AFFs, BPs, ONJ: Understanding Alphabet Soup of Osteoporosis Treatment

The American Society for Bone and Mineral Research recently reassessed the efficacy of bisphosphonate, long hailed as a wonder drug for patients with osteoporosis, and its risk factors. Through the course of two clinical trials by the society’s Professional Practice Committee, it was determined that bisphosphonate therapy should be evaluated carefully by treating physicians after five years for those taking it orally and three years for those receiving it intravenously.

At issue is the potential for fractures, specifically atypical femoral fractures, or AFFs. AFFs differ from traditional femoral fractures in that they occur spontaneously in the region of the bone where the shaft meets the pelvis.

“Recent epidemiologic evidence shows that the absolute incidence of atypical femoral fractures is small compared to the incidence of typical hip fractures,” reads a manuscript on the National Center for Biotechnology Information’s Web site titled “Atypical Femoral Fractures: Epidemiology, Etiology, and Patient Management.” “However, long-term bisphosphonate use may be an important risk factor for atypical fractures, and minimal additional antifracture benefit has been demonstrated for treatment durations longer than 5 years for patients with postmenopausal osteoporosis.”

Also at issue is the potential for the development of osteonecrosis of the jaw, or ONJ. The often-painful condition occurs when the jaw bone becomes exposed and lacks a fresh supply of blood, eventually weakening and dying.

“ONJ is associated with cancer treatments (including radiation), infection, steroid use, or potent antiresorptive medications,” according to the American College of Rheumatology. “Antiresorptive medications help slow down bone loss in patients suffering from conditions such as osteoporosis. Examples of potent antiresorptive medications include bisphosphonates such as alendronate (Fosamax); risedronate (Actonel and Atelvia); ibandronate (Boniva); and denosumab (Prolia).”

The bisphosphonates, or BPs, used in the clinical trials were alendronate and zoledronic acid (branded as Zometa.) The alendronate case, titled Fracture Intervention Trial Long-term Extension, or FLEX, showed that postmenopausal women receiving therapy for 10 years had a lower fracture risk. In the case involving zoledronic acid, titled HORIZON, women receiving six years of therapy also had a lower fracture risk. That is the good news. But bad news accompanies it.

“The risk of atypical femoral fracture, but not osteonecrosis of the jaw, clearly increases with BP therapy duration, but such rare events are outweighed by vertebral fracture risk reduction in high-risk patients,” states a review in the Journal of Bone and Mineral Research titled “Managing Osteoporosis in Patients on Long-Term Bisphosphonate Treatment: Report of a Task Force of the American Society for Bone and Mineral Research.” “For women not at high fracture risk after 3 to 5 years of BP treatment, a drug holiday of 2 to 3 years can be considered. The suggested approach for long-term BP use is based on limited evidence, only for vertebral fracture reduction, in mostly white postmenopausal women, and does not replace the need for clinical judgment.”

Patients taking bisphosphonates should talk with their doctors about the aforementioned risks and ask whether such conditions outweigh the benefits of the treatment. Patients experiencing symptom such as hip or thigh pain or jaw discomfort should see their doctors immediately. Symptomatic patients also should take the initiative to report their cases to the U.S. Food and Drug Administration, which recently reviewed lengthy bisphosphonate use and concluded “that some further investigation is needed on the long-term risks and benefits of these drugs.”