Bisphosphonates are the mainstay of osteoporosis treatment but also play a fundamental role in treating other bone diseases such as Osteogenesis Imperfecta, Pagets' disease, and in the prevention of adverse skeletal effects in certain cancers such as prostate cancer or multiple myeloma. In the last decades, the refinement of bisphosphonates and an increase in the number of new bisphosphonates commercialized has altered the clinical management of these diseases. Despite differences between randomized controlled trials and observational studies, overall all bisphosphonates licensed have proven to reduce the risk of fracture through the inhibition of bone resorption. Other beneficial effects include pain reduction in bone metastasis and potentially a decrease in mortality. However, the chronic nature of most of these disorders implies long-term treatments, which can be associated with long-term adverse effects. Some of the adverse effects identified include an increased risk of atypical femur fractures, osteonecrosis of the jaw, gastrointestinal side effects, or atrial fibrillation. The harm/benefit thinking and the constant update regarding these medications are vital in the day-to-day decision-making in clinical practices. The aims of this review are to compile the basic characteristics of these drugs and outline the most important benefits and side effects and provide a clinical context as well as a research agenda to fill the gaps in our knowledge.

Introduction Severe acute respiratory syndrome coronavirus‐2 has caused a pandemic of coronavirus disease (COVID‐19) with many patients developing hypoxic respiratory failure. Corticosteroids reduce the time on mechanical ventilation, length of stay in the intensive care unit and potentially also mortality in similar patient populations. However, corticosteroids have undesirable effects, including longer time to viral clearance. Clinical equipoise on the use of corticosteroids for COVID‐19 exists. Methods The COVID STEROID trial is an international, randomised, stratified, blinded clinical trial. We will allocate 1000 adult patients with COVID‐19 receiving ≥10 L/min of oxygen or on mechanical ventilation to intravenous hydrocortisone 200 mg daily vs placebo (0.9% saline) for 7 days. The primary outcome is days alive without life support (ie mechanical ventilation, circulatory support, and renal replacement therapy) at day 28. Secondary outcomes are serious adverse reactions at day 14; days alive without life support at day 90; days alive and out of hospital at day 90; all‐cause mortality at day 28, day 90, and 1 year; and health‐related quality of life at 1 year. We will conduct the statistical analyses according to this protocol, including interim analyses for every 250 patients followed for 28 days. The primary outcome will be compared using the Kryger Jensen and Lange test in the intention to treat population and reported as differences in means and medians with 95% confidence intervals. Discussion The COVID STEROID trial will provide important evidence to guide the use of corticosteroids in COVID‐19 and severe hypoxia.

The risk of osteoporosis in patients with MC is not increased. However, DXA scan is recommended in MC patients with known risk factors or active disease requiring longstanding budesonide treatment. Supplementation of calcium and vitamin-D in patients treated with budesonide is recommended.