The guidelines will provide more options for the treatment and prevention of glucocorticoid-induced osteoporosis and will inform rheumatologists about the requirements for anti-resorptive therapy after anabolic agents are discontinued.
The American College of Rheumatology (ACR) recently announced a summary of its guideline updates for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis (GIOP). Although glucocorticoids are a common and often essential step in treating rheumatic diseases, patients receiving these drugs who are at risk for developing osteoporosis are at an increased risk of developing GIOP.
The ACR’s 2022 GIOP Guideline co-investigators, Linda Russell, MD, and Mary Beth Humphrey, MD, PhD, spoke with Rheumatology Network to discuss changes in the guideline, which include the recommendation of abaloparatide (PTHrP) and romosozumab, sequential therapy protocols, and more flexibility in choosing medication with both the physician and patient in mind. In addition to serving on the ACR Guidelines Committee, Russell is Director of Perioperative Medicine, Director of the Osteoporosis and Metabolic Bone Health Center for the Hospital for Special Surgery, and Humphrey is interim Vice President for Research and a Professor of Medicine at the University of Oklahoma Health Sciences Center.
Rheumatology Network: What initially motivated the team to update these guidelines for the first time in 5 years?
Linda Russell, MD, Mary Beth Humphrey, MD, PhD: The ACR Guidelines Committee is making every effort to update guidelines every 5 years.
RN: Why was sequential therapy, previously unaddressed, included in the new updates?
LR, MBH: In 2017, studies showing rapid loss of bone after discontinuation of denosumab were just beginning to be published, so the need for sequential therapy was not evident at the time of the last guideline update. With the lapse in osteoporosis care due to the sudden disruption of health care during the peaks of the COVID-19 pandemic, many patients had disruption in their denosumab or teriparatide therapies with subsequent development of vertebral fractures, sometimes in just a few months after missed doses or drug discontinuation. Thus, we now understand that sequential therapy is needed to prevent rapid bone loss and/or possible vertebral fractures after treatment with denosumab, teriparatide, abaloparatide, and romosozumab.
RN: Why is it important to be more flexible in drug choices and to keep the preferences of both doctor and patient in mind when selecting treatment as opposed to rank-ordering the medications?
LR, MBH: The flexibility to use the most appropriate medication for your patient is critical. Therefore, we carefully reassessed our prior guidelines where osteoporosis medications were rank ordered based on fracture data, side effects, cost of care, and administration. The rank ordering led to some insurance programs adopting our rank order for their patient populations, an effect not intended by our guidelines.
Additionally, our prior ACR guideline development team did not include a robust patient panel to provide preferences concerning these issues. In this current guideline, we had a patient panel clearly indicate that they would want medication recommended by their provider independent of its delivery methods, including daily injections, infusions, or costs.Unlike the prior guideline where we considered fracture data only, this guideline considers gains in bone mineral density in randomized controlled studies not powered to show fracture results. Based on analysis of this data, the panel conditionally recommended oral or intravenous bisphosphonates, denosumab, teriparatide, and abaloparatide depending on the patient and physician preferences and discussions about risk and benefits. Romosozumab and selective estrogen receptor modulators were recommended for patients that cannot tolerate other agents and do not have cardiovascular or thrombotic risk factors.
RN: Why are bisphosphonates not generally recommended for patients with an estimated glomerular filtration rate (eGFR) < 35ml/min?
LR, MBH: Oral and intravenous bisphosphonates are excreted via the kidney and may accumulate in bone faster in advanced-stage chronic kidney disease patients with eGFR <35ml/min compared with those with a normal renal function. When eGFR <35ml/min, adynamic bone disease is more likely to occur. Additionally, there is limited large-scale clinical safety data on bisphosphonate use in patients with eGFR <35 mL/min.
RN: What is the clinical significance of these guideline updates?
LR, MBH: These guidelines provide more choices for osteoporosis therapy than prior guidelines.Education of providers and their patients concerning the need for anti-resorptive medications after denosumab, teriparatide, abaloparatide and romosozumab treatment will prevent vertebral fractures and bone loss when these drugs are discontinued.
RN: What are the implications for both rheumatologists and patients?
LR, MBH: These guidelines will provide rheumatologists and their patients more options for the primary treatment and prevention of glucocorticoid-induced osteoporosis. Additionally, based on the most recent literature, they will inform providers about the requirements for anti-resorptive therapy to help large bone gains remain after anabolic agents are discontinued.
The full manuscript is expected to be published in 2023.