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Study: Denosumab Bested Risedronate in Bone Mineral Density in Osteoporosis
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WASHINGTON — Patients with osteoporosis showed greater improvement in key bone mineral density parameters after treatment with denosumab than with risedronate, according to data presented at the American College of Rheumatology Annual Meeting, here.
Kenneth S. Saag, MD, of the University of Alabama at Birmingham, and colleagues, conducted a phase 3, randomized, double-blind, active-controlled study to assess whether the drug was safe and effective in comparison with risedronate in patients with glucocorticoid-induced osteoporosis.
“Glucocorticoid-induced osteoporosis remains the most common secondary cause of osteoporosis,” he said. “We know that the pathogenesis of this disease includes increased RANKL and decreased osteoprotegrin expression.”
The primary aim of the study was to demonstrate in patients who were continuing glucocorticoid therapy, and in those who were initiating glucocorticoid therapy, that denosumab was not inferior to risedronate in terms of lumbar spine bone mineral density at 12 months. Patients who received glucocorticoids for 3 or more months were in the glucocorticoid-continuing group, while those who received them for less than 3 months were in the glucocorticoid-initiating group. In the continuing group, there were 253 patients treated with denosumab and 252 patients treated with risedronate. For the initiating group, there were 145 patients in each of the two treatment groups.
Denosumab was administered at 60 mg every 6 months, while risedronate was administered orally at 5 mg daily for 24 months. Patients also received calcium and vitamin D supplements.
Results in the continuing group indicated a 4.4% increase from baseline in lumbar spine bone mineral density with denosumab, compared with 2.3% for risedronate. For total hip bone mineral density, the increase was 2.1% for denosumab and 0.6% for risedronate. In the glucocorticoid-initiating group, the increases were 3.8% for denosumab and 0.8% for risedronate in the lumbar spine, and 1.7% for denosumab and 0.2% for risedronate in total hip bone mineral density.
“We observed significant increases in bone mineral density with both treatments,” Saag said. “But there was a significantly greater level in both continuing and initiating populations in patients treated with denosumab.”
Saag said the observed changes in bone mineral density were comparable to previous data sets. Secondary endpoints showed denosumab also yielded greater gains than risedronate in terms of bone mineral density in the femoral neck in both the continuing and initiating groups. There were no significant differences between the two treatments with regard to turnover markers.
Adverse events were also balanced between the two drugs. Saag said pneumonia, diverticulitis and bronchitis incidence also were not different. New fractures also were similar in denosumab and risedronate.
“We saw no significant differences, but this study was not powered to look at new fractures,” Saag said.
Patients received greater than or equal to 7.5-mg prednisone daily or its equivalent for 3 months or more or for less than 3 months before screening. Eligibility criteria included a lumbar spine, total hip or femoral neck bone mineral density T-score less than or equal to ‒2.0; or a T-score less than or equal to ‒1.0 with a history of fracture.
“Denosumab has the potential to become another treatment option for patients newly initiating glucocorticoid therapy and those at risk for experiencing fractures,” he said. — by Rob Volansky
References:
Saag KS, et al. Abstract #2L. Presented at: American College of Rheumatology Annual Meeting; Nov. 11-16, 2016; Washington.
Disclosure: Saag reports he has associations with Amgen, Merck and Radius.
Perspective
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John R.P. Tesser, MD
Glucocorticoid-induced osteoporosis has a complex pathophysiology in which there is decreased bone formation and increased bone resorption reflected by multiple alterations in bone signals, including an increase in RANKL and decrease in osteoprotegerin expression. In the early phase of steroid initiation, prolonged osteoclastic survival and increased generation causes rapid bone loss. There follows a chronic bone loss phase of reduced osteoblasts and osteoclasts accompanied by low bone remodeling.
To date only alendronate, risedronate and zoledronic acid have been approved for glucocorticoid-induced osteoporosis (GIOP). This study demonstrated that denosumab was not inferior to and, in fact, was statistically significantly superior to risedronate in increasing bone mineral density in both lumbar spine and total hip in both groups of those who initiated and those who continued glucocorticoids. Similar differences were noted for the femoral neck, but not for bone turnover markers.
Several important points need to be made. First, this was not a study looking at fracture endpoints and indeed it is highly unlikely we will ever see comparative studies with fracture endpoints in the future. Second, the patient had either osteopenia or osteoporosis. Only zoledronic acid has the labelled indication for the prevention of osteoporosis as others are labelled for GIOP only. This highlights the great need we have for other medications that can not only treat but prevent GIOP. Finally, further study could potentially confirm superiority of denosumab against bisphosphonate therapies and might move the needle a bit further in the overall treatment and prevention of GIOP.
Reference:
Baschant U, et al. J Bone Miner Res. 2016;doi:10.1002/jbmr.2988.
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