1.Bone Biology and Anabolic Therapies for Bone: Current Status and Future Prospects.
Journal of Bone Metabolism 2014;21(1):8-20
Bone is continuously remodelled at many sites asynchronously throughout the skeleton, with bone formation and resorption balanced at these sites to retain bone structure. Negative balance resulting in bone loss and osteoporosis, with consequent fractures, has mainly been prevented or treated by anti-resorptive drugs that inhibit osteoclast formation and/or activity, with new prospects now of anabolic treatments that restore bone that has been lost. The anabolic effectiveness of parathyroid hormone has been established, and an exciting new prospect is presented of neutralising antibody against the osteocyte protein, sclerostin. The cellular actions of these two anabolic treatments differ, and the mechanisms will need to be kept in mind in devising their best use. On present evidence it seems likely that treatment with either of these anabolic agents will need to be followed by anti-resorptive treatment in order to maintain bone that has been restored. No matter how effective anabolic therapies for the skeleton become, it seems highly likely that there will be a continuing need for safe, effective anti-resorptive drugs.
Anabolic Agents
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Bone and Bones
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Bone Density Conservation Agents
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Osteoclasts
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Osteocytes
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Osteogenesis
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Osteoporosis
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Parathyroid Hormone
;
Skeleton
2.Strategies of Spinal Fusion on Osteoporotic Spine.
Sung Bae PARK ; Chun Kee CHUNG
Journal of Korean Neurosurgical Society 2011;49(6):317-322
The prevalence of osteoporosis has been increasing globally. Recently surgical indications for elderly patients with osteoporosis have been increasing. However, only few strategies are available for osteoporotic patients who need spinal fusion. Osteoporosis is a result of negative bone remodeling from enhanced function of the osteoclasts. Because bone formation is the result of coupling between osteoblasts and osteoclasts, anti-resorptive agents that induce osteoclast apoptosis may not be effective in spinal fusion surgery, necessitating new bone formation. Therefore, anabolic agents may be more suitable for osteoporotic patients who undergo spinal fusion surgery. The instrumentations and techniques with increased pullout strength may increase fusion rate through rigid fixation. Studies on new osteoinductive materials, methods to increase osteogenic cells, strengthened and biocompatible osteoconductive scaffolds are necessary to enable osteoporotic patients to undergo spinal fusion. When osteoporotic patients undergo spinal fusion, surgeons should consider appropriate osteoporosis medication, instrumentation and technique.
Aged
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Anabolic Agents
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Apoptosis
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Bone Remodeling
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Durapatite
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Humans
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Osteoblasts
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Osteoclasts
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Osteogenesis
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Osteoporosis
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Prevalence
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Spinal Fusion
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Spine
3.Spontaneous Corpus Cavernosum Abscess in a Healthy Man Using Long-Term Androgenic Anabolic Steroids.
The World Journal of Men's Health 2015;33(1):36-38
Abscess formation of the corpus cavernosum is very rare. Here, we report a case of long-term anabolic androgenic steroid (AAS) abuse that is suspected to have facilitated the development of a corpus cavernosum abscess in a healthy bodybuilder. Cultures obtained from the abscess contained Staphylococcus epidermidis, a microorganism that almost exclusively affects immunocompromised patients. Therefore, prompt drainage of pus from cavernosal bodies should be the primary aim of the treatment. This case illustrates the potential danger of AAS suppressing the immune system and causing a serious infection.
Abscess*
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Anabolic Agents
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Drainage
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Immune System
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Immunocompromised Host
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Staphylococcus epidermidis
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Steroids*
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Suppuration
4.Anabolic Effects of Recombinant Human Parathyroid Hormone (1-84) on Bone Histomorphometry in Overiectomized Rats.
Young Jun WON ; Du Hong PARK ; Jae Hyun NAM ; Jong In YOOK ; Jin KIM ; Kyung Rae KIM ; Hyun Chul LEE ; Kap Bum HUH ; Sung Kil LIM
Journal of Korean Society of Endocrinology 1999;14(1):81-90
To evaluate the anabolic effects of human recombinant parathyroid hormone [hrPTH(1-84)], we examined effect of low-dose and high-dose of [hrPTH(1-84)] and estradiol on bone histomorphometry in ovariectomized rats. Sixty Sprague-Dawley female rats aged 8~10 weeks were used. Eight weeks after ovariectomy, or sham operation, rats were given daily sc injection of hrPTH (1-84), 30 pg/kg (OVX+L group), 150 pg/kg (OVX+H group), 17-estradiol (30 pg/kg, OVX+E group) or vehicle (OVX+V group) for 4 weeks. After double tetracycline labeling, all rats were killed at day 84. We completed the histomorphometric analysis of distal femoral metaphyseal cancellous bone for trabecular bone volume (TBV), mean trabecular plate thickness (MTPT), mean trabecular plate density (MTPD), mean trabecular plate separation (MTPS), mean osteoid seam width (OSW) and appositional rate (AR). The histomorphometric parameters (TBV, MTPT, OSW and AR) of trabecular bone mass in (OVX+E) group were higher than those in (OVX+V) group. The TBV of trabecular bone in PTH treated groups were higher than that in sham operated, (OVX+V) and (OVX+E) group. The histomorphometric parameters (TBV, MTPD, OSW and AR) of trabecular bone mass in (OVX+H) group showed a tendency to be higher than those in (OVX+L) group, but statistically not significant. In conclusion, Low dose (30 mg/kg) hrPTH (1-84) also shows a sufficient anabolic effect on trabecular bone.
Anabolic Agents*
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Animals
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Estradiol
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Female
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Humans*
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Ovariectomy
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Parathyroid Hormone*
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Rats*
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Rats, Sprague-Dawley
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Tetracycline
5.Supraphysiologic glucocorticoid administration increased biomechanical bone strength of rats' vertebral body.
Azam NAJAR ; Mohammadjavad FRIDONI ; Fatemesadat REZAEI ; Saba BAYAT ; Mohammad BAYAT
Laboratory Animal Research 2015;31(4):180-187
The aim of this study is to assess the effects of different glucocorticoid administration protocols on biomechanical properties of the first lumbar vertebral body in rats. We divided 40 male rats into the following groups: control, dexamethasone (7 mg/week), dexamethasone (0.7 mg/week), methylprednisolone (7 mg/kg/week), methylprednisolone (5 mg/kg twice weekly), dexamethasone (7 mg/kg three times per week), dexamethasone (0.7 mg/kg three times per week, and low-level laser treated rats. Lumbar vertebrae in rats were exposed to the pulsed laser. We conducted a biomechanical test to examine the mechanical properties of vertebral body in rats' lumbar bone. Supraphysiologic glucocorticoid administration protocols did not impair the biomechanical properties of rats' vertebral bodies compared to control and laser-treated rats. Supraphysiologic glucocorticoid administration caused an anabolic effect on the vertebral bodies.
Anabolic Agents
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Animals
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Dexamethasone
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Humans
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Low-Level Light Therapy
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Lumbar Vertebrae
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Male
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Methylprednisolone
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Rats
6.Pleiotrophin (PTN) expression in osteoblastic cells
Byeongyol KIM ; Jaesuk RIM ; Jongjin KWON ; Hyonseok JANG ; Euiseok LEE ; Sangho JUN ; Youngjin KIM
Journal of the Korean Association of Maxillofacial Plastic and Reconstructive Surgeons 2007;29(6):494-498
anabolic effects attributed to PDGF-BB stimulation was examined in cell culture models of osteoblast differentiation. These studies will contribute fundamental insights to osteoblast biology and insights regarding the potential use of factors such as PTN in the clinical environment.]]>
Anabolic Agents
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Biology
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Bone Matrix
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Cell Culture Techniques
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Cell Line
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Negotiating
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Osteoblasts
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Osteogenesis
7.The Effects of Simvastatin on Bone Healing in Mandible Fractured Rats.
Jae Oo JEONG ; Yong Seok KWON ; Seok Kwun KIM ; Keun Cheol LEE
Journal of the Korean Society of Plastic and Reconstructive Surgeons 2009;36(5):525-530
PURPOSE: The hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) are widely used in the treatment of dyslipidemia for lowering of cholesterol level. And the studies in simvastatins have shown to enhance bone formation in vitro and in vivo in rodents. But some other researchers have reported that simvastatins' anabolic effect on bone does not exist. The peripheral distribution beyond the liver represents a small fraction of an orally administered dose. We hypothesized 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 1mg/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 histologically. The tensile strength in the simvastatin treated group was measured as 1.02, 2.25, 3.95, 4.42, 5.49 and 6.00 N/mm2 each week, while it was 0.60, 1.05, 2.17, 3.75, 4.15 and 5.17 N/mm2 in the control group. The average tensile strength was higher by 1.04N/mm2 in simvastatin treated group. CONCLUSION: The currently available data on the effects of simvastatin on bone confirms that simvastatin helps fracture healing. And the potential for simvastatin to be used as anabolic agents for bone when delivered by the subcutaneous route.
Anabolic Agents
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Animals
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Cholesterol
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Chondrocytes
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Coenzyme A
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Collagen
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Dyslipidemias
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Fracture Healing
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Liver
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Mandible
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Osteogenesis
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Oxidoreductases
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Rats
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Rodentia
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Simvastatin
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Tensile Strength
8.Matrix Synthesis of Human Intervertebral Disc Cells: Effect of Gene Transfer, Exogenous Growth Factor, Incubation Period, and Culture Methods.
Seong Hwan MOON ; Moon Soo PARK ; Hwan Mo LEE ; Eung Shick KANG ; Nam Hyun KIM ; Lars G GILBERTSON ; James D KANG
Journal of Korean Society of Spine Surgery 2001;8(4):447-454
STUDY DESIGN: In vitro experiment to determine the matrix synthesis of intervertebral disc (IVD) cell to various biologic interventions and conditions. OBJECTIVES: To elucidate biologic responses in terms of matrix synthesis of human IVD cells in vitro to various factors i.e. concentration of adenoviral vector and exogenous growth factor, duration of incubation, and type of culture methods. SUMMARY OF LITERATURE REVIEW: Sophisticated method to delivery of growth factors, in continuous manner, is the genetic modification of disc cells through gene transfer. Direct comparison of gene transfer and exogenous growth factor on matrix synthesis has not been reported. MATERIALS AND METHODS: IVD tissue was obtained from twenty three patients. Isolation and preparation of disc cells in monolayer (D) and alginate beads (3D) culture were performed. Disc cells in 2D and 3D were treated with either Ad/TGF-beta1 or exogenous TGF-beta1. Control cultures were treated with either saline or Ad/luciferase. Matrix synthesis (newly synthesized proteoglycan) was measured in various conditions (concentration of adenoviral vector and exogenous growth factor, duration of incubation, and type of culture methods). Newly synthesized proteoglycan were analyzed using chromatography on Sephadex G-25 in PD-10 columns after S35-sulfate incorporation. RESULTS: Ad/TGF-beta1 showed increase in proteoglycan synthesis (plateau at 75MOI) in 3D culture, (plateau at 25MOI) in 2D culture. In 3D culture, Ad/TGF-beta1 showed significant increase in proteoglycan synthesis on day 1, 2, and 3 of incubation. In 2D culture, Ad/TGF-beta1 showed significant increase in proteoglycan synthesis on day 2 of incubation with significant loss of anabolic effect on day 3. In 3D culture, exogenous TGF-beta1 showed increase in proteoglycan synthesis (plateau at 2ng/ml) while in 2D culture, there is no synthetic response to exogenous TGF-beta1 CONCLUSION: Therapeutic gene transfer provided sustained and increased anabolic responses than exogenous growth factor.
Anabolic Agents
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Chromatography
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Genetic Therapy
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Humans*
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Intercellular Signaling Peptides and Proteins
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Intervertebral Disc*
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Proteoglycans
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Transforming Growth Factor beta1
9.Androgenic-anabolic steroids and the Olympic Games.
Asian Journal of Andrology 2008;10(3):384-390
Androgenic-anabolic steroids (AAS) have been misused by athletes at the Olympic Games, both before and after they were prohibited in sport in 1974. Systematic doping with AAS occurred in the German Democratic Republic (GDR) from 1965 to 1989 which assisted that country to win many medals at Olympic Games, especially in female events. Currently, AAS are the most frequent category of prohibited substances detected in the urine of athletes both globally and at the last two Summer Olympic Games. Scientific confirmation that AAS are effective in enhancing sports performance was difficult because ethical approval was difficult for research involving male subjects taking massive doses of androgens as some athletes and bodybuilders did. Methods to detect AAS have evolved gradually over the past three decades and currently, despite an impressive array of sophisticated analytical equipment and methods, anti-doping authorities and analytical scientists continue to face challenges as have occurred from the use by athletes of designer AAS during the past few years. The future development and use of selective androgen receptor modulators (SARMs) can be anticipated to pose problems in the years ahead. Endocrinologists should be aware that on occasions, replacement testosterone (T) therapy may be authorized in sport as a therapeutic use exemption (TUE) and these circumstances are discussed.
Anabolic Agents
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administration & dosage
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Androgens
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administration & dosage
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Chromatography, Gas
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Doping in Sports
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Humans
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Mass Spectrometry
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Radioimmunoassay
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Spectrophotometry, Atomic
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Sports
10.Regulation of Osteoblast Metabolism by Wnt Signaling.
Megan C MOORER ; Ryan C RIDDLE
Endocrinology and Metabolism 2018;33(3):318-330
Wnt/β-catenin signaling plays a critical role in the achievement of peak bone mass, affecting the commitment of mesenchymal progenitors to the osteoblast lineage and the anabolic capacity of osteoblasts depositing bone matrix. Recent studies suggest that this evolutionarily-conserved, developmental pathway exerts its anabolic effects in part by coordinating osteoblast activity with intermediary metabolism. These findings are compatible with the cloning of the gene encoding the low-density lipoprotein related receptor-5 (LRP5) Wnt co-receptor from a diabetes-susceptibility locus and the now well-established linkage between Wnt signaling and metabolism. In this article, we provide an overview of the role of Wnt signaling in whole-body metabolism and review the literature regarding the impact of Wnt signaling on the osteoblast's utilization of three different energy sources: fatty acids, glucose, and glutamine. Special attention is devoted to the net effect of nutrient utilization and the mode of regulation by Wnt signaling. Mechanistic studies indicate that the utilization of each substrate is governed by a unique mechanism of control with β-catenin-dependent signaling regulating fatty acid β-oxidation, while glucose and glutamine utilization are β-catenin-independent and downstream of mammalian target of rapamycin complex 2 (mTORC2) and mammalian target of rapamycin complex 1 (mTORC1) activation, respectively. The emergence of these data has provided a new context for the mechanisms by which Wnt signaling influences bone development.
Anabolic Agents
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beta Catenin
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Bone Development
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Bone Matrix
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Clone Cells
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Cloning, Organism
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Fatty Acids
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Glucose
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Glutamine
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Lipoproteins
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Metabolism*
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Osteoblasts*
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Sirolimus