DENVER (FRONTLINE MEDICAL NEWS) – In May, the American College of Physicians released updated recommendations for treatment of low bone density and osteoporosis, but they have sparked criticism from endocrinologists, though they lauded efforts by the ACP to clarify matters for generalists.
“I think with just a bit of nuance, some of these recommendations could be changed in a way that makes them more consistent with our understanding of the pathophysiology of osteoporosis,” Benjamin Leder, MD , an endocrinologist at Massachusetts General Hospital, Boston, and chair of the American Society for Bone and Mineral Research Professional Practice Committee, said during a session at the society’s annual meeting.
The ACP guideline ( Ann Intern Med. 2017;166:818-39 ), is an update to the organization’s 2008 recommendations, and is one of few such documents available for generalists.
The guideline arrives at a time of increasing concern that osteoporosis is undertreated. Many older women with fractures and low bone mineral density (BMD) do not go on to receive osteoporosis medication, despite a range of effective therapies, and the rate of BMD scans has declined.
In that context, the ACP guideline has the potential to improve treatment uptake, especially since primary care providers are often at the front lines of osteoporosis diagnosis and treatment.
However, the guideline’s recommendations were a subject of pointed debate at the session. The ACP’s update of the guideline has “helped clarify what many view as a murky and complicated area of medicine, but the guidance needs to be balanced with consideration of the wide range of patient presentations in osteoporosis and the different properties of osteoporosis therapies,” said Dr. Leder, who delivered a point-by-point critique of the guideline’s six main points.
The guideline recommends the use of alendronate, risedronate, zoledronic acid, or denosumab to reduce the risk of hip and vertebral fractures in women with osteoporosis. Dr. Leder noted that the guideline omitted anabolic agents, including teriparatide and abaloparatide. There also are no recommendations regarding sequential therapy, which is increasingly viewed as an important therapeutic strategy. “We know that when we switch from teriparatide to a bisphosphonate or another antiresorptive agent, bone density increases as well or better than in patients treated de novo with bisphosphonates. When switching from bisphosphonates to teriparatide, bone mineral density increases are blunted compared to de novo teriparatide treatment,” Dr. Leder noted.
Other criticism of this first point, pointed out in an editorial by Liron Caplan, MD , of the University of Colorado at Denver, Aurora, and his colleagues, took issue with its exclusion of raloxifene, ibandronate, and teriparatide as first-line therapies, given that clinical trials have shown they reduce some types of fractures ( Arthritis Rheumatol. 2017 Sep 7. doi: 10.1002/art.40305 ). The authors of the editorial also worried that insurers may use these limited recommendations as an excuse to limit reimbursement for anabolic agents, which may be the best first-line choice in some high-risk patients.
The guideline also recommends limiting osteoporosis treatment to a 5-year duration, which Dr. Leder criticized as arbitrary. “It doesn’t reflect the wide range of disease severity,” he said. He was particularly critical of the recommendation in the context of denosumab. Studies have shown that the drug continues to increase bone density for many years, with no apparent plateauing effect. “The recommendation of 5 years of therapy may benefit from some more nuance,” Dr. Leder said.
He also sharply criticized one omission. “Denosumab cannot be stopped or switched to teriparatide without a transition to bisphosphonates. This is one of the most crucial missing pieces of the guidelines, and it could potentially harm patients,” he said.
The editorial writers also felt that the 5-year treatment window was oversimplified. They noted that a shorter-than-5-year period may be appropriate for intravenous zoledronate, oral bisphosphonates, and teriparatide.
The guideline also advised against bone density monitoring during the suggested 5-year treatment window. Dr. Leder disagreed. “I don’t know if it’s feasible to start a patient on a medication and then communicate that you’re not going to monitor the effectiveness of that medication. That would be a tough sell for a hypertension drug, or a cholesterol lowering agent,” he said.
The guideline recommendations were not without defenders. Carolyn J. Crandall, MD , professor of medicine at the University of California, Los Angeles, spoke about the positive aspects. She pointed out that the guideline focused on first-line therapies for osteoporosis, which she thinks will help physicians. “There are too many medications available. Which should [they] use? How do [they] prioritize them?” Dr. Crandall said.
The guideline also provides useful information on the rate of adverse events. For example, it notes that atypical femur fractures occur in 1.78 out of 100,000 women taking bisphosphonates for 2 years. That information is useful, according to Dr. Crandall, but she took issue with the fact that the guideline described osteonecrosis of the jaw as rare. “As a primary care provider, I need to know how rare a side effect is, and primary care providers often don’t know that. When I do osteoporosis consultations, I often see patients who believe that osteonecrosis of the jaw occurs in nearly all patients who take bisphosphonates. If PCPs don’t know how rare ONJ is, how can they confront media reports?” Dr. Crandall said.
Overall, Dr. Crandall praised the recommendations as an important step forward. “I think they’re going to move us in the right direction, because primary care physicians read ACP guidelines. They answer key primary care provider questions. The guidelines are clear. PCPs need clear and easy to understand guidelines,” she said.
Dr. Crandall also made a pitch for more research, especially to determine the optimal duration of therapy and fracture reduction in patients with osteopenia. “PCPs need that evidence,” she said.
Dr. Leder has consulted for and received research funding from Amgen, Lilly, and Merck. Dr. Crandall reported having no financial disclosures.