Management of osteoporosis in survivors of adult cancers with nonmetastatic disease: ASCO clinical practice guideline summary

In 2019, there are approximately 16 million cancer survivors in the United States and approximately 32 million worldwide.¹ These cancer survivors in the United States are increasingly in their sixth, seventh, and eighth decade of life. The two largest groups of cancer survivors are women with early-stage breast cancers and men with nonmetastatic prostate cancers, and these patients frequently have received cancer treatments that cause particularly high rates of bone loss. It is the coalescence of cancer survivors and osteoporosis, a health problem of near-epidemic proportions, that forms the underlying rationale for this evidence-based guideline. The prevalence of osteoporosis worldwide is estimated at 200 million people. At least 40% of postmenopausal women and 15% to 30% of men will experience a fragility fracture.² Osteoporosis can be thought of as an equation.³ The equation, simply stated, is the peak bone mass achieved by age 30 years minus the ongoing losses related to age and menopause. Osteoporosis is a complex genetic disease^4,5 and no genetic markers for either low peak bone mass or high later losses are yet being measured routinely in clinical settings. However, family history, especially of hip fracture, is an important predictor of fractures, as is advancing age.⁶ Lifestyle factors also affect bone loss. For example, cigarette smoking and excessive alcohol consumption, as well as noncancer-specific medications (eg, glucocorticoids) promote bone loss.⁷ In patients with nonmetastatic cancer, both the disease itself, through an association with increased local and systemic inflammation, and its treatment can pose challenges to skeletal integrity. Chronic inflammation can promote increased bone loss through altered systemic bone remodeling, increased bone resorption, and impaired bone formation.⁸ This is due to the effect of inflammatory mediators on the differentiation and activity of osteoclasts and osteoblasts.⁷ Osteoclastogenesis and osteoclasts’ activity can be influenced by proinflammatory cytokines, such as tumor necrosis factor, interleukin-1, interleukin-6, macrophage colony-stimulating factor, and RANK ligand.⁸ A number of cancer treatments also cause bone loss.⁷ Estrogens and androgens maintain bone mass and mitigate bone loss⁹ whereas cancer treatments such as gonadotrophin-releasing hormone agonists and chemotherapy-induced ovarian failure in premenopausal women, aromatase inhibitors in postmenopausal women, and antiandrogens in men with nonmetastatic prostate cancers cause cancer-treatment–induced bone loss.¹⁰ The estimated magnitude of bone loss due to cancer treatments is described in the guideline.⁷ Bone loss that occurs with cancer therapy is more rapid and severe than postmenopausal bone loss in women or normal age-related osteoporosis in men.¹⁰ Rates of bone loss occurring with cancer therapy can be more than seven-fold higher than in normal aging. The purposes of the systematic review and evidence-based guideline are to evaluate randomized controlled trials and other fundamental studies reported in the literature regarding osteoporosis in cancer survivors, compare outcomes among trials, and provide guidance to clinicians on the management of osteoporosis in survivors of adult-onset cancers.⁷ Additional information is available at www.asco.org/survivorshipguidelines. Patient information is available at www. cancer.net.