Biosimilar Denosumab Shows Cost-Effectiveness Over Bisphosphonates in PMO

At $150,000 per quality-adjusted life-year (QALY), biosimilar denosumab (Prolia; Amgen) clears the cost-effectiveness bar against every oral bisphosphonate and against zoledronic acid for postmenopausal women at high fracture risk—but drop the threshold to $100,000, and only 1 comparison holds up, according to a recent analysis.1

A Gap Left by Reference Denosumab Modeling

More than 2 million osteoporosis-related fractures occur annually in the US, with direct and indirect costs projected to climb from $57.0 billion in 2018 to more than $95.2 billion by 2040. Oral bisphosphonates remain first-line therapy for postmenopausal osteoporosis (PMO), yet roughly 70% of US patients receive no treatment at all, largely due to poor compliance, gastrointestinal (GI) adverse events (AEs), and high drug costs. Reference denosumab offers better adherence and convenience as a twice-yearly injection, but its price has nearly doubled since FDA approval, limiting affordability.

Sandoz's biosimilar denosumab, marketed in the US as Jubbonti (denosumab-bbdz), became the first FDA-approved denosumab biosimilar in March 2024 and launched commercially in June 2025, positioned by Sandoz as a lower-cost option intended to expand patient access.2 The economic question remained open, though: prior cost-effectiveness analyses evaluated reference denosumab against bisphosphonates, but none had assessed the biosimilar until a new cost-utility analysis took it on.1

A Lifetime Markov Model From the Payer's Chair

The analysis modeled a hypothetical cohort of women with PMO at high fracture risk using an 8-health-state Markov model with a lifetime horizon and 6-month cycles, tracking patients from treatment initiation until death or age 99 years. The starting age of 72.3 years mirrored the mean age enrolled in the pivotal FREEDOM trial (NCT00089791), which established reference denosumab's fracture-prevention efficacy. The model adopted a US payer perspective aligned with Medicare fee-for-service/Part B, counting only direct medical costs—drug acquisition, administration, disease monitoring, and fracture management—discounted at 3% annually.

Biosimilar denosumab was compared individually against alendronate, risedronate, ibandronate, and zoledronic acid; reference denosumab was excluded as a “dominated” comparator since the biosimilar was assumed to match its efficacy at a lower price. Because biosimilar denosumab's actual US price was not yet public at the time of modeling, the researchers estimated it at 80% of reference denosumab's cost, using Medicare pricing data and a 2022 Amgen biosimilar report. Treatment-effect estimates for hip, vertebral, wrist, and other osteoporotic fractures were drawn from published network meta-analyses.

ICERs Stayed Under $150,000, but Not Always Under $100,000

Biosimilar denosumab produced more QALYs than every bisphosphonate—0.043, 0.043, 0.042, and 0.030 additional QALYs per patient vs alendronate, risedronate, ibandronate, and zoledronic acid, respectively—at incremental costs of $4379, $4057, $4265, and $4390. The resulting incremental cost-effectiveness ratios (ICERs) were $101,017; $93,544; $100,515; and $144,995 per QALY gained, all of which fell under a willingness-to-pay threshold of $150,000 per QALY gained. Only the risedronate comparison cleared the more conservative $100,000 threshold outright; the alendronate and ibandronate comparisons missed it narrowly, and the zoledronic acid comparison missed it by the widest margin.

“As a lower-cost alternative to reference denosumab, biosimilar denosumab may enhance patient access to effective PMO treatment in the USA,” the researchers wrote.

A probabilistic sensitivity analysis of 1000 iterations reinforced that picture. At the $150,000 threshold, biosimilar denosumab was cost-effective in 100% of iterations against alendronate, risedronate, and ibandronate, but in only 55.4% of iterations against zoledronic acid. At the $100,000 threshold, it was cost-effective in 72.3% of iterations against risedronate, 29.9% against ibandronate, and 24.0% against alendronate, and not cost-effective against zoledronic acid.

Price and patient age were the 2 most influential drivers of the results. Dropping biosimilar denosumab's price to 40% of reference denosumab's cost pushed every ICER below $100,000 per QALY gained; at 20% of reference cost, the biosimilar dominated all 4 bisphosphonates—cheaper and more effective across the board. Starting age cut just as sharply: modeled ICERs ranged from roughly $164,000 to $215,000 per QALY gained at age 65 years but fell to $25,000 to $95,000 per QALY gained at age 85—the biosimilar's economic case strengthens in older, higher-risk patients and weakens in younger ones.

A Hypothetical Price, Built on Borrowed Data

The analysis carries meaningful caveats. Because biosimilar denosumab's US price was unknown at the time of modeling, the study's central estimate—a 20% discount to reference denosumab—was hypothetical, and the authors acknowledged that actual cost-effectiveness will depend on the biosimilar's real price. Jubbonti's June 2025 launch gives payers an actual contract price to test that assumption against as pricing data becomes available.2

Other inputs relied on non-US data where domestic evidence was lacking, including a Swedish study for postfracture risk and multinational trials for AE rates, and the analysis excluded societal costs like productivity losses, consistent with its payer-only perspective.

For health plans weighing formulary strategy, biosimilar denosumab clears a reasonable value bar even before the price erosion typical of biosimilar markets sets in. Combined with denosumab's twice-yearly dosing and lower GI-related discontinuation, the economic case could support broader coverage for older, high-risk patients, where the model's ICERs were most favorable, while bisphosphonates may remain the more cost-effective first choice for younger postmenopausal women.

References

1. Flanigan J, Kane S, Mirzayeh Fashami F, et al. Cost-effectiveness of biosimilar denosumab versus bisphosphonates in postmenopausal osteoporosis. PharmacoEconomics Open. 2026;10(4):733-748. doi:10.1007/s41669-026-00651-0
2. Jeremias S. Wyost and Jubbonti launch as first denosumab biosimilars in the US. The Center for Biosimilars®. June 2, 2025. Accessed August 4, 2026. https://www.centerforbiosimilars.com/view/wyost-and-jubbonti-launch-as-first-denosumab-biosimilars-in-the-us