Risk of venous thromboembolism among users of different anti-osteoporosis drugs: a population-based cohort analysis including over 200,000 participants from Spain and the UK

The venous thromboembolism risk among anti-osteoporotics is unknown. In this primary care study, the risk with other bisphosphonates [1.05 (0.94-1.18) and 0.96 (0.78-1.18)], strontium [0.90 (0.61-1.34) and 1.19 (0.82-1.74)], in the UK and Spain respectively, and denosumab [1.77 (0.25-12.66)] and teriparatide [1.27 (0.59-2.71)] in Spain, did not differ versus alendronate. Most of the known adverse drug reactions described for anti-osteoporosis medication (AOM) have been described in studies comparing AOM users to non-users. We aimed to compare the risk of venous thromboembolism (VTE) among incident users of different AOM compared to alendronate (first line therapy). Two cohort studies were performed using data from the UK (CPRD) and Spain (BIFAP) primary care records separately. All patients aged >= 50 years with at least 1 year of data available and a new prescription or dispensation of AOM (date for therapy initiation) during 2000-2014 (CPRD) or 2001-2013 (BIFAP) were included. Users of raloxifene/bazedoxifene were excluded from both databases. Five exposure cohorts were identified according to first treatment: (1) alendronate, (2) other bisphosphonates, (3) strontium ranelate, (4) denosumab, and (5) teriparatide. Participants were followed from the day after therapy initiation to the earliest of a treated VTE (cases), end of AOM treatment (defined by a refill gap of 180 days), switching to an alternative AOM, drop-out, death, or end of study period. Incidence rates of VTE were estimated by cohort. Adjusted hazard ratios (HR 95%CI) were estimated according to drug used. Overall, 2035/159,209 (1.28%) in CPRD and 401/83,334 (0.48%) in BIFAP had VTE. Compared to alendronate, adjusted HR of VTE were 1.05 (0.94-1.18) and 0.96 (0.78-1.18) for other bisphosphonates, and 0.90 (0.61-1.34) and 1.19 (0.82-1.74) for strontium in CPRD and BIFAP, respectively; 1.77 (0.25-12.66) for denosumab and 1.27 (0.59-2.71) for teriparatide in BIFAP. VTE risk during AO therapy did not differ by AOM drug use. Our data does not support an increased risk of VTE associated with strontium ranelate use in the community.