New Approaches to Prevent Radiation-Induced Bone Fractures
Wake Forest Innovations offers industry partners access to a novel method for monitoring radiation therapy-induced bone loss through the use of clinical cortical thickness and radiation dose mapping.
While improvements in cancer screening and treatment have decreased patient mortality for most types of cancer, many survivors still contend with severe treatment side effects. Of major concern are radiation therapy-induced bone fractures, which may impact nearly half of the 1.7 million new cancer diagnoses each year1-3. For example, 30-40% of lung cancer patients receiving high dose per fraction stereotactic body radiation therapy (SBRT)—about 33,000 to 44,000 people per year—experience a painful rib fracture within one to three years4,5. These types of fractures are a persistent and major source of functional impairment, pain and mortality in cancer survivors.
Radiation exposure rapidly increases the number and activity of bone-resorbing osteoclasts in rodents6. This acute burst of osteoclasts causes substantial premature bone loss. Administering a bisphosphonate to mice post-irradiation suppresses osteoclast activation and preserves bone area and trabecular connectivity, relative to placebo controls7.
Researchers at Wake Forest Baptist have developed a clinical cortical thickness and radiation dose mapping method for monitoring the bone loss in cancer patients over time8-9. They found that radiation therapy-induced bone loss occurred within one to four months from start of treatment. The sensitivity of their approach was enough to localize significant, early radiation dose-dependent cortical thinning to the exact site of an eventual rib fracture (approximately six months after treatment) in patients receiving SBRT for lung cancer8 (see Figure 1). This high rate of bone loss is almost certainly facilitated by increased osteoclast activity and there is also evidence of reduced bone formation. This research indicates that the suppression of osteoclast activity at the initiation of radiation therapy or treatment with bone anabolic agents may prevent or reduce bone fractures and also that this method of monitoring bone loss via image mapping can determine the efficacy of such treatments.
The preclinical and clinical knowledge generated indicates that:
- Patients at risk for fractures can be identified by bone loss rates during the course of their radiation therapy
- Bone agents may restore lost bone or prevent early bone loss and reduce fracture rate