Oklahoma City, OK—Updated guidelines on how to treat osteoporosis caused by glucocorticoid use offers new recommendations on the use of abaloparatide (PTHrP) and romosozumab, which have come on the market since the previous version in 2017.
Also discussed in the new document is sequential therapy, which was not addressed in the previous guideline.
The updated guidance was recently issued by the American College of Rheumatology (ACR), recognizing that patients using glucocorticoid medications for inflammatory conditions risk developing osteoporosis. The update was especially important because new osteoporosis medications—as well as clinical studies on the condition—have become available since the last ACR treatment guideline was published in 2017.
“One major side effect of glucocorticoid therapy is bone loss and an increase in the risk of fractures. Fractures can cause significant morbidity and be associated with an increased risk of mortality,” stated Mary Beth Humphrey, MD, PhD, coprincipal investigator of the guideline and interim VP for research and a Professor of Medicine at the University of Oklahoma Health Sciences Center, adding, “With newly approved osteoporosis medications and a review of the relevant literature, we felt it was important to update the guideline.”
To create the new guidelines, the ACR panel conducted an updated systematic literature review for clinical questions on nonpharmacologic and pharmacologic treatment addressed in the 2017 guideline. It also investigated new pharmacologic treatments, discontinuation of medications, and sequential and combination therapy. A voting panel, including clinicians and patients, reached a more than 70% consensus “on the direction (for or against) and strength (strong or conditional) of recommendations,” the authors pointed out.
“Some physicians may be surprised about the need for sequential therapy when completing a course of denosumab, parathyroid hormone/parathyroid hormone-related protein, or romosozumab. If not done, patients could be at risk of rapidly developing vertebral fractures and bone loss,” stated Linda Russell, MD, director of perioperative medicine, director of the Osteoporosis and Metabolic Bone Health Center for the Hospital for Special Surgery in New York and coprincipal investigator of the guideline.
Another change is that the updated guideline calls for more flexibility on drug selection and urges that patient and physician preferences be considered.
“The previous guideline rank-ordered medication for the treatment of glucocorticoid-induced osteoporosis. We felt it was important that this guideline reflect patient/physician decision making,” Dr. Humphrey noted.
The full manuscript is expected to be published in early 2023. A summary was released in September.
Specifically, the guidelines stated that patients completing a course of denosumab “should transition to 1-2 years of a bisphosphonate, or depending on the clinical scenario, transition to PTH [teriparatide], PTHrP, or romosozumab. Patients completing a course of PTH, PTHrP, or romosozumab need to transition to a bisphosphonate or denosumab; patients completing a course of PTH/PTHrP may transition to romosozumab followed by a bisphosphonate.”
The document advised that discontinuing denosumab without a transition to another therapy can result in vertebral compression fractures and bone loss. “Discontinuation of denosumab after two or more doses has been associated with rapid bone loss and development of new vertebral compression fractures as soon as 7-9 months after the last dose,” the document added. “As such, bisphosphonate therapy is recommended beginning at 6-7 months after the last dose of denosumab.”
The authors pointed out, however, that the “precise timing, dose, and duration of bisphosphonate use after denosumab cessation is under study, but treatment for a least 1 year seems prudent until additional research is available.”
The panel cautioned that stopping PTH/PTHrP without transition to another therapy can also result in rapid bone loss and new fractures, but that can be prevented with the use of oral or IV bisphosphonates, denosumab, or romosozumab. The authors also warned that halting romosozumab without transition to another therapy can result in bone loss; in that case, prevention can be achieved with the institution of oral or IV bisphosphonates or denosumab.
“Like the 2017 guideline, patients should be risk-stratified as being at low, moderate, or high risk of fracture (FRAX 10-year probability of major osteoporotic fracture <10%,10-19%, or ≥20%, respectively),” the guidance stated. “These cut points were used to stratify PICO (population/intervention/comparator/outcome) questions and weigh potential benefits versus harms when considering osteoporosis therapy.”
The new guidelines made a strong recommendation that any patients with long-term glucocorticoids and who are at high risk for fracture should receive oral bisphosphonates. For those at moderate-to-high risk of fracture, “…oral or intravenous bisphosphonates, PTH/PTHrP, and denosumab are preferred agents depending on patient and physician preferences. Selective estrogen receptor modulators (SERMs) and romosozumab may be used in selected patients after careful consideration of potential harms including thrombosis, stroke, and cardiovascular events.”
In terms of patients with chronic kidney disease or those who have had renal transplants, the guidance does not recommend bisphosphonates for those with an estimated glomerular filtration rate (eGFR) less than 35 mL/min, explaining, “When eGFR is <35 mL/min, the risk of renal osteodystrophy, including adynamic bone disease, osteomalacia, osteitis fibrosa cystica, and mixed uremic osteodystrophy, is increased. As such, metabolic bone disease expert evaluation for chronic kidney disease-mineral and bone disorder (CKD-MBD) is conditionally recommended to exclude these conditions.”
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