Search

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease that constitutes a major global health burden. A significant proportion of patients experience skeletal muscle wasting and loss of strength as a comorbidity of their COPD, a condition that severely impacts on their quality of life and survival. At present, the lung pathology is considered to be largely irreversible; however, the inherent adaptability of muscle tissue offers therapeutic opportunities to tackle muscle wasting and potentially reverse or delay the progression of this aspect of the disease, to improve patients' quality of life. Muscle wasting in COPD is complex, with contributions from a number of factors including inflammatory cytokines, oxidative stress, growth and anabolic hormones, nutritional status, and physical activity. In this review, we discuss current and emerging therapeutic approaches to treat muscle wasting in COPD, including a number of pharmacological therapies that are in development for muscle atrophy in other pathological states that could be of relevance for treating muscle wasting in COPD patients.

Introduction The hyper-catabolic state is a devastating pathophysiological response to severe injury, infection or burns. Nandrolone decanoate (ND) is a potent anabolic steroid have many clinical indications, but not investigated in burn injuries yet. Patients and methods A prospective randomized control study included 40 burned patients who were treated in Burn unit from burn injuries ranged from 20 to 40%. Both groups are objectively assessed, clinically and laboratory during treatment period till full recovery from burns’ injury. Recall assessment of the drug safety after many years is achieved. Results ND showed highly significant results supporting its use in combating catabolic insults in burns patient. Both clinical findings and laboratory findings are correlated and highly support the use of ND in burns as new effective and safe long-lasting indication. Conclusion This study results showed preservation of lean body mass and protein partition, as well as the near normal nitrogen balance in burn patients. Study proposes that nandrolone decanoate could be used in safe and effective way to combat hypercatabolic impact in burn injury.

Summary Selective androgen receptor modulators (SARMs) are a class of drugs presenting identical anabolic properties to usual anabolic steroids (testosterone, stanozolol, nandrolone…) in addition to marked reduced androgenic effects. These drugs have emerged in the doping area within the early 2000s. Ligandrol, ostarine, RAD-140 and andarine are the most popular agents belonging to this class. According to the world anti-doping agency (WADA) prohibited list, SARMs are prohibited at all times (i.e. in and out-of-competition) and are listed under the section S1.2 (other anabolic agents), a section that also contains clenbuterol. The compilation of the WADA testing figures reports from 2015 to 2019 has indicated a regular increase of adverse analytical findings (AAF) due to SARMs, particularly with ostarine and ligandrol. The implementation of highly sensitive chromatographic anti-doping analyses has induced high-profile challenges of anti-doping rules violations as athletes have claimed in numerous occasions that contamination was the reason for their AAF. As a result, hair tests were presented in order to establish the circumstances of these AAF. In case of an adverse analytical finding, hair testing can be a complement to document the claim of the athlete but of course, the result should not be considered as an alternative to urinalysis. This is because a negative hair result cannot exclude the use of the detected drug and cannot overrule the urine result. A review of the scientific literature, using the key words “SARMs” and “hair” has indicated that only 7 papers were published on this topic, including 3 dealing with equine hair. Although literature seems very limited, there is an increasing request for hair tests, which as prompted our laboratory to develop screening methods. Drugs are extracted from hair after decontamination under mild alkaline condition and submitted to LC-MS/MS and LC-HRMS assays. In this review, several original cases are provided, and the challenges of interpreting these findings are highlighted in light of the lack of controlled studies in the literature.

Considering the role of autonomic nerve activity in blood pressure control, this study aimed to investigate the cardiac autonomic nerve responses after an aerobic exercise session in Anabolic Androgenic Steroids (AAS) users. Twenty men (AAS, n = 9; control group, n = 11) performed an aerobic exercise session (60 min, 70 to 80% of HRmax). Heart rate variability (HRV) was assessed before and during a 60-min post-exercise recovery period. RMSSD (root mean square successive difference of the RR intervals) and the LF/HF ratio (low frequency/high frequency spectra) were also evaluated. The Student's t-test for independent samples was used to compare differences between initial group characteristics. Repeated measures ANOVA was used to compare pre- and post-exercise HRV recovery (p < 0.05). AAS had a lower SDNN (standard deviation of the intervals) (40.8 ± 16.8 vs. 71.6 ± 24.7 ms; p = 0.04, d = 1.4) and a higher LF/HF (3.4 ± 2.1 vs. 1.8 ± 0.9%; p = 0.03, d = 0.9) before exercise. AAS and controls had similar RMSSD (14.0 ± 15.8 vs. 18.9 ± 12.1 ms; p = 0.20) and a LF/HF (2.8 ± 1.6 vs. 2.4 ± 1.2 ms; p = 0.41) immediately post-exercise. The between-groups comparison revealed a higher HF/LF at 30 min (4.3 ± 1.4 vs. 2.5 ± 1.3%; p = 0.008, d = 1.3) and 60 min (5.0 ± 2.2 vs. 2.3 ± 0.8%; p = 0.001, d = 1.6) for the AAS group in the recovery time. This study demonstrated impaired parasympathetic activity at rest and immediately after the exercise session as an adverse effect of AAS usage, but similar behavior regarding the restoration of sympathetic activity.

The 2020 American Association of Clinical Endocrinologists guidelines for assessing osteoporosis among postmenopausal women stratified postmenopausal women with osteoporosis to "high" and "very-high" fracture risk categories and recommended anabolic agents as initial therapy followed by an antiresorptive agent. Switching the order can blunt the effect of anabolic agents, and failing to follow with an antiresorptive can lead to loss of bone generated by the anabolic agent. It would be helpful to understand the real-world prescribing patterns of anabolic agents. Using the 2010-2015 Medicare 100% osteoporosis database, we assessed patient profiles, teriparatide prescribers, persistence of teriparatide therapy, and antiresorptive agent use after teriparatide discontinuation among elderly women who initiated teriparatide from 2011 to 2013. This study included 14,786 patients. In the year before teriparatide initiation, 30.0% of them had a fracture, 67.6% had a dual energy x-ray absorptiometry scan, 74.4% had a diagnosis of osteoporosis, and 47.9% used antiresorptive agents (non-naïve teriparatide users). Among those who had fractures, 49.4% initiated teriparatide within 3 months postfracture. Teriparatide was prescribed for 37% of users by primary care doctors, 19% by rheumatologists, 13% by endocrinologists, and 7.0% by orthopedists. Median time of teriparatide use was 7.2 months. After teriparatide discontinuation, 40.8% switched to antiresorptive agents (31.9% among naïve teriparatide users, 50.5% among non-naïve users). Among switchers, 42.5% switched within 60 days, 50.5% switched to denosumab, and 31.6% switched to oral bisphosphonates. This study of real-world prescribing data found that about half of teriparatide users switched from an antiresorptive agent, and less than half switched to antiresorptive agents after teriparatide discontinuation. Persistence of teriparatide use was suboptimal. In the management of postmenopausal osteoporosis, increasing the persistence of teriparatide use and improving the appropriate treatment sequence of anabolic and antiresorptive drugs are critical to maximizing gains in bone mass, providing the greatest protection against fractures. © 2021 American Society for Bone and Mineral Research (ASBMR).

Background Nowadays bodybuilders use anabolic steroids frequently. Abuse of these substances can cause significant side effects; therefore, we aim to investigate the effect of anabolic steroids on DNA damage in bodybuilders’ blood lymphocytes.Methods and materials This case-control study was performed on 36 male bodybuilders in Gonabad. The case group included bodybuilders with a history of taking anabolic-androgenic steroids (n = 18), and the control group composed of bodybuilders who did not use anabolic-androgenic steroids (n = 18). Intravenous blood samples were obtained and then the lymphocytes, cells and electrophoresis of blood were extracted. Afterward, the coloured slides and DNA damage were measured using a fluorescent microscope and CometScore software. The DNA damage was compared using t-tests .Results Results showed that there was no significant difference between age, marital status, BMI, systolic and diastolic blood pressure in the case and control group. However, parameters related to the DNA damage including tail length, percent tail DNA, and tail moment were significantly higher in the case group.Conclusion The use of anabolic-androgenic steroids increases DNA damage in the bodybuilders’ blood lymphocytes.

Aim: The aim of the study is to assess the Pharmacological management of osteoporosis in postmenopausal women. Objective: The purpose of this study is to evaluate the treatment of osteoporosis in postmenopausal women. Methodology: This is an observational prospective study, carried out in a tertiary care hospital. Results: A total of 300 postmenopausal women were enrolled in the study. The mean ± standard deviation, of the age of postmenopausal women included in this study was 55.5 ± 5.0 years. 68.1% were prescribed with the combinational therapy of Teriparatide+Bisphosphonates. 39.2% of subjects were using acetaminophen for pain. Conclusion: Antiresorptive drugs (hormonal therapy, bisphosphonates, and denosumab) and, the anabolic agents (teriparatide) are commonly prescribed, in this study it is obvious that Sequential Therapy is highly prevailing in the clinical practice, with 68.1%.

Osteoporosis is a common chronic condition that markedly increases the risk of fractures. Osteoporotic-related fractures increase morbidity and mortality and impair quality of life. Therefore, a correct approach for fracture prevention seems mandatory. Lifestyle changes should be recommended to all patients, including weight reduction if patients are obese/overweight, increasing physical activity and avoiding alcohol consumption and smoking. Additionally, calcium and vitamin D3 should be prescribed until the vitamin D deficit is resolved. Osteoporosis treatment options mainly include antiresorptives (i.e. estrogens, selective estrogen receptor modulators, bisphosphonates, denosumab) and anabolic agents (i.e. teriparatide, abaloparatide, romosozumab). Although presenting differences in efficacy and side effects, they have all been shown to increase bone mineral density (BMD) and to reduce osteoporotic-related fractures. Monotherapy with antiresorptive agents, particularly oral bisphosphonates, should be considered routinely as the first option for treatment of postmenopausal women. However, in the case of side effects, therapeutic failure or the need for long-term use, anabolic agents may be considered. In high-risk patients, anabolic agents may be considered as an initial therapeutic option. The combination of antiresorptive and anabolic agents may be useful to increase BMD compared with monotherapy, but more information is warranted to determine the effects on fracture risk.

Osteoporosis is characterized by reduced bone mass leading to diminished skeletal integrity and an increased risk for fracture. Multiple agents exist that are effective for the treatment of osteoporosis. These can be broadly categorized into those that reduce the risk for additional loss of bone mass (anti-resorptive agents) and those that augment existing bone mass (anabolic agents). This article reviews the different medications within each class, and discusses more recent data regarding the combination and sequential use of these medications for optimization of skeletal health in patients at high risk for fracture.

A 59-year-old male was found dead at home, with two empty vials of an oily preparation obtained from a manufacturer from East Europe. There was no label on the vial. The subject was a former weightlifter, also known as an anabolic steroids abuser. The local prosecutor ordered a body examination, which was unremarkable, and allowed collecting femoral blood, urine and scalp hair (6 cm, brown). He was treated for cardiac insufficiency with quinidine. Biological specimens were submitted not only to standard toxicological analyses including a screening with liquid chromatography (LC)–quadrupole time of flight, but also to a specific LC–tandem mass spectrometry method for anabolic steroids testing. Ethanol was not found in both blood and urine. Quinidine blood concentration (791 ng/mL) was therapeutic. No drug of abuse was identified. In blood, testosterone was less that 1 ng/mL and no other steroid was identified. In urine, testosterone/epitestosterone was 1.56 and boldenone was present at a concentration of 9 ng/mL. The hair test results, performed on the whole length, demonstrated repetitive steroids abuse, including not only testosterone (140 pg/mg), testosterone propionate (605 pg/mg) and testosterone decanoate (249 pg/mg), but also boldenone (160 pg/mg), trenbolone (143 pg/mg) and metandienone (60 pg/mg). Since forensic laboratories have limited access to steroid urinary metabolite reference material due to specific regulations (to avoid testing athletes before anti-doping verifications), hair analyses seem to be the best approach to document anabolic agents abuse. Indeed, in hair, the target drug is the parent compound; in addition, when compared to blood or urine, this matrix has a much larger window of detection. The pathologist concluded cardiac insufficiency in a context involving repetitive abuse of anabolic drugs. This case indicates that more attention should be paid to anabolic steroids, in a context of sudden cardiac death.

Anabolic androgenic steroid (AAS) and performance-enhancing drug (PED) use is a prevalent medical issue, especially among men, with an estimated 2.9–4 million Americans using AAS in their lifetime. Prior studies of AAS use reveal an association with polycythemia, dyslipidemia, infertility, hypertension, left ventricular hypertrophy, and multiple behavioral disorders. AAS withdrawal syndrome, a state of depression, anhedonia, and sexual dysfunction after discontinuing AAS use, is a common barrier to successful cessation. Clinical resources for these patients and training of physicians on management of the patient using AAS are limited. Many men are hesitant to seek traditional medical care due to fear of judgment and lack of confidence in physician knowledge base regarding AAS. While proposed approaches to weaning patients off AAS are published, guidance on harm reduction for actively using patients remains sparse. Medical education regarding the management of AAS use disorder is paramount to improving care of this currently underserved patient population. Management of these patients must be non-judgmental and focus on patient education, harm reduction, and support for cessation. The approach to harm reduction should be guided by the specific AAS/PEDs used.

Background High-dose long-term use of anabolic-androgenic steroids (AASs) may cause a range of adverse effects, including brain and cognitive abnormalities. We performed age prediction based on brain scans to test whether prolonged AAS use is associated with accentuated brain aging. Methods T1-weighted magnetic resonance imaging (3D MPRAGE [magnetization-prepared rapid acquisition gradient-echo]) scans were obtained from male weightlifters with a history of prolonged AAS use (n = 130) or no AAS use (n = 99). We trained machine learning models on combinations of regional brain volumes, cortical thickness, and surface area in an independent training set of 1838 healthy male subjects (18-92 years of age) and predicted brain age for each participant in our study. Including cross-sectional and longitudinal (mean interval = 3.5 years, n = 76) magnetic resonance imaging data, we used linear mixed-effects models to compare the gap between chronological age and predicted brain age (the brain age gap [BAG]) for the two groups and tested for group differences in the rate of change in BAG. We tested for associations between apparent brain aging and AAS use duration, pattern of administration, and dependence. Results AAS users had higher BAG compared with weightlifting control subjects, which was associated with dependency and longer history of use. Group differences in BAG could not be explained by other substance use, general cognitive abilities, or depression. While longitudinal analysis revealed no evidence of increased brain aging in the overall AAS group, accelerated brain aging was seen with longer AAS exposure. Conclusions The findings suggest that long-term high-dose AAS use may have adverse effects on brain aging, potentially linked to dependency and exaggerated use of AASs.

Drug-induced lipid accumulation in the liver may induce two clinically relevant conditions, drug-induced steatosis (DIS) and drug-induced steatohepatitis (DISH). The list of drugs that may cause DIS or DISH is long and heterogeneous and includes therapeutically relevant molecules that cannot be easily replaced by less hepatotoxic medicines, therefore making specific strategies necessary for DIS/DISH prevention or treatment. For years, the only available tools to achieve these goals have been antioxidant drugs and free radical scavengers, which counteract drug-induced mitochondrial dysfunction but, unfortunately, have only limited efficacy. In the present review we illustrate how in vitro preclinical research unraveled new key players in the pathogenesis of specific forms of DISH, and how, in a few cases, proof of concept of the beneficial effects of their pharmacological modulation has been obtained in vivo in animal models of this condition. The key issue emerging from these studies is that, in selected cases, liver toxicity depends on mechanisms unrelated to those responsible for the desired, primary pharmacological effects of the toxic drug and, therefore, specific strategies can be designed to overcome steatogenicity without making the drug ineffective. In particular, the hepatotoxic drug could be given in combination with a second molecule intended to selectively antagonize its liver toxicity whilst, ideally, potentiating its desired pharmacological activity. Although most of the evidence that we discuss is from in vitro or animal models and will need to be further explored and validated in humans, it highlights new avenues to be pursued in order to improve the safety of steatogenic drugs.

RationaleAggression and irritability are notable psychiatric side effects of anabolic-androgenic steroid (AAS) use. However, no previous study has systematically reviewed and quantitatively synthesized effects reported by experimental studies on this topic.ObjectiveWe conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating the effect of AAS administration on self-reported and observer-reported aggression.MethodsTwelve RCTs comprising a total of 562 healthy males were identified through systematic searches of MEDLINE, PsycInfo, ISI Web of Science, ProQuest, Google Scholar, and the Cochrane Library.ResultsAfter excluding one outlier, AAS administration was associated with an increase in self-reported aggression under a random-effects model, albeit small (Hedges’g= 0.171, 95% CI: 0.029–0.312,k= 11,p= .018), and when restricting the analysis to the effect of acute AAS administration on self-reported aggression under a fixed-effect model (g= 0.291, 95% CI: 0.014–0.524,p= .014). However, the above effects were neither replicated in the analysis of observer-reported aggression nor after restricting the analysis to the effects of the administration of higher (over 500 mg) and long-term (3 days to 14 weeks) doses.ConclusionsThe present meta-analysis provides evidence of an increase, although small, in self-reported aggression in healthy males following AAS administration in RCTs. Ecologically rational RCTs are warranted to better explore the effect of AAS administration on aggression in humans.

Abstract:: Osteoporosis is a pathological loss of bone mass due to an imbalance in bone remodeling where osteoclast-mediated bone resorption exceeds osteoblast-mediated bone formation resulting in skeletal fragility and fractures. Anti-resorptive agents, such as bisphosphonates and SERMs, and anabolic drugs that stimulate bone formation, including PTH analogues and sclerostin inhibitors, are current treatments for osteoporosis. Despite their efficacy, severe side effects and loss of potency may limit the long term usage of a single drug. Sequential and combinational use of current drugs, such as switching from an anabolic to an anti-resorptive agent, may provide an alternative approach. Moreover, there are novel drugs being developed against emerging new targets such as Cathepsin K and 17β-HSD2 that may have less side effects. This review will summarize the molecular mechanisms of osteoporosis, current drugs for osteoporosis treatment, and new drug development strategies.

There are now three anabolic agents available for the treatment of postmenopausal women at high risk for fracture. The purpose of this review is to supply a rationale to aid in determining which agent should be used in which clinical settings. Studies over the last decade have shown that anabolic agents produce faster and larger effects against fracture than antiresorptive agents. Furthermore, trials evaluating anabolic antiresorptive treatment sequences have shown that anabolic first treatment strategies produce the greatest benefits to bone density, particularly in the hip region. However, there are no head-to-head evaluations of the three anabolic therapies with fracture outcomes or bone density, and these studies are not likely to occur. How to decide which agent to use at which time in a woman’s life is unknown. We review the most significant clinical trials of anabolic agents which have assessed fracture, areal or volumetric bone density, microarchitecture, and/or bone strength, as well as information gleaned from histomorphometry studies to provide a rationale for consideration of one agent vs another in various clinical settings. There is no definitive answer to this question; all three agents increase bone strength and reduce fracture risk rapidly. Since the postmenopausal lifespan could be as long as 40–50 years, it is likely that very high-risk women will utilize different anabolic agents at different points in their lives.

An estimated 4-6% of fitness center visitors uses anabolic-androgenic steroids (AAS). Reliable data about adverse reactions of AAS are scarce. The HAARLEM study aimed to provide insight into the positive and negative effects of AAS use. One hundred men (≥18 years) who intended to start an AAS cycle on short notice were included for follow-up. Clinic visits took place before (T0), at the end (T1), and three months after the end of the AAS cycle (T2), and one year after the start of the cycle (T3), and comprised a medical history, physical examination, laboratory analysis, and psychological questionnaires. During the follow-up period, four subjects reported a serious adverse event, that is, congestive heart failure, acute pancreatitis, suicidal ideation, and exacerbation of ulcerative colitis. All subjects reported positive side effects during AAS use, mainly increased strength (100%), and every subject reported at least one negative health effect. Most common were fluid retention (56%) and agitation (36%) during the cycle, and decreased libido (58%) after the cycle. Acne and gynecomastia were observed in 28% and 19%. Mean alanine transaminase (ALT) and creatinine increased 18.7 U/l and 4.7 µmol/L, respectively. AAS dose and cycle duration were not associated with the type and severity of side effects. After one-year follow-up (T3), the prevalence of observed effects had returned to baseline. There was no significant change in total scores of questionnaires investigating wellbeing, quality of life, and depression. In conclusion, all subjects experienced positive effects during AAS use. Four subjects experienced a serious adverse event. Other side effects were mostly anticipated, mild, and transient.

This review is intended to describe the therapeutic approaches for corneal blindness, detailing the steps and elements involved in corneal wound healing. It also presents the limitations of the actual surgical and pharmacological strategies used to restore and maintain corneal transparency in terms of long-term survival and geographic coverage. In addition, we critically review the perspectives of anabolic agents, including vitamin A, hormones, growth factors, and novel promitotic and anti-inflammatory modulators, to assist corneal wound healing. We discuss the studies involving nanotechnology, gene therapy, and tissue reengineering as potential future strategies to work solely or in combination with corneal surgery to prevent or revert corneal blindness.

Low back pain (LBP) is a major reason for disability, and symptomatic intervertebral disc (IVD) degeneration (IDD) contributes to roughly 40% of all LBP cases. Current treatment modalities for IDD include conservative and surgical strategies. Unfortunately, there is a significant number of patients in which conventional therapies fail with the result that these patients remain suffering from chronic pain and disability. Furthermore, none of the current therapies successfully address the underlying biological problem - the symptomatic degenerated disc. Both spinal fusion as well as total disc replacement devices reduce spinal motion and are associated with adjacent segment disease. Thus, there is an unmet need for novel and stage-adjusted therapies to combat IDD. Several new treatment options aiming to regenerate the IVD are currently under investigation. The most common approaches include tissue engineering, growth factor therapy, gene therapy, and cell-based treatments according to the stage of degeneration. Recently, the regenerative activity of small molecules (low molecular weight organic compounds with less than 900 daltons) on IDD was demonstrated. However, small molecule-based therapy in IDD is still in its infancy due to limited knowledge about the mechanisms that control different cell signaling pathways of IVD homeostasis. Small molecules can act as anti-inflammatory, anti-apoptotic, anti-oxidative, and anabolic agents, which can prevent further degeneration of disc cells and enhance their regeneration. This review pursues to give a comprehensive overview of small molecules, focusing on low molecular weight organic compounds, and their potential utilization in patients with IDD based on recent in vitro, in vivo, and pre-clinical studies.

Currently available agents improve bone mineral density (BMD) values on their own in monotherapy but may not completely restore microarchitecture and the patient may continue to sustain fragility fractures. Current monotherapies can only address either increased bone resorption or decreased bone formation. In this setting, combination therapy with antiresorptive and anabolic agents appears to be a promising option. A 49-year-old premenopausal woman presented with severe low backache associated with significant height loss. Evaluation elsewhere revealed severe osteoporosis, which prompted treatment with three doses of parenteral zoledronate 4 mg annually, followed by oral alendronate 70 mg once weekly for 7 years. However, her symptoms persisted despite treatment, and investigations done at our center confirmed severe osteoporosis, with multiple vertebral compression fractures. She was initiated on teriparatide therapy but despite 1 year of treatment, there was persistent height loss. In addition, there was a marked elevation of bone resorption, which prompted us to add denosumab which was administered subcutaneously every 6 months. On follow-up, there was marked relief from pain, no further decrease in height, and progressive improvement in BMD, and bone turnover markers were noted. A dual therapy with anabolic agent teriparatide and antiresorptive agent denosumab for osteoporosis may be a viable option in individuals with severe osteoporosis who do not respond well to a single agent.

Anabolic resistance to a mechanical stimulus may contribute to the loss of skeletal muscle mass observed with age. In this study, young and aged mice were injected with saline or human LM-111 (1 mg/kg). One week later, the myotendinous junction of the gastrocnemius muscle was removed via myotenectomy (MTE), thus placing a chronic mechanical stimulus on the remaining plantaris muscle for 2 weeks. LM-111 increased α7B integrin protein expression and clustering of the α7B integrin near DAPI+ nuclei in aged muscle in response to MTE. LM-111 reduced CD11b+ immune cells, enhanced repair, and improved the growth response to loading in aged plantaris muscle. These results suggest that LM-111 may represent a novel therapeutic approach to prevent and/or treat sarcopenia.

Over the past three decades, the mainstay of treatment for osteoporosis has been antiresorptive agents (such as bisphosphonates), which have been effective with continued administration in lowering fracture risk. However, the clinical landscape has changed as adherence to these medications has declined due to perceived adverse effects. As a result, decreases in hip fracture rates that followed the introduction of bisphosphonates have now levelled off, which is coincident with a decline in the use of the antiresorptive agents. In the past two decades, two types of anabolic agents (including three new drugs), which represent a novel approach to improving bone quality by increasing bone formation, have been approved. These therapies are expected to lead to a new clinical paradigm in which anabolic agents will be used either alone or in combination with antiresorptive agents to build new bone and reduce fracture risk. This Review examines the mechanisms of action for these anabolic agents by detailing their receptor-activating properties for key cell types in the bone and marrow niches. Using these advances in bone biology as context, the comparative effectiveness of these anabolic agents is discussed in relation to other therapeutic options for osteoporosis to better guide their clinical application in the future.

The detection of clostebol misuse in sports has been growing recently, especially in Italy, due to the ample availability of pharmaceutical formulations containing clostebol acetate (Trofodermin®) and the use of more sensitive instrumentation by the antidoping laboratories. Most of these cases have been claimed to be related to a nonconscious use of the drug or through contact with relatives or teammates using it. We have investigated, through the application of the well-known and currently used gas chromatographic mass spectrometric procedures, the likelihood of these allegations and have demonstrated that after a single transdermal administration of 5 mg of clostebol acetate and a transient contact with the application area, it is possible to generate adverse analytical findings in antidoping controls. We have reviewed the Phase I and Phase II clostebol metabolism in order to generate evidences that may help the sport authorities reviewing these cases. The main clostebol metabolite (4-chloro-androst-4-en-3α-ol-17-one, M1) generally used at the screening level as well as other three metabolites (M2-M4) are mainly excreted as glucuronides, whereas M5 (4ζ-chloro-5ζ-androstan-3β-ol-17-one) is predominantly excreted as sulfate. Neither the 5α-reductases activity (impaired by the presence of the chlorine in C4) nor specific sulfotransferases present in the skin allowed a clear distinction of the administration route. Studies with a larger number of volunteers and probably investigating another physiological fluid allowed in antidoping such as blood are needed for a deeper investigation. It is not unreasonable to establish a reporting level for M1, maybe creating some false negatives but excluding nonintentional doping scenarios.

Purpose of review Over the past 3 decades, Ilizarov technique namely distraction histogenesis (DH) technique has been widely accepted and applied in orthopaedics and traumatology with outstanding clinical outcomes and emerging novel applications. This review focuses on the recent advances in understanding the biological mechanisms of DH, new methods for promoting bone consolidation in DH procedures and novel clinical applications of DH techniques. Recent findings Tension stress regulates many genes during DH, including signaling transduction molecules, BMPs, inflammatory and angiogenic factors as well as epigenetic factors. DH also triggers systemic responses such as recruitment of mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs). These activities play important roles in regulating bone regeneration and remodeling during DH. To promote bone formation in DH is still a clinical challenge, and minimal or non-invasive means for promoting bone consolidation are preferable, such as weight-bearing exercise, ultrasound and electromagnetic stimuli; whereas systemic administration of anabolic agents and hormones may also achieve better outcomes. Local cell transplantation and application of various biological factors at the right time may also be the choices. With better understanding of the biological mechanisms, applications of DH technique have now been extended for managing skin wound, joint disorders and avascular diseases. However, more basic or clinical researches are still needed to unravel the “magic” of DH technique. Summary DH technique awakens and promotes human body’s self-regeneration potentials and leads to many novel treatment strategies. A substantial number of methods have been found to promote bone consolidation in DH to shorten the treatment duration and make the application of DH easier. Novel clinical applications of DH technique have now been extended to management of soft-tissue repair disorders, avascular diseases and others, with many more new biological mechanisms yet to be defined. The translational potential of this article A full understanding of DH technique may facilitate its wider and more appropriate clinical applications.

Anabolic androgens have been reported to be associated with cardiovascular complications. One study revealed that increase in vascular stiffness in bodybuilders is associated with anabolic androgens and improvement in vascular function may occur following anabolic androgens discontinuation. The aim of this study was to investigate any possible relation between aortic elastic properties and anabolic androgens. Study population was divided into 3 groups: Group-1 [n = 35] consisted of bodybuilders who denied any current or previous use of anabolic androgens. Group-2 [n = 18] was bodybuilders with regular using of anabolic androgens for at least 2 year prior to the start of our study. Group-3 was 13 healthy age-matched sedentary men as a control group. Cardiac echocardiography was performed in the bodybuilders and controls and indexes of aortic function were calculated. Aortic stiffness was approximately twofold higher in anabolic androgens user bodybuilders compared with drug-free bodybuilders [P

The treatment of a man who attempted suicide after experiencing symptoms of anxiety and aggressiveness associated with the use of androgenic-anabolic steroids (AAS) is described. This report includes 30 days of inpatient treatment and a 6-month follow-up. Regular use of fluoxetine apparently prevented the onset of anxiety, depression, aggressiveness, and suicide ideation, even with the concurrent use of AAS. The urinary concentration of androgens, metabolites of AAS, and fluoxetine were monitored through analysis of urinary samples by the Brazilian Laboratory of Doping Control. Our results are congruent with previous findings describing the risk of suicide prompted by AAS use as well as the efficacy of fluoxetine in the treatment of mood disorders associated with the use of anabolic steroids.

PURPOSE OF REVIEW: Compared to the current standard of implanting bone anabolics for fracture repair, bone fracture targeted anabolics would be more effective, less invasive, less toxic and would allow for control over what phase of fracture healing is being affected. We therefore sought to identify the optimal bone targeting molecule to allow for systemic administration of therapeutics to bone fractures. RECENT FINDINGS: We found that many bone targeting molecules exist, but most have been developed for the treatment of bone cancers, osteomyelitis, or osteoporosis. There are a few examples of bone targeting ligands that have been developed for bone fractures that are selective for the bone fracture over the body and skeleton. SUMMARY: Acidic oligopeptides have the ideal half-life, toxicity profile, and selectivity for a bone fracture targeting ligand and are the most developed and promising of these bone fracture targeting ligands. However, many other promising ligands have been developed that could be used for bone fractures.

Ostarine, also known as S22 or MK2866 and enobosarm, is a selective androgen receptor modulator (SARM). It has high anabolic potency, in addition to limited androgenic effects. At this time, ostarine has no therapeutic use, but can be abused for performance-enhancing purposes using the oral route, at dosages of 10-25 mg per day. As the drug can easily be obtained via the Internet or some fitness centers, athletes and more and more amateurs can use it without undergoing the deleterious physiological side effects that are generally associated with testosterone-related compounds. Since 2008, the World Anti-Doping Agency (WADA) has prohibited SARMs at-all-times in the category of "other anabolic agents" under section S1.2 of the WADA List. In a case of trafficking/abuse, ostarine was identified in nail (subject 1) and hair (subject 2) by LC/HRMS after incubation of 50 mg of matrix in a pH 9.5 buffer, followed by extraction with organic solvents. The drug was quantitated by LC-MS/MS. Ostarine tested positive at 61 pg/mg (toenails) and 111 pg/mg (fingernails) for subject 1. Ostarine was present at 146, 168, 93, and 101 pg/mg in the 4 × 3 cm hair sections of subject 2, clearly demonstrating long-term use.

Objective: Provide an update regarding anabolic medications for osteoporosis, which are often considered to be the last resort for patients with osteoporosis, after multiple fractures have already occurred and other medications have already been administered. Methods: Literature review and discussion. Results: Recent pivotal trial data for anabolic agents and randomized trials comparing anabolic and antiresorptive medications suggest that three anabolic agents (teriparatide, abaloparatide, and romosozumab) reduce nonvertebral and vertebral fractures faster and to a greater extent than potent antiresorptive treatments. Furthermore, bone density accrual is maximized when patients are given anabolic agents first, followed by potent antiresorptive therapy. Since total hip bone density during or after osteoporosis treatment has emerged as an excellent surrogate for future fracture risk, attaining a greater hip bone mineral density is a treatment goal for high-risk osteoporosis patients. Conclusion: This review defines the highest-risk patients and summarizes the rationale for the evolving role of anabolic therapy in the management of postmenopausal women at high risk for fracture. Abbreviations: ACTIVE = Abaloparatide Comparator Trial in Vertebral Endpoints; ARCH = Active Controlled Fracture Study in Postmenopausal Women with Osteoporosis at High Risk; BMD = bone mineral density; FRAME = Fracture Study in Postmenopausal Women with Osteoporosis; FRAX = Fracture Risk Assessment Tool; PTH = parathyroid hormone; TBS = trabecular bone score

Introduction: Myositis is a rare complication of extra-articular anabolic steroid injections, while osteitis has not been reported as an adverse effect from this cause. This case report provides information about imaging findings of these two entities. Case presentation: A 37-year-old male, bodybuilder, presented pain and edema in the left gluteal region, associated with functional limitation, 5 days after receiving an intramuscular anabolic steroid injection (stanozolol). The man underwent an ultrasound scan and magnetic resonance imaging of the pelvis with contrast, which allowed making the diagnosis of myositis of the left gluteus maximus and osteitis of the iliac bone. The patient was treated with piperacillin-tazobactam and vancomycin for 10 days, without complications. No surgical management was required. Conclusion: Myositis is a rare complication of anabolic steroid injections and the pathophysiological mechanism of this substance is unknown. Osteitis, on the other hand, is an even rarer complication and, to the best of our knowledge, this is the first known case associated with this cause. Given the findings, the myositis reported herein has an infectious nature; however, further studies are required to demonstrate the actual causal association. RESUMEN Introducción. La miositis es una complicación muy rara de las inyecciones extraarticulares de esteroides anabólicos y la osteítis no ha sido reportada como efecto adverso por esta causa. El presente reporte de caso aporta información sobre los hallazgos imagenológicos de estos dos tipos de inflamaciones. Presentación del caso. Paciente masculino de 37 años, dedicado al fisicoculturismo, quien cinco días después de recibir una inyección de estano-zolol presentó dolor y edema en la región glútea izquierda asociados a limitación funcional. El sujeto asistió a consulta por este motivo y se le realizó una ecografía y una resonancia magnética contrastada de pelvis, cuyos resultados permitieron diagnosticarle miositis del glúteo mayor izquierdo y osteítis del hueso ilíaco. Se indicó tratamiento con piperacilina-tazobactam y vancomicina por 10 días y no se requirió manejo quirúrgico dado que se obtuvieron buenos resultados. Conclusión. La miositis es una complicación rara de las inyecciones de esteroides anabólicos en donde el mecanismo fisiopatológico de estas sustancias es incierto. Por su parte, la osteítis es una complicación aún más rara de la cual se presenta el primer caso conocido por esta causa. Dados los hallazgos se plantea que la miositis reportada es de tipo infecciosa; sin embargo, se requieren estudios adicionales que demuestren la asociación causal real.

Skeletal muscle wasting is a frequent clinical problem encountered in patients with chronic diseases. Increased levels of inflammatory markers play a role in the imbalance between muscle protein synthesis and degradation. Although testosterone has long been proposed as a treatment for patients with muscle wasting, undesirable side effects have raised concerns about prostatic hypertrophy in men as well as virilization in women. Selective androgen receptor modulators (SARMs) have demonstrated similar results like testosterone at improving lean body mass (LBM) with less side effects on androgen-dependent tissue.This review outlines the ongoing clinical development in the field of SARMs and their effectiveness in improving body composition and physical function. The included articles were collected at pubmed.gov and analyzed integrally.There is an unmet clinical need for safe and effective anabolic compounds such as SARMs. Despite the effect on LBM shown by SARMs in phase II clinical trials, results on improved physical function and muscle strength are still lacking and long-term outcomes have to be assessed in these patients. Moreover, there is a need to determine the effect of resistance exercise training and protein intake associated with SARMs in the treatment of patients with muscle wasting.

Osteoporosis is a common and debilitating condition characterized by diminished bone mass and architecture leading to bone fragility. Antiresorptive medicines like bisphosphonates (and less commonly denosumab) are the typical first-line agents for the medical treatment of osteoporosis. However, newer anabolic agents have been shown to improve bone mass and architecture, as well as reduce fracture risk, to a greater degree than traditional antiresorptive therapies. Teriparatide (human recombinant parathyroid hormone (PTH) 1-34, Forteo, Ely Lilly, Indianapolis, IN), which was the first in class to be approved in the United States, is the most widely used anabolic osteoporosis medicine and has shown significant benefit over traditional antiresorptive therapies. However, abaloparatide (synthetic parathyroid-related peptide (PTHrP), Tymlos, Radius Health, Waltham, MA), the second drug in this family, has recently become available for use. In this narrative review, we review the mechanism, effects, and benefits of abaloparatide compared to alternative treatments as well as discuss the current literature in regard to its effect on osteoporosis-related complications in the spine.

Background A primary consequence of illicit drug markets and the absence of regulation is the variable quality or purity of the final product. Analysis of anabolic-androgenic steroid seizures shows that these products can contain adulterated products, product not included on the label, or product of unsatisfactory standard. While the potential negative effects of counterfeit anabolic-androgenic steroids (AAS) use is a recognised risk associated with use, no study has explored personal experiences associated with use. The aim of the present study was to use online discussion forums to investigate and explore the experiences associated with the purchase and consumption of counterfeit AAS among consumers. Methods An online search was conducted to identify online forums that discussed counterfeit or contaminated AAS; three were deemed suitable for the study. The primary source of data for this study was the ‘threads’ from these online forums, identified using search terms including ‘counterfeit’, ‘tampered’, and ‘fake’. Threads were thematically analysed for overall content, leading to the identification of themes. Results Data from 134 threads (2743 posts from 875 unique avatars) was included. Two main themes were identified from the analysis: (1) experiences with counterfeit product and (2) harms and benefits associated with counterfeit product. Conclusions The use of counterfeit or contaminated substances represents a public health concern. Those who report using performance and image enhancing drugs such as AAS for non-medical purposes report consuming these substances and experiencing harm as a result. Consumers take steps to limit coming into contact with counterfeit or contaminated product, though recognise that many of these have limitations. The implementation of accessible drug safety checking services may provide an opportunity to provide consumers with information to assist them with making healthier choices.

Anabolic androgenic steroids (AAS) are prohibited as performance-enhancing drugs in sports. Among them, testosterone and its precursors are often referred to as “pseudoendogenous” AAS, that is, endogenous steroids that are prohibited when administered exogenously. To detect their misuse, among other methods, the World Anti-Doping Agency-accredited laboratories monitor the steroid profile (concentrations and concentration ratios of endogenous steroids, precursors and metabolites) in urine samples collected from athletes in and out of competition. Alterations in steroid profile markers are used as indicators for misuse of anabolic steroids in sports. Therefore, especially their metabolic pathways with possible interactions are crucial to elucidate. As steroid metabolism is very complex, and many enzymes are involved, certain non-prohibited drugs may influence steroid metabolite excretion. One important group of steroid-metabolizing enzymes is aldo–keto reductases (AKRs). An inhibition of them by non-steroidal anti-inflammatory drugs (NSAIDs), which are neither prohibited nor monitored, but frequently used drugs in sports, was demonstrated in vitro. Thus, this work aims to investigate the influence of NSAID intake on the urinary steroid profile. Kinetic and inhibitory studies were performed using 5α-dihydrotestosterone as substrate. The results obtained from in vitro experiments show that ibuprofen inhibits AKR1C2 and thus influences steroid biotransformation. For in vivo investigations, urine samples prior, during and postadministration of ibuprofen were analyzed using routine methods to monitor the steroid profile. Changes in markers of the steroid profile of volunteers were observed. The combination of in vitro and in vivo results suggests that monitoring of ibuprofen may be useful in doping control analysis. The presented work illustrates the importance to consider co-administration of (non-prohibited) drugs during antidoping analysis. Intake of multiple substances is likely leading to interfering effects. Divergent results in antidoping analysis may therefore be observed and misinterpretation of analytical data may occur. Similar considerations may be appropriate for other fields of forensic applications.

Objective:\ud Beef protein extracts are growing in popularity in recent years due to their purported anabolic effects as well as to their potential benefits on hematological variables. The present randomized, controlled, double-blind, cross-over study aimed to analyze the effects of beef protein supplementation on a group of male elite triathletes (Spanish National Team).\ud \ud Methods:\ud Six elite triathletes (age, 21 ± 3 years; VO2max, 71.5 ± 3.0 ml·kg·min-1) were randomly assigned to consume daily either 25 g of a beef supplement (BEEF) or an isoenergetic carbohydrates (CHO) supplement for 8 weeks, with both conditions being separated by a 5 week washout period. Outcomes, including blood analyses and anthropometrical measurements, were assessed before and after each 8-week intervention.\ud \ud Results:\ud No effects of supplement condition were observed on body mass nor on skinfold thicknesses, but BEEF induced significant and large benefits over CHO in the thigh crosssectional area (3.02%, 95%CI=1.33 to 4.71 %; p=0.028, d=1.22). Contrary to CHO, BEEF presented a significant increase in vastus lateralis muscle thickness (p=0.46), but differences between conditions were not significant (p=0.173, d=0.87). Although a significantly more favorable testosterone-to-cortisol ratio (TCR) was observed for BEEF over CHO (37%, 95% CI=5 to 68 %; p=0.028, d=1.29), no significant differences were found for the hematological variables (i.e., iron, ferritin, red blood cell count, hemoglobin or hematocrit).\ud \ud Conclusion:\ud Beef protein supplementation seems to facilitate a more favorable anabolic environment (i.e., increased TCR and muscle mass) in male elite triathletes, with no impact on hematological variables.

Osteogenesis imperfecta (OI) is an inherited connective tissue disease. The disease has been linked to mutations in one of the type I collagen genes. The diagnosis is based on clinical and radiologic findings. The management of OI in adults is not well-established and includes physical rehabilitation, surgical procedures, the use of antiresorptive therapy and anabolic agents. The aim of the present work was to analyze the clinical and analytical characteristics of these patients in adulthood, as well as to evaluate the different treatments administered. We reviewed the cases of OI diagnosed in our centre over the last 12 years (2005–2017). We describe 15 adult patients with OI.

Venovenous extracorporeal membrane oxygenation (VV ECMO) induces a systemic inflammatory response, which may progress to persistent inflammation, immunosuppression, and catabolism syndrome (PICS). The anabolic steroid oxandrolone may improve the metabolic aberrations of PICS. We report our experience with 3 patients on VV ECMO who received oxandrolone after demonstrating refractory catabolism on serial nitrogen balance (NB) studies or persistent weakness. Patients in cases 1 and 3 were started on oxandrolone on VV ECMO days 45 and 29, respectively, for negative NB despite nutrition optimization. The case 2 patient started oxandrolone for persistent weakness 68 days after cannulation. All patients demonstrated improvements in NB results. One patient developed mild transaminitis while on oxandrolone, which did not alter his medication course and resolved after the medication was discontinued. The impact of oxandrolone on functional capacity varied between patients. Oxandrolone may be beneficial in persistently catabolic VV ECMO patients to improve NB results. In some patients, this may support functional recovery. Additional research is needed to identify optimal patients for therapy and to investigate the impact of oxandrolone in this population.

Introduction: Nandrolone decanoate is a synthetic testosterone analogue considered one of the most widely used anabolic androgenic steroids (AAS) among adolescents and athletes. Chronic ingestion of AAS increases the incidence of cardiovascular abnormalities in athletes, but the mechanism that causes these changes remains unknown. Objectives: The purpose of this study is to verify the possible effects of the use of anabolic androgenic steroids (AAS) on the morphology and oxidative metabolism of the heart in exercised and sedentary rats. Methods: This is a comparative prospective level II study. Twenty-four Wistar rats were distributed in groups that performed voluntary (TG) and sedentary (SG) running exercises, and used AAS: the Anabolic Training Group (ATG), and the Anabolic Sedentary Group (ASG). During the three months of the running protocol, the animals received an intramuscular injection of 5 mg/kg b.p. of AAS. After the training period, the rats were euthanized and the hearts were removed for evaluation of lipid peroxidation and antioxidant capacity, and for morphometric analysis. Results: The anabolic groups, ASG (0.3072 ± 0.0531) and ATG (0.2732 ± 0.0413), presented higher lipid peroxidation when compared to the non-anabolic groups SG (0.1705 ± 0.0224) and TG (0.1785 ± 0.0340). Conclusion: There was no change in total antioxidant capacity or in the thickness of the interventricular septum and left ventricular wall. Thus, the use of anabolic androgenic steroids did not cause morphological changes in the myocardium. However it did alter the oxidative metabolism. It was also verified that aerobic exercise had no protective effect against lipid peroxidation in the myocardium caused by the use of AAS. Level of evidence II; Prospective comparative study. RESUMO Introdução: O decanoato de nandrolona é um análogo sintético da testosterona, considerado um dos esteroides anabólicos androgênicos (EAA) mais utilizados entre adolescentes e atletas. Sua ingestão crônica aumenta a incidência de anormalidades cardiovasculares em atletas, porém o mecanismo que causa essas alterações ainda permanece desconhecido. Objetivos: O estudo teve como objetivo verificar os possíveis efeitos do uso de esteroides anabólicos androgênicos (EAA) na morfologia e no metabolismo oxidativo do coração de ratos treinados e sedentários. Métodos: Trata-se de um estudo prospectivo comparativo nível II. Vinte e quatro ratos Wistar foram distribuídos em grupos que realizaram exercícios de corrida voluntária (GT) e sedentários (GS) e faziam uso dos EAA, Grupo Treinado com Anabolizante (GTA) e Grupo Sedentário com Anabolizante (GSA). Durante os três meses do protocolo de corrida, os animais receberam injeção intramuscular de 5 mg/kg p.c. de EAA. Após o período de treinamento, houve a eutanásia e remoção do coração dos ratos para avaliação da peroxidação lipídica e capacidade antioxidante, além da análise morfométrica. Resultados: Verificaram-se que os grupos anabolizantes, GSA (0,3072 ± 0,0531) e GTA (0,2732 ± 0,0413), apresentaram maior peroxidação lipídica quando comparados aos grupos não anabolizantes GS (0,1705 ± 0,0224) e GT (0,1785 ± 0,0340). Conclusões: Não houve alteração na capacidade antioxidante total, assim como não houve alteração na espessura do septo interventricular e da parede ventricular esquerda. Portanto, o uso de esteroides anabólicos androgênicos não provocou alterações morfológicas no miocárdio, contudo alterou o metabolismo oxidativo. Verificou-se também que a prática de exercício aeróbico não teve efeito protetor contra a peroxidação lipídica no miocárdio provocada pelo uso dos EAA. Nível de evidência II; Estudo prospectivo comparativo. RESUMEN Introducción: El decanoato de nandrolona es un análogo sintético de la testosterona considerado uno de los esteroides anabólicos androgénicos (EAA) más utilizados entre los adolescentes y atletas. Su ingestión crónica aumenta la incidencia de anomalías cardiovasculares en atletas, aunque el mecanismo que causa esas alteraciones sigue siendo desconocido. Objetivos: El estudio tuvo como objetivo verificar los posibles efectos del uso de esteroides anabólicos androgénicos (EAA) en la morfología y en el metabolismo oxidativo del corazón de ratones entrenados y sedentarios. Métodos: Se trata de un estudio prospectivo comparativo nivel II. Fueron distribuidos 24 ratones Wistar en grupos que realizaron ejercicios de carrera voluntaria (GE) y sedentarios (GS), y hacían uso de los EAA, Grupo Entrenado con Anabolizante (GEA) y Grupo Sedentario con Anabolizante (GSA). Durante los tres meses del protocolo de carrera, los animales recibieron inyección intramuscular de 5 mg/kg p.c. de EAA. Después del período de entrenamiento, hubo la eutanasia y remoción del corazón de los ratones, para evaluación de la peroxidación lipídica y capacidad antioxidante, además del análisis morfométrico. Resultados: Se verificó que los grupos anabolizantes, GSA (0,3072 ± 0,0531) y GEA (0,2732 ± 0,0413), presentaron mayor peroxidación lipídica cuando comparados a los grupos no anabolizantes GS (0,1705 ± 0,0224) y GE (0,1785 ± 0,0340). Conclusiones: No hubo alteración en la capacidad antioxidante total, así como no hubo alteración en el espesor del septo interventricular y de la pared ventricular izquierda. Por lo tanto, el uso de esteroides anabólicos androgénicos no provocó alteraciones morfológicas en el miocardio, aunque alteró el metabolismo oxidativo. Se verificó también que la práctica de ejercicio aeróbico no tuvo efecto protector contra la peroxidación lipídica en el miocardio provocada por el uso de EAA. Nivel de evidencia II; Estudio prospectivo comparativo.

Hair testing is a complementary approach to document doping agent(s) use All prohibited substances but hormones should be detectable in hair Interest and limitations of hair testing for doping agents are reviewed based on the authors' experience Although a lot of data are available for drugs of abuse, controlled studies are missing for anabolic steroids, diuretics and some unusual classes of substances.

The effectiveness of doping control in sport has been improved continuously during the past 50 years. One of the major steps forward was the introduction of unannounced and targeted out-of-competition testing in order to control the misuse of anabolic-androgenic steroids (AAS), mainly during the end of the 1980s. It also led to the misuse of masking agents in case a surprise control was performed. Athletes tried to be "prepared", when the doping control officer showed up. The disclosure of the masking agent probenecid in 1987 is a perfect example of a memorable finding, of a suspected and purported case of performance manipulation. Probenecid and its metabolites were identified in five urine samples collected from Norwegian athletes in an out-of-competition test, while they were staying and training in the USA. Probenecid is a drug that reduces the urinary excretion of AAS from the body. It was the first time that it had showed up in a doping control sample. The athletes were sanctioned for hampering the analysis of their urine sample, although probenecid was not yet specified on the Prohibited List. Its detection was the result of a successful collaboration of laboratories and investigative diligence and enthusiasm following up suspicious observations in the actual samples. Immediately afterwards probenecid was added to the Prohibited List for 1988 as well as including the manipulation of doping control samples.

Critical-size bone defects after compound fractures, infection, or tumor resection are challenging to treat. The same is true for fractures in patients with impaired bone healing due to metabolic diseases and cancer. Despite considerable progress over the last decade in surgical techniques, material design, and dedicated imaging approaches, these scenarios represent unsolved clinical problems. The high socioeconomic burden of such conditions justifies increasing interest in novel osteoinductive drugs for adjuvant therapeutic approaches. There is an increasing body of experimental and clinical literature on potentially promising effects of growth factors, anti-resorptive, and anabolic agents. The true clinical efficacy of these, however, is discussed controversially. Therefore, we aimed to critically examine the hypothesis that targeted adjuvant therapies have the potential to enhance bone regeneration in critical-size bone defects and under systemic conditions that impair bone healing. This first approach to the topic deals with small molecule drugs and compounds that influence the immune response and inflammatory processes. In particular, literature reporting on selective cyclooxygenase-2 inhibitors has been reviewed with respect to their local and systemic mode of action and to stimulate further research on bone healing under critical conditions.

Polydrug use among adolescence is a widespread phenomenon and has increased in the last few years. In particular, most nandrolone decanoate (Nan) abusers combine its use with cannabis (Can); thus, studying the consequences of this combination in adolescent subjects is important because potentiation of their effects may increase their neurotoxicity. The present study was designed to study the neurotoxic effects of Nan and Can, alone and in combination, in adolescent male rats by studying the behavioural, biochemical, and histopathological effects. Nan (15 mg/kg, s.c.) and Can (20 mg/kg, s.c.) were given alone or in combination to rats once daily for one month. The combined administration of Can and Nan induced learning and spatial memory deficits, hypo-locomotion, anxiety and aggression in adolescent rats as evidenced by the Morris water maze, open field, elevated plus maze, and defensive aggression tests. In parallel, rats treated with the combination showed severe deleterious effects in the hippocampal and prefrontal cortex (PFC) neural architecture along with a decrease in brain-derived neurotropic factor. Furthermore, combined administration of Can and Nan increased oxidative stress (significantly increased malondialdehyde and nitric oxide levels and reduced glutathione content), elevated brain pro-inflammatory cytokines (tumour necrosis factor alpha and interleukin 1 beta), and upregulated caspase-3, caspase-8, and caspase-9 mRNA expression and cytochrome c levels. In conclusion, abuse of both Can and Nan conferred greater neurotoxic effects than either drug alone that were at least partially attributed to oxidative stress, inflammation, and intrinsic and extrinsic apoptosis in the hippocampus and PFC of rats.

Background and Objectives: Liver is one of the vital organs of the human body. Antioxidants have been shown to play important roles in reducing liver injuries. The aim of this study was to examine the effects of gallic acid supplementation and resistance exercise on liver damage biomarkers in male rats intoxicated by steroid anabolic. Materials and Methods: Forty-two male Wistar rats were randomly divided into six equal groups: control, sham, steroid anabolic (5 mg/kg), steroid anabolic (5 mg/kg) + gallic acid supplementation (50 mg/kg), steroid anabolic (5 mg/kg) + resistance exercise, and steroid anabolic (5 mg/kg) + gallic acid supplementation (50 mg/kg) + resistance exercise. Except for control and sham groups, all groups received (injection) steroid anabolic at a dose of 5 mg / kg body weight once a week. The resistance exercise protocol was comprised of three weekly exercise sessions by 5 rep/3 set of climbing ladder for eight weeks. Data were analyzed via ANOVA and Tukeychr('39')s post hoc test at a significance level of P

Introduction: Osteoporotic fractures represent a growing burden of mortality, morbidity and socioeconomic cost to health-care systems worldwide. Osteoporosis is a disease uniquely associated with aging, therefore, an understanding of the physiological mechanisms underpinning its development as we age may open new avenues for therapeutic exploitation. Novel treatments, as well as refinement of the current approaches, are vital in the effort to sustain healthy, independent patients across the lifespan.Areas covered: This review covers the anabolic and catabolic pathways seen in bone maintenance, highlighting how they are changed with age, leading to osteoporosis. It will also discuss how these changes may be targeted therapeutically, in the development of new therapies, and the refinement of those already in use.Expert opinion: New effective and safe treatments for osteoporosis are still needed. Bone anabolics seem to be the most appropriate therapeutic approach to osteoporosis in older persons. Considering that bone and muscle mass synchronically decline with aging thus predisposing older persons to falls and fractures, combined therapeutic approaches to osteosarcopenia with a dual anabolic effect on muscle and bone will be a major advance in the treatment of these devastating conditions in the future.

Background A 2014 Cochrane review evaluating the effect of anabolic steroids after hip fracture concluded that the quality of the studies was insufficient to draw conclusions on the effects and recommended further high-quality trials in the field. Therefore, the aim of this pilot trial is to determine the preliminary effect and feasibility of a 12-week multimodal intervention consisting of physiotherapy (with strength training), protein-rich nutritional supplement and anabolic steroid on knee-extension muscle strength and function 14 weeks after hip fracture surgery. Methods We plan to conduct a randomized, placebo-controlled pilot trial with 48 patients operated for acute hip fracture. The patients are randomized (1:1) to either (1) physiotherapy with protein-rich nutritional supplement plus anabolic steroid or (2) physiotherapy with protein-rich nutritional supplement plus placebo. Outcome assessments will be carried out blinded at baseline (3–10 days after surgery) and at 14 weeks after entering the trial. Primary outcome is the change from baseline to follow-up in maximal isometric knee-extension muscle strength in the fractured limb. Secondary outcomes are physical performance test, patient-reported outcomes, and measures of body composition. Discussion If the trial is found feasible and the results show an indication of anabolic steroid being a relevant addition to further enhance the recovery of muscle strength and function in an enhanced recovery after surgery program, this trial will constitute the basis of a larger confirmatory trial. Trial registration ClinicalTrials.gov, NCT03545347. Preregistered on 4 June 2018.

The use of Anabolic-Androgenic Steroids (AAS) has been associated with increased aggressiveness and violent behavior. We therefore investigated the proposed correlation between the use of AAS and criminality while controlling for important socio-economics covariates and for psychiatric comorbidity.The primary endpoints were prison sentences, and time to first prison sentence. A retrospective matched cohort study design consisting of 545 males, who tested positive for AAS in Danish gyms during the period January 3, 2006 to January 31, 2017. They were matched with 5450 randomly chosen male controls. Data were cross-referenced with national register information on education, employment status, substance abuse and psychiatric comorbidity. In addition, 638 males sanctioned because they rejected to participate in the doping control and 6380 controls were used as a replication cohort.Already at baseline, 20.6% of the AAS users had a previous prison sentence whereas the rate was 3.7% in the control cohort (p 0.0001). During the follow-up period the cumulative prevalence increased to 29.5% and 4.9%, respectively (unadjusted HR 9.15, 95% CI 6.33-13.20). The associations remained highly significant after controlling for socio-economic factors, drug abuse and psychiatric comorbidity. The results could be replicated in a similar cohort.Our study shows that AAS users have a 9-fold increased risk of being convicted of a crime compared to matched controls, randomly chosen from the general population. This association could not be explained by common socioeconomic factors or by psychiatric comorbidity.

Purpose To provide a summarized state of the art of the relative efficacy and rapidity of action of pharmacological treatments to prevent imminent osteoporotic fractures. Methods We reviewed metanalyses (MA) and network metaanalyses (NMA) published during the last 10 years concerning the pharmacological treatment of osteoporosis. We compared the anti-fracture efficacy and the rapidity of action of various agents versus placebo and versus risedronate. Results All bisphosphonates decrease the incidence of vertebral fractures compared with placebo. Ibandronate is the only one without demonstrated efficacy against non-vertebral and hip fractures. Zoledronate, denosumab and anabolic therapy are associated with a higher fracture risk reduction than oral bisphosphonates. Compared with risedronate, which significantly reduces the rate of hip fractures, zoledronate, denosumab, teriparatide, abaloparatide and romosozumab are more efficient for vertebral fractures but not for non-vertebral or hip fractures reduction. No studies have compared bone anabolic treatments with zoledronate or denosumab. Oral bisphosphonates significantly reduce fracture risk only after more than one year of therapy. A faster reduction of fracture risk is observed with zoledronate and denosumab, or with anabolic agents. For denosumab and anabolic agents, a sequential treatment is required to keep gains after treatment withdrawal. Conclusions In patients at high risk of imminent fracture, starting therapy with potent antiresorptive agents or with an anabolic agent seems most appropriate to promptly reduce the fracture risk. Available NMA/MA suggest that, compared to zoledronate and denosumab, anabolic agents have a higher efficacy for vertebral fractures but head-to-head studies are lacking., Highlights • The concept of imminent fracture has implications for the choice of therapy • We reviewed metanalyses and network metaanalyses published in the last 10 years • We compared the efficacy and rapidity of treatments to prevent imminent fractures • Potent antiresorptive and anabolic agents are most appropriate to promptly reduce fracture risk • Anabolic agents seem to be more efficient to reduce vertebral fracture risk