Romosozumab is a prescription medication for osteoporosis, primarily approved for postmenopausal women with a significant risk of bone fracture. Marketed under the brand name Evenity, it represents a targeted approach to building bone.
Mechanism of Action
Our bones are in a constant state of renewal through a process called remodeling, which balances the activity of bone-building cells, known as osteoblasts, and bone-resorbing cells, called osteoclasts. This equilibrium ensures the skeleton remains strong. A key regulator of this process is a protein called sclerostin, which is produced by osteocytes. Sclerostin’s primary function is to slow bone formation by inhibiting the Wnt signaling pathway, which is important for the development and function of osteoblasts.
Romosozumab is a type of engineered protein called a humanized monoclonal antibody. It is designed to specifically find and bind to sclerostin, effectively neutralizing it. By blocking sclerostin, romosozumab removes the inhibitory signal on the Wnt pathway. This action allows for the increased proliferation and activity of osteoblasts, leading to the creation of new bone tissue.
This inhibition of sclerostin produces a dual effect on bone metabolism. It strongly stimulates the bone-forming activity of osteoblasts and also leads to a reduction in bone resorption by osteoclasts. The combined effect of boosting bone creation while slowing its breakdown results in a net gain in bone mass and density.
Patient Candidacy and Treatment Protocol
The use of romosozumab is intended for a very specific group of individuals. It is approved for postmenopausal women who are considered to be at a high risk for fracture. This high-risk category includes women who have already sustained a fracture related to osteoporosis, those who have multiple risk factors for fracture, or patients for whom other osteoporosis therapies have either failed or were not tolerated. A clinician might use a tool like the Fracture Risk Assessment Tool (FRAX) to help determine a patient’s 10-year probability of a major fracture.
The treatment regimen for romosozumab has a limited duration. The recommended dose is 210 mg administered once every month for a total of 12 months. This dose is given as two separate subcutaneous injections of 105 mg each, one right after the other. A healthcare provider must administer the injections, and patients are also advised to take calcium and vitamin D supplements to support the new bone formation.
Because the bone-building effect of romosozumab diminishes after the 12-month course, patients should transition to an anti-resorptive osteoporosis medication immediately following therapy. These medications, such as bisphosphonates or denosumab, work to slow down bone loss. They are necessary to preserve the bone mineral density gains achieved during treatment.
Potential Side Effects and Safety Concerns
The primary safety issue associated with romosozumab is a black box warning from the U.S. Food and Drug Administration (FDA) concerning an increased risk of major adverse cardiovascular events (MACE). This warning highlights a potential for heart attack, stroke, and death from cardiovascular causes. The warning was based on clinical trial data that showed a higher rate of these events in patients taking romosozumab compared to those taking a different osteoporosis drug, alendronate.
Due to this cardiovascular risk, romosozumab is contraindicated, meaning it should not be used, in patients who have had a heart attack or stroke within the previous year. For patients with other cardiovascular risk factors, such as hypertension, diabetes, or a history of smoking, a careful assessment of whether the benefits of the medication outweigh the potential risks must be conducted. If a patient experiences a heart attack or stroke while undergoing treatment, the medication must be discontinued immediately.
Beyond the cardiovascular warning, other serious side effects are possible. One such risk is hypocalcemia, or low levels of calcium in the blood, which must be corrected before starting romosozumab. Osteonecrosis of the jaw (ONJ), a rare condition where the jawbone is damaged, has also been reported. A dental examination is often recommended before starting treatment. Other reported side effects include:
- An atypical femoral fracture in the thigh bone
- Joint pain and headaches
- Allergic reactions, ranging from rashes to swelling of the face and throat
Comparison to Other Osteoporosis Medications
The landscape of osteoporosis treatment includes several classes of drugs that work in different ways. The most common are anti-resorptive agents, which function by slowing the rate at which osteoclasts break down bone tissue. This category includes bisphosphonates, such as alendronate, and an injectable antibody called denosumab.
Another category of treatment is anabolic agents, which work primarily by stimulating the formation of new bone. Teriparatide, a synthetic form of parathyroid hormone, is an example of an anabolic drug that directly promotes the activity of bone-building osteoblasts. These medications are typically reserved for patients with severe osteoporosis due to their potent bone-building capacity.
Romosozumab distinguishes itself through its unique dual mechanism of action, simultaneously boosting new bone creation and reducing its resorption. This dual effect makes it an effective option for rapidly increasing bone mineral density. Unlike other medications used for long-term management, its use is limited to a 12-month period, after which patients must transition to an anti-resorptive agent. The choice between romosozumab and other agents depends on the patient’s fracture risk, treatment history, and cardiovascular health profile.