Elinzanetant’s Role in Preserving Bone Health: Insights from ENDO 2025 and the OASIS-3 Trial

This content was independently produced by Pharmacy Times in partnership with Bayer Healthcare.

Menopause is accompanied by a wide variety of symptoms, ranging from vaginal dryness to vasomotor symptoms. One particularly notable challenge, however, is bone loss.

Reduced estrogen during menopause significantly accelerates bone loss, thus raising the risk of osteopenia, osteoporosis, and fragility fractures. For decades, hormone therapy has been the primary way to alleviate vasomotor symptoms, such as hot flashes or night sweats, and to help maintain bone density. But many women are either unable or unwilling to use estrogen-based products due to safety concerns, contraindications, or personal preference. As a result, there is a high demand for nonhormonal therapies that are effective for menopausal symptom relief as well as for skeletal health maintenance.¹

Elinzanetant (Lynkuet; Bayer), a dual neurokinin (NK) 1 and 3 receptor antagonist, has emerged as a promising candidate in this space. By targeting the KNDy neurons in the hypothalamus that regulate thermoregulation, elinzanetant reduces vasomotor symptoms without altering hormone levels. Because bone loss is progressive during the postmenopausal period and due to the demand for a nonhormonal option, understanding the impact of elinzanetant is critical.²

OASIS-3 Trial and ENDO 2025 Poster

The phase 3 OASIS-3 trial (NCT05030584) was a 52-week study assessing elinzanetant’s long-term safety and effectiveness. The trial enrolled postmenopausal women with moderate to severe vasomotor symptoms and randomly assigned them to the elinzanetant or placebo group. Although the main objective was to alleviate the symptoms, the duration of the study has also allowed researchers to evaluate additional parameters such as bone mineral density (BMD), bone turnover markers, and body composition.³

At the Endocrine Society (ENDO) 2025 meeting, which took place July 12 through 15 in San Francisco, California, researchers shared a review of the exploratory end points, shedding light on the skeletal health potential of elinzanetant. Changes in BMD at the lumbar spine, total hip, and femoral neck were the primary bone parameters measured by dual-energy x-ray absorptiometry. Total bone mass by bioelectrical impedance analysis and changes in biomarkers such as PINP and osteocalcin were additional exploratory measures. These overall parameters allowed for the assessment of bone density and bone metabolism.³

Bone Mineral Density Outcomes

Throughout the 52-week period, BMD changes were minimal in both groups, which aligns with typical bone loss in postmenopausal women. Notably, patients who received elinzanetant showed less bone loss than the placebo group. The mean BMD at the femoral neck dropped by approximately 0.7% in the elinzanetant group compared with 1.2% in the placebo group. At the total hip, the rates in the groups were approximately 0.6% and 1.4%, respectively; and in the lumbar spine, 0.6% and 1.2%, respectively. Though small, these differences in BMD suggest that elinzanetant does not accelerate bone loss and may even attenuate the natural decline observed after menopause.^3,4

Though these changes were minor and tentative, they are still recognized as clinically relevant. Clinically, even very small variations in the rate of yearly bone loss may result in significant outcomes over a long treatment period.

Bone Turnover Biomarkers

In addition to bone density, a poster presented at ENDO 2025 included an examination of bone turnover markers. Bone turnover is the relationship between bone resorption and bone formation, and that turnover, if escalated, can cause fragility. Women who received elinzanetant showed no significant changes in the bone turnover markers for the 52-week study period. Additionally, 2 of the most important indicators of bone formation activity, PINP and osteocalcin, were only slightly higher in the placebo group than in the elinzanetant group. This result further reinforces that elinzanetant does not cause bone remodeling and could even prevent further skeletal decline.^3,4

Taken together, the stable biomarker profile and slight changes in BMD indicate that elinzanetant does not adversely affect bone health over the course of 1 year. When counseling women with questions about bone health and nonhormonal therapy, highlighting these data could help assuage their concerns.

Body Composition and Indirect Effects

Bone health is indirectly affected by body composition, whereby losing weight and lean muscle mass are among factors that lead to bone loss. In the OASIS-3 trial, elinzanetant treatment led to slight decreases in weight, body mass index, and waist circumference that were statistically insignificant compared with placebo. It should be noted that along with the maintenance of lean mass and fat mass, the distribution of body water did not show any alarming changes. These unremarkable outcomes imply that elinzanetant does not negatively alter body composition and, as a result, does not aggravate skeletal decline.³

From a clinical perspective, this is reassuring. Most patients with osteoporosis worry that therapeutic methods that influence fat or muscle composition will have an adverse effect on their osteoporosis. Maintaining lean mass and minor changes in the body with elinzanetant could help alleviate this fear.

Implications for Pharmacy Practice

For pharmacists counseling postmenopausal women, these data carry several important implications. Elinzanetant seems to be a safe nonhormonal choice to alleviate vasomotor symptoms while not driving bone loss. The availability of this option could also affect women ineligible for hormone therapy because of contraindications such as breast cancer, thromboembolism, or cardiovascular diseases.

Because bone outcomes were mostly neutral in the OASIS-3 study, routine preventive actions such as consumption of calcium and vitamin D, weight-bearing exercises, and lifestyle counseling should still be recommended for women initiating treatment with elinzanetant.

However, pharmacists should continue to individualize recommendations. Women at particularly high risk for osteoporosis, such as those with prior fragility fractures or very low baseline BMD, may still require pharmacologic bone-directed therapy in addition to elinzanetant. Pharmacists should continue to monitor ongoing trial results, including data from OASIS-3 and other studies, to offer evidence-based advice.

Limitations and Remaining Questions

It is important to recognize the limitations of the current evidence. In the OASIS-3 and ENDO 2025 poster presentation, bone results were considered secondary outcomes in exploratory work. Thus, the figures of statistical significance for these outcomes might be lower than those for vasomotor symptom outcomes.³ The enrolled population may also not completely reflect the characteristics of women who are most susceptible to osteoporosis, so the OASIS-3 results cannot be applied universally. Finally, although 1 year of data is a positive projection, menopause and bone loss are gradual processes, and it is still unclear whether bone safety will be sustained after several years of treatment.

Conclusion

The ENDO 2025 poster and results from OASIS-3 provide encouraging evidence that elinzanetant is not associated with accelerated bone loss or harmful changes in bone turnover over 52 weeks of treatment. In fact, modestly smaller reductions in BMD were observed with elinzanetant than with placebo, suggesting a neutral to slightly favorable effect on bone health. For postmenopausal women seeking nonhormonal relief from vasomotor symptoms, these findings are reassuring and expand the safety profile of elinzanetant. Although longer-term data are necessary, the results so far support elinzanetant as a promising therapy that addresses both quality of life and bone health concerns during menopause.^3,4

REFERENCES

1. Menopause. Endocrine Society. January 24, 2022. Accessed October 16, 2025. https://www.endocrine.org/patient-engagement/endocrine-library/menopause

2. Bayer provides regulatory update on elinzanetant for the treatment of moderate to severe hot flashes due to menopause. News release. Bayer. July 25, 2025. Accessed October 16, 2025. https://www.bayer.com/en/us/news-stories/regulatory-update-on-elinzanetant

3. Panay N, Joffe H, Maki PM, et al. Elinzanetant for the treatment of vasomotor symptoms associated with menopause: a phase 3 randomized clinical trial. JAMA Intern Med. Published online September 8, 2025. doi:10.1001/jamainternmed.2025.4421

4. Lewiecki EM, Kapoor E, Hurtado S, et al. The impact of elinzanetant treatment on bone health and body composition in postmenopausal women. Poster presented at: ENDO 2025; San Francisco, CA. July 12–15.