The use of denosumab to treat osteoporosis has increased rapidly since its FDA approval in 2010, and it is now the second most used medication after alendronate, according to data presented at the ENDO annual meeting.

“Between 2009 and 2020, alendronate was the most commonly used bone-directed therapy overall,” Sara Cromer, MD, a clinical and research fellow in endocrinology at Massachusetts General Hospital, and Seoyoung C Kim, MD, ScD, MSCE, associate professor of medicine in the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital, told Healio. “After its FDA approval in 2010, relative use of denosumab rose rapidly, overtaking use of all other medications except alendronate in patients with osteoporosis by 2017 and all other medications in patients with active malignancy by 2013. The rapid rise in use of denosumab outpaces growth in use of other similar medications and may be out of proportion to available clinical guidelines and data in osteoporosis populations.”

Cromer and colleagues analyzed de-identified commercial insurance claims data from the Optum Clinformatics Data Mart from 2009 to March 2020. Data were obtained for adults older than 50 years who received any bone-directed therapy. Researchers calculated the percent of individuals who received each medication for each quarter. Analysis was also performed on a subgroup of participants who had osteoporosis with no malignancy (n = 948,546, 92% women; mean age, 70 years) and a subgroup with malignancy likely to metastasize to bone assessed by an oncology provider (n = 131,557; 77% women, mean age, 68 years).

Denosumab use greatly increases

There were 15.48 million claims from 1.46 million unique individuals during the study period (89% women, mean age, 69 years). Alendronate was the most used medication during the entire study period, with its use increasing incrementally. Use of denosumab (Prolia, Amgen) increased greatly after being introduced in 2010, and it surpassed all medications except alendronate by 2017.

“We were surprised to see denosumab so profoundly surpass zoledronic acid, which has similar efficacy, a similar side effect profile — with some exceptions — and similar convenience,” Cromer said. “Additionally, in recent years, there has been increasing concern surrounding rapid decline in bone mineral density and increased vertebral fractures upon discontinuation of denosumab; evolving research suggests that this may be partially, but not entirely, attenuated by use of oral and possibly intravenous bisphosphonates, but it has been a major safety concern in the field. Our data do not clearly show any decline in denosumab use related to this safety concern.”

In subgroup analyses, medication trends for those receiving osteoporosis treatment parallel trends observed in the full study cohort. There were differences in medication use in the malignancy subgroup, with denosumab being the most common medication used from 2013 to the end of the study. Use of alendronate, zoledronic acid, other bisphosphonates and raloxifene all declined.

Few receive treatment after fracture

Researchers also analyzed a fracture cohort of 1.35 million older adults (72% women, mean age, 74 years) without malignancy and with fracture at key osteoporotic sites. Data for medication use in the same or subsequent calendar quarter (90 to 180 days after fracture) were obtained.

Most people included in the fracture cohort did not receive any treatment after 3 to 6 months. Additionally, the percent of adults receiving anytreatment to prevent further fractures declined over time from 15% in 2009 to 8% in 2020.

“Treatment for osteoporosis, which was already known to be low, continues to decline, suggesting major failings in management of this common chronic disease,” Cromer said. “Effective therapies for fracture prevention in osteoporosis are safe, widely available and cost-effective, and these low treatment rates are likely associated with many thousands of preventable fractures each year in the United States.”

Alendronate was the most common medication prescribed in the fracture cohort, with its relative use increasing marginally over time. Denosumab’s use increased rapidly and surpassed all other medications except for alendronate by 2016.

Cromer said more research is needed to explore the reasons and consequences behind the medication use trends.

References:

https://www.healio.com/news/endocrinology/20210329/denosumab-increasingly-prescribed-in-osteoporosis-treatment