Impact of androgenic anabolic steroid use on cardiovascular and mental health in Danish recreational athletes: protocol for a nationwide cross-sectional cohort study as a part of the Fitness Doping in Denmark (FIDO-DK) study.

INTRODUCTION: The use of androgenic anabolic steroids (AASs) among recreational athletes is steadily increasing. However, knowledge regarding the potentially harmful effects of AAS primarily originates from case reports and small observational studies. This large-scale study aims to investigate the impact of AAS use on vascular plaque formation, preclinical coronary disease, cardiac function, circulating cardiovascular risk markers, quality of life (QoL) and mental health in a broad population of illicit AAS users. METHODS AND ANALYSES: A nationwide cross-sectional cohort study including a diverse population of men and women aged ≥18 years, with current or previous illicit AAS use for at least 3 months. Conducted at Odense University Hospital, Denmark, the study comprises two parts. In part A (the pilot study), 120 recreational athletes with an AAS history will be compared with a sex-matched and age-matched control population of 60 recreational athletes with no previous AAS use. Cardiovascular outcomes include examination of non-calcified coronary plaque volume and calcium score using coronary CT angiography, myocardial structure and function via echocardiography, and assessing carotid and femoral artery plaques using ultrasonography. Retinal microvascular status is evaluated through fundus photography. Cardiovascular risk markers are measured in blood. Mental health outcomes include health-related QoL, interpersonal difficulties, body image concerns, aggression dimensions, anxiety symptoms, depressive severity and cognitive function assessed through validated questionnaires. The findings of our comprehensive study will be used to compose a less intensive investigatory cohort study of cardiovascular and mental health (part B) involving a larger group of recreational athletes with a history of illicit AAS use. ETHICS AND DISSEMINATION: The study received approval from the Regional Committee on Health Research Ethics for Southern Denmark (S-20210078) and the Danish Data Protection Agency (21/28259). All participants will provide signed informed consent. Research outcomes will be disseminated through peer-reviewed journals and scientific conferences. TRIAL REGISTRATION NUMBER: NCT05178537.

Exploring Anabolic Androgenic Steroid Use Among Cisgender Gay, Bisexual, and Queer Men.

Importance: Anabolic androgenic steroids (AAS) are disproportionately used by sexual minority men, with the physical and mental health implications of AAS use incompletely understood. Objective: To understand the reasons for use and health care needs of gay, bisexual, and queer cisgender men using AAS. Design, Setting, and Participants: This qualitative study was conducted from November 2021 to May 2023 using self-administered questionnaires and semistructured interviews that were transcribed and coded using reflexive thematic analysis. Participants were recruited through convenience and snowball sampling from lesbian, gay, bisexual, transgender, and queer clinical centers in New York, New York, as well as through online platforms. All patients self-identified as cisgender and gay, bisexual, or queer. Exposures: History of nonprescribed AAS use for a minimum of 8 consecutive weeks was required. Main Outcomes and Measures: The primary outcomes were reasons for and health implications of AAS use and interactions with health care practitioners, as determined through interviews. Interview transcripts were collected and analyzed. Results: Thematic saturation was reached after interviews with 12 male participants (mean [SD] age, 44 [11] years), with the majority of participants identifying as gay (10 participants [83%]), White non-Hispanic (9 participants [75%]), being in their 30s and 40s (9 participants [75%]), holding a bachelor's degree or higher (11 participants [92%]), and having used steroids for a mean (SD) of 7.5 (7.1) years. One participant (8%) self-identified as Black, and 2 (17%) identified as Hispanic. Seven men (58%) met the criteria for muscle dysmorphia on screening. Nine overarching themes were found, including internal and external motivators for initial use, continued use because of effectiveness or fear of losses, intensive personal research, physical and emotional harms experienced from use, using community-based harm reduction techniques, frustration with interactions with the medical community focused on AAS cessation, and concerns around the illegality of AAS. Conclusions and Relevance: In this qualitative study, AAS use among cisgender gay, bisexual, and queer men was found to be associated with multifactorial motivators, including a likely AAS use disorder and muscle dysmorphia. Despite all participants experiencing harms from use, men seeking medical help found insufficient support with practitioners insistent on AAS cessation and, thus, developed their own harm reduction techniques. Further research is needed to assess the utility of practitioner education efforts, the safety and efficacy of community-developed harm reduction methods, and the impact of AAS decriminalization on health care outcomes for this patient population.

Effect of Stanozolol and/or Cannabis Abuse on Hypertrophic Mechanism and Oxidative Stress of Male Albino Rat Cardiac Tissue in Relation to Exercise: A Sport Abuse Practice.

Adolescents commonly co-abuse many drugs including anabolic androgenic steroids either they are athletes or non-athletes. Stanozolol is the major anabolic used in recent years and was reported grouped with cannabis. The current study aimed at evaluating the biochemical and histopathological changes related to the hypertrophic effects of stanozolol and/or cannabis whether in condition of exercise practice or sedentary conditions. Adult male Wistar albino rats received either stanozolol (5 mg/kg, s.c), cannabis (10 mg/kg, i.p.), and a combination of both once daily for two months. Swimming exercise protocol was applied as a training model. Relative heart weight, oxidative stress biomarkers, cardiac tissue fibrotic markers were evaluated. Left ventricular morphometric analysis and collagen quantification was done. The combined treatment exhibited serious detrimental effects on the heart tissues. It increased heart tissue fibrotic markers (Masson's trichrome stain (p < 0.001), cardiac COL3 (p < 0.0001), and VEGF-A (p < 0.05)), lowered heart glutathione levels (p < 0.05) and dramatically elevated oxidative stress (increased malondialdehyde (p < 0.0001) and 8-OHDG (p < 0.0001)). Training was not ameliorating for the observed effects. Misuse of cannabis and stanozolol resulted in more hypertrophic consequences of the heart than either drug alone, which were at least largely assigned to oxidative stress, heart tissue fibrotic indicators, histological alterations, and morphometric changes.

Anabolic-androgenic steroids are linked to depression and anxiety in male bodybuilders: the hidden psychogenic side of anabolic androgenic steroids.

BACKGROUND: The prevalence of anabolic-androgenic steroids (AAS) use is on the rise among athletes and bodybuilders worldwide. In addition to the well-documented adverse effects on hepatic, renal, and reproductive functions, there is an increasing recognition of psychiatric complications associated with AAS use. This study aimed to investigate psychiatric morbidity among male bodybuilders who are AAS users. METHODS: In this cross-sectional study, 25 male bodybuilders using AAS (mean age 31.2 ± 8.9 years) were compared with a control group of 25 healthy male bodybuilders matched in age (31.3 ± 5.5 years). The demographic, hormonal, and biochemical parameters of the participants were recorded. The impact of AAS use on psychiatric morbidity was assessed using the Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) in both groups. RESULTS: The BDI and BAI scores were significantly higher in male bodybuilders using anabolic-androgenic steroids (p < 0.0001). While the control group showed no instances of anxiety, seven individuals in the AAS user group reported mild anxiety. No participants in the control group exhibited depression, whereas seven AAS users displayed depressive symptoms (4 mild, 3 moderate). Correlations were observed between lactate dehydrogenase (LDH) levels and BAI scores, creatinine levels and both BAI and BDI scores, as well as between estradiol levels and BDI. CONCLUSION: The study concluded that AAS use among male bodybuilders is associated with elevated levels of depression and anxiety. Our findings suggest a potential correlation between anxiety and depression levels and the levels of creatinine, LDH, and estradiol in AAS users.

Novel dummy molecularly imprinted polymer for simultaneous solid-phase extraction of stanozolol metabolites from urine.

Stanozolol, a synthetic derivative of testosterone, is one of the common doping drugs among athletes and bodybuilders. It is metabolized to a large extent and metabolites are detected in urine for a longer duration than the parent compound. In this study, a novel dummy molecularly imprinted polymer (DMIP) is developed as a sorbent for solid-phase extraction of stanozolol metabolites from spiked human urine samples. The optimized DMIP is composed of stanozolol as the dummy template, methacrylic acid as the functional monomer, and ethylene glycol dimethacrylate as the cross-linker in a ratio of 1:10:80. The extracted analytes were quantitively determined using a newly developed and validated ultrahigh-performance liquid chromatography tandem mass spectrometry method, where the limits of detection and quantitation were 0.91 and 1.81 ng mL-1, respectively, fulfilling the minimum required performance limit decided on by the World Anti-Doping Agency. The mean percentage extraction recoveries for 3'-hydroxystanozolol, 4ß-hydroxystanozolol, and 16ß-hydroxystanozolol are 97.80% ± 13.80, 83.16% ± 7.50, and 69.98% ± 2.02, respectively. As such, the developed DMISPE can serve as an efficient cost-effective tool for doping and regulatory agencies for simultaneous clean-up of the stanozolol metabolites prior to their quantification.

Platelet activity, coagulation, and fibrinolysis in long-term users of anabolic-androgenic steroids compared to strength-trained athletes.

INTRODUCTION: Use of anabolic-androgenic steroids (AAS) is associated with adverse cardiovascular (CV) effects, including potential prothrombotic effects. This study aimed to assess platelet activation and aggregation, coagulation, and fibrinolysis, in long-term AAS users compared to non-using strength-trained athletes. MATERIALS AND METHODS: Thirty-seven strength-trained men using AAS were compared to seventeen non-using professional strength-trained athletes at similar age (median 33 years). AAS use was verified by blood and urine analyses. Platelet Function Analyzer 100 (PFA-100) and whole blood impedance aggregometry with thrombin, arachidonic acid, and ADP as agonists, were performed to evaluate platelet aggregation. ELISA methods were used for markers of platelet activation. Fibrinogen, D-dimer, the coagulation inhibitors protein S and C activity, and antithrombin were measured by routine. Fibrinolysis was evaluated by Plasminogen Activator Inhibitor-1 (PAI-1) activity. RESULTS: There were no significant differences in platelet aggregation between the two groups. Von Willebrand factor was lower among the AAS users (p < 0.01), and P-Selectin was slightly higher (p = 0.05), whereas CD40 Ligand, ß-thromboglobulin, and thrombospondin did not differ significantly. No differences were found in the assessed coagulation inhibitors. Higher D-dimer levels (p < 0.01) and lower PAI-1 activity (p < 0.01) were found among the AAS users. CONCLUSIONS: The investigated long-term users of AAS did not exhibit elevated platelet activity compared to strength-trained non-using athletes. However, AAS use was associated with higher D-dimer levels and lower PAI-1 activity. These findings suggest that any prothrombotic effect of long-term AAS use may predominantly involve other aspects of the hemostatic system than blood platelets.

On-site monitoring of nandrolone in cattle farming samples by portable atmospheric pressure chemical ionization mass spectrometry with ambient sampling.

Nandrolone (NT) is a type of androgen anabolic steroid that is often illegally used in cattle farming, leading to unpredictable harm to human health via the food chain. In this study, a rapid detection method for NT in the samples of cattle farming was established using a portable mass spectrometer. The instrument parameters were optimized, including a thermal desorption temperature of 220 °C, a pump speed of 30 %, an APCI ionization voltage of 3900 v, and an injection volume of 6 µL. The samples of bovine urine, feed, sewage, and tissue were selected, and extracted using a solution of methanol:acetonitrile (1:1, v/v), followed by spiking a NT standard solution (1000 ng·mL-1) and ionization through the APCI ion source for detection. The results showed that NT could not be detected in beef and feed due to the complexity of the matrix, while clear signals of NT ions were observed in bovine urine and sewage samples, with LODs of 1000 and 100 ng·mL-1, respectively. Furthermore, quantitative analysis was attempted, and a good linear relationship (R2 = 0.9952) was observed for NT in sewage within the range of 100 to 1000 ng·mL-1. At spiked levels of 100, 500, 1000 and 2000 ng mL-1, the recovery rates ranged from 74.3 % to 92.8 %, with a relative standard deviation (n = 6) of less than 15 %. In conclusion, this detection method offers the advantages of simplicity, rapidity, strong timeliness, and specificity, making it suitable for on-site detection. It can be used for qualitative screening of nandrolone in bovine urine and quantitative analysis of nandrolone in sewage.

Screening anabolic androgenic steroids in human urine: an application of the state-of-the-art gas chromatography-Orbitrap high-resolution mass spectrometry.

Over the past few decades, anabolic androgenic steroids (AASs) have been abused in and out of competition for their performance-enhancing and muscle-building properties. Traditionally, AASs were commonly detected using gas chromatography-mass spectrometry in the initial testing procedure for doping control purposes. Gas chromatography-Orbitrap high-resolution mass spectrometry (GC-Orbitrap-HRMS) is a new technology that has many advantages in comparison with GC-MS (e.g., a maximum resolving power of 240,000 (FWHM at m/z 200), excellent sub-ppm mass accuracy, and retrospective data analysis after data acquisition). Anti-doping practitioners are encouraged to take full advantage of the updated techniques of chromatography-mass spectrometry to develop sensitive, specific, and rapid screening methods for AASs. A new method for screening a wide range of AASs in human urine using GC-Orbitrap-HRMS was developed and validated. The method can qualitatively determine 70 anabolic androgenic steroids according to the minimum required performance limit of the World Anti-Doping Agency. Moreover, the validated method was successfully applied to detect six metabolites in urine after the oral administration of metandienone, and their excretion curves in vivo were studied. Metandienone M6 (17ß-hydroxymethyl-17α-methyl-18-nor-androst-1,4,13-trien-3-one) has been identified as a long-term urinary metabolite which can be detected up to 7 weeks, thus providing a longer detection window compared with previous studies. This study provides a rationale for GC-Orbitrap-HRMS in drug metabolism and non-targeted screening.

Anabolic-Androgenic Steroid Abuse Causes Cardiac Dysfunction.

This article aims to review available literature evidence about the harmful effects of long-term anabolic-androgenic steroid (AAS) abuse on the heart. A review of 11 existing literature articles regarding this association has been used in the development of this review article. There is increasing medical literature documentation of the eventual harmful effect of AAS misuse or abuse on the heart. Individuals who misuse these steroids are susceptible to significant debilitation and loss of productive person-hours, and in severe cases, it can lead to death. Raising awareness about this potentially deleterious effect of anabolic steroids is crucial to prevent its misuse or abuse.

Combining anabolic loading and raloxifene improves bone quantity and some quality measures in a mouse model of osteogenesis imperfecta.

Osteogenesis imperfecta (OI) increases fracture risk due to changes in bone quantity and quality caused by mutations in collagen and its processing proteins. Current therapeutics improve bone quantity, but do not treat the underlying quality deficiencies. Male and female G610C+/- mice, a murine model of OI, were treated with a combination of raloxifene and in vivo axial tibial compressive loading starting at 10 weeks of age and continuing for 6 weeks to improve bone quantity and quality. Bone geometry and mechanical properties were measured to determine whole bone and tissue-level material properties. A colocalized Raman/nanoindentation system was used to measure chemical composition and nanomechanical properties in newly formed bone compared to old bone to determine if bone formed during the treatment regimen differed in quality compared to bone formed prior to treatment. Lastly, lacunar geometry and osteocyte apoptosis were assessed. OI mice were able to build bone in response to the loading, but this response was less robust than in control mice. Raloxifene improved some bone material properties in female but not male OI mice. Raloxifene did not alter nanomechanical properties, but loading did. Lacunar geometry was largely unchanged with raloxifene and loading. However, osteocyte apoptosis was increased with loading in raloxifene treated female mice. Overall, combination treatment with raloxifene and loading resulted in positive but subtle changes to bone quality.

Anabolic steroids in livestock production: Background and implications for chemical food safety.

The use of steroids in livestock animals is a source of concern for consumers because of the risks associated with the presence of their residues in foodstuffs of animal origin. Technological advances such as mass spectrometry have made it possible to play a fundamental role in controlling such practices, firstly for the discovery of marker metabolites but also for the monitoring of these compounds under the regulatory framework. Current control strategies rely on the monitoring of either the parent drug or its metabolites in various matrices of interest. As some of these steroids also have an endogenous status specific strategies have to be applied for control purposes. This review aims to provide a comprehensive and up-to-date knowledge of analytical strategies, whether targeted or non-targeted, and whether they focus on markers of exposure or effect in the specific context of chemical food safety regarding the use of anabolic steroids in livestock. The role of new approaches in data acquisition (e.g. ion mobility), processing and analysis, (e.g. molecular networking), is also discussed.

A screening method for the quantitative determination of selective androgen receptor modulators (SARMs) in capsules by high resolution 19F- and 1H-NMR spectroscopy.

A new method for rapid determination of the content of selective androgenic receptor modulators (SARMs) andarine, cardarine, ligandrol, ostarine and S-23 in capsules by 1H- and 19F-high resolution nuclear magnetic resonance spectroscopy was described and validated. Specificity, linearity, accuracy, precision, detection and quantification limits were considered as validation parameters. Full 1H-, 13C- and 19F-NMR structural assignment of the SARMs is provided as a tool for self-standing identification without a reference standard. Amounts of 7-15 mg of SARMs/capsule were detected in different products with an intermediate precision of 0.8-1.7% in 4 to 20 minutes of analysis time. The validation results and rapidity of analysis confirm the applicability of the method for large-scale screening. The statistical analysis of the results from 19F- and 1H-quantitative NMR showed that both approaches were equally effective, thus expanding the potential use of the methodology to non-fluorinated SARMs. At present, no SARM has been approved for human consumption; however, SARMs are actually used by bodybuilders and recreational athletes, who purchase them even though the risk-benefit ratio of these molecules has not been definitively established.

Body fluid contamination in the context of an adverse analytical finding in doping: About a case involving ostarine.

Ostarine, also known as MK-2866 or enobosarm, is a selective androgen receptor modulator (SARM). It has anabolic properties and as such is widely used in doping, accounting in 2021 for 25 % of the adverse analytical findings (AAF) among the class S1.2 "Other anabolic agents" of products banned by the World Anti-Doping Agency, to which it belongs. But in some cases, it can be responsible for an AAF following contamination. We report the case of an athlete who contaminated herself by exchanging body fluids while kissing her boyfriend, who took 25 mg per day of MK-2866 for 9 days prior to the athlete's AAF (urinary concentration evaluated at 13 ng/mL) without her knowledge. Both subjects came to our lab for hair testing. The athlete's hair was black and slightly frizzy. Six segments of 2 cm then 7 × 3 cm (33 cm) were analysed and showed increasing concentrations, from 2 pg/mg on the first segment to 17.8 pg/mg on the last segment. The boyfriend's hair, light-brown, analyzed on 4 × 2 cm, also showed increasing values, from 65 to 143 pg/mg. These gradients of concentration in the hair's athlete and in her boyfriend were compatible with external contamination of the hair, confirmed by analysis of washing baths, pillowcases (150 pg on each), and the athlete's hairbrush (250 pg). Fingernails were also contaminated, with 21 pg/mg in the athlete and 1041 pg/mg in the boyfriend, with highly contaminated washing baths, and toenails were less contaminated, with 2 pg/mg in the athlete and 17.3 pg/mg in the boyfriend. Urine samples taken 35 days after the start of MK-2866 treatment showed a value of 3690 ng/mL in the boyfriend and 5.7 ng/mL in the athlete. After 6 days off, these concentrations were 3.3 ng/mL and 0.1 ng/mL, respectively. A controlled transfer study was carried out 12 days after discontinuation (urine concentrations returned to negative level). After administration of 17 mg (the 25 mg/mL vial having been controlled at 17 mg/mL), urine samples were taken from the boyfriend and the athlete (n = 10 for each) for more than 25 h after they had been living normally with each other (regular kissing in particular). The boyfriend's urine concentrations ranged from 681 ng/mL to 12822 ng/mL (Tmax = 8:30 hrs), and the athlete's from 0.3 ng/mL to 13 ng/mL with Tmax = 8:30 hrs, i.e. at 22:30 hrs, which corresponded exactly to the time of collection of the urine that showed AAF, with a similar concentration. The dose ingested by the athlete was estimated at 15 µg. These results demonstrate the transfer of ostarine via body fluids between two subjects, with a high risk of AAF in one athlete, as observed in our case.

Mortality Among Users of Anabolic Steroids.

This cohort study investigates mortality and cause of death among a large cohort of androgenic anabolic steroid users, compared with a control group, in Denmark from January 3, 2006, to March 1, 2018.

Exploring the prevalence of anabolic steroid use among men and women resistance training practitioners after the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has had a significant impact on individual health and fitness routines globally. Resistance training, in particular, has become increasingly popular among men and women looking to maintain or improve their physical fitness during the pandemic. However, using Anabolic Steroids (AS) for performance enhancement in resistance training has known adverse effects. Thus, this study aimed to explore the prevalence of AS use among men and women resistance training practitioners after the COVID-19 pandemic. METHODS: A cross-sectional survey was conducted among 3,603 resistance training practitioners (1,855 men and 1,748 women) in various geographical locations impacted by COVID-19. The participants were asked to complete self-administered questionnaires, which included questions regarding demographic information, training habits, and current or prior usage of AS. The data were analyzed using SPSS statistical software and the chi-square method, with a significance level of (P < 0.05). RESULTS: A total of 3603 men and women resistance training practitioners completed the survey. In the study, 53.05% of men and 41.99% of women used anabolic and androgenic steroids. Of those men who used steroids, 29.47% used Testosterone, while 31.20% of women used Winstrol. Additionally, 50.30% of men used steroids via injection, while 49.05% of women used them orally. According to the study, 49.99% of the participants had 6 to 12 months of experience with resistance training, and 64.25% of them underwent three training sessions per week. The analysis using the χ2 test did not reveal any significant difference between men and women in terms of duration of bodybuilding, frequency per week, and engagement in other activities. CONCLUSION: This study shows that a significant proportion of men and women resistance training practitioners used AS, particularly among young adults with limited training experience. Thus, there is a need for targeted education and awareness campaigns to address the hazards of AS use and promote healthy training habits during the COVID-19 pandemic.

Oleanolic acid exerts bone anabolic effects via activation of osteoblastic 25-hydroxyvitamin D 1-alpha hydroxylase.

Oleanolic acid (OA) is previously shown to exert bone protective effects in aged animals. However, its role in regulating osteoblastic vitamin D bioactivation, which is one of major causes of age-related bone loss, remains unclear. Our results revealed that treatment of OA significantly increased skeletal CYP27B1 expression and circulating 1,25(OH)2D3 in ovariectomized mice (p <0.01). Moreover, OA upregulated CYP27B1 protein expression and activity, as well as the vitamin D-responsive bone markers alkaline phosphatase (ALP) activity and osteopontin (OPN) protein expression, in human osteoblast-like MG-63 cells (p<0.05). CYP27B1 expression increased along with the osteoblastic differentiation of human bone marrow derived mesenchymal stem cells (hMSCs). CYP27B1 expression and cellular 1,25(OH)2D3 production were further potentiated by OA in cells at mature osteogenic stages. Notably, our study suggested that the osteogenic actions of OA were CYP27B1 dependent. In summary, the bone protective effects of OA were associated with the induction of CYP27B1 activity and expression in bone tissues and osteoblastic lineages. Hence, OA might be a potential approach for management of age-related bone loss.

Comparative analysis of anti-osteoporosis medications in preventing vertebral body fractures after balloon kyphoplasty.

This retrospective study compared the efficacy of anabolic agents (romosozumab and teriparatide) with that of alendronate in preventing subsequent vertebral body fractures (SVBFs) after balloon kyphoplasty (BKP). All anabolic agents significantly reduced SVBFs. Romosozumab was most effective in increasing bone mineral density (BMD) and completely suppressed distant vertebral body fractures. INTRODUCTION: To determine optimal anti-osteoporosis medications, we compared romosozumab and teriparatide to alendronate as a control from perioperative BKP to the 1st postoperative year for treatment and secondary fracture prevention in osteoporosis. METHODS: A total of 603 patients who underwent initial BKP for osteoporotic vertebral fractures were evaluated and categorized into five groups based on drug administration: romosozumab (group R, 155 patients), twice-weekly teriparatide (group TW, 48), weekly teriparatide (group W, 151), daily teriparatide (group D, 138), and alendronate (control) (group C, 111). The 1-year incidence of SVBFs, BMD change rate, and probability of requiring BKP were compared among the groups. RESULTS: SVBF incidence was 3.9%, 6.5%, 8.3%, 6.0%, and 14.4% in groups R, D, TW, W, and C, respectively, with all other groups exhibiting significantly lower rates than group C. The groups that administered the anabolic agents had a notably lower incidence of distant fractures than group C. Compared with group C, group R showed significantly higher BMD change rates in lumbar vertebral bodies at 4, 8, and 12 months and group D at 12 months. Anabolic agent groups exhibited significantly higher improvement rates than group C after conservative treatment alone. CONCLUSION: The anabolic agents were found to be more effective at reducing the incidence of SVBF (especially distant vertebral fractures) than alendronate. These agents decreased the rate of repeat BKP even after the occurrence of a fracture. Overall, the use of an anabolic agent for the treatment of osteoporosis after BKP is better than the use of alendronate, even when treatment is initiated in the perioperative stage.

ß-Receptor blocker enhances the anabolic effect of PTH after osteoporotic fracture.

The autonomic nervous system plays a crucial role in regulating bone metabolism, with sympathetic activation stimulating bone resorption and inhibiting bone formation. We found that fractures lead to increased sympathetic tone, enhanced osteoclast resorption, decreased osteoblast formation, and thus hastened systemic bone loss in ovariectomized (OVX) mice. However, the combined administration of parathyroid hormone (PTH) and the ß-receptor blocker propranolol dramatically promoted systemic bone formation and osteoporotic fracture healing in OVX mice. The effect of this treatment is superior to that of treatment with PTH or propranolol alone. In vitro, the sympathetic neurotransmitter norepinephrine (NE) suppressed PTH-induced osteoblast differentiation and mineralization, which was rescued by propranolol. Moreover, NE decreased the PTH-induced expression of Runx2 but enhanced the expression of Rankl and the effect of PTH-stimulated osteoblasts on osteoclastic differentiation, whereas these effects were reversed by propranolol. Furthermore, PTH increased the expression of the circadian clock gene Bmal1, which was inhibited by NE-ßAR signaling. Bmal1 knockdown blocked the rescue effect of propranolol on the NE-induced decrease in PTH-stimulated osteoblast differentiation. Taken together, these results suggest that propranolol enhances the anabolic effect of PTH in preventing systemic bone loss following osteoporotic fracture by blocking the negative effects of sympathetic signaling on PTH anabolism.