'No holiday from denosumab' preserves bone density gains
SAN DIEGO — Taking a ‘holiday’ from many osteoporosis drugs can frequently negate gains in bone density, according to a presentation at the 2019 Congress of Clinical Rheumatology West.
Nelson B. Watts, MD, director of osteoporosis and bone health services at Mercy Health in Cincinnati, Ohio, provided some general guidelines for selecting agents for particular patients with osteoporosis. Route of administration — oral or parenteral — should be considered, as should frequency of administration. Some patients may be comfortable with a daily or weekly routine, while others may prefer monthly, quarterly or biannual injections. “Tolerability depends on the agent and the patient,” he noted.
Regarding specific agents, denosumab (Prolia, Amgen), an inhibitor of the RANK ligand, is given as a subcutaneous injection twice yearly. “This drug drops the C telopeptide level,” Watts said. Findings from the RANKL study indicated a 68% reduction in vertebral fractures, a 20% reduction in non-vertebral fractures and a 40% reduction in hip fractures. Other findings have indicated that denosumab may yield bone density gains of 22% in the spine and just over 9% in the hip.
However, Watts warned that the second injection each year is critical to maintaining these improvements. He discussed findings in a cohort of 24 women who had 112 fractures among them, most of those occurring 8 to 16 months after their final injection.
“Even after 8 years of treatment getting fairly spectacular gains in bone density, when you stop treatment, you go right back to where you started,” he said. “There is no holiday from denosumab.”
Looking deeper into the armamentarium, Watts noted that teriparatide (Forteo, Eli Lilly) can be effective in combination with denosumab. “Teriparatide has a limited duration,” he said.
For patients who are unable to tolerate denosumab, switching to alendronate (Fosamax, Merck) may be an option. “Bone loss did not occur in the lumbar spine and total hip in a study conducted by Freemantle and colleagues,” Watts said.
Switching to zoledronic acid after stopping denosumab, on the other hand, may not be as useful. “Zoledronic acid works on bone remodeling,” Watts said. “The problem is that at the end of treatment with denosumab, there is not much bone remodeling to be done.”
Two recent FDA approvals have strengthened the bench for physicians treating osteoporosis. Abaloparatide (Tymlos, Radius) and romosozumab (Evenity, Amgen) are anabolic agents as opposed to anti-resorptive agents, according to Watts.
Abaloparatide is an analog of PTHrP that is injected daily at a dose of 80 mcg. However, the drug can be used for no longer than 2 years.
“Compared with teriparatide, abaloparatide provides increases in bone mineral density that are greater and faster, especially at the hip,” Watts said. “The fracture reduction is at least as good, maybe better, with less hypercalcemia.”
Romosuzumab is an antibody to sclerostin. The drug has been shown to restore bone mass in rats. “It is currently in phase 2 study in humans,” Watts said. “Findings show early, marked, but transient increases in bone density. The benefit of romosozumab continues beyond the 12-month treatment period, provided it is followed by something else.” —by Rob Volansky
Watts NB. Update on osteoporosis. Presented at: Clinical Congress of Rheumatology West. September 26-29, 2019; San Diego.
Disclosure: Watts reports consulting relationships with AbbVie, Amgen and Sanofi, as well as speaking roles for Amgen and Radius.