Publication of the National Institute for Health and Care Excellence (NICE) guidelines on use of antiosteoporosis agents for the secondary prevention of osteoporotic fractures in 2005, coupled with the release of generic alendronate shortly thereafter, led to a spike in use of bisphosphonates in England and Wales and a clinically meaningful reduction in subsequent fractures among hip-fracture patients, a new large-scale observational study indicates.

“It is clear that the guidance, coupled with the availability of a low-cost bisphosphonate, drove a major change in prescribing by general practitioners,” senior author of the work, Andrew Judge, MD, University of Oxford, United Kingdom, says in a statement.

“It is unclear how much this was due to the new guidance and how much due to generic alendronic acid arriving on the market, but it is notable that prescriptions for alendronic acid clearly outstrip those for other treatments, suggesting that it had a part to play,” he adds.

The study results were published online July 6 in the Journal of Bone and Mineral Research.

Lead author Samuel Hawley, DPhil candidate, University of Oxford, United Kingdom, and colleagues conducted the REFReSH study by identifying 10,873 individuals who had sustained a hip fracture in England or Wales anywhere between April 1999 and September 2012.

The prescribing patterns of physicians for osteoporosis treatments among hip-fracture patients in England and Wales were then tracked following publication of the NICE guidelines in January 2005 and for the first three years following the introduction of generic alendronate, which came shortly thereafter.

The publication of the guidelines and the release of generic alendronate were considered the “intervention,” and prescribing and fracture rates were documented before and after the start of the intervention period.
Overall, Mr Hawley and colleagues estimate there was a 17.2% absolute increase in the use of antiosteoporosis agents within a year of patients sustaining their initial hip fracture across the 3-year observational interlude.

This increase represented a relative increase of 79% compared to the “preintervention” period.

The incidence of subsequent major refracture, defined as fractures of the hip, pelvis, proximal-humerus, rib, spine, or wrist/forearm, prior to the intervention was stable at 6.3%.

Following the intervention, “there was a significant (P = .001) downward trend by -0.19% per 6 months,” Mr Hawley notes.

This downward trend translated into an approximate 14% relative decrease in the risk of major refracture rates over a period of 3 years after the start of the intervention period.

The same trend was seen for subsequent hip fracture.

Initially, hip refracture rates were stable at a rate of 3.8% prior to the introduction of the intervention. Following the intervention, there was again a downward trend in hip refracture rates of -0.17% for every 6 months (P = .001), which translated into a 22% reduction in hip fractures over a period of 3 years.

Mr Hawley and colleagues caution that while the observed decrease in the incidence of refracture rates did dovetail with an increase in prescriptions for bisphosphonates, “we have not been able to establish whether increased prescribing caused the reduction in subsequent fracture.”

However, as they also note, evidence from randomized controlled trials suggests that alendronate does reduce the risk of hip fracture relative to placebo.

Other changes in the UK healthcare system, including initiation of the Fracture Liaison Service model of care, may also have contributed to the decline in fractures over the study interval, they suggest.