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Cancer patients' bone loss is treatable

By DR. V. UPENDER RAO
Published March 26, 2007


Breast cancer patients whose tumors bear hormone receptors are treated with antiestrogenic hormones either exclusively or following adjuvant chemotherapy. While such hormonal manipulation can prevent recurrence of hormone-positive breast cancers, it routinely causes progressive loss of bone mineral and predisposes to fracture of the spine and hip.

Supplemental treatment with vitamin D, calcium and an oral bisphosphonate are usually given to prevent treatment-related osteopenia and osteoporosis.

Oral bisphosphonates, Fosamax and Actonel, are presently used for this purpose. However, they frequently cause unpleasant gastrointestinal side effects, leading many patients to discontinue treatment.

Zoledronic acid (Zometa) is an intravenous bisphosphonate used to treat patients with breast and other solid tumors that have metastasized to the bones. Zometa decreases loss of bone density and prevents fractures and other skeletal events in these patients.

While its place is well established in patients whose cancer has spread to the bones, its role in preventing bone loss and related fractures in patients with early stage cancers is being actively investigated.

In preclinical studies, intravenous administration of Zometa showed inhibition of bone mineral loss in rats following surgical removal of ovaries (lack of estrogen causes osteoporosis) and antiestrogen therapy.

In the clinical setting, Zometa given intravenously every six months to postmenopausal women on antiestrogen therapy prevented bone mineral loss; similar results of bone preservation were seen with Zometa given intravenously once every three months to prostate cancer patients on hormone deprivation as a treatment modality.

Two important studies examining the prophylactic role of Zometa for breast cancer patients on hormone therapy were discussed in the March 1 issue of the Journal of Clinical Oncology.

The Austrian Breast and Colorectal Cancer Study Group evaluated more than 400 women on hormone treatments known to cause bone mineral loss. They were randomly assigned to receive either Zometa or placebo by a short intravenous infusion once every six months.

Study results showed that Zometa caused effective and significant inhibition of bone loss compared with the placebo.

The second study was a U.S.-based multi-institutional study of postmenopausal women with breast cancer on adjuvant Femara, an antiestrogenic hormone. These patients were randomized to receive Zometa up front or when they developed a bone loss consistent with a T score of -2.0 on the bone mineral densitometry.

Re-evaluation at the end of the first year of the study showed an increase in bone density of 4.4 percent at the lumbar spine and 3.3 percent at the hip bones in patients who took Zometa up front compared with those who did not.

At the present, the standard of care is to start an oral bisphosphonate when patients develop a T score of -2.5 on bone densitometry. This score usually indicates osteoporosis.

Both advancing age and antiestrogenic hormone treatment predictably cause osteoporosis over time. Since osteoporosis is inevitable for these patients, it is intuitive to believe that prevention may be the right strategy.

The two studies reviewed above seem to support this notion. Long term follow up of these patients will accurately assess the damage caused by with holding up front Zometa for breast cancer patients on hormone therapy.

In terms of cost and convenience, intravenous Zometa every six months may be better than oral bisphosphontes. Prevention of osteoporosis will eliminate a sizable fraction of the cost incurred in the management of chronic pain, surgical repair of fractures, hospitalization, rehabilitation and loss of wages due to disability.

Prevention of chronic pain, loss of function and decreasing the morbidity and mortality associated with fractures will add to the quality of life and to survival.

V. Upender Rao, MD, FACP, practices at the Cancer and Blood Disease Center in Lecanto.