- The Effects of Combination Therapy of Cathepsin K Inhibitor and PTH on Change in Bone Mineral Density in an Animal Model of Osteoporosis.
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Seung Hun Lee, Jung Min Koh, Young Sun Lee, Beom Jun Kim, Je Yong Choi, Ghi Su Kim
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Endocrinol Metab. 2011;26(4):303-309. Published online December 1, 2011
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DOI: https://doi.org/10.3803/EnM.2011.26.4.303
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- BACKGROUND
We hypothesized that combination therapy of cathepsin K inhibitor (CTKi) and human parathyroid hormone (1-34) (teriparatide, PTH) would overcome the coupling phenomenon of bone resorption and formation and thus may rapidly increase bone mass. METHODS: We selected a dose of zoledronic acid (ZA) that had shown similar effects with CTKi on body bone mineral density (BMD) change during the preliminary experiment. Female mice were subjected to ovariectomized (OVX control) or a sham operation (SHAM group). The mice were treated with CTKi (CTKi group), ZA (ZA group), PTH (PTH group) or with a combination of PTH with ZA (ZA + PTH group) or CTKi (CTKi + PTH group) for 8 weeks. Total BMD was measured before the operation and at 4 and 8 weeks. RESULTS: In the preliminary results, 10 microg/kg of ZA showed similar BMD changes with CTKi. Compared with the OVX control, BMD in the SHAM, ZA, CTKi, PTH, ZA + PTH, and CTKi + PTH groups was significantly increased after treatment. BMD in the CTKi + PTH group, but not in the ZA + PTH group increased more significantly than in the PTH group at the end of treatment. Compared with the OVX control, changes in BMD in the SHAM, ZA, CTKi, PTH, ZA + PTH, and CTKi + PTH groups increased significantly after 8 weeks of treatment. The change in BMD in the CTKi + PTH group, but not in the ZA + PTH group was more significantly increased than the change in BMD in the PTH group. CONCLUSION: When combined with PTH, CTKi augmented the anabolic action of PTH. Therefore, combination therapy with CTKi and PTH might be a new therapeutic modality capable of overcoming the coupling phenomenon, thereby markedly and rapidly increasing bone mass.
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Citations to this article as recorded by  - The Effects of Combination Therapy of Cathepsin K Inhibitor and PTH on Change of Bone Mineral Density in Animal Model of Osteoporosis
Yumie Rhee
Endocrinology and Metabolism.2011; 26(4): 295. CrossRef
- Effects of alpha-Lipoic Acid on Bone Metabolism in Rats with Low Bone Mass.
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Jung Min Koh, Hee Sook Lee, Duk Jae Kim, Ghi Su Kim
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J Korean Endocr Soc. 2005;20(5):476-487. Published online October 1, 2005
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DOI: https://doi.org/10.3803/jkes.2005.20.5.476
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Growing evidence has shown a biochemical link between increased oxidative stress and reduced bone density. In our previous study, alpha-lipoic acid (alpha-LA), a thiol antioxidant, suppressed both osteoclastogenesis and bone resorption, and also prevented TNF-alpha-induced apoptosis of osteoblast lineages. The effects of alpha-LA were investigated on bone metabolism in rats with a low bone mass. METHODS: An ovariectomy (OVX) or Talc injection (inflammation-mediated osteopenia, IMO) was performed in 12 week old female Sprague-Dawley rats. Diets containing either 0.3%, 0.5% or 1.0% alpha-LA were administered to the OVX rats for 16 weeks, and to the IMO rats for 21 days. The bone mineral densities (BMD) of the anterior-posterior lumbar spine and total femur were measured using dual-energy X-ray absorptiometry (Hologic QDR 4500-A), with small animal software. The plasma bone specific alkaline phosphatase activity (BSAP) and urinary free deoxypyridinoline concentration (DPD) were determined using enzyme immunoassay methods. RESULTS: The body weights were significantly decreased in the OVX rats on the diets containing 0.3 and 0.5% alpha-LA than in the OVX control. No significant differences in the BMD at either site were noted between rats administered the diets with or without alpha-LA. However, the administration of various doses of alpha-LA noticeably decreased the level of urinary DPD in both the OVX and IMO rats. High doses of alpha-LA (0.5% and/or 1.0%) also decreased the levels of plasma BSAP in both models. CONCLUSION: Although no increase in BMD was demonstrated by the administration of alpha-LA, these results suggest that alpha-LA suppresses the rates of bone turnover in rats with a low bone mass
- Completion Thyroidectomy in Patient with Differentiated Thyroid Cancer Who Initially Underwent Ipsilateral Operation.
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Eun Sook Kim, Jung Min Koh, Won Bae Kim, Suck Joon Hong, Young Kee Shong
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J Korean Endocr Soc. 2002;17(5):657-663. Published online October 1, 2002
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In some instances, thyroid cancer may be diagnosed only after resection of a putative or suspected benign nodule. In these cases a complete thyroidectomy is usually recommended to prevent recurrence. We analyzed the frequency of malignancy in the contralateral lobe after a complete thyroidectomy, and assessed the factors that may predict the presence of a malignancy, which might necessitate a complete thyroidectomy. METHODS: Between 1995 and 2001, 65 patients, who initially underwent a lobectomy and isthmectomy, but were finally diagnosed with differentiated thyroid carcinoma, underwent complete thyroidectomies. Their mean age was 39.8 +/- 12.4 years, ranging, 14 to 71 years. After initial surgery, 45 proved to have follicular carcinomas, 18 papillary carcinomas, 1 medullary and 1 insular carcinoma. The mean tumor size was 4.0 +/- 1.8 cm, ranging from 0.3 to 8.5 cm. After a complete thyroidectomy, the presence of a tumor the at contralateral lobe was assessed according to clinical parameters and the pathological findings in the ipsilateral lobe. RESULTS: The first surgeries revealed tumor multifocality in 27 cases, perithyroidal tumor extension in 4 and lymph node metastasis in 1. On completion of the thyroidectomy, 22 of the 65 patients had a malignancy in the contralateral lobe. Age, sex, size or the pathological primary tumor type, were not associated with the presence of additional tumors at the contralateral lobe. Tumor multifocality at the first surgery was the only significant variable to predict the presence of a tumor in the contralateral lobe. CONCLUSION: When thyroid cancer is diagnosed after ipsilateral surgery, the only predictive factor for the presence of a contralateral tumor was multifocality. We believe that a complete thyroidectomy is mandatory in these cases.
- Serum Leptin Levels in Relation to Quantitative Ultrasound Values of Calcaneus in Korean Postmenopausal Women in Chung-Up District.
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Sang Wook Kim, Jung Min Koh, Ha Young Kim, Duk Jae Kim, Ghi Su Kim
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J Korean Endocr Soc. 2002;17(1):79-86. Published online February 1, 2002
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Obese postmenopausal women usually have a tend to have greater bone mineral density than lean women. This has been attributed to either the mechanical effects of their excessive weight on bone tissue or to their high body fat content. A recent study demonstrated that leptin, the hormone produced in adipocytes, acts on bone metabolism. These findings have prompted speculations on the possible role of leptin in the protective effect of obesity on bone. METHEODS: We studied the relationship between serum leptin levels and quantitative ultrasound (QUS) values of calcaneus in 94 postmenopausal Korean women who were randomly selected from the population of the Chung-Up osteoporosis prevalence study. QUS values, broadband ultrasound attenuation and speed of sound; were measured at the calcaneus. RESULTS: Leptin values were strongly correlated with body mass index (r = 0.478, p< 0.001), confirming a positive relationship between leptin levels and fat mass. In contrast, no significant correlations were observed between serum leptin levels and calcaneal QUS values. CONCLUSION: Our results suggest that circulating plasma leptin does not have a significant influence on QUS values of calcaneus in Korean postmenopausal women.
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