Serious concerns about the recent NICE technology appraisal on bisphosphonate use have been raised – with experts fearing that unthinking application of the guidance will lead to potential harmful overtreatment in the general population, and detrimental effects on service provision.

In a letter published recently in The Lancet journal, leading experts have drawn attention to potentially harmful guidance resulting from the recent National Institute for Health and Care Excellence (NICE) updated Technology Appraisal on bisphosphonate use in osteoporosis (TA464). The concern is that the fracture risk thresholds demonstrated as cost-effective for the use of bisphosphonate in fracture prevention will be interpreted as guiding clinical intervention.

The NICE Committee aimed to update the previous NICE Technology Appraisals on anti-osteoporosis treatments, moving from cost-effectiveness thresholds based on age, risk factors and BMD T-score, to cost-effectiveness based on FRAX or QFracture measures of fracture probability/ risk respectively. This in itself is problematic as the tools are calibrated differently, but importantly, since all the bisphosphonates are now available as inexpensive generic medications, their use is cost-effective at very low risk: Thus for individuals “who qualify for osteoporosis assessment based on NICE Clinical Guideline CG146, the appraisal recommends treatment with oral bisphosphonates for anyone with a probability of major osteoporotic fracture that exceeds 1% over 10 years and treatment with intravenous bisphosphonates for those with a probability of more than 10%.”

The key concerns are:

• Interpretation of the cost-effectiveness thresholds as clinical intervention thresholds (as is already happening in some areas of the UK), is likely to result in excessive bisphosphonate prescription in the general population, with treatment of substantial numbers of people who are at very low risk of fracture.
• Treatment of large numbers of people at low fracture risk means that very rare, but serious, side-effects of bisphosphonate treatment would be observed far more commonly than at present, and would adversely affect the benefit-risk balance, which is clearly positive when treating high risk individuals.
• Since every man and women over the age of 50 years will have a fracture risk greater than 1% on clinical risk factors alone, the roles of DXA and osteoporosis services could be threatened, clearly compromising the long-term care of patients with osteoporosis.

Whilst the NICE Technology Appraisal references UK National Osteoporosis Guideline Group (NOGG; recently NICE accredited) guidance on assessment and treatment, unfortunately this is not within the summary recommendations and will easily be missed. Importantly, the NOGG guidelines are based on clinical appropriateness, with the treatment threshold set at the age-specific probability of fracture equivalent to an individual having already sustained a fracture. Importantly, economic thresholds were used to validate the use of clinically driven intervention thresholds, rather than to set the intervention thresholds directly. The NOGG algorithm has been shown to be cost-effective and avoids inappropriate over-treatment of older individuals and under-treatment of younger individuals.

It is vitally important that clinicians, healthcare commissioners and policy makers understand the potential harmful consequences of a literal interpretation and application of the NICE Technology Appraisal, and refer instead to a clinically appropriate guidance, such as NOGG, to determine interventions. As stated in the Lancet journal communication, the unthinking application of the NICE guidance “risks a generation of older individuals taking a bisphosphonate regardless of the individual benefit-to-risk ratio and an increased burden of rare long-term side-effects across the population.”