Two-year persistence and compliance with osteoporosis therapies among postmenopausal women in a commercially insured population in the United States

Osteoporosis is a chronic, systemic bone disorder that is characterized by low bone density, deterioration of bone tissue, loss of bone strength, and an increase in bone fracture risk [1]. Treatment goals for osteoporosis encompass managing bone fracture risk by minimizing bone loss, increasing bone mineral density (BMD), and improving bone microarchitecture [2, 3]. This is accomplished primarily through therapy with anti-resorptive agents, including bisphosphonates, estrogen receptor agonists and antagonists, parathyroid hormone or its analogues, and monoclonal antibody therapy [4].

Persistence and compliance are important for improving outcomes in patients with osteoporosis. Recent studies have shown that patients who are persistent and compliant have fewer total, vertebral, non-vertebral, and hip fractures [5, 6]. As persistence tends to decline over time, potentially leading to poorer outcomes, a long-term view of persistence is important in strategizing how to improve outcomes.

However, the majority of research to date has focused on persistence and compliance over a 1-year period, with limited information on long-term trends [7‐11]. In these short-term studies, rates of persistence and compliance with oral bisphosphonates were generally poor (<50%) [12‐17]. These studies have generally found that patients are more persistent and compliant with injectable osteoporosis therapies—including denosumab, teriparatide, and zoledronic acid—compared with oral osteoporosis therapies—including oral bisphosphonates [7, 8, 18‐20]. Similarly, Cheng et al. recently found that the rate of persistence among patients receiving denosumab was 68%, compared with 29–35% for bisphosphonates, 42% for raloxifene, and 59% for teriparatide during 1 year of follow-up [7].

The primary objective of this study was to evaluate short- and long-term (i.e., 1- and 2-year) persistence and compliance with osteoporosis therapies among postmenopausal women with osteoporosis with commercial or Medicare supplemental insurance. In addition, this study compared short- and long-term persistence and compliance across different osteoporosis therapies and dosing regimens.

In this US-based analysis of women initiating a new osteoporosis therapy, persistence and compliance were higher among those treated with injectable therapies compared with oral osteoporosis therapies over both a 1- and 2-year follow-up period, with the exception of ibandronate IV, which had a very low sample size. Persistence and compliance over 24 months were higher among patients initiating denosumab SC, an injectable therapy administered Q6M, compared with those initiating other, more frequently dosed osteoporosis therapies, including oral or injectable bisphosphonates and raloxifene.

Previous studies of persistence and compliance with osteoporosis therapies are generally limited to 1 year of follow-up. Even within that time period, persistence and compliance with osteoporosis therapies are generally poor for oral osteoporosis therapies, while injectable osteoporosis therapies are generally associated with higher rates of both persistence and compliance. The 12-month results from this study are consistent with those of other published studies. One study that pooled the data of all osteoporosis therapies found rates of overall persistence and compliance to be 50 and 68%, respectively [21]. Rates of persistence with denosumab SC over 1 year have ranged between 63 and 82%, while rates of compliance have ranged between 71 and 91% [7, 19, 22]. Rates of persistence and compliance with teriparatide have been shown to be 54 and 32%, respectively, at 1 year of follow-up and 19 and 48%, respectively, at 2 years of follow-up [17, 20]. Because zoledronic acid is taken once a year, studies of persistence and compliance at 1 year yield predictably high rates. For oral bisphosphonates (daily, weekly, and monthly), rates of persistence ranged from 15 to 50%, while rates of compliance ranged from 39 to 43% [6, 12‐16]. Rates of persistence with raloxifene ranged from 14 to 34% [12, 14, 15].

As persistence tends to decline over time, potentially leading to poorer outcomes, knowledge of a long-term view of persistence is important for developing strategies to improve persistence and, consequently, outcomes [23‐25]. Poor persistence and compliance increase the risk of fractures [16, 23, 26, 27]. In a study of over 35,000 women aged 45 years and older from an administrative claims database, compliant patients had a 21% reduction in overall fracture risk, while persistent patients had a 29% reduction in overall fracture risk [6]. In a meta-analysis of six studies pooling over 171,000 patients, non-compliant patients had a 46% greater risk of experiencing fracture than their compliant counterparts, with the risk of vertebral fracture higher than hip or non-vertebral fracture [10]. Poor compliance has also been shown to affect BMD: among a population of nearly 250 women in a managed care plan, those receiving bisphosphonates or estrogen with MPR ≥66% had greater increases in BMD than those with MPR <66% [28]. Because the clinical benefit of osteoporosis therapies diminishes over time upon discontinuation, persistence and compliance with medications is critical in minimizing the risk of bone fractures [4].

This study provides an additional contribution to the literature with regard to long-term persistence and compliance among postmenopausal women receiving one of the currently available osteoporosis therapies. Payers, practitioners, and policy makers would benefit from an understanding of long-term persistence and its effect on treatment outcomes. Additional research is needed to understand factors associated with improved persistence and compliance.