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Anabolic agents

Tomas K Kuprys, Leah M Steinmetz, Charla R Fischer, Themistocles S Protopsaltis, Peter G Passias, Jeffrey A Goldstein, John A Bendo, Thomas J Errico, Aaron J Buckland
STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The goals of this study were to (1) evaluate pre-operative bone quality assessment and intervention practice over time and (2) review the current evidence for bone evaluation in spine fusion surgery. SUMMARY OF BACKGROUND DATA: Deformity spine surgery has demonstrated improved quality of life in patients however its cost has made it controversial. If pre-operative bone quality can be optimized then potentially these treatments could be more durable however, at present, no clinical practice guidelines have been published by professional spine surgical organizations...
December 11, 2018: Spine
Caiwei Wang, Li Yan, Bo Yan, Li Zhou, Wan Sun, Lingying Yu, Fucun Liu, Wenxi Du, Guangping Yu, Zhengyan Hu, Qiang Yuan, Luwei Xiao, Hongwen Li, Peijian Tong, Jida Zhang, Letian Shan, Thomas Efferth
ETHNOPHARMACOLOGICAL RELEVANCE: Osteoarthritis (OA), characterized by joint pain and cartilage degradation, is the most common form of joint disease worldwide but with no satisfactory therapy available. The ethanol extract of Agkistrodon acutus (EAA) has been widely used as a traditional Chinese medicine (TCM) for the treatment of arthralgia and inflammatory diseases, but there is no report regarding its efficacy on OA to date. Here, we determined the effects of EAA on the pain behavior and cartilage degradation in vivo and clarified its target genes and proteins associated with chondrocyte hypertrophy and apoptosis in vitro...
December 5, 2018: Journal of Ethnopharmacology
Ioanna Athanasiadou, Sven Christian Voss, Wesal El Saftawy, Hind Al-Jaber, Najib Dbes, Sameera Al-Yazedi, Waseem Samsam, Vidya Mohamed-Ali, Mohammed Alsayrafi, Georgia Valsami, Costas Georgakopoulos
Low urinary luteinizing hormone (LH) values have been discussed as a marker to detect steroid abuse. However, suppressed LH concentrations related to highly diluted urine samples could be a misleading indication of anabolic steroid abuse. One aim of the present study was to examine the effect of hyperhydration on the interpretation of LH findings during doping control analysis and to investigate different possibilities to correct volume related changes in urinary LH concentrations. Seven healthy physically active non-smoking Caucasian males were examined for a 72-hour period using water and a commercial sports drink as hyperhydration agents (20 mL/kg body weight)...
December 3, 2018: International Journal of Sport Nutrition and Exercise Metabolism
Zachary J Solomon, Jorge Rivera Mirabal, Daniel J Mazur, Taylor P Kohn, Larry I Lipshultz, Alexander W Pastuszak
INTRODUCTION: Selective androgen receptor modulators (SARMs) differentially bind to androgen receptors depending on each SARM's chemical structure. As a result, SARMs result in anabolic cellular activity while avoiding many of the side effects of currently available anabolic steroids. SARMs have been studied in the treatment of breast cancer and cachexia and have also been used as performance-enhancing agents. Here, we evaluate and summarize the current literature on SARMs. AIM: To present the background, mechanisms, current and potential clinical applications, as well as risks and benefits of SARMs...
November 29, 2018: Sexual Medicine Reviews
Leili Aghebati-Maleki, Sanam Dolati, Reza Zandi, Ali Fotouhi, Majid Ahmadi, Ali Aghebati, Mohammad Nouri, Seyed Kazem Shakouri, Mehdi Yousefi
Osteoporosis is a systemic skeletal disease associated with reduced bone strong point that results in raised fracture risk, with decreased bone strength, leading to reduced bone mineral density and poor bone quality. It is the most common in older females but some men are also at high risk. Although considered as a predictable result of aging, it is can be avoidable and treatable. The existing treatment of osteoporosis mainly contains antiresorptive and anabolic agents. In spite of these improvements, concerns around unusual side-effects of antiresorptive drugs, and the lack of perfect confirmation in maintenance of their long-standing effectiveness is bring about many patients not receiving these drugs...
November 29, 2018: Journal of Cellular Physiology
Evangelia Kalaitzoglou, John L Fowlkes, Iuliana Popescu, Kathryn M Thrailkill
Persons with type 1 or type 2 diabetes (T1D, T2D) have a significantly higher fracture risk than age-matched persons without diabetes, attributed to disease-specific deficits in the microarchitecture and material properties of bone tissue. Therefore, independent effects of diabetes drugs on skeletal integrity are vitally important. Studies of incretin-based therapies have shown divergent effects of different agents on fracture risk, including detrimental, beneficial and neutral effects. The sulfonylurea class of drugs, owing to its hypoglycemic potential, is thought to amplify the risk of fall-related fractures, particularly in the elderly...
November 22, 2018: Diabetes/metabolism Research and Reviews
Niraj Tripathi, Divya Shrivastava, Bilal Ahmad Mir, Shailesh Kumar, Sumit Govil, Maryam Vahedi, Prakash S Bisen
BACKGROUND: Withania somnifera, a high value medicinal plant is a major source of pharmaceutically important active compounds withanolides. Withania somnifera has been used in ayurveda as health restorative and anabolic agent besides having anti-arthritic, antidepressant, anti-microbial, anti-inflammatory, anti-diabetic, anti-stress, neuroprotective and cardio-protective activities. HYPOTHESIS/PURPOSE: The mining of the compound(s) of interest offers opportunity to identify desired attributes in the therapeutic area of interest...
November 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Ajay Matta, Muhammad Zia Karim, Hoda Gerami, Peter Jun, Martha Funabashi, Greg Kawchuk, Alyssa Goldstein, Warren Foltz, Marshall Sussman, Bjorn C Eek, W Mark Erwin
The tremendous cost, pain and disability associated with degenerative disc disease (DDD) makes the development of a biological agent that can mitigate the course of DDD, a critical unmet need. We have identified and reported that a single injection of a combination of recombinant human (rh) Transforming growth factor beta 1 (TGF-β1) and Connective tissue growth factor (CTGF) proteins into the injured intervertebral disc (IVD) nucleus pulposus (NP) can mediate DDD in a pre-clinical rodent model. In this study, we developed and evaluated the efficacy of a novel molecular therapy (NTG-101) containing rhTGF-β1 and rhCTGF proteins suspended in an excipient solution using in vivo models of DDD including rat-tail and chondrodystrophic (CD) canines...
November 14, 2018: Scientific Reports
Michael Polet, Wim Van Gansbeke, Peter Van Eenoo
In anti-doping, a high number of classes of substances are prohibited and laboratories need to detect these at low urinary concentrations. Traditionally, testing is done using complimentary liquid chromatography mass spectrometry and gas chromatography mass spectrometry. High resolution mass spectrometric acquisition has some important advantages over triple quadrupole instruments (e.g., open screening due to full scan high resolution data acquisition with retrospectivity, compatibility with libraries and a straightforward and effortless addition and validation of new compounds in the future)...
December 26, 2018: Analytica Chimica Acta
Jules A A C Heuberger, Adam F Cohen
The World Anti-Doping Agency is responsible for maintaining a Prohibited List that describes the use of substances and methods that are prohibited for athletes. The list currently contains 23 substance classes, and an important reason for the existence of this list is to prevent unfair competition due to pharmacologically enhanced performance. The aim of this review was to give an overview of the available evidence for performance enhancement of these substance classes. We searched the scientific literature through PubMed for studies and reviews evaluating the effects of substance classes on performance...
November 8, 2018: Sports Medicine
Maiko Ohashi, Kazumasa Okubo, Sakiko Mizuno, Masaki Yoda, Hideyuki Shirasawa, Kazuhiro Chiba, Keisuke Horiuchi, Morio Matsumoto, Masaya Nakamura
Granulocyte-colony stimulating factor (G-CSF) is a cytokine crucially involved in the regulation of granulopoiesis and the mobilization of hematopoietic stem cells from bone marrow. However, emerging data suggest that G-CSF exhibits more diverse functions than initially expected, such as conferring protection against apoptosis to neural cells and stimulating mitogenesis in cardiomyocytes and skeletal muscle stem cells after injury. In the present study, we sought to investigate the potential contribution of G-CSF to the regulation of muscle volume...
November 3, 2018: Biochemical and Biophysical Research Communications
David C Currow, Matthew Maddocks, David Cella, Maurizio Muscaritoli
Cancer cachexia is a multilayered syndrome consisting of the interaction between tumor cells and the host, at times modulated by the pharmacologic treatments used for tumor control. Key cellular and soluble mediators, activated because of this interaction, induce metabolic and nutritional alterations. This results in mass and functional changes systemically, and can lead to increased morbidity and reduced length and quality of life. For most solid malignancies, a cure remains an unrealistic goal, and targeting the key mediators is ineffective because of their heterogeneity/redundancy...
November 5, 2018: International Journal of Molecular Sciences
Tilman D Rachner, Lorenz Hofbauer, Andy Göbel, Elena Tsourdi
Bone forming approaches to treat patients with severe osteoporosis are effective, but treatment options are limited and there is an unmet clinical need for additional drugs. This review discusses two novel and advanced anabolic therapeutic concepts that have successfully completed phase 3 trials. Romosozumab is a monoclonal antibody that targets the Wnt inhibitor sclerostin. Two phase 3 trials (FRAME and ARCH) of romosozumab for the treatment of postmenopausal osteoporosis have been completed. Both trials successfully reached their primary endpoint by reducing vertebral fractures by 75% compared to placebo (FRAME trial) and 48% compared to alendronate (ARCH trial), respectively...
September 1, 2018: Journal of Molecular Endocrinology
I Takács, E Jókai, D E Kováts, I Aradi
To demonstrate the clinical comparability between RGB-10 (a biosimilar teriparatide) and the originator, a comparative pharmacokinetic trial was conducted. The study was successful in establishing bioequivalence. Marketing authorisation for RGB-10 (Terrosa®) was granted by the European Medicines Agency in 2017. INTRODUCTION: Teriparatide, the first bone anabolic agent, is the biologically active fragment of human parathyroid hormone. The imminent patent expiry of the originator will open the door for biosimilars to enter the osteology market, thereby improving access to a highly effective, yet prohibitively expensive therapy...
October 24, 2018: Osteoporosis International
Sonia Vallet, Julia-Marie Filzmoser, Martin Pecherstorfer, Klaus Podar
Bone disease, including osteolytic lesions and/or osteoporosis, is a common feature of multiple myeloma (MM). The consequences of skeletal involvement are severe pain, spinal cord compressions, and bone fractures, which have a dramatic impact on patients' quality of life and, ultimately, survival. During the past few years, several landmark studies significantly enhanced our insight into MM bone disease (MBD) by identifying molecular mechanisms leading to increased bone resorption due to osteoclast activation, and decreased bone formation by osteoblast inhibition...
October 24, 2018: Pharmaceutics
Rolf Teschke
A list presenting a valid ranking of drugs most commonly implicated is hardly to be found. Areas covered: Published cases of drug-induced liver injury (DILI) with verified causality using RUCAM (Roussel Uclaf Causality Assessment Method) were used for a ranking of drugs most commonly implicated in causing DILI. Expert opinion: RUCAM-based DILI cases were retrieved from 15 reports published by six international databases of DILI registries and three large medical centers, which provided 3312 cases. Overall 48 drugs with the highest number of DILI cases were listed...
October 25, 2018: Expert Opinion on Drug Metabolism & Toxicology
Kun-Hung Lai, Chih-Yung Chiang, Rong-Sen Yang, Kai-Chiang Yang, Chang-Chin Wu
BACKGROUND: Patients with chronic obstructive pulmonary disease have a high prevalence of osteoporosis, and different osteoporosis drugs are used to prevent fractures in these patients. Although the overall incidence of complete or incomplete, atypical femoral fracture (AFF) is low, long-term use of antiresorptive agents is associated with an increased risk of developing AFF. METHODS: We present a patient with chronic obstructive pulmonary disease with recurrent symptoms of an incomplete AFF who had been treated with glucocorticoids, and sequentially with alendronate, zoledronic acid, strontium ranelate, raloxifene, denosumab and finally with teriparatide...
October 19, 2018: Acta Clinica Belgica
Guangtao Fu, Shixun Li, Nengtai Ouyang, Junyan Wu, Changchuan Li, Wei Liu, Junxiong Qiu, Peng Peng, Ling Qin, Yue Ding
Aseptic loosening due to wear particle-induced osteolysis is the main cause of arthroplasty failure and the influence of postmenopausal osteoporosis and anti-osteoporosis treatment on Titanium (Ti) particle-induced osteolysis remains unclear. 66 C57BL/6J female mice were used in this study. Ovariectomy (OVX) was performed to induce osteopenia mice and confirmed by micro-CT. The Ti particle-induced mouse calvaria osteolysis model was established subsequently and both OVX and Sham-OVX mice were divided into four groups, respectively: Ti (-) group, Ti group, Ti + zoledronic acid (ZOL) group (50ug/kg, local administration, single dose) and Ti + teriparatide (TPTD) group (40ug/kg/d, subcutaneous injection*14d)...
September 2018: Artificial Organs
Julia Paton-Hough, Simon Tazzyman, Holly Evans, Darren Lath, Jenny M Down, Alanna C Green, John A Snowden, Andrew D Chantry, Michelle A Lawson
Multiple myeloma is a plasma cell malignancy, which develops in the bone marrow and frequently leads to severe bone destruction. Current antiresorptive therapies to treat the bone disease do little to repair damaged bone; therefore, new treatment strategies incorporating bone anabolic therapies are urgently required. We hypothesized that combination therapy using the standard of care antiresorptive zoledronic acid (Zol) with a bone anabolic (anti-TGFβ/1D11) would be more effective at treating myeloma-induced bone disease than Zol therapy alone...
October 15, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
X Li, J Zhang, X Wang
The concept of minimodeling is defined as a kind of focal bone formation that features the absence of preceding bone absorption by osteoclasts. In the process of minimodeling, osteogenetic and osteoclastic activities are decoupled. Linear boundary between old bone and new bone can be discovered. Frost et al. presumed that minimodeling in trabeculae can continue throughout life. The concept of minimodeling is not new, however its function and nature are still imperfectly understood. Our review will focus on minimodeling-based formation in 5 aspects below: 1...
October 4, 2018: Current Molecular Medicine
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