Poor bisphosphonate adherence for treatment of osteoporosis increases fracture risk: Systematic review and meta-analysis

Agency for Health Technologies Assessment, Instituto de Salud Carlos III. Science and Innovation Ministry, 5 Monforte de Lemos, Madrid, 28029, Spain.
Osteoporosis International (Impact Factor: 4.17). 12/2009; 21(11):1943-51. DOI: 10.1007/s00198-009-1134-4
Source: PubMed


Systematic review of adherence to bisphosphonates for the treatment of osteoporosis finds suboptimal levels of persistence and compliance. Poor bisphosphonate compliance increases fracture risk.
The objectives of the study were to measure the persistence and compliance with bisphosphonates for the treatment of osteoporotic patients, and to estimate the influence of compliance on fracture risk.
A systematic review of bisphosphonate adherence in clinical practise provided new evidence to perform a meta-analysis of the means of bisphosphonate persistence and compliance, with a subsequent meta-analysis of fracture risk comparing poorly versus highly compliant patients.
Fifteen articles, totalling 704,134 patients, met our inclusion criteria. Most of the patients were postmenopausal women treated with bisphosphonates. The 3.95% of the patients received hormone replacement therapy, but the rest received bisphosphonates. The meta-analysis of five articles totalling 236,540 patients, who were followed for 1 year, provided a pooled persistence mean of 184.09 days. The meta-analysis of five articles, totalling 234,737 patients, who were also followed for 1 year, provided a pooled medication possession ratio mean of 66.93%. The meta-analysis of six articles, totalling 171,063 patients, who were followed for varying periods of time between 1 and 2.5 years, provided a pooled 46% increased fracture risk in non-compliant patients versus compliant patients. The increased fracture risk was lower for non-vertebral (16%) and hip (28%) than for clinical vertebral fractures (43%).
Persistence and compliance are suboptimal for postmenopausal women undergoing bisphosphonate therapy for osteoporosis. The clinical consequence of this low compliance is an increased risk of fracture, which is lower for non-vertebral than for clinical vertebral fractures.

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Available from: Iñaki Imaz-Iglesia, Oct 11, 2015
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    • "Another reason for the stagnation of BMD increase could be decreasing rates of adherence to bisphosphonates. The adherence has not been assessed in this trial, but a recent meta-analysis showed a suboptimal adherence with a pooled mean medication possession ratio of 67 % [43]. It is possible that suboptimal bisphosphonate intake in this trial has limited positive effects of bisphosphonates. "
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    ABSTRACT: Addition of 10 mg prednisone daily to a methotrexate-based tight control strategy does not lead to bone loss in early rheumatoid arthritis (RA) patients receiving preventive treatment for osteoporosis. A small increase in lumbar bone mineral density (BMD) during the first year of treatment was recorded, regardless of use of glucocorticoids. INTRODUCTION: This study aims to describe effects on BMD of treatment according to EULAR guidelines with a methotrexate-based tight control strategy including 10 mg prednisone daily versus the same strategy without prednisone in early RA patients who received preventive therapy for osteoporosis. METHODS: Early RA patients were included in the CAMERA-II trial: a randomized, placebo-controlled, double-blind 2-year trial, in which effects of addition of 10 mg prednisone daily to a methotrexate-based tight control strategy were studied. All patients received calcium, vitamin D and bisphosphonates. Disease activity was assessed every 4 weeks. Radiographs of hands and feet and dual-energy X-ray absorptiometry of lumbar spine and left hip were performed at baseline and after 1 and 2 years of treatment. RESULTS: BMD increased significantly over time in both treatment groups at the lumbar spine with a mean of 2.6 % during the first year (p < 0.001), but not at the hip; at none of the time points did BMD differ significantly between the prednisone and placebo group. Higher age and lower weight at baseline and higher disease activity scores during the trial, but not glucocorticoid therapy, were associated with lower BMD at both the lumbar spine and the hip in mixed-model analyses. CONCLUSION: Addition of 10 mg prednisone daily to a methotrexate-based tight control strategy does not lead to bone loss in early RA patients on bisphosphonates. A small increase in lumbar BMD during the first year of treatment was found, regardless of use of glucocorticoids.
    Osteoporosis International 08/2012; 24(4). DOI:10.1007/s00198-012-2073-z · 4.17 Impact Factor
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    • "Thus, the evidence available indicates that many generic formulations are less well tolerated than the proprietary products and that this leads to poorer adherence, in turn associated with a poorer clinical outcome in terms of effectiveness on BMD [51–53] and ultimately in effectiveness on fracture outcomes [44, 51, 54–56]. "
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    ABSTRACT: The competitive price of generic bisphosphonates has had a marked effect on practice guidelines, but an increasing body of evidence suggests that they have more limited effectiveness than generally assumed. The purpose of this study is to review the impact of generic bisphosphonates on effectiveness in the treatment of osteoporosis. This study is a literature review. A substantial body of evidence indicates that many generic formulations of alendronate are more poorly tolerated than the proprietary preparations which results in significantly poorer adherence and thus effectiveness. Poorer effectiveness may result from faster disintegration times of many generics that increase the likelihood of adherence of particulate matter to the oesophageal mucosa. Unfortunately, market authorisation, based on the bioequivalence of generics with a proprietary formulation, does not take into account the potential concerns about safety. The poor adherence of many generic products has implications for guideline development, cost-effectiveness and impact of treatment on the burden of disease. The impact of generic bisphosphonates requires formal testing to re-evaluate their role in the management of osteoporosis.
    Osteoporosis International 09/2011; 23(1):213-21. DOI:10.1007/s00198-011-1796-6 · 4.17 Impact Factor
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    • "Recently, a systematic review and meta-analysis has been published that measures the degree of compliance and persistence with bisphosphonate therapy [19]. The authors of that publication also present a quantitative analysis of the effects of compliance to bisphosphonate therapy on the risk of fracture. "
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    ABSTRACT: Therapy for osteoporosis reduces the risk of fracture in clinical trials; real-world adherence to therapy is suboptimal and may reduce the effectiveness of intervention. The objective was to assess the fracture risk among patients nonadherent versus adherent to therapy for osteoporosis. Medline, Embase, and CINAHL were searched for English-language publications of observational studies (January 1998-February 2009). Proceedings from two recent meetings of five relevant conferences were hand searched. Prospective and retrospective observational studies of patients with osteoporosis receiving bisphosphonates, parathyroid hormone, or selective estrogen receptor modulators denosumab were included. Studies were required to consider both fracture risk and adherence (compliance and/or persistence); any definition of adherence/fracture was acceptable. Data were analyzed using pooled comparisons of the odds and hazard ratios of fracture in noncompliance versus compliance and nonpersistence versus persistence. Sensitivity analyses were conducted to determine the effect of clinical heterogeneity on the results. Twenty-seven citations were identified, the majority of which were retrospective database analyses considering the effect of adherence to bisphosphonate therapy on fracture at any skeletal site. The absolute frequency of fracture ranged from 6% to 38% with noncompliance and from 5% to 19% with nonpersistence (104-159 weeks). Meta-analysis indicates that fracture risk increases by approximately 30% with noncompliance (odds ratio [95% confidence interval] 1.29 [1.22-1.38]; hazard ratio 1.28 [1.18-1.38]) and by 30% to 40% with nonpersistence (odds ratio 1.40 [1.29-1.52]; hazard ratio 1.32 [1.23-1.42]). Poor medication adherence is associated with a significantly increased risk of fracture versus optimal adherence. Improving medication adherence in patients with osteoporosis may lead to a greater reduction in fracture.
    Value in Health 06/2011; 14(4):571-81. DOI:10.1016/j.jval.2010.11.010 · 3.28 Impact Factor
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