Many guidelines, including the 2017 ACR Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis (GIOP), do not recommend anabolic therapy as initial treatment for osteoporosis and GIOP. However, some experts believe that anabolic treatments should be first-line therapy. This year’s Great Debate on Monday afternoon featured two experts in GIOP management who presented their cases for and against the use of anabolics.
Kenneth Saag, MD, MSc, opened the debate with a presentation supporting the use of anabolics as a first-line treatment for GIOP, particularly in patients at high risk of fractures.
“Most of the drugs we use in osteoporosis are antiresorptive. We do have some drugs that we term ‘anabolic,’ and that includes teriparatide, abaloparatide and, now most recently available in the U.S. and Europe, romosozumab,” said Dr. Saag, the Jane Knight Lowe Professor of Medicine in the Division of Clinical Immunology and Rheumatology at the University of Alabama at Birmingham and Professor of Epidemiology at the UAB School of Public Health.
During the debate, Dr. Saag focused on teriparatide, which has been tested and approved in steroid-induced osteoporosis.
The crux of the question, he said, is not whether everybody should get an anabolic as first-line therapy, but whether some high-risk patients should get an anabolic first. While the 2017 ACR guideline does not recommend it, Dr. Saag pointed out that other organizations have made the recommendation.
“Other groups have also put out guidelines, including the International Osteoporosis Foundation, as well as the European Calcified Tissue Society, who list teriparatide as a front-line therapy in their 2012 guidance,” Dr. Saag said.
In 2017, the UK National Osteoporosis Guideline Group did a systematic literature review, he said, and their rating for teriparatide was as good or better than the bisphosphonates.
“Anabolics have better biologic rationale in steroid-induced osteoporosis. They have better bone efficacy data in steroid-induced osteoporosis, and also in high-risk, post-menopausal osteoporosis when compared with antiresorptives,” Dr. Saag said. “And the safety profile of teriparatide, for example, after many years of use is acceptable with respect to the one major concern, which is osteosarcoma. So, in some patients on glucocorticoids at high fracture risk, I would definitely argue that we should prescribe an anabolic first.”
Arguing that anabolics should not be recommended as a first-line therapy, Mary Beth Humphrey, MD, PhD, cited, among other concerns, that the safety profiles have not been adequately tested and that the costs of anabolics, teriparatide in particular, are prohibitive. Dr. Humphrey, Professor of Medicine and the Associate Dean of Research for the College of Medicine at the University of Oklahoma Health Sciences Center, was a member of the ACR guideline development group that formulated the 2017 guideline.
“This really is an important question, especially when you consider the prevalence of glucocorticoid-induced osteoporosis,” Dr. Humphrey said. “Data from 2008 showed that glucocorticoid use in the U.S. was roughly 2.5 million, and that number has gone up as we have an aged population. Elderly users are actually the highest users of steroids, which is disappointing because they already have osteoporosis risk factors.”
She said that current estimates are that 3.5% of men over the age of 80 and 2.7% of women between the ages of 70 and 79 are on some dose of either daily steroid or steroid dose packs.
“And the mean duration of glucocorticoid use is more than four years, and more than five years for nearly 30% of patients taking them,” she said. “So, we’re looking at long-term treatment and ongoing risk to the bone and, unfortunately, only one in five patients that are prescribed glucocorticoids are also prescribed a bone-preserving osteoporosis medication.”
While there are still many unanswered questions regarding the safety of anabolics, Dr. Humphrey said there is no question that the cost of anabolic drugs, namely teriparatide, make them difficult to recommend without more efficacy and safety studies.
“The average cost of alendronate, for example, in the U.S. is $96 a year, and you need 31 patients to be treated to prevent one fracture, so the cost would be about $3,000 to prevent one fracture,” she said. “The cost of teriparatide, on the other hand, is currently about $33,000 a year in the non-generic form. It’s true that you only need 14 patients, which is great, but to prevent one fracture in those 14 patients, you’re approaching $500,000 a year.”
Treatment length is another major concern, she said, noting that oral bisphosphonates can be taken for up to 10 years safely, while the treatment length for teriparatide is limited to 24 months.
“And then, after discontinuation of teriparatide, you still have to follow that with another agent, either denosumab or an oral or IV bisphosphonate,” Dr. Humphrey said. “There are also side effects with teriparatide that can be quite challenging for many patients, such as hypercalcemia, dizziness, and cramps. Overall, there are still just too many questions and reasons to just say no to anabolics.”