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
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    • "Reasons for poor persistence include conflicting patient beliefs, patient preferences, financial limitations , and previous adverse effects including rash, myalgia, nausea, and diarrhea [7] [10] [11]. Impaired compliance and persistence to long-term bisphosphonate treatment can ultimately lead to an increased risk of fracture [7]. Denosumab is a fully human monoclonal antibody against RANK ligand used in the treatment of osteoporosis [11]. "
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    ABSTRACT: Although denosumab (Prolia) has been shown to be a safe and efficacious therapy for osteoporotic patients in numerous clinical trials, few studies have determined its effectiveness in real world clinical practice. A retrospective review of patients prescribed Prolia assessing the impact that noncompliance from the regular dosing regimen of six months for denosumab has on bone mineral density (BMD) was performed. 924 patient records were reviewed between August 2012 and September 2013 with 436 patients meeting the eligibility criteria. Patients were divided into three groups: subsequent injection of denosumab (1) less than five months, (2) between five and seven months, and (3) more than seven months after their initial subcutaneous injection. A multivariable regression analysis was conducted comparing the differences among the three prespecified groups in BMD change (g/cm 2 ) after one year of denosumab therapy at both the lumbar spine (LS) and femoral neck (FN). The differences in LS and FN BMD have shown that the relationship between the timing of drug administration in these three groups and change in BMD over 1 year was not clinically or statistically significant ( p > 0.05 ). A follow-up study with a larger sample size and longer follow-up duration is required to further characterize this relationship.
    Full-text · Article · Jan 2016 · Journal of Osteoporosis
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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.
    Full-text · Article · Aug 2012 · Osteoporosis International
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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.
    Full-text · Article · Sep 2011 · Osteoporosis International
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