Great Debate Tackles First-line Anabolic Therapy for Glucocorticoid-induced Osteoporosis
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ATLANTA — The 2019 iteration of the ACR/ARP Great Debate tackled the issue of whether anabolic therapies are appropriate for patients with glucocorticoid-induced osteoporosis.
Kenneth Saag, MD, MSc, Jane Knight Lowe Professor of Medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham, took the “pro” side, while Mary Beth Humphrey, MD, PhD, associate dean of research, professor of medicine, McEldowney Chair in Immunology, and division chief of rheumatology at the University of Oklahoma Health Sciences Center, handled the “cons.”
In defense of anabolic treatment as first-line therapy
Saag zeroed in on teriparatide (Forteo, Lilly) as they key anabolic therapy and framed his argument by tackling the likely points Humphrey would make. Those included cost, biologic rationale, convenience and lack of data. “But the question is not whether everybody should get an anabolic first,” he said. “The question is whether some of our high-risk patients should get an anabolic first. That is the position I’m going to take.”
Saag acknowledged that it will be “hard to argue” the cost. “Teriparatide is a very expensive therapy,” he said.
However, he noted that anabolic therapies are less expensive in Europe and Asia than they are in the U.S., and that many guidelines outside of North America call for teriparatide as first-line therapy in this patient population. He suggested that this means that the key argument against first-line anabolic has nothing to do with efficacy. Rather, he called for a reduction in prices domestically.
In terms of the biologic rational, Saag cited the Wnt signaling pathway and sclerostin as two key factors arguing in favor of teriparatide use in these patients. “Through these pathways, teriparatide stimulates bone formation,” he said.
There is a growing body of evidence showing that teriparatide improves trabecular bone score and bone mineral density, according to Saag. He cited the VERO study in post-menopausal women, which was a large randomized, controlled trial pitting teriparatide against bisphosphonates. Results showed improvements associated with teriparatide in new vertebral fractures.
Regarding both clinical decision-making and practice management, Saag offered another reason for using teriparatide first. “Anabolics work better when you use them first,” he said. “They can work in combination with a bisphosphonate, but denosumab attenuates teriparatide effects.”
In conclusion, Saag reiterated that although not every patient with glucocorticoid-induced osteoporosis should be treated with an anabolic first, some high-risk individuals represent strong candidates for this approach.
He closed with a final comment on cost. “There may be fear that the cost of these therapies could lead to bedside rationing,” he said. “This is morally unjustified.”
Humphrey handles the “cons”
Saag was correct in that Humphrey would cite cost of anabolic therapy as a key argument against their use. She pointed out that the cost to prevent one fracture is $3,000 for alendronate and $450,000 for teriparatide. Moreover, the average yearly cost for a patient treated with alendronate is $96, while that cost is $1,104 for zoledronate and $2,092 for denosumab. “By comparison, the yearly cost of therapy for teriparatide is $33,192,” she said.
Humphrey’s follow-up argument was that the most recent guidelines for treatment of this patient population include a red asterisk with both denosumab and teriparatide. “They should be followed by another antiresorptive agent to maintain bone mineral density gains,” she said. “Teriparatide should be followed by denosumab, or a bisphosphonate. If you choose these drugs, you are setting the patient up for a prolonged treatment plan that involves two drugs.”
Another reason teriparatide was designated as a third-line treatment after oral and IV bisphosphonates for these patients was convenience. “Cost and the burden of daily injections were the reasons teriparatide was third,” she said.
Another argument against teriparatide is treatment duration. For example, alendronate is approved for treatment up to 10 years in patients with glucocorticoid-induced osteoporosis, while the FDA contraindicates use of teriparatide for more than 24 months. “There is no need for an additional agent with alendronate,” Humphrey said. “After treatment with teriparatide, it is necessary to add another antiresorptive agent.”
Regarding clinical outcomes, Humphrey added that teriparatide is not as effective at preventing wrist fractures as alendronate. “Alendronate is effective at preventing fractures at all sites,” she said.
In terms of adverse events, Humphrey cited hypercalcemia, dizziness and cramps as frequently reported complaints among patients treated with teriparatide.
“Just say no to first-line anabolics,” Humphrey concluded. – by Rob Volansky
Reference:
Humphrey MB, Saag K. The Great Debate: Anabolic agents are/are not appropriate first-line therapy for glucocorticoid-induced osteoporosis. Presented at: American College of Rheumatology/Association of Rheumatology Professionals Annual Meeting; Nov. 9-13, 2019; Atlanta.
Disclosure: Humphrey reports no relevant financial disclosures. Saag reports research funding from Ardea, AstraZeneca, Horizon and Takeda, as well as consulting fees from AstraZeneca, Ironwood, Horizon, Sobi and Takeda.