Osteoporosis: Shin CS

Chan SP, Chen JF, Chu LW, Van DP, Hosking D, Ip TP, Koh L, Kung A, Lai NS, Lau E, Lee JK, Leewattana R, Min YK, Nghia ND, Boonsong O, Park HM, Ringe J, Setyohadi B, Shin CS, Soontrapa S, Taechakraichana N, Tanjung F, Tobing D, Tsai KS, Woo J, Yang RS. · c/o Department of Medicine, University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China. · Public Health Nutr. · Pubmed #18647434 No free full text.

Abstract: BACKGROUND: Vitamin D is essential for Ca absorption, prevention of falls and fracture, and maintenance of muscle strength and balance. Lack of awareness of the importance of vitamin D in bone health is common in Asia. OBJECTIVE: To define key statements, objectives and actions for improving osteoporosis management and vitamin D inadequacy in Asia. RESULTS AND CONCLUSION: This declaration was jointly produced by specialists at the Asia Metaforum on the Role of Vitamin D and the Management of Osteoporosis, held in September 2006 in Hong Kong, to define actions to prevent vitamin D insufficiency in Asia. Although developed specifically for Asia, some or all of these statements may be applicable to other regions of the world.

Kim SW, Park DJ, Park KS, Kim SY, Cho BY, Lee HK, Shin CS. · Department of Internal Medicine, Seoul National University College of Medicine, Seoul. · Endocr J. · Pubmed #16410657 links to  free full text

Abstract: Biochemical markers of bone turnover have been suggested to be useful in monitoring the efficacy of antiresorptive therapy. In this study, we investigated the predictive value of bone turnover markers to determine short-term response in bone mineral density (BMD) and to identify nonresponders in 138 postmenopausal women (mean age 58 years) with osteoporosis given with either hormone thearpy (HT) or alendronate. Urinary type I collagen N-telopeptide (NTx) and serum osteocalcin (OC) at baseline, 3, and 6 months after treatment as well as spine and femoral neck BMD at baseline and 12 months were measured. Significant decreases in both NTx and OC were evident in women on treatment with antiresorptive agents as early as 3 months (p<0.01). Percent change of NTx at 3 months correlated with the percent change of spinal BMD at 12 months of treatment. When bone turnover markers were stratified by tertiles, the average rate of lumbar spine BMD gain increased significantly with increasing tertiles of baseline value (p<0.05) and percent change (p<0.05) of urinary NTx at 3 month of treatment. In terms of BMD response, urinary NTx at 3 months decreased significantly more in BMD responders group than in nonresponders group. Logistic regression analysis demonstrated that percent change of NTx at 3 months is an independent predictor to identify BMD nonresponders, defined as those whose BMD gain remained within the precision error range of dual energy X-ray absorptiometer (DXA). We conclude that biochemical markers of bone turnover, especially percent change in urinary NTx levels, can be used to determine BMD response to antiresorptive therapy in Korean postmenopausal women with osteoporosis.

Lim S, Koo BK, Lee EJ, Park JH, Kim MH, Shin KH, Ha YC, Cho NH, Shin CS. · Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongun-Dong, Chongno-Gu, Seoul 110-744, Korea. · J Bone Miner Metab. · Pubmed #18600408 No free full text.

Abstract: Osteoporosis is a major public health problem in both Western and Asian populations. Because the aged population in Korea is increasing, the number of osteoporotic fractures is thought to be also increasing. However, there has been no nationwide analysis of osteoporotic fractures in Korea. We analyzed the incidence and cost of hip fracture from 2001 to 2004 by using data from the Health Insurance Review Agency, Korea. In the over 50 years age group, the number of hip fractures in women increased from 250.9/100,000 persons in 2001 to 262.8/100,000 in 2004, a 4.7% increase. However, that in men decreased from 162.8/100,000 in 2001 to 137.5/100,000 in 2004, a 15.5% decrease. Direct medical care costs of hip fracture increased from $62,707,697 in 2001 to $65,200,035 in 2004, and the proportional cost of hip fractures in the national medical costs increased by 4.5% over 4 years (from 0.200% in 2001 to 0.209% in 2004). On analysis of the population-based data obtained from the whole country from 2001 to 2004, the incidence rate of hip fractures in women, not in men, and its cost have increased in Korea. The gender distribution of hip fractures underlines the need for aggressive intervention in osteoporosis in elderly women.

Lee HW, Suh JH, Kim HN, Kim AY, Park SY, Shin CS, Choi JY, Kim JB. · School of Biological Sciences, Seoul National University, Seoul, Korea. · J Bone Miner Res. · Pubmed #18410224 No free full text.

Abstract: Berberine (BBR) has been implicated in bone biology. Although BBR reduces osteoporosis by enhancing BMD and inhibiting osteoclast activity, the effects of BBR on osteoblasts during the process of osteogenesis have not been thoroughly studied. In osteoblastic cells, BBR enhanced the expression of osteogenic marker genes including osteopontin and osteocalcin and promoted the transcriptional activity of the key osteogenic transcription factor Runx2. In osteoblasts, BBR increased the binding of Runx2 to the promoter region of osteopontin. The recruitment of co-factors such as p300 and HDAC1 to the promoter regions of osteopontin and osteocalcin was regulated by BBR, resulting in an enhancement in the expression of those genes. Furthermore, BBR activated p38 mitogen-activated protein kinase (MAPK) and increased cyclooxygenase 2 (COX2) expression, which are key factors in osteoblast differentiation. Consistently, a p38 MAPK-specific inhibitor attenuated the effect of BBR on osteogenesis, whereas p38 MAPK overexpression augmented BBR-induced osteogenic gene expression. Moreover, BBR stimulated bone area formation in calvarial organ culture. Taken together, these findings indicate that BBR promotes osteoblast differentiation through activation of Runx2 by p38 MAPK. Therefore, BBR may be a potential therapeutic agent to treat bone-related disorders including osteoporosis.

Kim D, Cho SW, Her SJ, Yang JY, Kim SW, Kim SY, Shin CS. · Department of Internal Medicine, Seoul National University College of Medicine, Chongno-Gu, Korea. · Stem Cells. · Pubmed #16556708 links to  free full text

Abstract: Postmenopausal osteoporosis is characterized by increased bone resorption due to estrogen deficiency. Receptor activator of nuclear factor-kappaB-Fc (RANK-Fc), a fusion protein that specifically blocks receptor activator of nuclear factor ligand binding to RANK, has been known to be efficient and well tolerated in animal models of osteoporosis. Here we show that cell-based gene therapy with RANK-Fc effectively prevented bone loss in ovariectomized (OVX) mice. Thirty-one young adult female C57Bl/6 mice were used, and repeated intraperitoneal injection of mesenchymal stem cells (MSCs) transduced with retrovirus was performed as follows: 1) Sham-operated mice (n = 8); 2) OVX mice treated with phosphate-buffered saline (OVX-PBS; n = 8); 3) OVX mice injected with MSCs transduced with control retrovirus (OVX-green fluorescent protein [GFP]; n = 7); and 4) OVX mice injected with MSCs transduced with RANK-Fc (OVX-RANK-Fc; n = 8). Cellular expression of RANK-Fc was confirmed by Western blot analysis of cell lysates and conditioned medium and also by enzyme-linked immunosorbent assay for the mice serum. Measurement of bone mineral density (BMD) by dual-energy x-ray absorptiometry (PIXImus) revealed that the OVX-RANK-Fc group gained significantly higher BMD than either the OVX-PBS group or OVX-GFP group after 8 weeks. The expression of GFP, which is coexpressed with RANK-Fc, was detected by polymerase chain reaction analysis of DNA isolated from femur and intra-abdominal fat, whereas no GFP signal was identified in liver, brain, heart, lung, or bone marrow aspirates. These suggest that expression of RANK-Fc by genetically modified MSCs may be a feasible option for the prevention of bone loss induced by ovariectomy.

Choi JY, Shin A, Park SK, Chung HW, Cho SI, Shin CS, Kim H, Lee KM, Lee KH, Kang C, Cho DY, Kang D. · Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea. · Calcif Tissue Int. · Pubmed #16151677 No free full text.

Abstract: To evaluate the effects of genetic polymorphisms of OPG, RANK, and ESR1, which regulate osteoclastogenesis, on bone mineral density (BMD), a cross-sectional study was conducted in 650 Korean postmenopausal women. BMDs of the distal radius and the calcaneus were measured by dual energy X-ray absorptiometry (DXA). Genetic polymorphisms of OPG 163 A > G, 1181 G > C; RANK 421 C > T, 575 T > C; and ESR1 1335 C > T, 2142 G > A were determined by matrix-assisted laser desorption/ionization-time of flight (MALDI-ToF) mass spectrometry. The differences between the BMDs of the genotypes of OPG, RANK, and ESR1 were analyzed by multiple linear regression model adjusted for age and body mass index. Women with the OPG 1181 CC genotype had higher BMDs at the distal radius (7%) and calcaneus (10%) than those with the GG genotype; and these differences were statistically significant (P = 0.001 and P = 0.007, respectively). A significant association was also observed between RANK 575 T > C and calcaneus BMD (P for trend = 0.017). No significant association was observed between BMDs and the polymorphisms of ESR1. The association between OPG 1181 G > C and BMD was profound in subjects with the RANK 575 TT or ESR1 2142 GG genotypes; women with OPG 1181 CC had higher BMDs at the distal radius (11%) and calcaneus (11%) than those with OPG 1181 GG only in women with RANK 575 TT genotype (P = 0.002 and P = 0.021, respectively). These results suggest that OPG genetic polymorphisms, especially with the RANK 575 TT or ESR1 2142 GG genotypes, are related to low BMD in postmenopausal Korean women.

Lim S, Joung H, Shin CS, Lee HK, Kim KS, Shin EK, Kim HY, Lim MK, Cho SI. · Seoul National University School of Public Health, Seoul, South Korea. · Bone. · Pubmed #15336618 No free full text.

Abstract: Body weight, smoking, alcohol, physical activity, and diet have been proven to affect bone mineral density (BMD) directly or indirectly. Of these, body weight is perhaps best known to affect BMD. However, there is some debate as to whether lean body mass (LBM) or fat mass (FM), the two components of body weight, most determines BMD. Recently, newer peripheral densitometry devices have been developed, which have the advantages of low cost and portability, and this has made field epidemiologic study of osteoporosis possible. As the number of studies that have focused on the contribution made by body composition to BMD is limited, we investigated the relative contribution of LBM and FM to BMD in healthy Korean subjects. 402 age- and weight-matched subjects over 45 years old were selected from a population-based cohort. The mean ages of men and women were 64.1 +/- 8.7 (mean +/- SD) and 64.2 +/- 12.7 years, and mean weights were 63.0 +/- 8.2 and 63.1 +/- 8.2 kg, respectively. BMD was measured by peripheral dual-energy X-ray absorptiometry (DEXA) and body composition by bioelectrical impedance. Sociodemographic characteristics and physical activities were investigated using a standard questionnaire delivered by face-to-face interview. BMDs were 0.48 +/- 0.01 and 0.37 +/- 0.11 g/cm2 in men and women, respectively. In men, age, weight, body mass index (BMI), LBM, FM, physical activity, smoking, alcohol, and education were significantly correlated with BMD. In women, age, weight, BMI, LBM, FM, education, years since menopause, number of deliveries, and number of children breast-fed were significantly correlated with BMD. By multiple regression, LBM, education, smoking, and alcohol in men, and age, LBM, FM, smoking, and number of delivery in women were independent determinants of BMD. LBM was an important contributor for BMD in men, but both LBM and FM were equally important contributors in female to BMD. This stems from the fact that body composition changes with age differ in men and women. Thus, the augmentation of muscle mass in men and the maintenance of an optimal weight in women act to prevent osteoporosis.

Shin A, Choi JY, Chung HW, Park SK, Shin CS, Choi YH, Cho SI, Kim DS, Kim DI, Lee KM, Lee KH, Yoo KY, Kang D. · Department of Preventive Medicine, Seoul National University College of Medicine, 28 Yongon-Dong Chongno-Gu, 110-799, Korea. · Osteoporos Int. · Pubmed #15042282 No free full text.

Abstract: To estimate the prevalence and the related risk factors of low bone mineral density of the calcaneus and the distal radius, a community-based study was conducted in three rural areas of Korea. A total of 1420 women and 732 men aged 40 years and older participated in this study. Information on sociodemographic characteristics and the potential risk factors for osteoporosis were collected by an interviewer-administered standardized questionnaire. Bone mineral density (BMD) of the calcaneus and the distal radius were measured by dual-energy X-ray absorptiometry (DXA). Three hundred and seventeen women and 183 men aged 20-29 years who participated in a regular health check-up were used as a reference population. Osteoporosis was defined using WHO criteria. Odds ratios of the risk factors of osteoporosis were calculated by the unconditional logistic regression model. The standardized prevalence of osteoporosis of the calcaneus was 8.4% for males and 27.3% for females using the Korean population of year 2000 as a standard population. The standardized prevalence of osteoporosis of the distal radius was 4.2% for males and 18.8% for females. Older age and lower body mass index (BMI) were related with low BMD in both the calcaneus and distal radius in males and females. The duration after menopause and the number of live births were an independent risk factor for osteoporosis of the calcaneus (OR = 1.1, 95% CI = 1.00-1.11; the duration after menopause; OR = 2.0, 95% CI = 1.20-3.35, the number of live birth) and a familial history of non-traumatic fractures or osteoporosis among the first-degree relatives was significantly related to a increased risk of osteoporosis of the distal radius in females (OR = 2.9, 95% CI = 1.36-6.31).

Kim JG, Shin CS, Choi YM, Moon SY, Kim SY, Lee JY. · Department of Obstetrics and Gynaecology, College of Medicine, Seoul National University, Seoul, Korea. · Clin Endocrinol (Oxf). · Pubmed #10469009 No free full text.

Abstract: OBJECTIVES: The changes in circulating IGF components after the menopause and the potential role of new markers of bone turnover and circulating IGF components in predicting bone mass in postmenopausal women are still controversial and the relationship between these two systems has not been investigated. The aims of this study were to investigate the changes in circulating IGF components after the menopause, to evaluate whether new markers of bone turnover and circulating IGF components reflect bone mass in postmenopausal women under the age of 60 and to study the relationship between these two systems. DESIGN, PATIENTS AND MEASUREMENTS: Serum IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3, osteocalcin (OST), bone specific alkaline phosphatase (BAP), urinary deoxypyridinoline (DPYD) and N-telopeptide of type I collagen (NTX) were measured in 31 premenopausal women aged 31-43 and 65 postmenopausal women aged 47-60: this latter group comprised 30 normal healthy women and 35 osteoporotic women. RESULTS: Compared with premenopausal women or normal postmenopausal women, serum IGF-1 and IGFBP-3 levels were significantly lower in osteoporotic postmenopausal women while no significant differences in serum levels of IGF-II, IGFBP-1 and IGFBP-2 were observed. The correlations between bone turnover markers and circulating IGF components (except between serum BAP and IGF-II), and between bone turnover markers and bone mineral density (BMD) in postmenopausal women were not significant. However, serum IGF-I and IGFBP-3 correlated positively with BMD of the lumbar spine and/or Ward's triangle even if age, BMI and menopause duration were taken into account in a multiple regression analysis model. CONCLUSIONS: Circulating IGF-I and IGFBP-3 may be involved in the mechanism of bone loss in postmenopausal women under the age of 60. They may also provide indirect information on the current bone microenvironment different from that provided by new markers of bone turnover.