Multiple Myeloma Hypercalcemia: Causes, Symptoms, Treatment & More

If you’ve been told you have multiple myeloma and high calcium, it can feel like your body is trying
to run its own chemistry experiment without your permission. The medical term for this high calcium is
hypercalcemia, and when it shows up with multiple myeloma, it needs attentionfast, but not
necessarily panicked.

In this guide, we’ll walk through why multiple myeloma causes hypercalcemia, what symptoms to watch for,
how doctors usually treat it, and what day-to-day life can look like while you’re juggling both the cancer
and the calcium. Think of this as a friendly, plain-English walkthroughwith a little bit of humor, a lot of
medical accuracy, and zero judgment.

Important note before we dive in: this article is for education, not a substitute for medical care. If you
think you have symptoms of dangerously high calcium, you need real-life clinicians, not just a really smart
web page.

What Is Multiple Myeloma, and Why Does It Affect Calcium?

Multiple myeloma is a type of blood cancer that starts in plasma cellsspecialized white blood cells that
normally help your immune system make antibodies. In myeloma, these plasma cells become abnormal, grow out
of control, and build up in the bone marrow. They crowd out healthy blood-forming cells and release substances
that damage bone.

Doctors often talk about the “CRAB” features of multiple myeloma:

• C – Calcium elevation (hypercalcemia)
• R – Renal (kidney) problems
• A – Anemia (low red blood cells)
• B – Bone lesions (bone damage or fractures)

Hypercalcemia is one of the classic complications of myeloma. It usually means that the cancer is causing
significant bone damage or that the kidneys are struggling to clear excess calcium from the blood. When blood
calcium rises above the normal range, nerves, muscles, kidneys, and even the heart can be affected.

How Common Is Hypercalcemia in Multiple Myeloma?

Not everyone with multiple myeloma develops hypercalcemia, but it’s far from rare. In many large cancer
series, hypercalcemia appears in a noticeable portion of people with myeloma, sometimes even as a first sign
of the disease. In some patients, high calcium shows up at diagnosis; in others, it develops later, often
when the disease is more active or progressing.

The big takeaway: if you have multiple myeloma, your care team will almost always keep an eye on your calcium
levels, especially when your disease is flaring up or changing treatments.

Why Multiple Myeloma Causes Hypercalcemia: The Science (In Human Language)

To understand why calcium goes rogue in multiple myeloma, you need to know what’s happening inside the bones.
Myeloma cells don’t just sit quietly in the bone marrow; they change the behavior of the cells that build
and break down bone.

1. Overactive Bone Breakdown

Bone is constantly being remodeled: osteoclasts break down old bone, and
osteoblasts build new bone. In multiple myeloma:

• Myeloma cells stimulate osteoclasts (the “bone-eating” cells) to work overtime.
• They suppress osteoblasts (the “bone-building” cells) so repair can’t keep up.

The result? Bone becomes weaker and develops “lytic lesions”areas where bone has been eaten away. As bone
breaks down, calcium stored in the bone is released into the bloodstream, driving calcium levels up.

2. Chemical Messengers That Stir the Pot

Myeloma cells and surrounding bone marrow cells release a variety of signaling molecules (cytokines), such as:

• RANKL (Receptor activator of nuclear factor-κB ligand)
• MIP-1α (Macrophage inflammatory protein-1 alpha)
• Tumor necrosis factors and other inflammatory signals

These messengers tell osteoclasts to get busy and destroy more bone. That bone breakdown is the main fuel for
hypercalcemia in multiple myeloma.

3. Kidney Stress

Your kidneys normally help fine-tune calcium levels by filtering and excreting what the body doesn’t need.
In multiple myeloma:

• Myeloma proteins (also called M-protein or light chains) can damage kidney filters.
• Dehydration from vomiting, poor intake, or high calcium itself makes it harder for kidneys to work.
• Some medications and contrast dyes can add extra stress.

When kidneys can’t clear calcium efficiently, even modest increases in bone breakdown can push calcium into
the danger zone.

4. Other Cancer-Related Mechanisms

In some cancers, tumor cells make a hormone-like substance called PTHrP
(parathyroid hormone-related protein) or alter vitamin D metabolism, both of which canraise blood calcium.
While myeloma hypercalcemia is usually driven by bone destruction, those hormonal mechanisms may contribute
in some cases, especially when disease is advanced.

Symptoms of Hypercalcemia in Multiple Myeloma

Hypercalcemia can be sneaky at first. Early signs may feel like “I’m just tired” or “I’m a bit off today,”
which, to be fair, pretty much everyone with a busy life could say. The difference with high calcium is that
symptoms often cluster and escalate.

Mild to Moderate Symptoms

• Fatigue or feeling “slowed down”
• Thirst and drinking a lot more fluids than usual
• Frequent urination, especially at night
• Constipation or sluggish bowels
• Loss of appetite or nausea
• Mild abdominal discomfort
• Muscle weakness or achiness

More Severe Symptoms (Red Flags)

• Confusion, foggy thinking, or feeling “out of it”
• Severe fatigue or drowsiness that’s new or worsening
• Vomiting and inability to keep fluids down
• Severe constipation or abdominal pain
• Irregular heartbeat, palpitations, or chest discomfort
• Shortness of breath
• Worsening kidney function (rising creatinine on blood tests)

Very high calcium is a true medical emergency. If you or a loved one with multiple myeloma has these symptoms,
especially confusion, chest pain, or trouble breathing, it’s time for urgent evaluationoften in the emergency
department.

How Doctors Diagnose Hypercalcemia in Multiple Myeloma

You don’t feel your calcium level directly, so lab work carries most of the diagnostic weight. If your care
team suspects hypercalcemia, they’ll typically order:

• Serum calcium – This may be reported as total calcium and sometimes corrected for albumin
  (a blood protein).
• Ionized calcium – The “free” calcium that’s actually active in the body, used in some
  cases for a more accurate picture.
• Kidney function tests – Blood urea nitrogen (BUN), creatinine, and electrolytes.
• Parathyroid hormone (PTH) and sometimes PTHrP or vitamin D levels – To
  distinguish hypercalcemia from other causes.
• Myeloma workup – Such as serum protein electrophoresis, free light chains, and bone marrow
  evaluation (to track the underlying myeloma).

Imaginglike X-rays, CT scans, PET scans, or whole-body MRIsmay show bone lesions or fractures that fit the
picture of myeloma-related bone disease. These don’t directly measure calcium, but they explain where all that
extra calcium is coming from.

Treatment: How Multiple Myeloma Hypercalcemia Is Managed

Treating hypercalcemia in multiple myeloma usually follows two big goals:

1. Lower calcium quickly to a safer range.
2. Control the myeloma so the calcium doesn’t keep spiking.

1. Emergency Treatment to Lower Calcium

If calcium is significantly elevated or symptoms are serious, treatment often starts in a hospital or infusion
center. Common steps include:

Intravenous (IV) Fluids

High calcium dehydrates you by making you pee more. Ironically, one of the best ways to lower calcium is to
give IV normal saline to restore hydration, increase blood flow through the kidneys, and help
flush out excess calcium.

Loop Diuretics (Sometimes)

Once you’re adequately hydrated, doctors may use a medication like furosemide (a loop diuretic)
to encourage the kidneys to excrete even more calcium in the urine. This is carefully monitored so you don’t
get overly dehydrated or lose too many other electrolytes.

IV Bisphosphonates

Drugs like zoledronic acid or pamidronate bind to bone and shut down
overactive osteoclasts. They don’t work instantly, but they are a backbone treatment for
cancer-related hypercalcemia and myeloma bone disease. The peak effect may take a few days, but the benefit
can last weeks.

Denosumab

Denosumab is an antibody that blocks RANKL, one of the key signals that drives osteoclast
activation. It’s especially helpful when:

• Bisphosphonates haven’t worked well enough, or
• Kidney function is too impaired to safely use some IV bisphosphonates.

Denosumab can lower calcium effectively but requires careful monitoring because it can sometimes overshoot and
cause low calcium once the dust settles.

Calcitonin

Calcitonin is a hormone that temporarily lowers calcium by reducing bone resorption and
increasing calcium excretion. It acts fastwithin hourswhich is great for emergencies. The downside is that
the body quickly becomes tolerant, so it’s usually used only for a couple of days while other treatments,
like bisphosphonates or denosumab, begin to work.

Glucocorticoids

Steroids like prednisone or dexamethasone can help in several ways:

• They decrease inflammation and bone resorption.
• They directly treat myeloma as part of standard regimens.
• They may help in vitamin D–related hypercalcemia.

You’ll see steroids appear again in the “treating the myeloma” section, because they pull double duty here.

Dialysis

For severe hypercalcemia, especially in people with significant kidney failure or fluid overload, dialysis may
be used as a more aggressive way to remove calcium. This is generally a last-line approach reserved for the
most critical situations.

2. Treating the Multiple Myeloma Itself

If hypercalcemia is the fire alarm, multiple myeloma is the actual fire. Lowering calcium buys time, but
controlling the myeloma is what really prevents repeated spikes.

Modern myeloma treatment often includes combinations of:

• Proteasome inhibitors (such as bortezomib, carfilzomib)
• Immunomodulatory drugs (lenalidomide, pomalidomide)
• Monoclonal antibodies (like daratumumab, isatuximab)
• Steroids (dexamethasone is a frequent co-star)
• Alkylating chemotherapy in certain regimens
• Autologous stem cell transplant in eligible patients
• Newer options, such as CAR T-cell therapies and bispecific antibodies, in some settings

As treatment shrinks the myeloma burden in the bone marrow, bone destruction tends to slow down, and calcium
levels are easier to manage. This is why your oncologist is so focused on the overall myeloma plan, not just
the calcium number on today’s lab printout.

3. Ongoing Bone and Kidney Protection

Beyond emergency fixes and systemic therapy, there are long-term strategies to protect your bones and kidneys:

• Regular bone-strengthening therapy – Ongoing IV bisphosphonates or denosumab are commonly
  used in myeloma to reduce fractures and skeletal complications.
• Careful vitamin D and calcium supplementation – These may be adjusted based on your bone
  density, labs, and risk of hypocalcemia or recurrent hypercalcemia. Never change these on your own; always
  consult your care team.
• Kidney-friendly habits – Staying well hydrated, avoiding non-steroidal anti-inflammatory
  drugs (NSAIDs) unless specifically approved, and letting your doctors know before imaging that uses
  contrast dye.
• Monitoring – Regular blood work to track calcium, kidney function, and markers of myeloma
  activity.

Everyday Life with Multiple Myeloma Hypercalcemia: Practical Tips

Living with multiple myeloma is already a full-time job. Adding hypercalcemia can feel like your body added a
surprise side project. Here are some practical points people often find helpfulalways filtered through your
own doctor’s advice.

Hydration, But Make It Realistic

Hydration is a key player in helping kidneys manage calcium. Your team may encourage you to drink more fluids,
assuming your heart and kidneys can handle it. Simple strategies:

• Keep a reusable bottle nearby and track how often you refill it.
• Spread fluids throughout the day instead of chugging all at once.
• Plain water is great, but broths or electrolyte drinks may also help (as your team recommends).

Watch for Subtle Symptom Changes

Many people with myeloma get used to feeling “off,” which can make it hard to spot new problems. It can help
to pay attention to patterns:

• Are you suddenly more confused, forgetful, or foggy than usual?
• Has your thirst or urination significantly increased?
• Is constipation more stubborn than your normal baseline?

These may be early hints of rising calciumor of other issues that deserve a check-in.

Medication and Appointment Organization

Hypercalcemia often means extra medications, more lab work, and more infusion visits. A few organizational
tricks:

• Use a pill organizer and set phone alarms for time-sensitive meds.
• Keep a simple log (on paper or an app) of infusion dates and how you felt afterward.
• Bring a short list of questions to every visit. Brain fog + medical appointments is not a fair fight.

Real-World Experiences: What Living with Myeloma Hypercalcemia Can Feel Like

Numbers on a lab report tell one story; the lived experience tells another. While everyone’s journey is unique,
there are common themes in how people describe life with multiple myeloma and episodes of hypercalcemia.

The “Something Is Really Off” Phase

Many people describe the lead-up to a hypercalcemia diagnosis as a vague but persistent feeling that something
isn’t right. It might start with:

• Bone pain that feels deeper and more constant than usual.
• Dragging fatigue where even getting dressed feels like a chore.
• A combination of thirst and constant bathroom trips that interrupts sleep.

Because myeloma itself can cause fatigue and bone pain, it’s easy to chalk these symptoms up to “just the
cancer.” Often, it’s the change in intensity or the addition of confusion, nausea, or
worsening constipation that pushes people to seek helpand leads doctors to check calcium levels.

Infusion Days: Hydration, Meds, and Waiting

When hypercalcemia is treated in a hospital or infusion center, the experience can be oddly repetitive but
emotionally loaded. You might:

• Arrive early, get weighed, and have vital signs checked.
• Get IV access (port or peripheral line) and start fluids.
• Receive bisphosphonates or denosumab, often alongside other myeloma medications.
• Spend several hours in a recliner, scrolling your phone, napping, or chatting with whoever came with you.

People often describe a mix of relief (“something is being done”) and frustration (“I’d rather be literally
anywhere else”). It’s normal to feel both. Small comfortsnoise-canceling headphones, a favorite show, a
blanket, or a snack approved by your care teamcan make these days more tolerable.

Caregiver Perspective: Watching and Worrying

Hypercalcemia can be especially stressful for caregivers, who may notice confusion, odd behavior, or weakness
before the person with myeloma fully recognizes it. Caregivers often:

• Track symptoms, appointments, and medication changes.
• Advocate for urgent evaluation when “something is off.”
• Juggle practical tasks (rides, insurance, childcare) on top of emotional support.

If you’re a caregiver, you’re not overreacting by calling the clinic about new confusion, sudden fatigue, or
serious constipation. Those calls are exactly what healthcare teams want you to make.

Rebuilding Confidence After a Scare

A serious hypercalcemia episode can feel like a turning point. Some people describe a lingering fear every
time lab draws come up, wondering, “Is my calcium high again?” Over time, understanding the pattern of your
own disease can help restore a sense of control:

• You may learn what early warning signs look like for youmaybe it’s a certain kind of fatigue or a
  shift in appetite.
• You and your team may build a clear action plan: which symptoms mean “call the clinic today” versus
  “go straight to the ER.”
• As myeloma comes under better control with treatment, long stretches of stable lab results can rebuild
  confidence.

It’s also completely fineand commonto seek emotional support, whether through counseling, peer support
groups, or online communities for people living with myeloma. Understanding that others have walked a similar
path can make the road feel less lonely.

Small Wins Matter

When you’re dealing with a serious illness and its complications, victory doesn’t always look like a movie
moment. Sometimes it’s:

• Seeing your calcium back in the normal range on the patient portal.
• Getting through an infusion day with minimal side effects.
• Walking a little farther than you did last week without needing to stop.
• Having one full day where you didn’t think about your calcium level at all.

Those are real wins. They’re worth noticing and celebrating, even quietly.

When to Seek Emergency Help

While some mild hypercalcemia can be managed as an outpatient, certain symptoms should prompt immediate
evaluation (urgent care or emergency department, depending on local resources and your doctor’s advice):

• Sudden or worsening confusion, disorientation, or agitation
• Chest pain, new palpitations, or irregular heartbeat
• Severe shortness of breath
• Inability to keep fluids down due to vomiting
• Severe abdominal pain or no bowel movement for several days with pain and bloating
• Very reduced urine output, especially if you’re still drinking fluids

If you’re not sure whether a symptom is serious, err on the side of calling your oncology team. They would
much rather reassure you or bring you in early than treat a full-blown crisis later.

Key Takeaways

Multiple myeloma–related hypercalcemia is serious, but it’s also something doctors know how to treat. It
usually reflects a combination of:

• Increased bone breakdown caused by myeloma activity, and
• Kidneys struggling to clear the excess calcium.

With prompt treatmentIV fluids, bone-targeted therapies like bisphosphonates or denosumab, and effective
myeloma regimenscalcium levels often improve. Long-term, the best strategy to prevent repeated hypercalcemia
is to keep the myeloma itself under the best control possible, while protecting bone and kidney health.

You’re not expected to manage this alone. Your oncology team, nephrologists, nurses, and pharmacists are all
part of the squad. Your job is to report symptoms, ask questions, and bring your lived experience to the
conversationbecause that’s data too.