E-Poster Presentation ESA-SRB-ANZBMS 2021

Background: Osteoporosis is an incurable, progressive, chronic disease that requires long-term treatment. Recent studies have brought the long-term safety of the pharmacologic treatment of osteoporosis into question.

Aim:  To investigate and clarify the morbidity (serious adverse events) and all-cause mortality of commonly used anti-osteoporosis drugs.

Methods: PubMed and Cochrane electronic databases for searched for clinical trials that enrolled osteoporotic men and postmenopausal women. Randomised controlled trials, post hoc analysis of randomised controlled trials and cohort studies published after 1990 were selected. These included placebo-controlled, active-controlled and head-to-head studies.

Results:

Raloxifene (selective serotonin receptor modulator) increases the risk of thromboembolic events 2-3-fold compared to placebo but reduces the risk breast cancer by more than 75%. In patients with cardiovascular risk, the reduction in arterial adverse events outweighs the increased risk of venous thromboembolic adverse events to significantly reduce morbidity. Bisphosphonates and Denosumab have a serious adverse event profile similar to that of placebo for up to 10 years of continuous use. The risk of osteonecrosis of the jaw and atypical femoral fracture with antiresorptive therapy is low but numerically increases with cumulative dose and duration. However, the benefits of denosumab are rapidly reversible after cessation increasing fracture risk. Bisphosphonates may increase arrhythmia risk (3% vs 1.8%) but reduces cardiovascular mortality by up to 30% at 3 years. Romosozumab is inferior to alendronate with regards to cardiovascular and cerebrovascular risk.

Conclusion: This review moderates concerns about the safety of bisphosphonates and additionally demonstrates that zoledronic acid and alendronate appear to have a cardiovascular mortality and major morbidity benefit. Commonly used anti-osteoporosis drugs are safe and well tolerated with a favourable serious adverse event profile. Raloxifene has an overall cardiovascular benefit. Bisphosphonates may increase arrhythmia but have a mortality benefit.  Denosumab benefits are precipitously reversible on discontinuation.