasis on pelvic magnetic resonance imaging. After a bone biopsy report that was highly suggestive of a brown tumor, serum calcium and intact parathyroid hormone levels were determined. The lesion was ultimately diagnosed as a brown tumor and a parathyroidectomy was performed. After 1 year, the lesion has nearly regressed by follow up of the anteroposterior view of the pelvis and bone mineral density has improved. The present case highlights the importance of considering brown tumors in the evaluation of patients presenting with hypercalcemia and osteolytic lesions without definite primary neoplasm.

A Case of Type I Osteogenesis Imperfecta Differentially Diagnosed as a Cause of a Spinal Compression Fracture.: Sang Youl Rhee, Soo Young Moon, Suk Chon, In Kyung Jeong, Seungjoon Oh, Kyu Jeung Ahn, Ho Yeon Chung, Jeong Taek Woo, Sung Woon Kim, Young Seol Kim, Jin Woo Kim; J Korean Endocr Soc. 2007;22(6):446-452. Published online December 1, 2007; DOI: https://doi.org/10.3803/jkes.2007.22.6.446

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Abstract PDF: Osteogenesis imperfecta (OI) is a genetic disease that is caused by a synthetic anomaly of type I collagen. It is characterized by such features as low bone density, multiple fractures, bone deformities and chronic bone pain. According to the hereditary pattern and degree of phenotypical expression, it also has various extraskeletal manifestations such as blue sclera, hearing deformities and dentinogenesis imperfecta. Recently, an expanded seven subgroup classification of OI has been suggested by means of its clinical severity and mutational characteristics. However, most of the OI cases reported in Korea have been classified as type II or III that can be diagnosed easily and present with severe clinical manifestations. Only rare type I OI cases have been currently reported in Korea. Herein, we report a case of type I OI that was differentially diagnosed as a cause of a spinal compression fracture.

Original Articles

The Relationship between Lumbar Spine Bone Mineral Density and Cardiovascular Risk Factors in Korean Female Adults.: Young Yul Koh, Eun Jung Rhee, Se Yeon Kim, Chan Hi Jung, Cheol Young Park, Won Young Lee, Ki Won Oh, Sung Woo Park, Sun Woo Kim; J Korean Endocr Soc. 2006;21(6):497-505. Published online December 1, 2006; DOI: https://doi.org/10.3803/jkes.2006.21.6.497

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Abstract PDF

BACKGROUND
Recent studies suggest a possible pathogenic linkage between the osteoporosis and atherosclerosis. We investigated the relationship between cardiovascular risk factors, including high sensitivity C-reactive protein (hs-CRP), insulin resistance, lipid profiles and bone metabolism in Korean females. METHODS: Anthropometric measurements were performed on 437 women (mean age 52 yrs), and cardiovascular risk factors, including fasting blood glucose, fasting blood insulin, lipid profiles and hs-CRP, measured. An atherogenic index was calculated using the serum total cholesterol level divided by the high-density lipoprotein cholesterol (HDL-C) level. The lumbar spine bone mineral density (BMD) was measured using dual X-ray absorptiometry. RESULTS: From bivariate analyses, the lumbar spine BMD showed negative correlations with age, systolic and diastolic blood pressures, serum total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglyceride levels and atherogenic index, and a positive correlation with the HDL-C level. After adjustment for age and BMI, the atherogenic index and HDL-C showed consistent correlation with the lumbar spine BMD. The log-transformed hs-CRP showed no correlation with the lumbar spine BMD. In premenopausal women, age, BMI and atherogenic index showed significant associations with the lumbar spine BMD and the atherogenic index showed consistently significant correlation, even after adjustment for age and BMI. In postmenopausal women, only age and BMI showed significant correlations with the lumbar spine BMD. From multiple linear regression analyses of all the study subjects, age, BMI, atherogenic index and the presence of menopause were found to be determinants of the lumbar spine BMD (R2 = 0.422, p < 0.05), which was consistently significant in analysis performed on premenopausal women (R2 = 0.157, P < 0.05). In postmenopausal women, age and BMI were found to be the determinants of the lumbar spine BMD (R2 = 0.257, P < 0.05). CONCLUSIONS: The lumbar spine BMD was negatively correlated with the atherogenic index in all and in premenopausal women. The menopause seems to play an important role in the relationship of cardiovascular risk factors with BMD in Korean females.

Citations

Citations to this article as recorded by

Comparison of Relationship between Biochemical Indices and Bone Mineral Densityof Pre- and Post- Menopausal Women in Gyeongnam Area
Mi-Young Park, Sung-Hee Kim
Journal of the East Asian Society of Dietary Life.2017; 27(4): 408. CrossRef
Relationship between Plasma Lipids and Osteoporosis in Korean Postmenopausal Women
Kyung Shik Lee, Jae Hwan Cho, Chang Hae Park, Bo Seung Kim, Kyung Hwan Cho, Seung Hwan Lee, Byung Jun Ko, Do Hoon Kim
Journal of the Korean Geriatrics Society.2011; 15(2): 99. CrossRef
Relationships among Obesity, Bone Mineral Density, and Cardiovascular Risks in Post-menopausal Women
Heeyoung So, Sukhee Ahn, Rhayun Song, Hyunli Kim
Korean Journal of Women Health Nursing.2010; 16(3): 224. CrossRef
Association of the Metabolic Syndrome and Bone Mineral Density in Postmenopausal Women
Jong-Chang Park, Hyuk-Jung Kweon, Yun-Kyo Oh, Hyun-Jin Do, Seung-Won Oh, Youl-Lee Lym, Jae-Kyung Choi, Hee-Kyung Joh, Dong-Yung Cho
Korean Journal of Family Medicine.2010; 31(1): 9. CrossRef

The Effects of Osteoprotegerin Polymorphism on Bone Mineral Metabolism in Korean Women with Perimenopause.: Ki Won Oh, Eun Joo Yun, Eun Jung Rhee, Won Young Lee, Ki Hyun Baek, Moo Il Kang, Cheol Young Park, Sung Hee Ihm, Moon Gi Choi, Hyung Joon Yoo, Sung Woo Park; J Korean Endocr Soc. 2005;20(3):204-215. Published online June 1, 2005; DOI: https://doi.org/10.3803/jkes.2005.20.3.204

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Abstract PDF: BACKGROUND
Osteoprotegerin(OPG) is a recently identified cytokine, which acts as a decoy receptor for the receptor activator of the NF-kappaB ligand(RANKL), and has also been shown to be an important inhibitor of osteoclastogenesis in animal models. However, the relationship between OPG gene polymorphism and female bone stati in human populations is unclear. In this study, the relationship between OPG gene polymorphisms and bone mineral metabolism in healthy Korean women was investigated. METHODS: We observed 251 healthy women(mean age, 51.3+/-6.9 yr). The serum OPG concentrations were determined using ELISA, and the biochemical markers of bone turnover and FSH measured using standard methods. The bone mineral densities at the lumbar spine and femoral neck were measured by dual energy x-ray absorptiometry. The A163G, G209A, T245G and T950C polymorphisms of the OPG gene were analyzed by allelic discrimination using the 5 nuclease polymerase chain reaction assay. RESULTS: The lumbar spine BMD of premenopausal women was marginally decreased in the variant allele group compared to the wild type group(A163G, 0.98+/-0.14g/cm2[GG+GA] vs. 1.05+/- 0.15g/cm2[AA], P =0.070; T245G, 0.97+/-0.13g/cm2[GG+GT] vs. 1.04+/-0.15g/cm2[TT], P=0.056). In the linkage of polymorphisms A163G and T245G, the lumbar spine BMD of premenopausal women was marginally decreased in the variant allele group compared to the wild type group([AATT] vs. [AGTG+AGGG+GGTG+GGGG]: 1.04+/-0.15 vs. 0.97+/- 0.13; P=0.072). However, there were no differences in the serum OPG levels and bone turnover markers among the different genotypes. CONCLUSION: The A163G and T245G polymorphisms of the OPG gene were observed to be marginally associated with the lumbar spine BMD in healthy premenopausal Korean women, but further studies will be needed to clarify this relationship

The Changes in the Serum RANKL and OPG levels after Bone Marrow Transplantation: Association with Bone Mineral Metabolism.: Hyun Jung Tae, Ki Hyun Baek, Eun Sook Oh, Ki Won Oh, Won Young Lee, Hye Soo Kim, Je Ho Han, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang, Choon Choo Kim, Moo Il Kang; J Korean Endocr Soc. 2005;20(1):40-51. Published online February 1, 2005; DOI: https://doi.org/10.3803/jkes.2005.20.1.40

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Abstract PDF: BACKGROUND
The loss of bone mass is usually detected after bone marrow transplantation(BMT), particularly during the early post-transplant period. We recently reported that enhanced bone resorption following BMT was related to both the steroid dose and increase in IL-6. It was also suggested damage of the marrow microenvironment due to myeloablation and changes in bone growth factors contribute to post-BMT bone loss. Recently, the interactions of OPG and RANKL have been reported to be crucial in osteoclastogenesis and therefore in bone homeostasis. There are few data on the changes in RANKL/OPG status during the post-BMT period. This study investigated the changes in the levels of RANKL and OPG during the post-BMT period, and also assessed whether the changes in these cytokine levels actually influenced bone turnover and post-BMT bone loss. METHODS: We prospectively investigated 110 patients undergoing allogenic BMT and analyzed 36 (32.4+/-1.3 years, 17 men and 19 women) where DEXA was performed before and 1 year after the BMT. The serum bone turnover marker levels were measured before and 1, 2, 3, 4 and 12 wks, 6 Ms, and 1 yr after the BMT. The serum sRANKL and OPG levels were measured in all patients before and 1, 3 and 12 wks after the BMT. RESULTS: The mean bone losses in the lumbar spine and total proximal femur, which were calculated as the percent change from the baseline to 1 yr, were 5.2(P<0.01) and 11.6%(P<0.01), respectively. The mean serum ICTP, a bone resorption marker, increased progressively until 3 and 6 months after the BMT, but decreased gradually thereafter, reaching the basal values after 1 year. The serum osteocalcin levels decreased progressively until 3 wks after the BMT, then increased transiently at 3 and 6 Ms, but returned to the basal level by 1 yr. The serum sRANKL and OPG levels had increased significantly by weeks 1 and 3 compared with the baseline(P<0.01), but decreased at 3 months. The sRANKL/OPG ratio increased progressively until 3 weeks, but then decreased to the basal values. During the observation period, the percent changes from the baseline in the serum RANKL levels and RANKL/OPG ratio showed positive correlations with the percent changes from the baseline serum ICTP levels. Patients with higher RANKL levels and RANKL/OPG ratio during the early post-BMT period lost more bone mass at the lumbar spine. CONCLUSION: In conclusion, dynamic changes in the sRANKL and OPG levels were observed during the immediate post-BMT period, which were related to a decrease in bone formation and loss of L-spine BMD during the year following the BMT. Taken together, these results suggest that increased sRANKL levels and sRANKL/OPG ratios could be involved in a negative balance in bone metabolism following BMT.

Effects of Pamidronate Treatment on Osteogenesis Imperfecta.: Seung Won Lee, Hyon J Kim, Jae Hyun Cho, Hyoung Suk Lee, Youn Mu Jung, Dae Jung Kim, Kwan Woo Lee, Yoon Sok Chung; J Korean Endocr Soc. 2004;19(5):485-491. Published online October 1, 2004

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Abstract PDF: BACKGROUND
Osteogenesis imperfecta (OI) is a congenital disorder of type I collagen, with variable phenotypes, due to increased bone fragility and low bone mass. Previous pharmacological treatments for OI have been attempted with calcitonin and growth hormone but with little beneficial effects. Recently, Glorieux reported the beneficial effects of bisphosphonates in OI. METHODS: In this study, the effects of pamidronate treatment were evaluated in 9 patients with OI. All patients received intravenous pamidronate infusions, which was dose adjusted according to the patients' age. The outcome measures included the biochemical bone markers; serum alkaline phosphatase, urine deoxy-pyridinoline, urine Ca/Cr ratio, and bone mineral density (BMD). RESULTS: Serum alkaline phosphatase, urine deoxypyridinoline, and urine Ca/Cr ratio were slightly decreased after 1 year of therapy, although these changes were not statistically significant. The BMDs of the lumbar spine and proximal femur were significantly increased after 1-year of pamidronate treatment. No fractures were reported during the 1 year treatment periods. CONCLUSION: Pamidronate treatment had an effect on the BMD in osteogenesis imperfecta, probably due to decreasing bone resorption

Relationship between Serum Leptin, Adiponectin, Resistin and Ghrelin Levels, and Bone Mineral Density in Men.: Ki Won Oh, Eun Joo Yun, Eun Jung Rhee, Won Young Lee, Ki Hyun Baek, Kun Ho Yoon, Moo Il Kang, Cheol Young Park, Sung Hee Ihm, Moon Gi Choi, Hyung Joon Yoo, Sung Woo Park; J Korean Endocr Soc. 2004;19(4):379-392. Published online August 1, 2004

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Abstract PDF: BACKGROUND
Fat mass is an important determinant of bone mineral density (BMD), but the mechanism involved in this relationship is uncertain. Several lines of evidence have suggested the effects of fat mass on BMD may be mediated by hormonal factors, with the principal candidates being serum sex hormones, insulin, leptin and adiponectin. Thus, the aim of this study was to investigate the relationship between the serum adipocytokine and ghrelin levels, and BMD in men. METHODS: Eighty men, aged 42~70 (mean age, 54.5 yr), were selected as the study subjects. The serum concentrations of leptin and ghrelin were measured with RIA, the adiponectin with ELISA and the resistin with EIA. The serum concentrations of estradiol, total testosterone and the biochemical markers of bone turnover were measured by standard methods. The BMD at the lumbar spine and femoral neck were measured by dual energy x-ray absorptiometry. RESULTS: The serum leptin level was found to correlate to the BMI, waist to hip ratio (WHR), blood pressure, fasting blood sugar, serum fasting insulin, total cholesterol, triglyceride and calcium levels. Although the serum leptin level was not significantly correlated to the serum estradiol level, it did show a weak trend. The serum adiponectin level were correlated to the BMI, WHR and serum fasting insulin level; and the resistin to serum total cholesterol and low density lipoprotein cholesterol levels; ghrelin to age, WHR and serum triglyceride levels. A significant negative correlation was observed between the serum resistin level and lumbar spine BMD. Also, there was a significant negative correlation between the serum leptin level and lumbar spine BMD. The above correlations were observed only when the BMI and the serum estradiol and insulin levels were included as independent variables in the regression analysis model. The serum adiponectin level was not significantly correlated with the BMD, either in the presence or absence of the BMI and serum insulin level. CONCLUSION: The serum adipocytokine level was observed to be partly associated with the BMD in men. Therefore, these data suggest that leptin and resistin may play roles in the bone mineral metabolism in men. Further studies are needed to larify this relationship

The Effects of C161-->T Polymorphisms in Exon 6 of Peroxisome Proliferator-Activated Receptor- Gene on Bone Mineral Metabolism and Serum Osteoprotegerin Levels in Healthy Korean Middle-aged Men.: Eun Jung Rhee, Won Young Lee, Se Yeon Kim, Eun Sook Oh, Ki Hyun Baek, Ki Won Oh, Kyung Chang Park, Ki Ok Han, Hyun Koo Yoon, Moo Il Kang, Sun Woo Kim; J Korean Endocr Soc. 2004;19(2):181-193. Published online April 1, 2004

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Abstract PDF: BACKGROUND
The peroxisome proliferator-activated receptor (PPAR) is a member of the nuclear receptor family known to be involved in adipocyte differentiation. Recent studies have revealed the inhibitory role of PPAR in osteoblastogenesis, which suggests its possibility as a candidate gene for osteoporosis. The frequency of C161-->T substitution in exon 6 of PPAR was observed in Korean men and the association of different genotypes with bone turnover markers, bone mineral density (BMD) and serum osteoprotegerin (OPG), which play inhibitory roles in osteoclastogenesis, examined. METHODS: In 72 healthy Korean men (mean age 54.5 6.4 yrs; range 42~69 yrs), anthropometric measurements, and lumbar spine and femoral neck BMD, and bone turnover markers, such as alkaline phosphatase (ALP), serum calcium, phosphorus, osteocalcin and cross-linked C-telopeptides of type I collagen (ICTP) measurements were performed. The levels of serum testosterone, estradiol and insulin-like growth factor (IGF-I), and those of serum OPG levels, were measured with a sandwich enzyme-linked immunosorbent assay (ELISA) method. The DNAs were extracted from the samples, and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the sequencing of the products were performed to confirm the substitution. RESULTS: The allele frequencies were 0.799 and 0.201 for the C and T allele, respectively, which were in Hardy-Weinberg equilibrium (p=0.80). Subjects with the CT genotype were older and those with the T allele showed higher blood pressure levels and lower body mass indices (p<0.05) than those with the CC genotypes. There were no differences in the bone turnover markers between the different genotypes (p>0.05). The levels of serum testosterone, estradiol, IGF-I and OPG were not different among the different genotype groups (p>0.05). The lumbar, femoral neck BMD (g/cm2) and T scores were significantly lower in subjects with T alleles, and those with CT genotypes showed the lowest BMD values (p<0.05). When the subjects were divided into 3 groups, i.e., normal, osteopenic and osteoporotic groups, according to the lumbar spine BMD, the group with the T allele had a significantly higher prevalence of osteopenia and smaller numbers with normal BMD than those with the CC genotype (p=0.032). CONCLUSION: The frequencies of the C161-->T substitution in exon 6 of the PPAR gene in Korean men were similar to those observed in other races, and those with the T alleles showed significantly lower BMD values. These data imply the PPAR gene might be a candidate gene for the pathogenesis of osteoporosis

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