A 30 mg monthly dose of the bisphosphonate Aredia prevents bone disease as effectively as a 90 mg dose in newly diagnosed multiple myeloma patients, according to a recent Nordic study. The study also found that the lower dose resulted in fewer side effects than the higher dose.

Based on their findings, the researchers recommended 30 mg Aredia be administered to multiple myeloma patients for the prevention of bone disease.

“I believe that our study can lead to a reduction in the cost of treatment and maybe more importantly a reduction in the risk of long-term toxicity (e.g. osteonecrosis of the jaw and renal [kidney] failure),” said Dr. Peter Gimsing, professor at Copenhagen University and lead author of the study.

Dr. Gimsing pointed out that the minimal effective dose may be even lower than 30 mg.  To his knowledge, however, there are no studies being conducted to test this hypothesis.

Bone disease is frequently associated with multiple myeloma and can cause pain and fractures (see related Beacon news). While the symptoms of bone disease can be treated with radiation therapy and surgical fractures, bisphosphonates are currently the only available treatment that prevents bone disease.

Bisphosphonate therapy can decrease bone pain and prevent the development of fractures. Bisphosphonates do not, however, have antitumor effects and, therefore, do not treat the underlying causes of multiple myeloma.

Bisphosphonate treatment is associated with a number of severe side effects, including kidney damage and the loss of blood supply to the jaw (osteonecrosis), which can lead to death of the jawbone.

Due to kidney damage associated with bisphosphonate use, Dr. Gimsing noted that they should be used cautiously for limited periods of time in patients with kidney failure.

Aredia (pamidronate) is a commonly used bisphosphonate in multiple myeloma. It is administered intravenously once a month.

The dosage of Aredia that provides the maximum preventative effect against bone disease in multiple myeloma patients has not yet been determined. Prior Phase 3 trials of Aredia were conducted with the currently recommended dose of 90 mg.

In order to avoid side effects associated with Aredia treatment, the authors of this study felt that research needed to be done to determine the lowest effective dose.

To address this issue, the researchers compared the effect of a high (90 mg) and a low (30 mg) dose of Aredia in newly diagnosed multiple myeloma patients.

A total of 504 newly diagnosed multiple myeloma patients were enrolled in the study. Half of the patients received 90 mg of intravenous Aredia monthly, while the remaining participants received 30 mg monthly.

Patients were evaluated using a questionnaire. Physical function, fatigue, and pain were scored on a scale from 0 to 100. Radiological assessments were also carried out.

Following 12 months of Aredia treatment, both 30 mg and 90 mg treatment groups reported a similar improvement in physical function.

Prior to treatment, patients reported physical function scores close to 50 points. After 12 months of Aredia treatment, scores increased to 68 points and 66 points for 30 mg and 90 mg treatment groups, respectively.  These improvements were maintained for up to 36 months of Aredia treatment.

Both treatment groups also reported comparable improvements in pain, fatigue, and quality of life. Radiological findings were also consistent between the two groups.

Although patients in the 90 mg treatment group experienced skeletal events sooner (9.2 months) than those in 30 mg treatment group (10.2 months), these differences were not considered statistically significant.

While both doses of Aredia were equally effective, the severity of side effects varied between the two treatment groups. Fifteen patients in the 90 mg group were forced to stop treatment due to kidney damage associated with treatment, compared to seven patients in the 30 mg group.

Results also indicate an increased risk of osteonecrosis of the jaw for patients who received the 90 mg dose of Aredia. Eight patients in the 90 mg group developed osteonecrosis of the jaw, compared to two patients in the 30 mg group.

For more information, please see the study in The Lancet Oncology (abstract).