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Annual dose of Zoledronic acid better than daily bisphosphonates at improving bone density

Patients who take glucocorticoid drugs ( such as Prednisolone or Prednisone ) to treat a variety of inflammatory/immune-mediated diseases ( such as rheumatoid arthritis or asthma ) can suffer side effects such as bone loss, leading to excess risk of fractures.
The HORIZON study has shown that a single annual infusion of Zoledronic acid ( Aclasta, Reclast ) improves bone mineral density ( BMD ) more than the current standard treatment of daily oral bisphosponates.

While studies have shown that use of oral bisphosphonates increases BMD and reduces fracture risk, compliance and adherence with such therapy can be poor or incomplete. An association between poor adherence or compliance and increased fracture risk has been documented in women with postmenopausal osteoporosis who were treated with bisphosphonates.
Zoledronic acid is much more potent, and needs only to be given in a once-yearly infusion.

In this randomised controlled trial, David M Reid, University of Aberdeen, UK, and the HORIZON investigation team compared the effects of Zoledronic acid with a standard bisphophonate in 833 patients at 54 Centres across 12 European countries, Australia, Hong Kong, Israel, and the USA.
The patients, who were all on glutocorticoid medications, were randomised to one 5 mg intravenous infusion of Zoledronic acid ( 416 patients ) or 5 mg daily of the standard bisphosphonate Risedronate ( 417 patients; Actonel ).
Patients were assigned to subgroups dependent on how long they had been on glucocorticoids: more than three months ( the treatment group: 272 Zoledronic acid / 273 Risedronate ); or less than three months ( the prevention group: 144 patients on each drug ).
The trial measured the improvement in lumbar spine BMD.

The researchers found that in the treatment group, BMD was increased by an average 4.1% in Zoledronic acid patients compared with 2.7% in those given Risedronate. In the prevention group, Zoledronic acid increased BMD by 2.7%, compared with 2.0% in patients given Risedronate. However adverse events were also more common in the Zoledronic acid group, largely due to transient symptoms during the first three days after infusion.
Serious adverse events were a deterioration in symptoms from rheumatoid arthritis in the treatment subgroup, and fever for the prevention subgroup. But the authors conclude that Zoledronic acid has an acceptable safety and tolerability profile.

In conclusion, guidelines recommend prescription of Risedronate or Alendronate in many patients given glucocorticoids, who are at increased risk of fracture. However, the study has shown that one intravenous infusion of Zoledronic acid provides greater increases in bone mineral density and more rapid and substantial decreases in bone turnover than does daily Risedronate.
The effect of Zoledronic acid on percentage change in bone mineral density, and the overall low vertebral fracture rate suggests that a much larger trial than this study is needed to establish whether the changes in bone mineral density and bone turnover translate to improved fracture risk reduction.

Source: The Lancet, 2009