Osteoporosis: Lee JK

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.

Lee JK, Park C, Kimm K, Rutherford MS. · National Genome Research Institute, National Institute of Health, 5 Nokbun-dong, Eunpyung-ku, Seoul, Republic of Korea. · Biochem Biophys Res Commun. · Pubmed #12127958 No free full text.

Abstract: In postgenomic era, searching and identification of disease genes associated with complex diseases are still one of the great challenge for dissecting human complex diseases. To improve the disease gene localization for complex diseases, a group of closely immune-mediated disease loci were overlapped on each chromosome based on previously reported genome-wide scanning data. Interestingly, five overlapping chromosomal regions (1q21, 2q33, 5q31.1-q33.1, 6p21, and 11q13) were identified by co-localizing disease loci for the following diseases: diabetes, asthma, atopic dermatitis, osteoporosis, and inflammatory bowel disease. The development of specific disease was associated with different combinations of disease loci among five overlapped chromosomal regions. Therefore, the analysis of multiple genetic loci should be considered to determine the effects of multiple genes responsible for complex diseases resulting from the influence of multiple genes.

Kim HJ, Park JB, Lee JK, Park EY, Park EA, Riew KD, Rhee SK. · Department of Orthopaedic Surgery, Uijeongbu St Mary's Hospital, The Catholic University of Korea School of Medicine, Uijongbu, South Korea. · Eur Spine J. · Pubmed #18815818 No free full text.

Abstract: Bone marrow stem cells (BMSCs) are pluripotent cells that have been used to facilitate bone repair because of their capability of differentiating into osteoblasts. However, it is well known that the number of BMSCs with osteogenic potential decreases in patients with old age, osteoporosis, and metabolic diseases. In such conditions, xenogenic BMSCs may provide an alternative to autologous BMSCs. In the current study, we investigated the potential of transplanted xenogenic BMSCs to survive and generate new bone formation in the posterolateral lumbar spine of non-immunosuppressed rabbits. The BMSCs were obtained from bilateral femurs of four male rats, cultured and expanded in medium with osteoinduction supplement. The BMSCs (1,000,000 cells) of male rats loaded onto 5 cc compression resistant matrix (CRM; Medtronic Sofamor Danek, USA) were implanted bilaterally onto the L4-5 intertransverse processes of 16 female rabbits (xenogenic BMSCs + CRM group). The 16 female rabbits that received 5 cc CRM alone were used as controls (CRM alone group). To exclude the possibility of migration of BMSCs from the transverse processes of the recipient rabbits, we did not decorticate the transverse processes. No rabbits received any immunosuppressive medications during the experiment. Four rabbits each in both of the experimental and control groups were killed at 1, 2, 4, and 6 months postimplantation, and the lumbar spine underwent radiological and histological analyses for evaluation of new bone formation. The polymerase chain reaction (PCR) for Sry gene (Y-chromosome-specific marker) was used to evaluate the survival of transplanted xenogenic BMSCs. The expression of Sry gene was clearly identified in the lumbar spines of all the 16 rabbits in the xenogenic BMSCs + CRM group at 1-6 months postimplantation. Serial plain radiographs showed gradual resorption of CRM; however, it was difficult to clearly identify the presence of new bone formation due to the radiopacity of the remaining CRM. Histologically, mature lamellar and woven bone with osteoblasts and osteocytes were identified in all eight rabbits in the xenogenic BMSCs + CRM group at 4 and 6 months postimplantation, but in none of the eight rabbits at 1 and 2 months postimplantation. None of CRM alone group showed new bone formation at 1-6 months postimplantation. Mild-to-moderate infiltration of inflammatory cells was identified around the CRM carriers in both the groups. No post-operative wound infection was found in either group. Our results indicate that xenogenic BMSCs loaded onto CRM survive and generate new bone formation when placed into the posterolateral lumbar spine of rabbits without immunosuppression. To determine if a solid fusion can be achieved with such techniques, further studies are needed to investigate the appropriate dose of xenogenic BMSCs, amounts of CRM, and the requisite incubation time.

Kwak HJ, Lee JK, Kim YS, Moon KS, Joo SP, Kim JH, Kim SH, Chang WC. · Department of Neurosurgery, Chonnam National University Hospital, 8 Hak-Dong, Gwangju, 501-757, South Korea. · J Clin Neurosci. · Pubmed #17884506 No free full text.

Abstract: Percutaneous vertebroplasty is a commonly used procedure for the treatment of painful vertebral fractures induced by osteoporosis or metastatic disease. It is generally considered to be safe and effective. However, infectious complications can be serious. We present a patient in whom pyogenic spondylitis developed 3 months after vertebroplasty. During the debridement, profuse bleeding was encountered from injury to the aorta and the patient was managed with primary closure. Two months after the initial surgery, an aortic aneurysm was detected. A wide resection of all infected tissue, including the bony lesion and aortic aneurysm was performed, and the descending thoracic aorta was replaced with a vascular graft. A titanium mesh cage filled with bone graft was employed for anterior reconstruction. Our patient illustrates that a life-threatening aortic aneurysm can indeed occur as an infectious complication of this minimally invasive procedure due to the proximity of the aorta to the thoracolumbar vertebra. The spine surgeon should be aware of the possibility of aortic wall erosion caused by long-standing spondylitis, and be prepared to manage an inadvertent injury to the aorta during surgical debridement.

Koh JM, Oh B, Lee JY, Lee JK, Kimm K, Park BL, Shin HD, Lee IK, Kim HJ, Hong JM, Kim TH, Kim GS, Kim SY, Park EK. · Skeletal Diseases Genome Research Center, Kyungpook National University Hospital, Daegu, Korea. · J Bone Miner Res. · Pubmed #17620055 No free full text.

Abstract: The genetic effects of FLT3 polymorphisms on BMD and fracture risk in postmenopausal women were studied. We found that FLT3+13348C>T polymorphism and haplotype 2 were significantly associated with low BMD and high risk of fracture. INTRODUCTION: FMS-related tyrosine kinase 3 (FLT3) has been shown to play a critical role in the development of myelolymphoid progenitors and in the development of osteoclasts, but any possible genetic effect of FLT3 on bone metabolism has not been studied. MATERIALS AND METHODS: To study a possible genetic effect of FLT3, we directly sequenced the FLT3 gene in 24 Korean individuals and identified 23 sequence variants. Seven polymorphisms were selected and genotyped in Korean postmenopausal women (n = 946). RESULTS: We found that FLT3+13348C>T was associated with low BMD at the lumbar spine (p = 0.04) and femoral neck (p = 0.04). Haplotype analysis revealed that FLT3-ht2 (TTCTT) containing the rare allele in the +13348 position also showed significant association with low BMD in the lumbar spine (p = 0.04) and femoral neck (p = 0.05). Consistent with these results, the FLT3+13348C>T polymorphism and FLT3-ht2 were also significantly associated with high risk of fracture in the vertebrae (OR = 1.44-1.58; p = 0.03-0.04 and OR = 1.45-1.59; p = 0.02-0.03, respectively) and in any sites (OR = 1.34-1.81; p = 0.02-0.03 and OR = 1.34-1.81; p = 0.02-0.03, respectively). CONCLUSIONS: These results suggest that FLT3 polymorphisms play a role in determination of BMD and subsequent fractures in postmenopausal women.

Hwang JY, Lee JY, Park MH, Kim KS, Kim KK, Ryu HJ, Lee JK, Han BG, Kim JW, Oh B, Kimm K, Park BL, Shin HD, Kim TH, Hong JM, Park EK, Kim DJ, Koh JM, Kim GS, Kim SY. · National Genome Research Institute, National Institute of Health, 5 Nokbun-dong, Eunpyung-gu, Seoul, 122-701, South Korea. · Osteoporos Int. · Pubmed #16932874 No free full text.

Abstract: INTRODUCTION: Plexin A2 (PLXNA2) is a receptor that recognizes secreted or membrane-bound semaphorin 3A, which is implicated in neural regulation of bone metabolism. MATERIALS AND METHODS: In the present study, we identified 48 genetic polymorphisms in PLXNA2 by resequencing, and 10 single nucleotide polymorphisms (SNPs) were selected for further investigation into their potential involvement in osteoporosis in a postmenopausal population (n=560). RESULTS: Two SNPs, +14G>A (Gln5Arg) and +183429C>T (Tyr1621Tyr), and Block1-ht2 were associated with risk of vertebral fracture (p=0.01-0.05), and three SNPs, +799G>A (Ala267Thr), +135391G>A, and +190531G>C, were associated with bone mineral density at various femur sites (p=0.003-0.03). Particularly, the minor allele of +14G>A was associated with a protective effect on vertebral fracture and higher lumbar bone mineral density, suggesting that +14G>A may be a useful marker for osteoporosis and its related fracture. CONCLUSION: These results provide, for the first time, evidence supporting the association of PLXNA2 with osteoporosis in postmenopausal women.

Koh JM, Oh B, Lee JY, Lee JK, Kimm K, Kim GS, Park BL, Cheong HS, Shin HD, Hong JM, Kim TH, Park EK, Kim SY. · Skeletal Diseases Genome Research Center, Kyungpook National University Hospital, 44-2, Samduk 2-ga, Jung-gu, 700-412 Daegu, Republic of Korea. · J Hum Genet. · Pubmed #16372136 No free full text.

Abstract: Bone mineral density (BMD), the major factor determining bone strength, is closely related to osteoporotic fracture risk and is determined largely by multiple genetic factors. Semaphorin 7a (SEMA7A), a recently described member of the semaphorin family, has been shown to play a critical role in the activation of monocyte/macrophages that share progenitors with bone-resorbing osteoclasts and thus might contribute to osteoclast development. In the present study, we directly sequenced the SEMA7A gene in 24 Korean individuals, and identified 15 sequence variants. Five polymorphisms (+15667G > A, +15775C > G, +16285C > T, +19317C > T, +22331A > G) were selected and genotyped in postmenopausal Korean women (n = 560) together with measurement of the areal BMD (g/cm2) of the anterior-posterior lumbar spine and the non-dominant proximal femur using dual-energy X-ray absorptiometry. We found that polymorphisms of the SEMA7A gene were associated with the BMD of the lumbar spine and femoral neck. SEMA7A + 15775C > G and SEMA7A+22331A > G were associated with low BMD of the femoral neck (P = 0.02) and lumbar spine (P = 0.04) in a recessive model. SEMA7A-ht4 also showed an association with risk of vertebral fracture (OR = 1.87-1.93, P = 0.02-0.03). Our results suggest that variations in SEMA7A may play a role in decreased BMD and risk of vertebral fracture.

Somjen D, Waisman A, Lee JK, Posner GH, Kaye AM. · Institute of Endocrinology, Tel-Aviv Sourasky Medical Center and the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 64239, Israel. · J Steroid Biochem Mol Biol. · Pubmed #11457658 No free full text.

Abstract: We have reported that multiple treatments with so-called 'non-hypercalcemic' analogs of 1 alpha,25(OH)(2) vitamin D(3) (1,25(OH)(2)D(3)) stimulate the specific activity of creatine kinase BB (CK) in ROS 17/2.8 osteoblast-like cells, and that pretreatment with these analogs upregulates responsiveness and sensitivity to 17 beta estradiol (E(2)) for the induction of CK. However, since the analogs showed toxicity in vivo, we have now studied the action of a demonstrably non-calcemic hybrid analog of vitamin D in ROS 17/2.8 cells, and prepubertal rats. The analog JKF was designed to separate its calcemic activity from other biological activities by combining a calcemic-lowering 1-hydroxymethyl group with a potentiating C, D-ring side chain modification including 24 difluoronation. Treatment with 1 pM JKF alone significantly stimulated CK specific activity at 4 h by 30+/-10%. However after three daily pretreatments, JKF upregulated the extent of induction by 30 nM E(2) by 33% at 1 pM and by 97% at 1 nM; the E(2) dose needed for a significant stimulation of CK activity was lowered to 30 pM. The action of the SERMS tamoxifen, tamoxifen methiodide and raloxifene, at 3 microM, was also upregulated by three daily pretreatments with 1 nM JKF; unexpectedly, this pretreatment prevented the inhibition of E(2) stimulation by the SERMS. Upregulation of E(2) action by 1 nM JKF was inhibited by 1 nM ZK159222, an inhibitor of the nuclear action of 1,25(OH)(2)D(3). In vivo, three daily injections of 0.05 ng/g body weight of JKF augmented the response of prepubertal female rat diaphysis and epiphysis to E(2). Therefore, demonstrably non-calcemic analogs of 1,25(OH)(2)D(3) may have potential for use in combination with estrogens or SERMS in the prevention and/or treatment of metabolic bone diseases such as postmenopausal osteoporosis.

Lau EM, Lee JK, Suriwongpaisal P, Saw SM, Das De S, Khir A, Sambrook P. · Department of Community and Family Medicine, The Chinese University of Hong Kong, Hong Kong. · Osteoporos Int. · Pubmed #11315243 No free full text.

Abstract: The Asian Osteoporosis Study (AOS) is the first multicenter study to document and compare the incidence of hip fracture in four Asian countries. Hosital discharge data for the year 1997 were obtained for the Hong Kong SAR, Singapore, Malaysia and Thailand (Chiang Mai). The number of patients who were 50 years of age and older and who were discharged with a diagnosis of hip fracture (ICD9 820) was enumerated. The age-specific incidence rates were deduced and were directly adjusted to the US white population in 1989. The age-adjusted rates for men and women (per 100,000) are as follows: Hong Kong, 180 and 459; Singapore, 164 and 442; Malaysia, 88 and 218; Thailand, 114 and 289; compared with US White rates of 187 in men and 535 in women, published in 1989. We conclude that there is moderate variation in the incidence of hip fracture among Asian countries. The rates were highest in urbanized countries. With rapid economic development in Asia, hip fracture will prove to be a major public health challenge.

Lau EM, Suriwongpaisal P, Lee JK, Das De S, Festin MR, Saw SM, Khir A, Torralba T, Sham A, Sambrook P. · Department of Community and Family Medicine, The Chinese University of Hong Kong, Hong Kong. · J Bone Miner Res. · Pubmed #11277276 No free full text.

Abstract: The objectives of the Asian Osteoporosis Study (AOS) were to determine risk factors for hip fracture in men and women in four Asian countries, that is, Singapore, Malaysia, Thailand, and the Philippines. A total of 451 men and 725 women (aged 50 years and over) with hip fractures were compared with an equal number of community controls. A standardized questionnaire was administered by interview. The following relative risks (RRs) were found in women and men by multiple logistic regression: dietary calcium intake < 498 mg/day, 2.0 for women (95% CI, 1.5-2.8) and 1.5 for men (95% CI, 1.0-2.2); no load bearing activity in the immediate past, 2.0 for women (95% CI, 1.4-2.7) and 3.4 for men (95% CI, 2.3-5.1); no vigorous sport activities in young adulthood, 7.2 for women (95% CI, 4.0-13.0) and 2.4 for men (95% CI, 1.6-3.6); cigarette smoking, 1.5 for men (95% CI, 1.0-2.1); alcohol consumption 7 days a week, 2.9 for women (95% CI, 1.0-8.6) and 1.9 for men (95% CI, 1.1-3.2); fell twice or more in the last 12 months, 3.0 for women (95% CI, 1.8-4.8) and 3.4 for men (95% CI, 1.8-6.6); a history of fractures after 50 years of age, 1.8 for women (95% CI, 1.1-2.9) and 3.0 for men (95% CI, 1.6-5.6); a history of stroke, 3.8 for women (95% CI, 2.0-7.1) and 3.6 for men (95% CI, 1.8-7.1); use of sedatives, 2.5 for women (95% CI, 1.0-6.3) and 3.0 for men (95% CI, 1.0-9.7); and use of thyroid drugs, 7.1 for women (95% CI, 2.0-25.9) and 11.8 for men (95% CI, 1.3-106.0). Women who were 1.56 m or taller had an RR of 2.0 (95% CI, 1.3-3.0) for hip fracture and men who were 1.69 m or taller had an RR of 1.9 (95% CI, 1.2-3.1) for hip fracture. Based on these findings, primary preventive programs for hip fracture could be planned in Asia.

Oh B, Kim SY, Kim DJ, Lee JY, Lee JK, Kimm K, Park BL, Shin HD, Kim TH, Park EK, Koh JM, Kim GS. · No affiliation provided · J Med Genet. · Pubmed #17209132 No free full text.

Abstract: BACKGROUND: Oxidative stress has been recently suggested to play a part in the development of osteoporosis. Catalase is a major antioxidant enzyme that detoxifies hydrogen peroxide by converting it into water and oxygen, thereby preventing cellular injury by oxidative stress. AIMS: To examine the associations between the catalase gene (CAT) polymorphisms and bone mineral density (BMD) and bone turnover markers in postmenopausal Korean women. METHODS: All exons, their boundaries and the promoter region (approximately 1.5 kb) were directly sequenced in 24 individuals. Among 18 variants identified by a direct sequence method, four polymorphisms were selected and genotyped in all study participants (n = 560). BMD at the lumbar spine and proximal femur was measured using dual-energy x ray absorptiometry. Serum osteocalcin concentrations and bone-specific alkaline phosphatase activity were determined by an immunoradiometric assay and an immunoassay, respectively. RESULTS: The mean (standard deviation) age of the participants was 59.4 (7.2) years. Multivariate analysis showed an association of the +22348C-->T polymorphism with BMD at the lumbar spine (p = 0.01 in the dominant model) and at femur neck (p = 0.05 in the dominant model), and with serum osteocalcin level (p = 0.008 in the dominant model). Haplotype analyses showed that HT4 (-20T, +144C, +22348T, +33078A) was significantly associated with higher BMD at various sites (p<0.001-0.03) and with lower serum osteocalcin levels (p = 0.01 in the codominant model). CONCLUSIONS: These findings indicate that the +22348C-->T polymorphism and HT4 of CAT may be useful genetic markers for bone metabolism.