CHICAGO — More than a third of women at very high risk for fracture from postmenopausal osteoporosis were not receiving treatment, and over half of those receiving treatment were taking oral bisphosphonates, which is not the first-line recommended treatment, according to a retrospective cohort study presented at the American College of Rheumatology (ACR) 2025 Annual Meeting.

Current clinical practice guidelines from the American Association of Clinical Endocrinologists/American College of Endocrinology and the Endocrine Society for postmenopausal women with osteoporosis advise treating them based on fracture risk with either injectable osteoanabolic therapies, such as romosozumab, teriparatide, or abaloparatide, or with an injectable antiresorptive, such as denosumab, or with the intravenously infused antiresorptive zoledronic acid.

“Only a small percentage of postmenopausal women with osteoporosis at very high risk for fracture received osteoanabolic therapies that have demonstrated greater fracture risk reduction than oral bisphosphonates in head-to-head randomized controlled trials of high-risk populations,” Xiaodong Li, PhD, medical director for US Bone Health at Amgen, Thousand Oaks, California, told attendees.

Further, over half the women receiving treatment and a third of untreated women were at very high risk for fracture despite not having a bone mineral density (BMD) T-score recorded in their electronic health records (EHRs), Li reported. “It is important to consider fracture history and perform fracture risk assessments to identify patients at very high risk for fracture in order to guide treatment recommendations,” he said.

The researchers analyzed data from the Optum Market Clarity database of administrative claims linked to EHRs of patients either commercially insured or insured with Medicare Advantage Plans. They looked for all postmenopausal women at least 55 years old who had a diagnosis of osteoporosis or fracture or of osteoporosis medication use. Patients were excluded if they had a history of Paget disease or metastatic cancer, if their records lacked data on BMI or race/ethnicity, or if they had been enrolled less than 455 continuous days before the index date of diagnosis or prescription.

Patients were classified as being at very high risk for fracture if they had experienced a fracture within the previous year, if they had a BMD T-score of -3.0 or less, or if they had a 10-year probability of fracture according to the Fracture Risk Assessment tool (FRAX) greater than 30% for major osteoporotic fracture or greater than 4.5% for hip fracture. Patients were classified as high risk if they had experienced a fracture more than a year earlier or if they had a FRAX score of 20%-30% for major osteoporotic fracture or between 3% and 4.5% for hip fracture.

Then the researchers assessed how many of those women had no history of osteoporosis treatment in the 15 months before January 2023 vs those who had initiated osteoporosis treatment with oral bisphosphonates, zoledronic acid, denosumab, or osteoanabolic therapies for the first time between April 2019 and September 2023.

Dissected Data Reveal Scale of Undertreatment

The 41,597 women who had begun treatment were an average 73 years old. Just over half (51.6%) were at very high risk for fracture, 21.3% were at high risk, and 27.1% were at low risk. Over half (56.3%) had started treatment with oral bisphosphonates while 23.2% had started with denosumab, 15.7% with zoledronic acid, and 4.7% with osteoanabolic therapies.

About 1 in 5 of those women had a fracture history, and among those 9364 women, 42.5% had initiated therapy with oral bisphosphonates, 29.9% with denosumab, 17.2% with zoledronic acid, and 10.3% with osteoanabolic therapies.

From there, the researchers split the 5245 women (12.6% of total population) with a recent fracture — those at very high risk — from those only at high risk because of a more distant fracture history (9.9%). Among those at very high risk, 41.5% had begun therapy with oral bisphosphonates, 29.5% with denosumab, 15.2% with zoledronic acid, and 13.8% with osteoanabolic therapies.

When the researchers analyzed data on the women without a fracture history, 0.8% of the original population had no fracture history but were at very high risk based on a low T-score, and 38.2% of women had no fracture history but were at very high risk based on their FRAX score. Another 11.4% of women had no fracture history but were at high risk based on their FRAX score.

Among those at very high risk based on their FRAX score, 55.5% had begun taking oral bisphosphonates, 25.4% denosumab, 16.1% zoledronic acid, and 3% osteoanabolic therapies. Those at high risk and the small group at very high risk based only on T-score also predominantly initiated therapy with oral bisphosphonates, followed by denosumab, then zoledronic acid, then osteoanabolic therapies.

Overall, among the combined cohort of women at very high risk for fracture by any metric who had begun therapy, 51.7% were taking oral bisphosphonates, 26.5% denosumab, 16% zoledronic acid, and 5.7% osteoanabolic therapies.

Meanwhile, among the 318,140 women who were untreated, 37.1% were at very high risk for fracture, and 47% were at high risk. Just 15.9% were at low risk.

‘A Tremendous Gap’

“We know that there is a tremendous gap in terms of the number of postmenopausal women, as well as older men, who are eligible for treatment of osteoporosis based on fracture history or screening bone mineral density who don’t receive treatment, despite the availability of multiple treatments in the landscape,” said Marc C. Hochberg, MD, MPH, professor emeritus of medicine at the University of Maryland School of Medicine, Baltimore. He would like to see the data that were presented followed and then re-analyzed to assess subsequent fracture risk down the line, based on treatment groups.

Tahir Khan, MD, rheumatologist from Abu Dhabi, said he would be interested in finding out who the main treating physicians were for the different populations. “This is an important part of the clinical care because we are addressing clinical care gaps,” he said. “Then we could focus as a community on where we should intervene most.”

The study was funded by Amgen, which manufactures denosumab and romosozumab, and UCB, and all authors are employees and stockholders at Amgen. Hochberg and Khan had no disclosures.

Tara Haelle is a science/health journalist based in Dallas.