Evenity (Romosozumab) Liver Function Impact: What Clinicians and Patients Need to Know

Does romosozumab affect liver function?

The Evenity label lists five warnings and precautions: major adverse cardiac events, hypersensitivity reactions, hypocalcemia, osteonecrosis of the jaw and atypical femoral fractures [1]. Liver injury is not one of them.

The label's table of adverse reactions occurring in 2% or more of Evenity-treated women lists arthralgia, headache, muscle spasms, peripheral edema, asthenia, neck pain, insomnia and paresthesia. No liver-related term appears [1].

Romosozumab is a monoclonal antibody that inhibits sclerostin, given by subcutaneous injection. The FDA approved it under BLA 761062 on April 9, 2019, and the label is dated July 16, 2026 [4][1]. It is labeled for osteoporosis in postmenopausal women at high risk for fracture, and treatment is limited to 12 monthly doses because the anabolic effect wanes [1].

What the label does flag

The boxed warning is titled WARNING: POTENTIAL RISK OF MYOCARDIAL INFARCTION, STROKE AND CARDIOVASCULAR DEATH. The label says Evenity should not be initiated in patients who have had a myocardial infarction or stroke within the preceding year, that benefits and risks should be weighed in patients with other cardiovascular risk factors, and that Evenity should be discontinued if a myocardial infarction or stroke occurs during therapy. It also says to monitor for signs and symptoms of myocardial infarction and stroke [1].

In the alendronate-controlled trial, adjudicated major adverse cardiac events were 2.0% (41 of 2,040) on Evenity versus 1.1% (22 of 2,014) on alendronate, hazard ratio 1.87 (95% CI 1.11 to 3.14). The placebo-controlled trial found 0.8% in both groups, hazard ratio 1.03 (95% CI 0.62 to 1.72) [1].

What the main trials were built to measure

ARCH randomized 4,093 postmenopausal women with osteoporosis and a fragility fracture to monthly romosozumab 210 mg or weekly alendronate 70 mg for 12 months, then open-label alendronate in both groups. Its primary end points were new vertebral fracture and clinical fracture [3]. FRAME randomized 7,180 postmenopausal women to romosozumab or placebo for 12 months, followed by denosumab for 12 months. Its coprimary end points were new vertebral fractures at 12 and 24 months [2].

Both trials were designed around fracture outcomes, and the label's safety sections do not report liver findings. These sources therefore cannot answer whether Evenity is safe or unsafe for people with pre-existing liver disease [1][2][3].