IOF guidelines describe, define failure of osteoporosis therapies

When patients comply with osteoporosis treatment for at least 6 months, their response to treatment can be identified by the number of fractures, the changes in bone turnover markers, and any changes in bone mineral density they have, according to a recent International Osteoporosis Foundation position paper.

“Treatment issues are extremely complex. In addition, there is a scarcity of data about the effectiveness of alternative treatments when one has been deemed to have failed,” Adolfo Diez-Perez, MD, PhD, of Barcelona, chair of the International Osteoporosis Foundation (IOF) Inadequate Responders Working Group, stated in an IOF news release. “Notwithstanding these complexities and limitations, the Working Group has used the best available evidence to create a checklist of pragmatic criteria which can help doctors define treatment failure and take appropriate action.”

For example, researchers found the number of fractures a patient has can indicate the treatment has failed. However, it is difficult to conclude whether treatment has failed in patients being treated for osteoporosis who do not have fractures, since most patients who are in a placebo control group will never sustain a fracture during a treatment period, according to the press release.

While bone mineral density is also representative of treatment success, the margin of error with this factor is often the same as the rate of bone gain or loss, according to the position paper.

Regarding bone turnover markers, a decrease in the serum C-telopeptide of type I collagen (βCTX) and the serum procollagen I N-propeptide (PINP) less than the least significant change (LSC) is a failure of treatment with anti-resorptive agents. Additionally, an increase in PINP less than the LSC indicates failure of treatment with parathyroid hormones, based on the paper.

Furthermore, some patients who adhere to treatment ultimately fail to respond to it. However, “no treatments eliminate the risk of fragility fractures so that treatments will be perceived as failing in those who sustain a further fracture by patients, carers and physicians alike,” the researchers wrote in the paper.

In the release, Cyrus Cooper, MBBS, DM, FRCP, FFPH, FmedSci, chair of the IOF Committee of Scientific Advisors, stated, “Recent advances in the management of osteoporosis have led to large numbers of patients being treated with a variety of drugs. An increasingly frequent clinical conundrum is the management of a patient who sustains a fracture while on treatment. Although patient and physician may view this as a sign of treatment failure, this is not always the case.”

Reference:

Diez-Perez, A, Adachi JD, Agnusdei D, et al. Treatment failure in osteoporosis. Osteoporos Int. 2012. Published online July 27, 2012. doi:10.1007/s00198-012-2093-8.

Disclosures: Diez-Perez has given lectures and provided advice for Novartis, Amgen, Lilly and MSD. His institution received research grants from Amgen and Servier. Cooper has received honoraria and consulting fees from Servier, Amgen, Eli Lilly, Merck, Medtronic and Novartis. The Inadequate Responders Working Group is funded by the IOF.