Hormone ablative therapy (treatment with drugs that stop the production of specific hormones) increases the risk of fractures due to bone loss. Adjuvant hormonal therapies for women with breast cancer involve antiestrogens (eg, tamoxifen) and aromatase inhibitors, the latter of which may lead to bone loss and subsequent increased risk of fractures due to estrogen suppression. 1 Most men with prostate cancer are treated with androgen deprivation therapy (ADT) (eg, gonadotropin-releasing hormone [GnRH] agonists) when they develop biochemical progression in locally advanced or metastatic prostate cancer. 2 GnRH agonists inhibit production of testosterone, which acts as a growth factor for prostate cancer cells. However, this treatment also leads to a decrease in bone mass, thus increasing the risk of fractures due to osteoporosis. 3,4
Prevalence and Impact
Breast cancer is the most prevalent cancer in the world, accounting for 23 percent of all cancers and an estimated 4.4 million women alive who have had the disease diagnosed within the last 5 years. Rates are highest in North America, according to the American Cancer Society.
Approximately 1 in 8 women in the United States will have breast cancer in her lifetime, with more than 40,000 deaths in 2005. 5 The 5-year survival rate is improving, having risen to 87%, mainly due to early detection and treatment. 5 The majority of women are postmenopausal at diagnosis. Women treated with aromatase inhibitors are at more than a 1.5- to 2-fold higher risk of experiencing vertebral fracture, compared with patients receiving tamoxifen alone.6,7
Prostate cancer poses major challenges in developed countries. Globally, it is the fourth most common form of cancer in males, comprising 9.2% of all cancers. In England, it is now the most commonly diagnosed cancer in men and the second most commmon cause of death from cancer in men (after lung cancer). An estimated 26,027 new cases were diagnosed in England in 2001. The reported number of new cases is rising rapidly (over 35% in the last 5 years). In the Netherlands, the cost of care for patients with prostate cancer and bone metastases and the effect of skeletal-related events was estimated recently at €13,051 per patient, with almost half of that due to treatment of the skeletal-related event.8
Men in the United States have a 1 in 6 chance of developing prostate cancer within their lifetime. 5 In 2003, there were approximately 221,000 cases of prostate cancer diagnosed and approximately 29,000 deaths from the disease. 9 The incidence of prostate cancer increases exponentially with age—eventually reaching a histologic prevalence of 50% in those 70-80 years of age. 10 For 1 in 4 men, androgen deprivation therapy (ADT), a standard treatment for metastatic prostate cancer, produces skeletal complications such as fracture within 2 years. 4,11 To date, limited data have been available on the prevention or treatment of osteoporosis in men receiving such treatment. 4
Current Treatments and Guidelines
The American Society of Clinical Oncology (ASCO) recognizes the risk of osteoporosis due to age and/or treatment in women with breast cancer and recommends regular assessment of bone health in this population. Similar monitoring has been suggested for men undergoing treatment for prostate cancer. Although there are currently no approved treatments for cancer treatment-induced bone loss, there is some suggestion that bisphosphonates may have a potential role in this area.12
Role of RANKL in Cancer Treatment-induced Bone Loss
Hormone ablative therapies are believed to lead to excess RANKL activity, which results in osteoclast-driven bone resorption and subsequent bone loss. 3,4,12 Treatment for breast cancer patients with aromatase inhibitors results in a deficiency of estrogen and resulting bone loss through the OPG/RANK/RANKL pathway. 12 Similarly, men with prostate cancer receiving ADT with GnRH agonists have a significant decrease in bone mass and increase in bone turnover through this same pathway. 3,4 These findings suggest that the inhibition of RANKL may provide a new therapeutic approach to inhibiting the processes involved in cancer treatment-induced bone loss.
References
