No drug can abolish fracture risk, he said. Fractures in patients on long-term therapy may still occur. A certain type of fracture, the atypical subtrochanteric femur fracture, has been associated with long-term (five years or longer) use of bisphosphonates, although no causality has yet been established. “When these fractures happen, they’re dramatic…with an oblique pattern on the slant of the femoral shaft.”
Such fractures have also been the target of widespread media coverage, such as a 2010 ABC-TV News segment by Diane Sawyer, he said, noting that Richard Dell, MD, an orthopedic surgeon with Kaiser Permanente, has calculated that for every atypical fracture related to ongoing treatment, about 100 to 115 hip fractures are prevented.8 Considerations for the clinician include: why to stop treatment; when—and if—to restart it; whether a different osteoporotic therapy should be started in high-risk patients who discontinue bisphosphonates; and what happens for patients who go off treatment and subsequently experience fractures.
“The atypical subtrochanteric fracture risk seems to drop off abruptly when the treatments are discontinued, although no one knows why,” Dr. Miller said, adding that there is a prodrome of anterior pain in the thigh that precedes the atypical fracture by some months and might aid in its prevention. “I tell my patients if they have this [symptom] to call me,” he says. When there is concern about atypical fractures, he discontinues the bisphosphonate treatment, confirms symptoms radiologically, and encourages the patient to use some kind of extremity support such as a cane or crutch.
Other current topics discussed by Dr. Miller include the optimal interval for repeating bone-density tests, which were once targeted for a specific population of postmenopausal women, but now are used more widely. “Clinical judgment is still a good thing, and we have medications to improve bone-mass loss,” he says, “while inadequately managed osteoporosis is associated with poor outcomes.”9
He also reviewed new drugs for treating osteoporosis, including denosumab, which has been shown to decrease fracture risks at all skeletal sites.10 “Concerns about infections associated with denosumab use in the postmenopausal or cancer population are becoming less, but we still must be vigilant about this side effect as more people get treated.” Other research targets include the new drug odanacatib, a cathepsin-K inhibitor now in phase V trials; the antisclerostin antibody; and monoclonal antibodies to neutralize Dickkoff-1 inhibitory function on osteoblasts. The latter two will represent novel agents to increase new bone formation, he said.
Current Lupus Treatments are Not Enough
David Wofsy, MD, professor of medicine and microbiology/immunology at the University of California, San Francisco, reported on recent advances in the treatment of systemic lupus erythematosus (SLE). The challenge of developing new biologic therapies for SLE is underscored by the inadequacy of conventional therapies, he said. For example, hydroxychloroquine, an antimalarial drug, has demonstrated effectiveness in treating active disease, reducing frequency of flares, preventing thrombosis, and reducing mortality in people with SLE. “Unless there are contraindications to its use, it is now considered the standard of care for everyone with a diagnosis of lupus to be on this drug,” he says. “However, it is equally clear that this approach is insufficient for the majority of lupus patients.”
