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Bisphosphonate Drugs and Lupus


General Introduction about Bisphosphonate Drugs and Lupus

 In this article, we will explore the relationship between bisphosphonate drugs and lupus, their potential benefits, considerations, and their role in supporting bone health for individuals living with lupus.

The latter section of this article contains the bisphosphonate section from The Lupus Encyclopedia: A Comprehensive Guide for Patients and Healthcare Providers, edition 2. The book organizes a good example of how it classifies medications used to treat lupus. It gives practical information such as which side effects are most common, what to do about them, what to do with the drugs around the time of surgery, what to do if you miss a dose, and much more.

To see the practical section about bisphosphonates from The Lupus Encyclopedia, edition 2, click here

Understanding Bisphosphonate Drugs

Doctors use bisphosphonate drugs as a class of medications to treat and prevent osteoporosis. They work by inhibiting the breakdown of bone tissue, thus reducing bone loss and enhancing bone strength. Bisphosphonates are available in various forms, including oral tablets and intravenous injections.

The Benefits of Bisphosphonate Drugs for Lupus Patients

  1. Reducing Bone Loss: Lupus patients are at a higher risk of developing osteoporosis due to the disease itself and certain medications used in its treatment. Bisphosphonates can help slow down bone loss and preserve bone density, reducing the risk of fractures.
  2. Managing Glucocorticoid-Induced Osteoporosis: Glucocorticoids (also called steroids, such as prednisone), commonly prescribed to manage lupus inflammation, can lead to bone loss. Bisphosphonates are effective in countering the bone-weakening effects of glucocorticoid medications.

Considerations for Lupus Patients

  1. Individual Assessment: Each lupus patient’s medical history, disease activity, and risk factors for osteoporosis may vary. It is crucial for healthcare providers to conduct a thorough assessment before prescribing bisphosphonate drugs for lupus, considering factors such as age, sex, disease duration, and glucocorticoid usage. Not everyone responds well to bisphosphonates. If they do not help to reduce the loss of bone density or if someone gets broken bones in spite of taking a bisphosphonate, then doctors will often change it to a different type of osteoporosis drug. Examples of other osteoporosis drugs include parathyroid hormone analogs (teriparatide and abaloparatide; also known as Forteo and Tymlos), denosumab (Prolia), and romosozumab (Evenity).
  2. Potential Side Effects: Discussed below. Discussing potential risks and benefits with healthcare providers is essential.
  3. Duration of Treatment: The optimal duration of bisphosphonate therapy in lupus patients is a subject of ongoing research. Healthcare providers may periodically assess the need for continued treatment based on individual response and risk factors.

Bisphosphonates and Bones

Bisphosphonates incorporate into the bone structure and continue exerting their effects. As bone recycles itself, the body reuses the bisphosphonate. Therefore, they continue to help build bone density even after they are stopped. However, as the bisphosphonate is recycled if it is discontinued, the body also slowly gets rid of the drug. At some point, the treated individual experiences a reduction in the benefits obtained from the bisphosphonate and may require re-treatment. Doctors usually figure this out by monitoring the bone density on a DXA (dual x-ray absorptiometry) scan. If doctors observe a loss of bone density, it is a common time to restart the bisphosphonate.

If there is evidence that a bisphosphonate is helping someone (such as seeing stabilization or improvements in bone density on a DXA scan), then the doctor may consider stopping the drug. A common regimen is to use an oral bisphosphonate for 5 years or IV zolendronic acid (Reclast) for 3 years, then stop the drug. Doctors call this putting the patient on a “drug holiday.” If the doctor notes any loss of bone density on repeat DXA scans (often done yearly), then treatment is usually resumed. Drug holidays are discussed in more detail below.

The reason patients are put on drug holidays is to prevent the rare complications of osteonecrosis of the jaw (where a piece of the jaw bone dies) and atypical femoral fractures (an unusual break in the large upper bone of the leg). Both of these potential complications are overall rare. However, they are incredibly rare if patients are put on a drug holiday off the bisphosphonate.

Maintaining Bone Health Holistically

While bisphosphonate drugs can play a crucial role in managing bone health in lupus patients, a comprehensive approach to bone health is recommended. Here are some additional strategies to consider:

  1. The Lupus Secrets: Read and follow the recommendations in the Lupus Secrets. Some of these specifically address lifestyle changes that are important to help keep bones strong.
  2. Calcium and Vitamin D: Adequate calcium and vitamin D intake are important for maintaining bone health. Consult with a healthcare provider to ensure sufficient dietary intake or discuss the need for supplements. Most people need 1000 to 1200 mg daily of calcium in their diet to help with bone density.
  3. Weight-Bearing Exercises: Engaging in weight-bearing exercises, such as walking or strength training, can help improve bone density and strength. Jumping exercises have especially been shown to help with bone density. However, it is crucial to consult with a healthcare provider or physical therapist to tailor an exercise plan suitable for individual needs and limitations.
  4. Lifestyle Modifications: Adopting a healthy lifestyle that includes a balanced diet, avoiding smoking and excessive alcohol consumption, and fall prevention measures can contribute to overall bone health.

Bisphosphonate drugs play a significant role in managing bone health for individuals with lupus, particularly those at risk of osteoporosis. These medications can help reduce bone loss and fractures, especially in the context of glucocorticoid-induced osteoporosis. However, individual assessment, consideration of potential side effects.

Below is the excerpt about bisphosphonates from The Lupus Encyclopedia: A Comprehensive Guide for Patients and Healthcare Providers, edition 2

Bisphosphonates Section of The Lupus Encyclopedia, edition 2

NOTE: This is a good example of how each drug used in lupus patients is presented in The Lupus Encyclopedia. The information is meant to be very practical. Instead of trying to read a laundry list of possible side effects from your pharmacist (many of which are not important and the long list will only scare you), we list those side effects that truly deserve attention. We also talk about subjects such as food interactions, what to do if you miss a dose, what to do around the time of surgery, and what to do if you become pregnant or want to breast feed.

A list of the bisphosphonates and their forms

  • alendronate (Fosamax, Binosto)
    • Pill, 5 or 10 mg a day; 35 mg or 70 mg a week
    • Strawberry-flavored effervescent tablet (Binosto), 70 mg, dissolved in water weekly
  • ibandronate (Boniva)
    • Pill, 150 mg a month
    • 3 mg IV infusion every 3 months
  • risedronate (Actonel, Atelvia)
    • Pill 5 mg a day, 35 mg a week, or 150 mg a month
    • Delayed-release form (Atelvia), 35 mg, with food weekly
  • zoledronic acid (Reclast)
    • 5 mg IV infusion yearly

Are generics available?

Yes, for all except Binosto.

Patients generally experience similar efficacy and tolerability with generic drugs as they do with brand-name counterparts. However, alendronate has lower absorption, is less effective, and can have more side effects than Fosamax. This is one instance where you may want to insist on the brand name.

How bisphosphonates work

Bisphosphonates attach directly to bone and prevent the cells that break down the bone (osteoclasts) from working. This allows the cells that produce bone (osteoblasts) to lay down more bone than what is reabsorbed.

What benefits to expect from bisphosphonates

They aim to reduce osteoporotic fractures. Bisphosphonates are slow to work, generally taking 6 to 18 months before significant bone-strengthening, and work best if you consume adequate amounts of calcium and vitamin D.

Not all bisphosphonates are equally effective. Risedronate and ibandronate may not be as effective as Fosamax. Furthermore, intravenous (IV) zoledronic acid may be better at preventing vertebral fractures than oral forms, but experts are not sure if this is because Reclast is a stronger drug or because doctors know 100% that patients are getting their medicine.

Oral bisphosphonates do not work if taken incorrectly (see below).

How bisphosphonates are taken

Bisphosphonates can be administered by pill form or intravenously (IV). The pills (table 24.9) have daily, weekly, and monthly types. They are not absorbed well if there is any food, medicines, or liquid (other than water) in the stomach or intestines, so they need to be taken first thing in the morning on an empty stomach along with water. It is important not to eat or drink anything else or take any other drugs for at least 30 to 60 minutes afterward. Even one sip of coffee prevents absorption.

There is one exception. Risedronate comes in a delayed-release form called Atelvia, which can be taken with breakfast. Atelvia now comes in a generic form.

The IV forms are preferred for people with stomach and esophagus problems. The FDA has approved two IV forms. Doctors infuse Ibandronate every three months, and they administer zoledronic acid yearly.

So which bisphosphonate is best?

There are various reasons for choosing one over another.

If you do not want to put up with a complicated regimen with most of the pills, consider the delayed-release form of risedronate (Atelvia).

For people who prefer liquids, alendronate has a generic liquid form. Strawberry-flavored effervescent alendronate tablets (Binosto) tablets are another option. You dissolve it in four ounces of room-temperature water. After it stopples bubbling (effervescing), you stir and drink it. This must still be taken on an empty stomach first thing in the morning with no other food or medications for at least 30 minutes afterward. Binosto is the only bisphosphonate that does not come in a generic form and is, therefore, more expensive. A generic might become available in 2023.

In addition to not missing doses, not smoking, and not drinking too much alcohol, you need an adequate amount of vitamin D and calcium and regular exercise.

If your bone density worsens on an oral bisphosphonate, your doctor may recommend that you switch from a pill form to one of the IV forms. You could also switch to a drug type (such as Evista, Tymlos, Forteo, Prolia, or Evenity).

What to do if you miss a dose of a bisphosphonate

Take your oral (pill) form of bisphosphonate as soon as you remember (in the morning) and then take your next dose as scheduled. Do not take two doses on the same day. Doctors schedule IV form infusions one year apart. Ask your doctor to confirm these recommendations.

Alcohol/food interactions of bisphosphonates

Alcohol can exacerbate esophagus and stomach inflammation from the pill forms. Excess alcohol prevents your bones from getting stronger. Atelvia (but not the other oral forms) can be taken with food.

Potential side effects of bisphosphonates

Most people tolerate bisphosphonates with few side effects (table 24.10). There are exceptions.

If bisphosphonate pills are in contact with the lining of the esophagus for very long, irritation can occur, causing stomach upset, heartburn, chest pain, and potentially an ulcer. Taking the bisphosphonate with 8 ounces of water and not lying down for at least 30 minutes after taking it lowers this risk. The pill forms should be avoided in people with severe esophagus and stomach problems, such as hiatal hernia, severe gastroesophageal reflux, or esophageal dysmotility.

Zoledronic acid can cause a flu-like reaction twenty-four to seventy-two hours after treatment. It is termed flu-like because it can cause body aches and low-grade fevers, resembling the flu. Taking acetaminophen (Tylenol) several times daily after the infusion usually prevents this or makes it less severe. This flu-like reaction is less likely to develop after the second infusion.

Below is a practical list of side effects that can potentially occur from bisphosphonate drugs

Nuisance side effects that occur in more than 5% of bisphosphonate users and how to address them

  • Low calcium and phosphate levels: Eat foods that are rich in calcium and phosphate or take mineral supplements.
  • Stomach upset, heartburn, nausea, gas, diarrhea: Switch to a different drug or treat the symptoms. For example, take Imodium for diarrhea or Pepcid for heartburn. Always ask your doctor first.
  • Flu-like symptoms after IV zoledronic acid (Reclast): Prevention is the best thing to do. Take acetaminophen (Tylenol) around the clock after the infusion (such as two 650 mg tablets three times daily for a few days after the infusion). Never take acetaminophen without asking your doctor first.

Nuisance side effects that occur in 1% to 5% of bisphosphonate users and how to address them

  • Chest pain from esophagus irritation: Switch to a different drug.
  • Body aches and pains: Take pain relievers such as acetaminophen (Tylenol). Always ask your doctor first. Switch to a different drug if severe.

Serious side effects that occur in 1% to 5% of bisphosphonate users and how to address them

  • Ulcers in the esophagus or stomach: Take anti-ulcer drugs. Ask your doctor. Also may need to stop taking the bisphosphonate and switch to something else.

Serious side effects that occur in 1% to 5% of bisphosphonate users and how to address them

  • Atypical femur fractures and osteonecrosis of the jaw. Read the sections below

Atypical femoral shaft fractures: a rare side effect of bisphosphonates

One rare potential side effect of bisphosphonates is an atypical femoral shaft fracture (or subtrochanteric fracture). “Atypical” means that these fractures (broken bones) are different from the typical fractures (called intertrochanteric fractures) that occur in the neck of the femur, which is the large leg bone that connects to the hip.

If someone breaks their hip from osteoporosis, the fracture usually occurs in the femoral neck, right next to the hip joint, high up in the leg. In contrast, atypical hip fractures occur farther down the bone in the femur’s middle section (shaft). There are usually warning signs because tiny fractures (stress fractures) occur first. An achy discomfort or pain in the thigh during or after exercise is common. An MRI can identify these early stress fractures.

These types of fractures have rarely been reported rarely from bisphosphonates. Asians appear to be at higher risk than whites (by as much as eight times higher). Women are three times more likely than men.

Some atypical fractures are due to osteoporosis itself and can occur in people not taking osteoporosis drugs.

Between 1996 (soon after Fosamax first came into use) and 2006, the number of hospital admissions for broken hips decreased by 33%. A 2020 research study showed that the number of hip fractures in Americans in their 80s dropped by half to a third of what they were before osteoporosis drugs were available. These numbers show the effectiveness of these drugs in decreasing broken hips. While osteoporotic hip fractures dropped markedly during the era of osteoporosis drugs, the numbers of atypical subtrochanteric hip fractures remained the same during this same time. This suggests that bisphosphonates rarely cause atypical hip fractures.

Osteonecrosis of the jaw: another rare side effect of bisphosphonates

Another potential rare side effect of bisphosphonates is osteonecrosis of the jaw (ONJ). Osteo- means “bone,” while -necrosis refers to “death,” so “osteonecrosis” means “death of a piece of bone.” In ONJ, a small part of the jaw’s bone dies, an open sore develops in the gum over the bone, and jaw pain occurs. Medical professionals have primarily observed ONJ with the use of large, frequent doses of IV bisphosphonates in bone cancer patients. It is estimated that it occurs in only 1 out of every 10,000 to 50,000 people (depending on the study) who take a bisphosphonate, so it is rare. When someone with osteoporosis develops ONJ, it is more commonly due to some other reason.

Below is a list of other causes of osteonecrosis of the jaw:
  • Sjögren’s
  • Dental disease (like gingivitis, periodontitis, tooth decay)
  • Smoking
  • Diabetes
  • Steroids
  • Cancer treatments
  • Dental implants
  • Poor-fitting dentures

Some ONJ risk factors are avoidable. People with diabetes should keep their glucose under good control. SLE patients should work with their rheumatologist to get on the lowest dose of steroids possible and not smoke. They also should work hard at good dental care (brushing, flossing, teeth cleaning, and avoiding sweets). If they wear dentures, they should ensure that they fit perfectly. It is also a good idea to perform any major dental work before starting a bisphosphonate, since ONJ usually occurs after teeth removal and other dental surgeries.

If someone needs major dental work while on a bisphosphonate for less than four years, it is possible to proceed without stopping the medication, according to the American Association of Oral and Maxillofacial Surgeons. If the medicine has been taken for more than four years, or if they have problems that increase the chances for ONJ (table 24.11), the doctor should consider stopping the drug for two months before the procedure. It can then be restarted after the bone has healed.

Note, though, that these recommendations are not based on solid research. Stopping the drug before the procedure may not make any difference. Bisphosphonates become part of the bone and slowly recycle over time. It takes much longer than two months for bones to remodel. Therefore, many experts do not recommend stopping bisphosphonates for dental procedures.

Drug holidays

Osteoporosis experts recommend a “drug holiday” from bisphosphonates for most people. This temporary cessation is like a vacation, not a retirement, and usually occurs around five years after someone has been taking an oral bisphosphonate and three years after receiving IV bisphosphonates. A drug holiday should be delayed for people with a high risk of broken bones or if their DXA shows worsening bone density. For example, an 80-year-old, 110-pound smoker with an increased risk of falling should wait 7 to 10 years before starting a drug holiday from an oral bisphosphonate or up to 6 years on an IV form. Another option is switching to a different type of medicine, such as Forteo.

Drug holidays are recommended because atypical femur fractures and ONJ are more likely to occur when someone has been taking bisphosphonates for a long time. For example, atypical femur fractures occur five times more often in women who take a bisphosphonate for more than eight years compared to those who take it for less than five years. After stopping the drug, the risk for these fractures rapidly decreases.

The Risks of Drug Holidays

During a drug holiday, though, the risk for osteoporotic fractures gradually increases over time. At years two and three into a drug holiday, the risk for a broken hip is about 40% higher than when stopping the drug.

Bisphosphonate drug holidays are possible because the drug is inside the bones and continues to work after stopping. The drug is recycled as the bones are remodeled (broken down and rebuilt by osteoclasts and osteoblasts, respectively). At the same time, the kidneys slowly get rid of (excrete) some of the recycled medicine. Over time, less of the drug is available, and fracture risk gradually increases. The best-studied drug is alendronate. One out of three patients loses bone density in the first two to three years of the drug holiday off alendronate.

The best time to restart the bisphosphonate is unknown. Most experts agree that this should be done if a DXA worsens during the drug holiday or if new risk factors for broken bones develop. Based on research showing that the longer the drug is stopped, the more fractures occur, some experts routinely restart the medicine after three to five years of a drug holiday. Other experts base their decision on the patient’s urine tests for what is known as bone turnover, or how much the bones are rebuilding themselves. If these labs indicate an increase in bone loss, the doctor restarts the bisphosphonate.

What needs to be monitored while taking bisphosphonates

Your doctor will most likely check blood tests for calcium, vitamin D, and kidney function before and while you are on the drug. Patients can repeat a DXA scan after one to three years to assess the effectiveness of the treatment.

Reasons not to take bisphosphonates (contraindications or precautions)

  • If you have esophagus problems, such as esophageal dysmotility, esophageal strictures, achalasia, or severe hiatal hernia. Most people with gastroesophageal reflux disease can take these safely.
  • If you cannot sit or stand upright for at least 30 minutes after taking the pill forms.
  • If you have persistently low calcium levels.
  • If your kidney function (eGFR or CrCl, chapter 4) is < 30 ml/min. Some studies show that lower doses may be safe.

While taking bisphosphonates, tell your doctor

  • If you get stomach upset, nausea, vomiting, chest pain, or body pain.
  • If you develop an open sore on your gums, especially if the bone is exposed.
  • If you develop thigh or hip pain, your doctor will need to exclude atypical hip fracture.

Pregnancy and breastfeeding while taking bisphosphonates

Bisphosphonates are not recommended during pregnancy. However, case reports of women taking oral bisphosphonates have not shown any problems. IV bisphosphonates should be avoided due to case reports of problems after using them during pregnancy. If the mother does take bisphosphonates the newborn’s calcium level should be checked after delivery. If you are taking a bisphosphonate and wish to become pregnant, it is recommended that you wait six months after stopping it before becoming pregnant.

Women capable of becoming pregnant who need to take a bisphosphonate should use adequate contraception. Note that healthcare professionals consider IUDs as one of the safest and most effective contraceptive methods for women with lupus. Discuss your options with your gynecologist.

Geriatric use of bisphosphonates

No change in dose needed for older people.

What to do with bisphosphonates at the time of surgery

Check with your rheumatologist and surgeon for specific instructions. However, bisphosphonates are generally safe before surgery.


For more in-depth information on bisphosphonates and other osteoporosis drugs in greater detail:

Read chapter 24 of The Lupus Encyclopedia, edition 2

It includes complete, easy-to-understand information on Prolia, Forteo, Tymlos, Evenity, and raloxifene. 

Look up your symptoms, conditions, and medications in the Index of The Lupus Encyclopedia.

If you enjoy the information from The Lupus Encyclopedia, please click the “SUPPORT” button at the top of the page to learn how you can help. 

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