• Journal of Korean Academy of Oral and Maxillofacial Radiology
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• v.19 no.1
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• pp.69-87
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• 1989

It is well known that the glucocorticoid induces osteoporosis by suppression of the osteoblast, but its effect on the osteoclast hRS some controversy whether it activates or suppresses the osteoclast. If the calcitonin, which is known to suppress the osteoclast, prevents the osteoporosis by glucocorticoid, then the suppression of the osteoclast by the glucocorticoid is not so significant. And if the calcitonin increases the osteoblastic activity, Tc-99m MDP uptake will be increased in spite of the glucocorticoid effect on the osteoblast. The immobilization operation was performed to the right leg of male Wistar rats weighing about 200gm. each. For 16 weeks after operation, rats were injected glucocorticoid alone or glucocorticoid anci calcitonin. The bone density was measured by means of photodensitometry under reference aluminum step wedge and Tc-99m MDP uptake was available to the index of the osteoblastic activity. 1. The bone density of femora! head was markedly reduced than that of femoral shaft following ration of cancellous and cortical components in both site. 2. Glucocorticoid caused decrease in bone density of spine and femur, md there is significantly increase of it when medication of glucocorticoid and calcitonin injection simultaneously than that of glucocorticoid. 3. Tc-99m MDP uptake was revealed significant reduction in medication of glucocorticoid but increase in gi;.:cocorticoid and calcitonin injection simultaneously in later experimental period. 4. There wail, a slight reduction in plasma osteocalcin in medication of glucocorticoid through experimental periods and an increase in its value in case of giving glucocorticoid and calcitonin simultaneously in later experimental period. From these results, we suggest that osteoporosis by immobilization is more pronounced by glucocorticoid hormone and osteoporosis induced by immobilization and glucocorticoid use is prevented by calcitonin administration with increasing osteoblastic activity.

• Journal of Nutrition and Health
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• v.52 no.4
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• pp.323-331
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• 2019

Purpose: Glucocorticoids (GCs) are implicated in secondary osteoporosis, and the resulting fractures cause significant morbidity. Polyunsaturated fatty acids (PUFAs) play a vital role in bone metabolism. However, few trials have studied the impact of omega-3 PUFA-containing oils against GC-induced osteoporosis. Therefore, the present study was undertaken to determine whether supplementation with omega-3 PUFA-containing dietary oils such as fish oil, flaxseed oil or soybean oil can impede the development of GC-induced osteoporosis. Methods: The fatty acids (FAs) content of oils was determined using gas chromatography. Male rats were subdivided into 5 groups (8 rats each): normal control (balanced diet), prednisolone control (10 mg/kg prednisolone daily), soybean oil (prednisolone 10 mg/kg + soybean oil 7% w/w), flaxseed oil (prednisolone 10 mg/kg + flaxseed oil 7% w/w), and fish oil (from cod liver; prednisolone 10 mg/kg + fish oil 7% w/w). Results: The study data exhibited a significant depletion in bone mineral density (BMD) and femur mass in the prednisolone control compared to the normal control, accompanied with a marked decrease in the levels of plasma calcium and 1,25-$(OH)_2$-vitamin $D_3$, and elevated levels of C-terminal telopeptide (CTX), tumor necrosis factor-alpha (TNF-${\alpha}$) and malondialdehyde (MDA). Supplementation with fish oil, soybean oil or flaxseed oil helped to improve plasma calcium levels, and suppress oxidative stress and inflammatory markers. Additionally, bone resorption was suppressed as reflected by the decreased CTX levels. However, fish oil was more effective than the other two oils with a significant improvement in BMD and normal histological results compared to the normal control. Conclusion: This study demonstrated that supplementation with dietary oils containing omega-3 PUFAs such as fish oil, soybean oil or flaxseed oil can play a role in the prevention of bone loss and in the regulation of bone metabolism, especially fish oil which demonstrated a greater level of protection against GC-induced osteoporosis.

• Biomolecules & Therapeutics
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• v.20 no.1
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• pp.89-95
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• 2012

Poncirus trifoliata fruit (PTF) affects the digestive and cardiovascular systems, and kidney function. The authors studied the effects of ethyl acetate (EtOAc) extract of PTF on the activities of osteoblasts and in an animal model. The main compounds of the EtOAc extract, naringin and poncirin have been confirmed by HPLC and NMR analysis. Effects of osteoblastic differentiation were measured by alkaline phosphatase (ALP) activity, osteopontin (OPN) protein expression and osteoprotegerin (OPG) mRNA expression in MC3T3-E1 cells. Also, osteoclast differentiation was measured by multinucleated cells (MNCs) formation through tartrate resistance acid phosphatase (TRAP)-positive staining. Bone mineral density (BMD) was measured before and after treatment with EtOAc extract of PTF in prednisolone-induced osteoporotic mice. Dexamethasone (DEX) decreased OPN and OPG expression level in MC3T3-E1 cells and ALP activity was decreased by DEX dose-dependently. EtOAc extract of PTF recovered the levels of ALP activity, and the expression of OPN and OPG in MC3T3-E1 cells treated with DEX. In osteoclast differentiation, multinucleated TRAP-positive cell formation was significantly suppressed by the EtOAc extract of PTF. Total body BMD was restored by EtOAc extract of PTF in prednisolone-induced osteoporotic mice. In conclusion, EtOAc extract of PTF recovered DEX-mediated deteriorations in osteoblastic and osteoclastic functions, and increased BMD in glucocorticoid-induced osteoporosis.

• The Journal of Korean Obstetrics and Gynecology
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• v.29 no.2
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• pp.15-28
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• 2016

Objectives : The purpose of this study is to evaluate the effect of water extract of Samki-eum Gamibang (SKG) on osteoblast proliferation in murine calvarial cells. Methods : The osteoblast separated from calvariae of murine was cultivated and evaluated the function of cell. After the addition of SKG on the culture medium, we investigated the effect of SKG on the cell viability, cell proliferation, alkaline phosphatase (ALP) activity, bone matrix protein synthesis and collagen synthesis of the cultivated osteoblast.Results : SKG increased the survival rate and proliferation of rat calvarial osteoblast. SKG increased ALP activity, bone matrix protein synthesis and collagen synthesis of rat calvarial osteoblast. Conclusions : This study suggests that SKG has effect on glucocorticoid-induced osteoporosis (GIO) resulting from increase of osteoblast function.

• Proceedings of the Korean Society of Veterinary Pathology Conference
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• 2003.10a
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• pp.19-19
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• 2003

Osteoporosis is usually considered a disease of older women reported the rate, pattern and determinants of bone loss, far less information is available for men although it is also common in men [1,2]. The three major causes of osteoporosis in men are excessive alcohol intake, long-term glucocorticoid therapy, and hypogonadism [3,4]. In process of bone resorption, type I collagen crosslinking molecules, pyridinoline (PYD) are released into the circulation and cleared by the kidney. $^2$H$_2$O as a tracer has been applied to measure synthesis rates of slow-turnover proteins and successfully applied to bone collagen synthesis, skeletal muscle and cardiac muscle in rat. The objective of this study was to examine osteoporosis and alcohol-induced changes of femur and liver in post-menopausal males using the developed method. (omitted)

• The Korean Journal of Nuclear Medicine
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• v.24 no.1
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• pp.108-118
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• 1990

It is well known that the glucocorticoid suppresses the osteoblast and the calcitonin suppresses the osteoclast. If the calcitonin prevents the osteoporosis with increased Tc-99m MDP uptake in the long-term use of glucocorticoid, then the calcitonin has some activating effect on the bone formation. The immobilization operation was done on the left hind-leg of 16 male Sprague-Dawley rats weighing about 300 g each. For 12 weeks after operation,8 rats were injected 0.5 mg/kg dexamethasone, and the other 8 rats were injected 0.5 mg/kg dexamethasone and $1\;\bar{u}/kg$ eel calcitonin. The bone mineral content was measured by the single photon absorptiometry and the Tc-99m MDP uptake was used as an index of the osteoblastic activity. 1) The Tc-99m MDP uptakes in the dexamethasone treated group were lower than those in the dexamethasone and calcitonin treated group, and there was no significant difference in Tc-99m MDP uptakes between the immobilized and normal femurs. 2) The bone mineral contents in the dexamethasone treated group were significantly lower than in the dexamethasone and calcitonin treated group, and the immobilized femurs had tower BMC than normal femurs. 3) The slope of regression between the BMC and Tc-99m MDP uptake was stiff in the dexamethasone treated group, and flat in the dexamethasone and calcitonin group, which shows discrepancy between the bone resorption and formation resulting prevention of net bone loss in the dexamethasone and calcitonin treated group. In conclusion, the calcitonin has some effect on the bone formation, and further studies with urinary hydroxyproline and cyclic AMP are expected.

• Journal of Ginseng Research
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• v.39 no.1
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• pp.46-53
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• 2015

Background: Glucocorticoids (GCs) are commonly used in many chemotherapeutic protocols and play an important role in the normal regulation of bone remodeling. However, the prolonged use of GCs results in osteoporosis, which is partially due to apoptosis of osteoblasts and osteocytes. In this study, effects of Korean Red Ginseng (KRG) on GC-treated murine osteoblastic MC3T3-E1 cells and a GC-induced osteoporosis mouse model were investigated. Methods: MC3T3-E1 cells were exposed to dexamethasone (Dex) with or without KRG and cell viability was measured by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Realtime polymerase chain reaction was performed to evaluate the apoptotic gene expression; osteogenic gene expression and alkaline phosphatase (ALP) activity were also measured. Western blotting was performed to evaluate the mitogen-activated protein kinase (MAPK) proteins. A GC-induced osteoporosis animal model was used for in vivo study. Results and conclusion: The MTT assay revealed that Korean Red Ginseng (KRG) prevents loss of cell viability caused by Dex-induced apoptosis in MC3T3E1 cells. Real-time polymerase chain reaction data showed that groups treated with both Dex and KRG exhibited lower mRNA levels of caspase-3 and -9, whereas the mRNA levels of Bcl2, IAPs, and XIAP increased. Moreover, groups treated with both Dex and KRG demonstrated increased mRNA levels of ALP, RUNX2, and bone morphogenic proteins as well as increased ALP activity in MC3T3-E1 cells, compared to cells treated with Dex only. In addition, KRG increased protein kinase B (AKT) phosphorylation and decreased c-Jun N-terminal kinase (JNK) phosphorylation. Moreover, microcomputed tomography analysis of the femurs showed that GC implantation caused trabecular bone loss. However, a significant reduction of bone loss was observed in the KRG-treated group. These results suggest that the molecular mechanism of KRG in the GC-induced apoptosis may lead to the development of therapeutic strategies to prevent and/or delay osteoporosis.

• Journal of Bone Metabolism
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• v.25 no.4
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• pp.195-211
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• 2018

Background: To develop guidelines and recommendations to prevent and treat glucocorticoid (GC)-induced osteoporosis (GIOP) in Korea. Methods: The Korean Society for Bone and Mineral Research and the Korean College of Rheumatology have developed this guideline based on Guidance for the Development of Clinical Practice Guidelines ver. 1.0 established by the National Evidence-Based Healthcare Collaborating Agency. This guideline was developed by adapting previously published guidelines, and a systematic review and quality assessment were performed. Results: This guideline applies to adults aged ${\geq}19years$ who are using or plan to use GCs. It does not include children and adolescents. An initial assessment of fracture risk should be performed within 6 months of initial GC use. Fracture risk should be estimated using the fracture-risk assessment tool (FRAX) after adjustments for GC dose, history of osteoporotic fractures, and bone mineral density (BMD) results. All patients administered with prednisolone or an equivalent medication at a dose ${\geq}2.5mg/day$ for ${\geq}3months$ are recommended to use adequate calcium and vitamin D during treatment. Patients showing a moderate-to-high fracture risk should be treated with additional medication for osteoporosis. All patients continuing GC therapy should undergo annual BMD testing, vertebral X-ray, and fracture risk assessment using FRAX. When treatment failure is suspected, switching to another drug should be considered. Conclusions: This guideline is intended to guide clinicians in the prevention and treatment of GIOP.

• Childhood Kidney Diseases
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• v.8 no.1
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• pp.33-42
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• 2004

Purpose : Children with nephrotic syndrome(NS) are under high risk for metabolic bone disease(MBD) as a complication of long-term glucocorticoid therapy. We prospectively evaluated the effect of oral bisphosphonate(alendronate) therapy in children with NS, which has proven efficacy in adult patients with glucocorticoid induced MBD. Methods : Among 58 children with NS, aged 5 to 8 years and haying a disease duration of more than 2 years, 30(51.7%) were enrolled to meet the selection criteria, less than -1.0 Z-scores of lumbar spine bone mineral density(BMD) by dual energy X-ray absorptiometry (DEXA). These 30 children were divided into three groups and each were assigned to receive alendronate, calcitriol, and no-medication, respectively for one year. Lumbar spine BMD was followed up every 6 months and the biochemical indexes were measured before and 1 year after the treatment. There were no significant difference among groups with respect to the average age, the initial BMD, and the cumulative steroid doses. Analysis of the treatment efficacy was done by the % change of BMD and by the changes in Z-scores of lumbar spine BMD. Results : Mean age and disease duration of patients at the initial lumbar spine BMD evaluation was $7.4{\pm}1.7$ years and $2.2{\pm}1.2$ years, respectively. Twenty-three of 30 children(76%) had osteopenia, and seven(23%) had osteoporosis. There was no difference in the biochemical values among the groups, before and 1 year after the treatment(P<0.05). Twenty two children(73.3%) with frequent relapsing or steroid dependant NS had more frequent MBD, compared to the 8 children(26.6%) with infrequent relapsing NS. The one year % changes of BMD were 8.56 in alendronate group, 5.79 in calcitriol group, and 1.9 in no-medication group. The changes in Z-score of lumbar spine BMD increased in the alendronate group and the calcitriol group, but not in the no-medication group. One year % changes of BMD were different among groups(P=0.0002). Significant differences were found between the alendronate and the no-medication group, and between the calcitriol and the no-medication group(P<0.05). There was no difference between the alendronate and the calcitriol group. No serious adverse effect was observed in the alendronate group. Conclusion : Children with NS receiving high dose steroids are under the high risk of BMD and should undergo regular BMD evaluation. Z-score of lumbar spine BMD was a useful parameter in diagnosing low bone mass in children. Alendronate weekly oral therapy was effective and relatively safe in increasing the lumbar spine BMD in children with NS having steroid induced MBD.

• Childhood Kidney Diseases
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• v.18 no.2
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• pp.92-97
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• 2014

Purpose: Bisphosphonates are widely used for the management steroid-induced osteoporosis (SIO) in children. With the increasing use of bisphosphonates, there have been reports of abnormal radiological findings in the growing skeleton. Therefore, their use in pediatric patients remains controversial. The present study was conducted to evaluate the long-term follow-up radiographic features, particularly metaphyseal sclerotic lines, in children who receive pamidronate therapy for nephropathy. Methods: Twenty-four children with nephropathy treated with oral calcium and pamidronate (mean duration, 9 months; dose, 100 mg daily), were evaluated retrospectively. All patients had SIO secondary to chronic glucocorticoid therapy for treating nephropathy. Long bone radiographic imaging was performed before treatment with pamidronate, and at follow-up, several years later. Physeal growth rates were estimated by measuring the distance that the sclerotic lines moved on the radiographs during the corresponding time intervals. Results: The mean follow-up period was 138 months. Long bone radiographs showed well-defined sclerotic lines at the metaphyseal ends, progressively moving from the physeal plate to the diaphysis, in all patients. The mean rate of movement of the sclerotic line was 6.21 mm per year. In 12 patients, the lines disappeared. The mean rate of growth in height was 7.33 cm per year. Conclusions: Results of long-term follow-up suggest that the metaphyseal sclerotic lines associated with pamidronate treatment tend to disappear without affecting overall skeletal growth. Bisphosphonate treatment for SIO in children with nephropathy seems to be safe, although further studies in larger number of patients are needed.