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Anabolic agents

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
Benjamin Z Leder
As osteoporosis therapy options have expanded, and clinical guidelines have begun to embrace the concept of limited treatment courses and "drug holidays," the choices that physicians must make when initiating, electing to continue, or switching therapies have become more complex. As a result, one of the fundamental issues that must be carefully considered is whether, when, and in what sequence anabolic therapies should be utilized. This review evaluates the current evidence supporting the optimal sequence for the use of anabolic and antiresorptive drugs and assesses the expanding number of clinical trials favoring the initial use of anabolic therapy followed by an antiresorptive agent...
March 2018: JBMR Plus
Diarra K Williams, Sean G Parham, Eric Schryver, Nisreen S Akel, R Shane Shelton, Jessica Webber, Francis L Swain, Jami Schmidt, Larry J Suva, Dana Gaddy
Down syndrome (DS), characterized by trisomy of human chromosome 21, is associated with a variety of endocrine disorders as well as profound skeletal abnormalities. The low bone mass phenotype in DS is defined by low bone turnover due to decreased osteoclast and osteoblast activity, decreasing the utility of antiresorptive agents in people with DS. Sclerostin antibody (SclAb) is a therapeutic candidate currently being evaluated as a bone anabolic agent. Scl, the product of the sclerostin gene ( SOST ), inhibits bone formation through its inhibition of Wnt signaling...
January 2018: JBMR Plus
Sabashini K Ramchand, Ego Seeman
The prevalence of fragility fractures increases as longevity increases the proportion of the elderly in the community. Until recently, the majority of studies have targeted women with osteoporosis defined as a bone mineral density (BMD) T score of < -2.5 SD, despite evidence that the population burden of fractures arises from women with osteopenia. Antiresorptive agents reduce vertebral and hip fracture risk by ~50 percent during 3 years but efficacy against non-vertebral fractures, 80% of all fractures in the community, is reported in few studies, and of those, the risk reduction is only 20-30%...
2018: Frontiers in Endocrinology
Harshad O Malve
Abuse of substances or methods to enhance the performance is becoming very common in the sports, which often destroys the spirit of competition. The regulatory bodies for sports have reported rates ranging from 5% to 31% for the use of performance-enhancing substances among athletes. Athletes can have serious injuries and morbidities, leading to poor health with the use of such substances. Commonly abused agents in sports include anabolic-androgenic steroids and its analogs, blood, erythropoietin, growth hormone and its derivatives, nutritional supplements, creatine, amphetamines, beta-hydroxy-beta-methylbutyrate (HMB), stimulants, and analgesics...
July 2018: Journal of Pharmacy & Bioallied Sciences
Gaia Tabacco, John P Bilezikian
Teriparatide (TPTD) and Abaloparatide (ABL) are the only osteoanabolic drugs available, at this time, for treatment of osteoporosis. TPTD is a 34-amino acid fragment that is identical in its primary sequence to the 34 amino acids of full-length human parathyroid hormone [hPTH(1-84)]. ABL is identical to parathyroid hormone related peptide (PTHrP) through the first 22 residues with significantly different amino acids inserted thereafter, between residues 22 and 34. The osteoanabolic actions of PTH are due directly to its effects on cells of the osteoblast lineage and indirectly by stimulating IGF-I synthesis and suppressing sclerostin and associated enhancement of Wnt signaling...
September 15, 2018: British Journal of Clinical Pharmacology
Diego Costa Astur, Igor Neves Sbampato, Gustavo Gonçalves Arliani, Carlos Eduardo da Silveira Franciozi, Pedro Debieux, Moises Cohen
Objective: To determine a relationship between smoking, alcohol abuse and anabolic steroids and meniscoligamentous injuries. Methods: A total of 239 patients underwent surgical treatment of isolated anterior cruciate ligament (ACL) lesion, ACL associated with meniscal injury and isolated meniscal injury, and were inquired by a single team of surgeons about their habits: smoking, alcoholism and use of artificial anabolic agents. In addition, quality of life was assessed using the SF-36 questionnaire...
2018: Acta Ortopedica Brasileira
Michael Kriegbaum Skjødt, Morten Frost, Bo Abrahamsen
Osteoporosis is a common condition that leads to substantial morbidity and mortality and affects an increasing number of persons worldwide. Several pharmacological therapies that inhibit bone resorption, promote bone formation, or both, are available for the treatment of osteoporosis. The osteoanabolic treatment spectrum was recently expanded by the introduction of a novel bone-forming agent in the United States, and clinical trials indicate that a new class of bone anabolic therapy may become available. Both antiresorptive and bone anabolic therapies are associated with common and rare adverse effects, which are particularly important to address as these drugs are used for long-term treatment in numerous patients with a large proportion being elderly and/or having multimorbidity...
September 7, 2018: British Journal of Clinical Pharmacology
Jinsong Liu, Janak L Pathak, Xiaohui Hu, Yifan Jin, Zuosu Wu, Mohammed A Al-Baadani, Shuyi Wu, Hualin Zhang, Sandor Farkasdi, Yi Liu, Jianfeng Ma, Gang Wu
Implant surface modification that provides local sustained release of osteoinductive therapeutic agents enhances implant stability. We designed a mesoporous TiO2-layered titanium implant (MLT) by modified anodization technique that allowed local sustained release of zoledronic acid up to 21 days. Mesoporous layer has pore size 15 nm, depth ∼30 μm, volume 0.32 cm3/g, surface area 112.3 m2/g, surface roughness 20 nm and water contact angle 18.3°. Zoledronic acid-loaded MLT (MLT-Z) was biocompatible, showed anabolic effect on bone forming osteoblasts and catabolic effect on bone resorbing osteoclasts...
November 1, 2018: Journal of Biomedical Nanotechnology
Yanmei Yang, Bin Wang
Metastatic breast cancer (BrCa) is currently incurable despite great improvements in treatment of primary BrCa. The incidence of skeletal metastases in advanced BrCa occurs up to 70%. Recent findings have established that the distribution of BrCa metastases to the skeleton is not a random process but due to the favorable microenvironment for tumor invasion and growth. The complex interplay among BrCa cells, stromal/osteoblastic cells, and osteoclasts in the osseous microenvironment creates a bone-tumor vicious cycle (a feed-forward loop) that results in excessive bone destruction and progressive tumor growth...
2018: International Journal of Endocrinology
Fan Yang, Haoran Hu, Wenjing Yin, Guangyi Li, Ting Yuan, Xuetao Xie, Changqing Zhang
Background: Platelet-rich plasma (PRP) has been shown to be a promising therapeutic agent against osteoarthritis (OA), whereas its chondroprotection mechanism is not fully elucidated. Autophagy is considered an important biological process throughout the development of OA. Therefore, the objective of the present study is to investigate the role of autophagy in the chondroprotection and compare the effects of releasate between L-PRP and P-PRP. Methods: PRP were prepared from rat blood...
2018: BioMed Research International
Bin Zhao, Wenqian Zhao, Yiqiang Wang, Zhao Zhao, Changfeng Zhao, Shue Wang, Chunzheng Gao
Zoledronic acid (ZA) exerts complex influence on bone by suppressing bone resorption, mostly due to the direct osteoclasts inhibition and uncertain influence on osteoblasts. Vitamin K2 (VK2, Menaquinone-4) as an anabolic agent stimulates bone formation via anti-apoptosis in osteoblasts and mild osteoclasts inhibition. Based on these knowledge, the therapeutic effect of the combined or sequential therapy of VK2 and ZA depends on the influence on the osteoblasts, since both cases exert similar inhibitory effect on osteoclasts...
2018: PloS One
Brendan T Finicle, Vaishali Jayashankar, Aimee L Edinger
While cancer cell proliferation depends on access to extracellular nutrients, inadequate tumour perfusion means that glucose, amino acids and lipids are often in short supply. To overcome this obstacle to growth, cancer cells utilize multiple scavenging strategies, obtaining macromolecules from the microenvironment and breaking them down in the lysosome to produce substrates for ATP generation and anabolism. Recent studies have revealed four scavenging pathways that support cancer cell proliferation in low-nutrient environments: scavenging of extracellular matrix proteins via integrins, receptor-mediated albumin uptake and catabolism, macropinocytic consumption of multiple components of the tumour microenvironment and the engulfment and degradation of entire live cells via entosis...
October 2018: Nature Reviews. Cancer
Andrea V Haas, Meryl S LeBoff
Medications for osteoporosis are classified as either antiresorptive or anabolic. Whereas antiresorptive agents prevent bone resorption, anabolic agents promote new bone formation. Anabolics should be considered in individuals with severe osteoporosis, failure of alternative osteoporosis agents, intolerability or contraindications to other osteoporosis agents, and glucocorticoid-induced osteoporosis. There are currently two approved anabolic therapies, teriparatide and abaloparatide, and a third anabolic agent, romozosumab, is under review by the US Food and Drug Administration...
August 1, 2018: Journal of the Endocrine Society
Yanzhi Liu, Zhenshan Jia, Mohammed P Akhter, Xiang Gao, Xiaobei Wang, Xiaoyan Wang, Gang Zhao, Xin Wei, You Zhou, Xiuli Wang, Curtis W Hartman, Edward V Fehringer, Liao Cui, Dong Wang
Delayed fracture union is a significant clinical challenge in orthopedic practice. There are few non-surgical therapeutic options for this pathology. To address this challenge, we have developed a bone-targeting liposome (BTL) formulation of salvianic acid A (SAA), a potent bone anabolic agent, for improved treatment of delayed fracture union. Using pyrophosphorylated cholesterol as the targeting ligand, the liposome formulation (SAA-BTL) has demonstrated strong affinity to hydroxyapatite in vitro, and to bones in vivo...
August 2, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
Jeffrey P Chmielewski, Sarah C Bowlby, Frances B Wheeler, Lihong Shi, Guangchao Sui, Amanda L Davis, Timothy D Howard, Ralph B D'Agostino, Lance D Miller, S Joseph Sirintrapun, Scott D Cramer, Steven J Kridel
Tumor cells require increased rates of cell metabolism to generate the macromolecules necessary to sustain proliferation. They rely heavily on NAD+ as a cofactor for multiple metabolic enzymes in anabolic and catabolic reactions. NAD+ also serves as a substrate for PARPs, sirtuins, and cyclic ADP-ribose synthases. Dysregulation of the cyclic ADP-ribose synthase CD38, the main NAD'ase in cells, is reported in multiple cancer types. This study demonstrates a novel connection between CD38, modulation of NAD+ , and tumor cell metabolism in prostate cancer...
August 3, 2018: Molecular Cancer Research: MCR
Joseph Matthew Armstrong, Ross A Avant, Cameron M Charchenko, Mary E Westerman, Matthew J Ziegelmann, Tanner S Miest, Landon W Trost
Background: To describe the impact of supra-physiologic anabolic-androgenic steroid (AAS) use, including agent, dosage, and duration of therapy, on sexual function. Methods: We reviewed data from an online survey of AAS users to evaluate their sexual function on and off AAS. The online survey consisted of questions addressing demographics, anabolic steroid use and patterns, ancillary medications, testosterone (T)-related symptoms while on and off of therapy, as well as sexual function which was assessed using the 5-item, International Index of Erectile Function (IIEF-5)...
June 2018: Translational Andrology and Urology
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