Bisphosphonates and spontaneous hip fractures: safety update for the clinical nurse specialist.

B isphosphonates are widely used to treat osteoporosis, Paget disease, multiple myeloma, and the hypercalcemia of malignancy. Oral agents include alendronate, risedronate, and ibandronate. Intravenous agents include pamidronate, ibandronate, and zoledronic acid. Adverse events appear to be a function of dose and route. Intravenous agents have an overall greater severity of adverse effects. Adverse events include upper gastrointestinal tract events (nausea, vomiting, epigastric pain, and dyspepsia), secondary hyperparathyroidism, musculoskeletal pain, osteonecrosis of the jaw, ocular effects (nonspecific conjunctivitis), and atrial fibrillation. Bisphosphonates are essential in the treatment of postmenopausal osteoporosis and can reduce vertebral fracture by almost 50%and hip fracture by 20% to 50%. Overall serious adverse events are rare. However, there are increasing number of reports of subtrochanteric stress and fractures in postmenopausal women. In a retrospective study, 17 patients (mean age, 66 years) on alendronate therapy an average of 4.8 years sustained lowenergy subtrochanteric fractures over a 20-month period. Plain radiographs demonstrated configurations suggesting insufficiency stress fractures. Markers included cortical thickening in the lateral side of the subtrochanteric region, transverse fractures, and medial cortical spikes. Fifty-three percent of the patients had bilateral findings of stress, and 75% had reported prodromal pain. Findings suggested oversuppression of bone turnover from prolonged bisphosphonate therapy and a possible adverse effect. Alendronate inhibits the production of membrane anchoring molecules required by osteoclasts to adhere to the osteoid surface, also inducing apoptosis of osteoclasts. Alendronate also acts as a specific inhibitor of osteoclastmediated bone resorption related to preferential localization to bone resorption sites under osteoclasts, which normally adhere to bone. There is no interference with osteoclast recruitment; however, alendronate does inhibit osteoclast activity. Alendronate must be continuously administered to suppress osteoclasts on newly formed resorption surfaces to reduce bone turnover or the number of sites where bone is remodeled. As a result, bone formation is promoted and exceeds bone resorption, which adds bone mass. All bisphosphonates are incorporated into bone matrix over time and gradually released over years. As a result, the osteoclast activity needed for repair of microdamage is not available, which may increase the risk for stress fracture. Alendronate is a first-line treatment for osteoporosis in postmenopausal women worldwide, and benefits are well established. Low bone mass present in osteoporosis increases risk of fracture. With increasing bone turnover in menopause and bone resorption exceeding bone formation, the result is progressive bone loss. Fractures in the hip, spine, and wrist are common and are associated with increased mortality, morbidity, and disability. Emerging evidence suggests that indefinite treatment with bisphosphonates is not without complications. Related to the mechanisms of action, potential reduction in bone turnover, alterations in microdamage repair, and reduced bone toughness may increase the risk of fracture with long-term use. Early evidence suggests that there is a pattern midfemoral fracture in women on long-term bisphosphonate therapy, and risk significantly increases after 3 to 10 years of regular use. A recent case study spontaneous bilateral subtrochantericdiaphyseal fracture in a patient with multiple risk factors and an 8-year history of treatment with alendronate, may provide additional clues. Bone biopsy revealed decreased bone Patricia O’Malley, PhD, RN, CNS