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1.  Atrial fibrillation and the use of oral bisphosphonates 
Background:
Epidemiological studies investigating a possible association between bisphosphonates and atrial fibrillation (AF) have reported conflicting findings. The objective of our study was to determine whether exposure to oral nitrogen-containing bisphosphonates alendronate and risedronate are associated with increased incidence of atrial fibrillation.
Methods:
In a retrospective cohort study we analyzed data from three large independent databases, two from the United States (MarketScan® and Ingenix®) and one from the United Kingdom (THIN). 144,548 women, age 50–89, bisphosphonate users during 2002–2005 were compared to 668,891 sex- and age-matched controls (1:4). Our primary outcome measure was new incident atrial fibrillation for up to three years; Cox models adjusted for disease and drug history were used to estimated relative risks.
Results:
We identified a total of 8,001, 1,984, and 817 AF cases in oral bisphosphonate users and nonusers during 744,340 (MarketScan), 243,898 (Ingenix), and 148,779 (THIN) person-years of follow-up, respectively. Compared to nonusers, overall adjusted relative risk (adjRR) (95% confidence interval [CI]) for AF in oral bisphosphonates users was 0.92 (0.85–0.99; MarketScan), 1.00 (0.87–1.16; Ingenix), and 0.97 (0.79–1.20; THIN); overall adjRR (95% CI) for any cardiac dysrrhythmia for MarketScan was 1.01 (0.98–1.05), Ingenix 1.06 (0.99–1.13), and THIN 0.97 (0.79–1.20).
Conclusions:
In all three databases from the two countries, the risk of AF or cardiac dysrrhythmia was not increased in postmenopausal women treated for up to three years with oral alendronate or risedronate.
doi:10.2147/TCRM.S17899
PMCID: PMC3071350  PMID: 21479144
atrial fibrillation; chemically induced osteoporosis; drug therapy; alendronate or risedronate; bisphosphonates; adverse effects
2.  Long-term treatment with bisphosphonates and their safety in postmenopausal osteoporosis 
Bisphosphonates are the leading drugs for the treatment of osteoporosis. In randomized controlled trials (RCTs), alendronate, risedronate, and zoledronate have shown to reduce the risk of vertebral, nonvertebral, and hip fractures, whereas RCTs with ibandronate show antifracture efficacy at vertebral sites. Bisphosphonates are generally well tolerated and safe. Nevertheless, adverse events have been noted, and it is important to consider the strength of the evidence for causal relationships. Effects on the gastrointestinal tract and kidney function are well recognized, as are transient acute-phase reactions. Atrial fibrillation was first identified as a potential adverse event in a zoledronate trial, but subsequent trials and analyses failed to substantiate an association with bisphosphonates. Case reports have suggested a relationship between oral bisphosphonates and esophageal cancer, but this has not been demonstrated in epidemiologic studies. A possible association between bisphosphonate use and osteonecrosis of the jaw (ONJ) has also been suggested. However, the risk of ONJ in patients with osteoporosis appears to be very low, with no evidence from prospective RCTs of a causal association. There are reports of occasional occurrence of subtrochanteric or diaphyseal fractures in osteoporotic patients, but an association with bisphosphonate therapy is not substantiated by epidemiologic studies or prospective RCTs.
PMCID: PMC2909499  PMID: 20668715
bisphosphonates; osteoporosis; safety

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