• Journal of Yeungnam Medical Science
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• 제16권2호
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• pp.155-168
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• 1999

Osteoporosis is one of the most important public health problems facing the aging population. Drug therapy for osteoporosis can be divided operationally into two main categories: drugs that inhibit bone resorption, and thus reduce bone turnover, and those that stimulate bone formation, exerting an anabolic effect. Antiresorptive agents such as estrogens, calcitonin, and bisphosphonates are most effective in the prevention of osteoporosis. Formation-stimulating agents such as sodium fluoride or monofluorophosphate, parathyroid hormone fragments, and anabolic steroids are of potential value in the treatment of established osteoporosis, where bone mass is already low and benefit from antiresorptive drugs is likely to be small Recently, raloxifene, a selective estrogen receptor modulator, has become available in various countries for clinical use in the treatment of involutional osteoporsis. This paper will review the use of these drugs in postmenopausal woman.

• Archives of Plastic Surgery
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• 제36권5호
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• pp.525-530
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• 2009

Purpose: The hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) are widely used in the treatment of dyslipidemia for the lowering of cholesterol. And studies about simvastatins have been shown to enhance bone formation in vitro and in vivo in rodents. But some other researchers have reported that there was no anabolic effect abouts simvastatins on bone. The peripheral distribution beyond the liver represents a small fraction of an orally administered dose. We hypothesize that this poor peripheral distribution is the likely reason that simvastatins, yield ambiguous results as anabolic agents. We therefore investigated whether the effects of simvastatins on bone may be enhanced by subcutaneous administration, providing better peripheral delivery of these drugs. Methods: 36 rat unilaterally mandible fractured models were prepared and divided into two groups. The simvastatin treated group where 1 mg/kg of simvastatin was daily injected subcutaneously. The same dose of normal saline was injected on the control group. And 3 rats in each group were sacrificed and taken bone samples in each week. Bone sample was evaluated with tensile strength and histological morphology after 1, 2, 3, 4, 5 and 6 weeks. Results: In simvastatin treated group, the fracture healing process, chondrocyte aggregation, collagen formation and trabecular bone formation was rapidly proceeded than the control group in histologically. The tensile strength of the simvastatin treated group was 1.02, 2.25, 3.95, 4.42, 5.49 and $6.00N/mm^2$ by weeks. The control group data was 0.60, 1.05, 2.17, 3.75, 4.15 and $5.17N/mm^2$ by weeks. The average tensile strength was higher by $1.04N/mm^2$ in simvastatin treated group. Conclusion: The currently available data on the effects of simvastatin on bone has done to confirm the finding that simvastatin helps fracture healing. And the potential for simvastatin to be used as anabolic agents for bone when delivered by the subcutaneous route.

• 한국한의학연구원논문집
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• 제13권1호통권19호
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• pp.139-145
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• 2007

Emodin is one of the main active components of a traditional Korean medicine isolated from the root and rhizomes of Rheum palmatum L. In this study, of 222 natural compounds to evaluate the anabolic activities, emodin activated bone morphogenetic protein (BMP)-2 promoter in the differentiation process of mouse osteoblastic MC3T3-E1 cells. Emodin was shown to significantly stimulate the activity and expression of alkaline phosphatase, an earlyphase marker of osteoblastic differentiation, on the differentiation day 7, and induce the osteopontin mRNA expression from the differentiation day 14. In addition, low concentration (up to 5 M) of emodin dramatically promoted the induction of mineralization in MC3T3-E1 subclone 4 cells. The stimulatory effect of emodin on the osteoblast differentiation/mineralization could be associated with its potential to stimulate the BMP-2 gene expression. Although further studies are needed to determine the precise mechanism, this study suggests that the use of herbal medicine containing natural compounds with anabolic activity such as emodin could have a beneficial effect on bone health.

• 대한의생명과학회지
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• 제9권1호
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• pp.15-19
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• 2003

Parathyroid hormone has clearly emerged as the most promising new anabolic treatment for osteoporosis by increasing the activation of osteoblast. It is known that chlorella increases both bone mineral density (BMD) and the rate of bone formation. The purpose of the present study was to determine whether the chlorella dietary supplementation could effect the thyroid or parathyroid hormones associated with increased BMD and bone formation. Twenty-two postmenopausal woman were treated for four month with 4 gm of chlorella dietary supplementation per day, then assessed serum calcium,25 OH vitamin D$_3$, thyroid hormone and parathyroid hormone before and after treatment. The mean 25 OH vitamin D$_3$ and parathyroid hormone were shown to marked increases by 193% and 265% respectively, in contrast to decreases by 9.4%, 37%, 33% and 14% in serum calcium, triiodo-thyroxine, free thyroxine and thyroxine stimulation hormone. In conclusion, treatment of postmenopausal women with chlorella dietary supplementation resulted in an increase in BMD and bone formation through enhancement of parathyroid hormone and 25 OH vitamin D$_3$, and a decrease in thyroid hormones.

• 셀메드
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• 제8권3호
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• pp.13.1-13.8
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• 2018

In the field of osteoporosis, there has been growing interest in anabolic agents that enhance bone formation. The purpose of this study was to examine the effects of NNMBS 246 osteoblastic differentiation with associated signaling pathways. NNMBS 246 markedly increased alkaline phosphatase (ALP) activity and calcium nodule formation. Stimulation with NNMBS 246 not only increased the differentiation markers (ALP, OPN, OCN) level and transcription markers (RUNX2, Osterix) mRNA expression but also upregulated the ECM molecules and OPG mRNA expression. Treatments of NNMBS 246 downregulated MMPs (MMP-1, MMP-2, MMP-9), but RANKL mRNA expression. Furthermore, NNMBS 246 activated osteoblastic differentiation markers and formed calcium nodules in human periodontal ligament cells (hPDLCs) and cementoblast cells. NNMBS 246 induced phosphorylation of MAPKs, Akt, nuclear p65 and IkB-${\alpha}$. BMP-2/Smad and ${\beta}$-catenin signaling pathways were activated by NNMBS 246. Sirtinol (SIRT1 inhibitor) inhibited NNMBS 246-induced osteoblastic differentiation markers mRNA expression. These results suggested that NNMBS 246 has the potential to enhance osteoblastogenesis probably through the activation of BMP/Smad and ${\beta}$-catenin signal pathways, and SIRT1 plays as critical mediator in bone anabolic effect of NNMBS 246.

• Journal of Periodontal and Implant Science
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• 제26권2호
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• pp.448-468
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• 1996

To maintain its functional integrity, bone is continuously remodelled by a process involving resorption by osteoeclasts and formation by osteoblasts, In order to respond to changes in the physical environment or to trauma with the relevant action, this process is strictly regulated by locally synthesized or systemic fators, Prostaglandin $E_2(PGE_2$) is perhaps one of the best studied factors, having been known to affect bone cell function for several decades.$PGE_2$ has both anabolic and catabolic activities. Excess of $PGE_2$ has been implicated in a number of pathological states associated with bone loss in a number of chronic inflammatory conditions such as periodontal disease and rheumatoid arthritis. $PGE_2$ and other arachidonic acid metabolites have been shown to be potent stimulators of osteoclastic bone resorption in organ culture. The anabolic effects of $PGE_2$ were first noticed when an increase in periosteal woven bone formation was seen after the infusion of $PGE_2$ into infants in order to prevent closure of the ductus arteriosus. The cellular basis for the catabolic actions of $PGE_2$ has been well characterized. $PGE_2$increases osteoclast recruitment in bone marrow cell cultures. Also $PGE_2$ has a direct action on osteoclast serving to inhibit activity and can also indirectly activate osteoclast via other cells in the vicinity, presumably osteoblast. The cellular mechanisms for the anabolic actions of $PGE_2$ are not nearly so well understood. The purpose of this paper was to study the effects of $PGE_2$ and dibutyl(DB)cAMP on osteoblastic clone MC3T3El cells and on the generation of osteoclasts from their precursor cells. The effect of $PGE_2$ and DBcAMP on the induction of alkaline phoaphatase(AlP) was investigated in osteoblastic clone MC3T3El cells cultured in medium containing 0.4% fetal bovine serum. $PGE_2$ and DBcAMP stimulated ALP activity and MTT assay in the cells in a dose-dependent manner at concentrations of lO-SOOng/ml. Cycloheximide, protein synthesis inhibitor, inhibited the stimulative effect of $PGE_2$ and DBcAMP on ALP activity in the cells. $PGE_2$also increased the intracellular cAMP content in a dose-dependent fashion with a maximal effect at 500ng/ml. The effect of $PGE_2$ on the generation of osteoclasts was investigated in a coculture system of mouse bone marrow cells with primary osteoblastic cells cultured in media containing 10% fetal bovine serum.After cultures, staining for tartrate-resistant acid phosphatase(TRAP)-marker enzyme of osteoclast was performed. The TRAP(+) multinucleated cells(MNCs), which have 3 or more nuclei, were counted. More TRAP(+) MNCs were formed in coculture system than in control group. $PGE_2(10^{-5}10^{-6}M)$ stimulated the formation of osteoclast cells from mouse bone marrow cells in culture. $PGE_2(10^{-6}M)$ stimulated the formation of osteoclast cells from mouse bone marrow cells in coculture of osteoblastic clone MC3T3E1 cells This results suggest that $PGE_2$ stimulates the differentiation of osteoblasts and generation of osteoclast, and are involved in bone formation, as well as in bone resorption.

• Journal of Korean Dental Science
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• 제8권2호
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• pp.65-73
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• 2015

Purpose: Parathyroid hormone (PTH) therapy has drawn attention, as an alternative to anti-resorptive drugs since PTH accelerates bone density by anabolic action. The purpose of this study was to identify the effect of intermittent PTH administration on jaw bones of rat undergone bilateral ovariectomy. Materials and Methods: Nine female Sprague-Dawley rats were divided into three groups. PTH group was ovariectomized (OVX) to induce osteoporosis and PTH $30{\mu}g/kg$ was administered 1 week after the surgery. In OVX group, ovariectomy was performed and only vehicle was administered by subcutaneous injection 3 times per week. Control group was subjected to sham surgery. The animals were sacrificed 8 weeks after the surgery and specimens were obtained from ilium and upper and lower jaw bones. Histological investigation was carried out by using an optical microscope and micro-computed tomography was taken to examine structural property changes in each bone sample. Result: In the ilium, the bone volume ratio (bone volume/total volume, BV/TV) of PTH, OVX and control groups was $53.75%{\pm}7.57%$, $50.61%{\pm}12.89%$, $76.20%{\pm}5.92%$ (P=0.061) and bone mineral density (BMD) was $1.12{\pm}0.09$, $0.88{\pm}0.48$, $1.38{\pm}0.07g/cm^3$ (P=0.061). In the mandible, BV/TV of PTH, OVX and control groups was $64.60%{\pm}12.17%$, $58.26%{\pm}9.63%$, $67.54%{\pm}14.74%$(P=0.670) and BMD was $1.21{\pm}0.17$, $1.19{\pm}0.13$, $1.27{\pm}0.18g/cm^3$ (P=0.587). In the maxilla, BV/TV of PTH, OVX and control groups was $61.19%{\pm}8.92%$, $52.50%{\pm}11.22%$, $64.60%{\pm}12.17%$ (P=0.430) and BMD was $1.20{\pm}0.11$, $1.11{\pm}0.16$, $1.21{\pm}0.17g/cm^3$ (P=0.561). No statistically significant difference was found in any variables in all groups. Histological observation revealed that the ilium in OVX group demonstrated sparsely formed trabecular bones compared with other groups. However, upper and lower trabecular bones did not present significant differences. Conclusion: Intermittent administration of PTH appears to affect the microstructure of rat jaw bones, but statistical significance was not found. However, the measurements in this study partly implicated the possible anabolic effect of PTH in vivo.

• International Journal of Oral Biology
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• 제42권4호
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• pp.163-168
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• 2017

Osteoporosis is a metabolic bone disease that is characterized by low bone mass resulting from an increase in bone resorption relative to bone formation. The most current therapies for osteoporosis have focused on inhibiting bone resorption by osteoclasts. The purpose of this study is to develop new anabolic agents for treatment of osteoporosis that have fewer risks compared to conventional therapies. We searched the natural products that were derived from the traditional Asian medicines which have been used for treatment of bone related diseases. Icaritin is a flavonoid glycoside derived from the herb Epimedium which has beneficial effects on bone formation. To determine the effect of icaritin on bone formation, we examined the effect of icaritin on MC3T3-E1 cell proliferation and differentiation. For determining the effects of icaritin on proliferation, we performed the MTT assay using MC3T3-E1 cells. To evaluate whether icaritin could promote the osteogenic differentiation of MC3T3-E1 cells, alkaline phosphatase (ALP) activity and mRNA expressions of Runx2, osteocalcin (OCN), RANKL, and osteoprotegerin (OPG) were determined. Icaritin increased MC3T3-E1 cell proliferation. Icaritin increased the ALP activity of MC3T3-E1 cells on 72 hour culture in osteogenic media. mRNA expression of Runx2 was increased after 24 hour culture with icaritin. mRNA expression of osteocalcin was increased after 72 hour culture with icaritin. In addition, icaritin increased the mRNA expressions of OPG and RANKL. However, icaritin increased the mRNA expression of OPG much more than that of RANKL, and then, it increased the OPG/RANKL ratio. These results suggest that icaritin promotes osteogenic differentiation of osteoblasts and decreases osteoclast formation regulated by osteoblasts.

• 한국임상수의학회지
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• 제22권4호
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• pp.336-341
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• 2005

개에서 Nandrolone decanoate(ND)의 수술 후 외고정 등에 의한 불용성 근위축과 골절 치유에 미치는 영향을 평가하기 위하여 본 실험을 실시하였다 $3.3\~5.5kg,\;2\~4$세의 건강한 잡종견 20두를 대조군(A군, 4두), 1.5mg/kg ND 투여군(수술 직후 투여 - B군, 8두), 7.5mg/kg ND 투여군(수술 직후 투여 - C군, 8두)으로 나누어 무작위로 실험에 사용하였다. 요골의 골간에 골절을 유발하여 1mm 간격을 유지하며 plate로 고정하였다 ND (Deca-Durabolin 50mg/ml, 한화제약 주식회사)투여 군은 1.5mg/kg혹은 7.5mg/kg용량의 ND를 수술 직후, 일주일에 일회씩 근육 내로 8주간 투여하였다. 수술 후 4주간 로버트 존스 포대법을 실시한 후 제거하였다. 체중과 근육의 변화를 수술 직후, 수술 2, 4, 8주 후에 각각 측정하였다 ND 투여 후 4주와 8주에 조직학적 검사를 실시하였다. 근육량의 변화는 A, B 및 C 각 군에서 수술 8주 후에 수술 전 근육량의 $-2.75\pm0.16\%,\;1.68\pm0.11\%$및 $1.74\pm0.48\%$의 변화를 보였다. 근육량은 대조군과 비교하여 투여군에서 투여 4주 후부터 유의적으로 증가하였다 (p<0.05). 투여군에서 용량 의존적 차이는 보이지 않았다. 조직학적 평가에서 ND투여 4주 후 투여군에서 골절된 골 사이에 형성된 섬유 결합조직층이 대조군과 비교하여 더 많이 형성되었다. 5주 후 투여군에서 섬유결합 조직층이 더욱 치밀해졌다. 이상의 결과로 보아 ND투여는 수술 후 외고정 등에 의한 불용성 근위축의 예방과 골절 치유에 유용할 것으로 사료된다.

• 한국웰니스학회지
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• 제7권2호
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• pp.101-111
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• 2012

The benefits and risks of whole body vibration (WBV) based acceleration training on the human body have been documented for many years. WBV training has been shown to increase muscular strength, explosive power, bone strength, performance, mobility, cardiovascular function, circulation and anabolic hormone level and so on. The purpose of this review is correct understanding and application of WBV training. Without proper understanding, rather, to apply WBV to the human body can be fatal harm, and therefore know that what is vibration and has advantages and disadvantages. If there is anything positive side there is bound to the negative aspects. In this regard, WBV training can have a positive impact on the already confirmed by several studies and also, there have been scientifically proven. But still we are part of a scientific approach that is acceptable even to keep in mind that you will always coexist. Once again, the effect of WBV with a physical stimulus that risk and should be remembered. In addition, given the momentum and how to exercise and well-being well aware that vibration exercise as a way to think of how not to be familiar with.