When women reach menopause, their estrogen levels drop sharply, which is important for keeping the balance between bone loss and bone formation. According to the National Osteoporosis Foundation, 9.1 million women in the US have osteoporosis, and 26 million more women have low bone mass. Moreover, a 60-year-old woman has about a 44% lifetime risk of breaking a bone due to osteoporosis, compared to 25% for men of the same age.
Evenity (romosozumab-aqqg) is a prescription injection used to treat osteoporosis in postmenopausal women who are at high risk for fracture. It works by increasing bone formation and decreasing bone breakdown. While this dual effect makes Evenity an effective option for severe osteoporosis, it also comes with a range of possible side effects you should be aware of.
In this article, you’ll learn about common and uncommon side effects that may occur after Evenity injections, how they’re managed, and when to seek medical help.
Common Side Effects of Evenity Injection
Over 11,000 postmenopausal women took part in the clinical trials of Evenity. More than 5,600 of them received the drug in two large, year-long studies that assessed its safety and side effects compared to placebo and alendronate.
Here’s a look at the most commonly reported side effects.
1. Joint pain (Arthralgia)
Joint pain is one of the most frequently reported side effects that Evenity users experience. According to FDA data and clinical trials, joint pain was reported in about 8-13% of participants receiving Evenity, often beginning within days to weeks after the first dose.
Evenity works by building new bone and slowing down bone loss at the same time. That quick change in your bones can affect the way your joints feel. As your bones get stronger, the pressure on nearby joints, tendons, or cartilage might change too, and that can lead to pain or stiffness, particularly in the:
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- Hips
- Shoulders
- Hands
- Knees
- Smaller joints like fingers
Using over-the-counter pain relievers like acetaminophen or NSAIDs may help. Gentle stretching or physical therapy could also ease the discomfort. However, if the pain is intense or does not improve, consult your doctor.
2. Muscle spasms
Alongside joint issues, some patients experience sudden, involuntary muscle contractions after getting their Evenity shot. Muscle spasms on Evenity may be a sign that your calcium levels have dipped. This can happen if your bones are using up calcium quickly to rebuild. It might also reflect nerve sensitivity due to changes in how your musculoskeletal system responds to the drug.
In one study, calcium levels dropped by an average of 3.1% after one month of romosozumab treatment. The biggest drops in calcium were more likely in older patients.
Make sure you’re taking calcium and vitamin D exactly as prescribed. If spasms keep happening, you may need a blood test to check your levels. Adding magnesium-rich foods (like nuts or leafy greens) or gentle stretching at night may also help.
3. Injection site reactions
Because Evenity is given as a subcutaneous injection, typically in the abdomen, upper arm, or thigh, it can lead to localized skin reactions. This includes mild redness, swelling, or itchiness at the spot where you got your shot. Sometimes it’s just a little bump under the skin that goes away within a day or two.
About 5% of people reported injection site reactions, but these usually didn’t happen again with future doses. The reaction is usually your immune system’s response to the injection process, not the drug itself. Still, irritation may be worse if your injection technique is rushed or the needle goes too deep.
Applying a cold compress right after the shot can reduce swelling. If the reaction becomes painful or lingers for more than 3 days, bring it up at your next visit.
4. Headache
Some people report headaches after starting Evenity treatment. While not severe in most cases, this side effect can affect daily comfort and concentration. It’s believed to be a general reaction to the body adjusting to the medication, possibly related to vascular changes or immune response.
In a Reddit post, someone created a post asking about the side effects of Evenity after their 81-year-old mother experienced intense headaches and worsening back pain following her first injection. The user asked whether these symptoms were temporary or if they persisted throughout treatment.
Several commenters shared their experiences with Evenity. One user reported having mild headaches initially, but later developed daily, worsening frontal headaches and nausea after months on Evenity.
Try tracking when the headaches show up, if they happen after every injection, let your doctor know. Keeping hydrated and avoiding caffeine overload may help. If the pain is strong, medications like ibuprofen can take the edge off, but don’t use them too often without checking in with your doctor.
5. Swelling in the arms, legs, hands, or feet
Evenity can cause fluid to shift in your body, possibly due to how it affects your blood vessels or the balance of proteins involved in circulation. If you’ve had issues with swelling before, like varicose veins or kidney problems, you may be more likely to notice this.
Your fingers might puff up, your ankles may look swollen, or your socks might leave deeper marks than usual. You may also feel heavier or bloated.
Elevate your legs when sitting, wear compression socks if your doctor approves, and reduce your salt intake. Let your provider know if the swelling is new or getting worse. In some cases, they might check your kidneys, heart function, or suggest spacing out your injections.
6. Feeling of weakness or lack of energy
Evenity works fast to build bone, which uses a lot of energy and nutrients. This process can leave you feeling run down, especially if your vitamin D or calcium levels aren’t where they should be. Your immune system might also be working harder after each injection.
In a Reddit post, a user reported experiencing persistent fatigue and malaise nearly a month after starting Evenity. They also noted itching, which began in the second week and was starting to subside, but the fatigue continued. Some users shared that they did not experience fatigue at all. Others reported having fatigue initially, which subsided after a few doses.
7. Neck pain
Neck pain could result from tension in your muscles and joints as your body adapts to rapid bone changes. For some, it might be related to postural strain caused by how you sleep or how you’re holding tension due to stress.
You could wake up with a stiff neck, or feel sharp twinges when turning your head. Sometimes it spreads to your shoulders or upper back.
Try switching pillows or using a warm pack at the base of your neck. Gentle neck stretches can help, but skip heavy lifting until you feel better. If the pain travels down your arms or is paired with numbness, that could mean a nerve issue, and your doctor should take a closer look.
8. Insomnia
Insomnia can be caused by your body’s stress response to new medications, inflammation, or subtle hormonal shifts. For some people, Evenity may slightly increase blood pressure, which can also disrupt restful sleep.
To cope, give your brain signals that it’s time to wind down. Dim the lights in the evening, avoid screens, and try calming routines like deep breathing. Don’t rely on sleeping pills without medical advice. Your provider may recommend ways to balance your sleep cycle more naturally.
9. Prickling sensation (Paresthesia)
Paresthesia may be tied to lower calcium levels or minor nerve irritation after your injection. Since Evenity speeds up bone activity, your body may use calcium more quickly, which can briefly disrupt how your nerves signal. You might notice a pins-and-needles sensation in your fingers, toes, or face. It can be brief and mild, or feel like a buzzing or crawling sensation that comes and goes.
Make sure you’re taking your calcium and vitamin D daily. If tingling happens a lot or feels sharp or painful, your doctor might check for nerve compression or electrolyte imbalances.
Serious Side Effects
In addition to the nine Evenity side effects discussed above, there are a few rare complications that have been documented in post-marketing surveillance and clinical trials. These include:
1. Hypocalcemia (low levels of calcium)
Evenity can cause a drop in blood calcium, especially in individuals who already have low calcium or vitamin D levels.
If you’re taking other medications that can also lower calcium, the risk is higher, so your calcium levels should be checked regularly. People with serious kidney problems or those on dialysis have an even higher risk and need close monitoring. To help prevent low calcium, patients are usually advised to take calcium and vitamin D supplements while on romosozumab.
2. Cardiovascular Risks (Heart Attack or Stroke)
One of the most serious potential side effects linked to Evenity is an increased risk of cardiovascular events. In the BRIDGE and ARCH trials alone (about 4,300 people), romosozumab was linked to nearly 3 times higher risk of heart attacks compared to other treatments.
Due to this risk, the US FDA advises against using Evenity in people who’ve had a heart attack or stroke within the past year.
Symptoms that warrant urgent care include:
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- Sudden chest pain or tightness
- Difficulty speaking or facial drooping
- Loss of balance or vision
If you notice any of these symptoms after your injection, seek emergency medical care right away.
3. Allergic Reaction
Some individuals may develop an allergic reaction to romosozumab or the inactive ingredients in the injection. Warning signs are:
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- Skin rash or hives
- Swelling of the face, lips, or throat
- Difficulty breathing or wheezing
An allergic reaction is a medical emergency. If you experience these symptoms, go to the emergency room or call 911. Before taking Evenity, let your doctor know if you have a history of allergies to other injectable medications.
4. Osteonecrosis of the Jaw (ONJ)
This condition involves the breakdown of jawbone tissue and has been linked to medications that affect bone remodeling, including Evenity. It’s more likely in people who’ve had invasive dental procedures.
Your doctor will likely recommend a dental check-up before starting Evenity. Certain other medications, like bisphosphonates, chemotherapy, denosumab, steroids, and angiogenesis inhibitors, can raise the risk of ONJ, especially when used alongside Evenity.
Other factors that make ONJ more likely include:
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- Cancer or past radiation to the head/neck
- Poor dental hygiene
- Ongoing dental problems or infection
- Conditions like anemia or blood clotting issues
If you need major dental work, your doctor or oral surgeon should decide the best course of action based on your overall health.
If ONJ is suspected or develops while you’re on Evenity, you should be referred to a dentist or oral surgeon for care. In some cases, dental surgery can make ONJ worse, so it needs to be handled carefully. Your doctor may consider stopping Evenity depending on your situation and how severe the issue is.
Although not common in trials, some patients have reported minor dental side effects, such as gum sensitivity or slow healing after dental work. Always tell your healthcare provider and dentist before treatment.
5. Atypical Femur Fractures
Unusual thigh bone fractures (called atypical femoral fractures) have been reported in some people taking Evenity. These can happen with little or no trauma and usually occur in the middle part of your thigh bone. Sometimes, they can affect both legs.
These fractures often start with a dull, aching pain in your thigh, hip, or groin weeks or even months before the bone actually breaks. That’s why it’s important to tell your doctor right away if you notice new or unusual pain in those areas.
If you do report this kind of pain, your doctor may want to check your thigh bones to rule out a possible fracture, even if the pain doesn’t seem serious. If a fracture is found, they’ll likely examine your other leg too, since it could be affected as well.
Depending on your condition, your doctor may decide to pause or stop Evenity to reduce your risk, based on how the benefits compare to the risks.
Summary
Evenity can help strengthen your bones, but it also comes with side effects you should be aware of. Common ones, such as joint pain and headaches, usually appear in the first few weeks and often improve over time.
Serious side effects are rare but possible. These include low calcium levels, heart attack or stroke, allergic reactions, jawbone problems, and unusual thigh fractures. If you notice chest pain, facial drooping, groin or thigh pain, or signs of an allergic reaction, get medical help right away.
Talk to your doctor about any side effects you notice, especially if you have a history of heart issues or dental procedures. Staying informed helps you get the most out of your treatment while avoiding serious risks.
