Standard of care for delivering bisphophonates

In the past, we have given patients with breast cancer adjuvant bisphosphonates orally for life, especially if the patient is on hormonal modulation therapy (ie, aromatase inhibitors); however, I have seen several patients with femoral fractures. As a result, I tend to give the patient a break after 5 years if her bone mineral density (BMD) has improved and her T score is higher than –2.0. I also have the same issue with patients with metastatic disease. In the past, we gave them bisphosphonates (zoledronic acid [Zometa], pamidronate disodium [Aredia], or denosumab [Xgeva]) monthly for 2 years. After seeing several cases of osteonecrosis of the jaw (ONJ) and large bone fractures, we now hesitate to push so hard. If a patient’s bone pain is improved, we tend to push dosing out to every 2 months after 6 months of therapy. What protocol would you recommend in these settings? —Susan Siemsen, PA-C

Guidelines recommend that patients use IV bisphosphonates, such as zoledronic acid (Zometa), due to results from a recent clinical trial that suggested this bisphosphonate may extend survival. In addition, they recommend that physicians administer standard doses of bisphosphonates every 3 to 4 weeks. How long bisphosphonates should be used is still unclear. And currently, there is no randomized data on bisphosphonate use for more than 2 years. As a result, physicians should assess a patient’s risk and benefit of using bisphosphonate treatment after 2 years. There is no standard for the application of a more attenuated schedule as opposed to complete discontinuation.

Researchers have speculated that long-term use of bisphosphonates increases the risk of developing ONJ, a rare but serious side effect of bisphosphonate use in which there is a loss of blood supply to the jaw, causing jawbone tissue to die. To prevent ONJ, patients treated with bisphosphonates should maintain good dental hygiene and should stop bisphosphonate treatment for 90 days before and after invasive dental procedures. Fractures of the upper leg and in the feet have also been reported after long-term use of bisphosphonates; however, this effect is rare.

The guidelines also recommend that patients make sure to get enough vitamin D and calcium, nutrients essential for strong and healthy bones. This is especially a concern for patients with myeloma because 60% of these patients are vitamin D- and calcium-deficient. Calcium supplementation should be used cautiously for patients with kidney problems. Denosumab (Xgeva), a human RANKL compound, may be preferred for patients with renal insufficiency, but the ONJ risk remains and denosumab is not indicated for myeloma. As far as adjusting plans based on repeat bone density studies, this is not supported by the literature as even those patients who lose bone density seem to benefit. —Donald R. Fleming, MD