Postmenopausal Osteoporosis: Clinical Burden, Treatment Barriers, and the Evolving Role of Denosumab Biosimilars

Sponsored by Sandoz Pharmaceuticals.

Key Takeaways and Payer Implications

• We interviewed experts Stuart Silverman, MD; and Angela Cheung, MD; to discuss the substantial clinical and economic burden of postmenopausal osteoporosis, persistent gaps in treatment despite effective therapies, and ways that denosumab biosimilars may reshape access, affordability, and care delivery in the US and Canada.
• Postmenopausal osteoporosis drives substantial and growing health care costs, largely due to fractures that result in excess mortality, long-term disability, and sustained use of medical resources.
• Fractures are costly but preventable, and earlier identification and treatment of high-risk patients represent a great opportunity for payers to reduce downstream spending.
• Osteoporosis remains undertreated despite FDA approval of effective therapies, partially due to delayed diagnosis, adherence challenges, fragmented care, and restrictive access policies.
• Denosumab is highly effective for patients at high fracture risk, yet its use has often been constrained by cost and utilization management rather than by clinical evidence.
• Denosumab biosimilars offer clinically equivalent efficacy and safety, enabling payers to expand access to effective biologic therapy without compromising outcomes.

Introduction

Postmenopausal osteoporosis continues to be a growing and costly global public health challenge. In recent interviews conducted by the American Journal of Managed Care®, this topic was explored by experts Stuart Silverman, MD, clinical professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles, and at Cedars-Sinai Medical Center; and Angela Cheung, MD, PhD, director of the University Health Network Osteoporosis Program, associate director of the University Health Network Women’s Health Program, and professor of medicine and related disciplines at the University of Toronto in Ontario, Canada. These experts discussed the clinical and economic burden of postmenopausal osteoporosis, persistent gaps in treatment despite effective therapies, and ways that denosumab biosimilars may reshape access, affordability, and care delivery in the US and Canada.

The Clinical and Economic Burden of Postmenopausal Osteoporosis

Overall, osteoporosis affects an estimated 10 million Americans, with the highest prevalence noted among postmenopausal women.1,2 About 1 of 2 women older than 50 years will experience an osteoporosis-related fracture in her lifetime; by 2040, the number of fractures reported annually is expected to grow to 3.2 million.2,3

“The burden of postmenopausal osteoporosis is profound, and its negative impacts are primarily due to fractures,” stated Silverman. Fractures, particularly those affecting the hip, are associated with loss of independence, long-term disability, and high mortality. Over the year following a hip fracture, the mortality rate can be 20% to 30%, 20% to 24%.4 Economically, costs associated with osteoporosis-related fractures are substantial and rising. In 2018, the total annual cost of care (both direct costs and indirect costs [eg, loss of productivity and caregiver expenses]) related to fractures was approximately $57 billion; it is expected to grow by almost 70% to $95 billion in 2040.3

Effectively managing postmenopausal osteoporosis and preventing fractures should be prioritized. However, the condition is currently undertreated.3

Why Osteoporosis Remains Undertreated

“There are many challenges [associated with managing postmenopausal osteoporosis],” said Silverman. Silverman and Cheung reviewed the following contributing factors to undertreatment, which involved both patient-level and system-level barriers.

Patient-Level Barriers

Misconceptions about postmenopausal osteoporosis can lead to poor therapy and/or treatment adherence. If patients do not experience symptoms of osteoporosis prior to fracture, they may believe that they do not need therapy, or they may mistakenly believe that prophylactic therapy will not help them. Some patients believe fractures are an inevitable consequence of aging rather than a preventable outcome of a treatable disease. “It's not uncommon for my patients to [ask] me, ‘Isn't [getting a fracture] part of normal aging?’” said Silverman. “It's not. They are not random, inevitable events of aging. Rather, they're a consequence of a treatable condition.”

Cheung also noted that many patients think that hip fractures don’t happen until 80 years of age; however, she sees hip fractures in 50-year-old patients, which again highlights the importance of preventive therapy. In addition to misperceptions, some patients struggle with adhering to their therapy due to polypharmacy and complex dosing requirements.

System-Level Barriers

At the system level, fragmented care models and inconsistent guideline recommendations contribute to undertreatment. “Osteoporosis requires a multidisciplinary approach involving physical therapists, doctors, allied health professionals, nutritionists, and social workers,” said Silverman. “It's hard to coordinate unless there is an osteoporosis program.” Diagnoses may be delayed due to inadequate screening and risk assessments, and patients who have not had a fracture typically don’t know whether they have osteoporosis. “It’s what we call the silent thief,” said Cheung. “If you don’t test for it, you don’t know you have it.”

In the clinical setting, prior authorization requirements and insurance coverage restrictions add to administrative burdens. “Insurers and pharmacy benefit managers often require prior authorization for biologics,” said Silverman. “That's a labor [intensive] process,…and it’s a process that can delay or deny access.” In his office, the process requires a full-time staff member, which is costly.

Traditionally higher costs of biologic osteoporosis therapies (eg, denosumab, anabolics including teriparatide) can lead patients to delay treatment initiation or to stop treatment. “The problem with the exorbitant prices,” Silverman commented, “is that many patients ration doses, skip treatments, or stop altogether.” Many patients face substantial co-payments and coinsurance. Out-of-pocket costs and formulary restrictions disproportionately affect older patients, particularly Medicare beneficiaries who are ineligible for many manufacturer assistance programs.

Therapeutic Landscape—Bisphosphonates vs Denosumab

Currently, guidelines for individuals at high risk of fracture recommend oral bisphosphonates and/or denosumab, Silverman pointed out. Denosumab is administered as an injection in a doctor's office every 6 months. Denosumab is more effective than bisphosphonates for reducing fracture risk, and it also has a favorable safety profile when appropriately managed; however, denosumab often is not prioritized as first-line therapy due to cost and access barriers.5 Oral bisphosphonates, which are widely used, typically are given orally once a day, once a week, or once a month; however, they are associated with gastrointestinal upset and esophagitis that frequently lead to frequent discontinuation. Silverman acknowledged the need for more cost-effective therapeutic options—such as biosimilars—that offer greater affordability and patient access.

Biosimilars as a Lever for Change

“Biosimilars have played a crucial role in significantly reducing the price of biologic drugs,” noted Silverman. “They introduce competition and lead to billions of dollars in savings for health care systems. Initially, they'll launch at [prices] 10% to 20% lower than the reference products. And then, over several years, [the cost] can drop [up to] 50% lower.” This competition also compels the original biological manufacturer to further lower its own prices, often through rebates to pharmacy managers and insurers to maintain market share. Importantly, Silverman commented, an increase in biosimilar availability has “translated to increased patient access to essential therapies,” said Silverman.

A denosumab biosimilar has demonstrated pharmacokinetics, pharmacodynamics, immunogenicity, and clinical outcomes comparable to those of the reference denosumab.6 “Trials such as ROSALIA [have shown] that the biosimilar is [equivalent] to the brand name compound,” said Cheung. Silverman emphasized that the FDA approval pathway showed no clinically meaningful differences in safety or efficacy for the denosumab biosimilar compared to the reference product. “Biosimilar approval is…a comprehensive, stepwise, totality-of-evidence approach that includes extensive analytical preclinical clinical data to confirm similarity,” he said. “Clinical trials are designed to rule out any meaningful difference, not a re-established safety and efficacy from scratch.”

Interchangeability

In the US, interchangeability is a regulatory designation established under the Biologics Price Competition and Innovation Act to support pharmacy-level substitution of biosimilars with prescriber intervention.7 An interchangeability designation given to a biosimilar can help facilitate access to these products by allowing pharmacy-level substitutions, Silverman said. “For example, if I write a prescription for the reference product, Prolia [denosumab; Amgen], it may be possible that the pharmacy or the health plan is going to switch to the biosimilar… Jubbonti (denosumab-bbdz; Sandoz).” If the biosimilar is interchangeable, the prescribing physician does not need to be involved with a switch.

Despite the options offered with interchangeability, physicians need to use discretion in using biosimilars. In its 2024 updated draft guidance and recent public workshops focused on future regulatory and science needs, the FDA signaled an evolving position on interchangeability.7

Real-World Experience With Denosumab Biosimilars

Canada Perspective

Cheung shared her experiences with switching from denosumab to a biosimilar in Canada. “I have a lot of confidence in [the ROSALIA trial] data, and I'm happy to change people to a biosimilar.” Her confidence in prescribing a biosimilar further increases when real-life patients experience the expected outcome after use. As of December 2025, more than 100 patients had switched to a biosimilar in Cheung’s program, which comprises 15 physicians.

Regarding cost, Cheung noted that biosimilars have saved her patients money. This is particularly impactful for patients without health insurance. “If [patients] pay out of pocket, it does make a difference whether someone is using a biosimilar or not. And so, certainly, it has made access easier for our patients.” In addition to experiencing improved treatment access through biosimilars, patients in Canada can receive support through programs such as Fracture Liaison Services, which helps identify high-risk patients and prevent secondary fractures.

Cheung emphasized the importance of educating patients and the health care team—including nurses and pharmacists—on biosimilars and the concept of interchangeability. “Once people understand, they have more confidence with the switch,” she said.

US Perspective

Silverman also addressed the importance of educating patients about switching to a biosimilar. In the US, many patients have little knowledge about biosimilars, and others are aware of biosimilars but are concerned about their efficacy or safety. “Patients may ask, ‘If something costs less, is it less safe and effective?’” Silverman noted. “So, I have to reassure them. ‘Yes, it costs a little less to your insurance company, but it's equally safe and equally effective.’”[Silverman,p5] It is also important to talk with patients about the totality of evidence and the regulatory processes, including FDA approvals, to ensure that a biosimilar is just as safe and effective.

Silverman predicted that denosumab biosimilars eventually will be prescribed as a first-line therapy, and a switch will no longer be necessary. “I think that over time, when the price reaches a point on the biosimilars [at which] it is within range, I'll be able to prescribe denosumab as a [first-line] therapy without any prior authorization or challenge. And it will be preferred....We [will be able to] save money, because a more effective drug means less fractures. Less fractures are less costly to the health plan.”His sentiments were reflected in outcomes of a preliminary economic analysis that showed denosumab given as a first-line therapy becomes more cost-effective as the price decreases, even dominating (ie, being more effective and less costly than) oral bisphosphonates at certain price scenarios.8

Conclusion

In summary, postmenopausal osteoporosis represents a major—but modifiable—driver of morbidity, mortality, and health care spending.2,4,9 Denosumab biosimilars offer a clinically sound opportunity to improve access to effective therapy.6 Prioritizing fracture prevention through earlier intervention, coordinated care, and evidence-based use of biosimilars may yield meaningful benefits for patients and health care systems alike. “I think the access to biosimilars will open patient access to treatments for osteoporosis,” said Cheung. “We will see more biosimilars, and I think physicians need to feel comfortable with using them.”

REFERENCES

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7. Considerations for demonstrating interchangeability with a reference product: update. Draft guidance for industry. FDA. June 2024. Accessed February 5, 2026. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-demonstrating-interchangeability-reference-product-update
8. Li E, McTavish R, Fashami FM, Kane S, Schauf M. Cost-effectiveness analysis of biosimilar denosumab for the treatment of women with post-menopausal osteoporosis in the United States: a risk based analysis. Abstract presented at: the American College of Rheumatology Convergence 2025; October 24-29, 2025; Chicago, IL. Abstract 2111. Accessed February 5, 2026. https://acrabstracts.org/abstract/cost-effectiveness-analysis-of-biosimilar-denosumab-for-the-treatment-of-women-with-post-menopausal-osteoporosis-in-the-united-states-a-risk-based-analysis/
9. Bazell C, Hansen D, Pelizzari P, Pyenson B. Medicare cost of osteoporotic fractures. Milliman Research Report. September 11, 2019. Accessed February 5, 2026. https://frm.milliman.com/en/insight/Medicare-cost-of-osteoporotic-fractures