Temporal Trends and Factors Associated with Bisphosphonate Discontinuation and Restart

Abstract

Adverse events related to long‐term use of bisphosphonates have raised interest in temporary drug discontinuation. Trends in bisphosphonate discontinuation and restart, as well factors associated with these decisions, are not fully understood at a population level. We investigated temporal trends of bisphosphonate discontinuation from 2010 to 2015 and identified factors associated with discontinuation and restart of osteoporosis therapy. Our cohort consisted of long‐term bisphosphonate users identified from 2010 to 2015 Medicare data. We defined discontinuation as ≥12 months without bisphosphonate prescription claims. We used conditional logistic regression to compare factors associated with alendronate discontinuation or osteoporosis therapy restart in the 120‐day period preceding discontinuation or restart referent to the 120‐day preceding control periods. Among 73,800 long‐term bisphosphonate users, 59,251 (80.3%) used alendronate, 6806 (9.2%) risedronate, and 7743 (10.5%) zoledronic acid, exclusively. Overall, 26,281 (35.6%) discontinued bisphosphonates for at least 12 months. Discontinuation of bisphosphonates increased from 1.7% in 2010, reaching a peak of 14% in 2012 with levels plateauing through 2015. The factors most strongly associated with discontinuation of alendronate were: benzodiazepine prescription (adjusted odds ratio [aOR] = 2.5; 95% confidence interval [CI] 2.1, 3.0), having a dual‐energy X‐ray absorptiometry (DXA) scan (aOR = 1.8; 95% CI 1.7, 2.0), and skilled nursing facility care utilization (aOR = 1.8; 95% CI 1.6, 2.1). The factors most strongly associated with restart of osteoporosis therapy were: having a DXA scan (aOR = 9.9; 95% CI 7.7, 12.6), sustaining a fragility fracture (aOR = 2.8; 95% CI 1.8, 4.5), and an osteoporosis or osteopenia diagnosis (aOR = 2.5; 95% CI 2.0, 3.1). Our national evaluation of bisphosphonate discontinuation showed that an increasing proportion of patients on long‐term bisphosphonate therapy discontinue medications. The factors associated with discontinuation of alendronate were primarily related to worsening of overall health status, whereas traditional factors associated with worsening bone health were associated with restarting osteoporosis medication. © 2019 American Society for Bone and Mineral Research.

<p>Ultra-Small Lysozyme-Protected Gold Nanoclusters as Nanomedicines Inducing Osteogenic Differentiation</p>

“…The proliferation of MC3T3-E1 was investigated based on Cell Counting Kit-8 (CCK8) assays. First, the cells were seeded at a density of 4×10 3 per well in a 96-well plate and incubated overnight. Furthermore, the cells were exposed to the mediums in the absence (Control), and the presence of 50 μM of lysozyme, and 50 μM of Lys-AuNCs for 1 day respectively.…”

“…1,2 Nowadays, the clinical treatment of osteoporosis mainly depends on traditional drugs, such as bisphosphonates, androgens, the combination of vitamin D and calcium supplements. [3][4][5] However, osteoporosis is still not completely curable using these treatments, which fail to offer long-term solutions. [6][7][8] For instance, significant side effects occur due to their drugresistant problems.…”

A Prospective Open‐Label Observational Study of a Buffered Soluble 70 mg Alendronate Effervescent Tablet on Upper Gastrointestinal Safety and Medication Errors: The GastroPASS Study

“…Although alendronate has been shown to reduce the risk of vertebral, non-vertebral, and hip fractures by 55%, 64%, and 47%, respectively, (7) adherence is problematic, with >50% discontinuing treatment within the first year. (8,9) Upper gastrointestinal (GI) side effects are one of the main reasons for discontinuing bisphosphonate treatment, observed in both real-life studies (10)(11)(12) and clinical trials, (13)(14)(15)(16) resulting in reduced anti-fracture efficacy and increased health care costs. (17)(18)(19)(20) The International Osteoporosis Foundation and the European Calcified Tissue Society recognize the challenges with adherence associated with oral bisphosphonates.…”

“…Upper gastrointestinal (GI) side effects are one of the main reasons for discontinuing bisphosphonate treatment, observed in both real‐life studies ( 10–12 ) and clinical trials, ( 13–16 ) resulting in reduced anti‐fracture efficacy and increased health care costs. ( 17–20 )…”

Duration of Bisphosphonate Drug Holidays in Osteoporosis Patients: A Narrative Review of the Evidence and Considerations for Decision-Making

“…Importantly, the threshold treatment length of three to five years recommended prior to a drug holiday is based on a priori defined durations of the FLEX and HORIZON trials that were driven by study power [ 17 ]. Real-world zoledronate use appears mostly in-line with these treatment duration recommendations, with most patients beginning a drug holiday after three years of intravenous bisphosphonate treatment [ 37 ], yet some studies indicate many patients undergo a drug holiday after fewer than five years of oral bisphosphonate treatment [ 37 , 45 , 46 ]. In addition, in clinical practice, low adherence has been frequently documented with oral bisphosphonate treatment [ 47 , 48 , 49 ] and so some patients may have suboptimal adherence prior to a drug holiday.…”