Background:

Bisphosphonates are a class of medication commonly used to treat osteoporosis. Alendronate is recommended as the first-line treatment; however, long-term adherence (both treatment compliance and persistence) is poor. Alternative bisphosphonates are available, which can be given intravenously and have been shown to improve long-term adherence. However, the most clinically effective and cost-effective alternative bisphosphonate regimen remains unclear. What is the most cost-effective bisphosphonate in clinical trials may not be the most cost-effective or acceptable to patients in everyday clinical practice.

Objectives

1. Explore patient, clinician and stakeholder views, experiences and preferences of alendronate compared to alternative bisphosphonates.
2. Update and refine the 2016 systematic review and cost-effectiveness analysis of bisphosphonates, and estimate the value of further research into their benefits.
3. Undertake stakeholder/consensus engagement to identify important research questions and further rank research priorities.

Methods:

The study was conducted in two stages, stages 1A and 1B in parallel, followed by stage 2:

• Stage 1A – we elicited patient and healthcare experiences to understand their preferences of bisphosphonates for the treatment of osteoporosis. This was undertaken by performing a systematic review and framework synthesis of qualitative studies, followed by semistructured qualitative interviews with participants.
• Stage 1B – we updated and expanded the existing Health Technology Assessment systematic review and clinical and cost-effectiveness model, incorporating a more comprehensive review of treatment efficacy, safety, side effects, compliance and long-term persistence.
• Stage 2 – we identified and ranked further research questions that need to be answered about the effectiveness and acceptability of bisphosphonates.

Results:

Patients and healthcare professionals identified a number of challenges in adhering to bisphosphonate medication, balancing the potential for long-term risk reduction against the work involved in adhering to oral alendronate. Intravenous zoledronate treatment was generally more acceptable, with such regimens perceived to be more straightforward to engage in, although a portion of patients taking alendronate were satisfied with their current treatment. Intravenous zoledronate was found to be the most effective, with higher adherence rates compared to the other bisphosphonates, for reducing the risk of fragility fracture. However, oral bisphosphonates are more cost-effective than intravenous zoledronate due to the high cost of zoledronate administration in hospital.

The importance of including patients and healthcare professionals when setting research priorities is recognised. Important areas for research were related to patient factors influencing treatment selection and effectiveness, how to optimise long-term care and the cost-effectiveness of delivering zoledronate in an alternative, non-hospital setting.

Conclusions:

Intravenous zoledronate treatment was generally more acceptable to patients and found to be the most effective bisphosphonate and with greater adherence; however, the cost-effectiveness relative to oral alendronate is limited by its higher zoledronate hospital administration costs.

Future work:

Further research is needed to support people to make decisions influencing treatment selection, effectiveness and optimal long-term care, together with the clinical and cost-effectiveness of intravenous zoledronate administered in a non-hospital (community) setting.

Limitations:

Lack of clarity and limitations in the many studies included in the systematic review may have under-interpreted some of the findings relating to effects of bisphosphonates.

Trial registration:

This trial is registered as ISRCTN10491361.

Funding:

This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR127550) and is published in full in Health Technology Assessment; Vol. 28, No. 21. See the NIHR Funding and Awards website for further award information.

Background:

Bisphosphonates are drug treatments commonly used to treat osteoporosis. Alendronate is the most used and is taken by mouth, weekly at a specific time of the week, which can be challenging. Less than one in four people continue this treatment beyond 2 years. Alternative bisphosphonates are available, which vary in frequency and how they are administered. The most acceptable and best value-for-money regimen is unclear.

Aim:

Our aim was to determine how effective alternative bisphosphonates are compared to alendronate at preventing fractures and whether reduction in fracture risk was achieved at a reasonable financial cost, but acceptable to patients.

Design and methods:

The study was conducted in two stages, stages 1A and 1B in parallel, followed by stage 2:

• Stage 1A: a review of the published evidence on patients’ and doctors’ views, experiences and preferences regarding different bisphosphonate treatment regimens, followed by interviews with patients and healthcare professionals.
• Stage 1B: an update of an existing study on how effective bisphosphonates are in preventing fragility fractures caused by osteoporosis and whether they are good value for money.
• Stage 2: identification of questions that need to be answered about the effectiveness and acceptability of bisphosphonate treatments.

Results:

Taking bisphosphonate medication often involves quite a lot of effort by patients, particularly when taking alendronate tablets. A yearly infusion of zoledronate treatment was more acceptable, easier to engage with and the most effective treatment compared to alendronate. However, the cost of administering zoledronate in hospital made alendronate better value for money.

Conclusions:

Bisphosphonates are effective in reducing the risk of fracture, but ‘continuing with treatment’, particularly alendronate tablets, remains a challenge. A yearly infusion of zoledronate offers an acceptable and effective treatment, but further research is needed to support patients and healthcare professionals in making decisions about the various treatments, benefits and cost savings of administering zoledronate outside of hospital and in the community.

Article history

The research reported in this issue of the journal was funded by the HTA programme as award number NIHR127550. The contractual start date was in October 2019. The draft report began editorial review in June 2022 and was accepted for publication in May 2023. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ manuscript and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this manuscript.