INTRODUCTION: Prolonged exposure to microgravity is associated with a significant reduction in bone density, exposing astronauts to renal calculi in flight and osteoporotic fractures on return to Earth. While physical countermeasures and bisphosphonates may reduce demineralization, additional therapies are needed for future interplanetary missions. This literature review aims to understand the current background pertaining to denosumab (a monoclonal antibody therapy used in osteoporosis) and its potential use for long duration spaceflight.METHOD: A literature review was conducted using the following keywords: “osteoporosis”; “osteopaenia”; “microgravity”; “space flight”; “bed rest”; “denosumab”; “alendronate”; “bisphosphonates”; and “countermeasures”. Additional articles were identified through references. Included for discussion were 48 articles, including systemic reviews, clinical trials, practice guidelines, and textbooks.RESULTS: No previous bed rest or in-flight studies regarding denosumab were identified. In osteoporosis, denosumab is superior to alendronate in maintaining bone density with a lower rate of side-effects. Emerging evidence in reduced biomechanical loading state suggests denosumab improves bone density and decreases fracture risk. Concerns exists over vertebral fracture risk following discontinuation. The dosing regimen of denosumab offers practical advantages over bisphosphonates. Existing spaceflight studies with alendronate serve as a template for a study with denosumab and allow for a direct comparison of efficacy and safety.DISCUSSION: Denosumab has numerous potential advantages as a countermeasure to microgravity-induced osteopenia when compared to alendronate, including: improved efficacy; fewer side-effects: better tolerability; and a convenient dosing regimen. Two further studies are proposed to determine in-flight efficacy and the suitability of monoclonal antibody therapy in the spaceflight environment.Rengel A, Tran V, Toh LS. Denosumab as a pharmacological countermeasure against osteopenia in long duration spaceflight. Aerosp Med Hum Perform. 2023; 94(5):389–395.

Introduction Transthyretin cardiac amyloidosis (ATTR) can be reliably diagnosed in the absence of histology if grade 2 or 3 cardiac uptake is demonstrated on 99mTc-DPD scan (DPD) in the absence of a detectable monoclonal component. Diagnosis requires a high degree of clinical suspicion in the presence of often non-specific findings and that it may be one of the reasons to under-diagnose ATTR. The aim of the study is to identify clinical, analytical and ECG variables that best predict a positive DPD result. Methods This is a multicentre retrospective study including all patients undergoing consecutive 99mTc-DPD scintigraphy in a reference area of 750,000 inhabitants between January 2016 and January 2021 for suspected ATTR. AL amyloidosis patients were excluded. Clinical, analytical, ECG and echocardiographic data were analyzed. We identified variables that independently predicted a positive DPD study using a multivariable logistic regression analysis. Receiver Operating Curve (ROC) analysis and the Area under the Curve (AUC) were calculated to assess the discrimination capacity of the model to predict a positive DPD study. Results DPD scans from a total of 181 patients were analyzed. Mean age of the sample: 78 years (42–96), 100% caucasians, 77% male. 54.7% (N=99) had a positive DPD study (defined as grade 2 or 3 Perugini uptake) and 45.3% (N=82) were negative. Independent predictors of a positive study were age, male gender, left ventricular septum thickness, any grade of atrioventricular block, low QRS voltage, Carpal tunnel syndrome, history of hypotension or need to lower antihypertensive drugs and a NT-proBNP value above 1800 pg/ml (See Table 1). The diagnostic accuracy of the model was excellent, with an AUC of 0.92 (IC 95% 0.87–0.96) (see Figure 1). Conclusions There are clinical-analytical factors and ECG and echocardiogram findings accessible in daily clinical practice that are able to predict a positive result on cardiac scintigraphy requested for suspected ATTR. Identifying these factors may improve the non-invasive diagnosis of ATTR. FUNDunding Acknowledgement Type of funding sources: None. Table 1. Multivariable logistic regression analys Figure 1. ROC curve

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