• Avascular Necrosis
  The Disease & The Treatments

What is AVN?

AVN is an acronym for Avascular Necrosis.

What is Avascular Necrosis?

Avascular Necrosis is death of bone tissue due to a temporary or permanent lack of proper blood supply.

Avascular Necrosis and Osteonecrosis are often interchangeably used. Both terms mean bone death secondary to (i.e. because of) a circulatory disturbance.

Our bones constantly renew themselves by way of new bone tissue replacing old bone tissue. In order to grow new tissue, the bones must receive a good flow of oxygenated blood cells.

If the flow of blood to a bone area is disrupted, new bone growth may be stifled, and the bone may begin to die. That process is called Osteonecrosis.

During Osteonecrosis, bone breaks down faster than the body can produce new bone tissue to replace it. As the blood flow diminishes, the joint may develop small hairline fractures, and it may eventually collapse.

Osteonecrosis primarily occurs in the larger and more complex joints. The hip joint is the largest and one of the most complex joints in the body. It is also one of the first joints attacked by AVN. However, AVN can occur in any joint or bone in the body.

What causes Avascular Necrosis?

Avascular Necrosis can have many different causes, including those listed below.

• Idiopathic - unknown cause - about 25% of all cases
• Radiation and other cancer treatments may weaken bones and damage blood vessels
• Steroid (Prednisone) use, including:
  • single blasts of steroids (such as with/for thyroid tests, treatment for multiple sclerosis, or treatment for acute Graft versus Host Disease)
  • any dosage for long term treatment of a chronic ailment
• Blood clots, inflammation, and damage to the vascular system
• Fracture or dislocation of a bone, especially to the thigh bone or hip area
• Alcohol, excessive use of alcohol can increase lipids in the bloodstream
• Aplastic Anemia, Sickle cell anemia, Lupus, Pancreatitis, Immune system diseases, HIV/Aids, Gaucher’s disease
• Diabetes
• Lipids (fat) in the small blood vessels may block blood flow (Note: Prednisone causes and increase in the level of lipids in the blood).
• Bisphosphonates, which are prescribed to increase bone density and used in high doses for treatment of multiple myeloma and metastatic breast cancer, have been identified as a cause of AVN in the jaw
• Organ transplant, such as kidney transplant

For most people in the Graft-versus-Host Disease Group, the most common cause of Avascular Necrosis is the ongoing use of Prednisone. In addition to steroids, most people in the GVHD group may also have an underlying disease, which may have began the bone degradation resulting in AVN, or be a primary cause of AVN. Aplastic Anemia*, for instance, contributes to AVN because it limits, reduces or eliminates the production of blood cells necessary for bone health.

The initial health of a person’s bones can predispose them to AVN or contribute to its progression. As well, AVN can develop in an otherwise healthy bone or joint. An abrupt, hard impact or trauma from a broken bone or dislocated joint can cause AVN in an otherwise healthy bone.

In many (perhaps most) cases, Avascular Necrosis causes are unknown, referred to as idiopathic.

Is Avascular Necrosis Deadly or Life Threatening?

Avascular Necrosis is not considered to be a life-threatening disease.

While Avascular Necrosis is most often caused by use of Prednisone, for a person who has Graft-versus-Host, stopping Prednisone is not an option. Avascular Necrosis isn’t life threatening, but Graft verus Host is life threatening.

What are the symptoms of Avascular Necrosis?

Initially, AVN may cause no symptoms. As the condition worsens, symptoms often range from mild discomfort, which may have an effect on range of motion, up to severe pain, and can be very debilitating.

The discomfort associated with hip AVN ranges from mild discomfort when walking and applying pressure to the hip to very severe pain when walking. It can also affect a person when they are laying at rest, and the pain can range the gambit.

In a study of 18 patients on steroids presented for MRI’s to determination of AVN, two patients had no symptoms at all, but were in advanced stages of AVN.

AVN pain usually develops very slowly. Pain medication is usually required to manage the pain.

Where does Avascular Necrosis occur?

Because of the nature of the disease, AVN most commonly affects the major joints, and usually develops in one hip, or bilaterally (in both hips).

AVN can also develop in the knees, shoulders, hands, ankles, feet, fingers and any bone.

Diagnosis - How is Avascular Necrosis diagnosed?

AVN is often asymptomatic in its early stages. In fact, a study of several patients on high-dose steroids presented for MRI’s revealed that some of those patients had progressed AVN, but were without any symptoms. As the disease progresses however, symptoms usually appear, ranging from mild discomfort to extreme pain. Those symptoms often cause a person to seek medical attention. If you are having continuous joint or bone pain, seek medical attention right away.

In the early stages of Avascular Necrosis, an MRI is usually required to see the minute changes in bone that indicate AVN. In the later stages, doctors can see the bone changes in an x-ray. Doctors may also employ a bone scan for diagnostic purposes, as well as a CT scan.

A common complaint from people with GvHD who take steroids and have AVN is that their doctors do not attend to their complaints about continuous hip or other joint pain, which dismissive attitude is then believed to be the root cause for the person’s loss of their hip.

Due to insurance limitations on treatment, AVN may not be able to be treated until surgical intervention is required. Previously, treatments aside from surgery were unavailable.

Early diagnosis of AVN however can lead to other measures that help with the pain and prolong the time before surgical intervention is required. While some reports identify medications that can arrest AVN, thus being seen as hope to prevent surgery, the ongoing repeated treatments of steroids for people with GvHD almost makes those medications futile attempts. Whole body MRI for diagnosis of AVN: https://www.birpublications.org/doi/full/10.1259/bjr.20180822

In a UK medical journal, we found these cautions:

• Common risk factors for AVNFH are alcoholism, use of steroids, chemotherapy and immunosuppressant medication, and sickle cell anemia
• Consider MRI scan of the hip and referral to an orthopedic team if a patient has a painful hip for longer than six weeks with normal radiographs
• Early treatment improves the chances of hip survival by up to 88% at seven years

Does Avascular Necrosis worsen?

AVN is a progressive disease that can spread from joint to joint by way of bone to bon implicatione. It can be very debilitating. Untreated, Avascular Necrosis will worsen, and the affected bone can eventually splinter, fracture, and eventually collapse. AVN degrades bone tissue, which will result in causing dead spots on previously smooth rotator bones, such as the hip socket. The constant eroding can cause arthritis.

Does Avascular Necrosis spread?

This is an odd question, but it may surprise you to know that doctors have warned us that AVN can indeed spread. It can spread even after the steroid treatment is terminated, and even if the underlying disease is cured, such as a bone marrow transplant might cure Aplastic Anemia.

What is the treatment for Avascular Necrosis?

For people in the GvHD group, treatments may greatly differ for many reasons, including the fact that you may undergo future repeated doses of steroids. The trade-off between steroids and AVN is a no-brainer: AVN is not life threatening; untreated GvHD is life threatening.

A person with Graft-versus-Host Disease may and usually already takes a wide variety of medications. Your transplant doctor or team should handle any changes to your prescribed and over-the-counter medication regime. That said, you might want to discuss the following treatments with them.

• Ibuprofen, Naproxen or similar medication, as a non-steroid anti-inflammatory to relieve inflammation and pain - be sure to ask about these, because there may be concern over the impact of this on your liver
• Bisphosphonates / Disphosphonates: Medications, such as Bisphosphonates, may be used to treat the AVN and build bone. Bisphosphonates are a class of drugs that prevent the loss of bone density. They are the most commonly prescribed drugs used to treat osteoporosis. They are called Bisphosphonates because they have two phosphonate groups. They are also called Disphosphonates. Other Osteoporosis medications, such as Alendronate (Fosamax, Binosto) may also be prescribed. Consult with your transplant doctor. Keep in mind that these drugs have very mixed reviews as to their efficacy, but it worth asking...
• Crestor and like cholesterol medications can reduce the number of lipids and help control your cholesterol, particularly if you are on steroids, which increases fats in the bloodstream if it is believes that your AVN is associated with lipids
• Electrical stimulation - electrodes can be applied to your skin to deliver electrical stimulation to the affected area; this method can also be used during surgery
• Physical therapy - PT can help to improve range of motion, but a therapist is wise, because certain movements can cause more damage to the affected area
• Blood thinners have been used to prevent clots in the vessels
• Cane - if you have issues with your major joints, and you are or have taken Prednisone, a cane may be a very wise choice to prevent a fall or very devastating event, such as a broken hip. A wheelchair may later be necessary, and shouldn’t be avoided, because the trade-off is much more devastating.
• Hip joint injections of a mixture of anesthetic and anti-inflammatory cortisone injected into the hip joint by use of a fluoroscopy go to a great length of relieving the pain. Fluoroscopy is a type of medical imaging that shows a continuous X-ray image on a monitor, much like an X-ray movie. During a fluoroscopy procedure, an X-ray beam passes through the body taking several x-ray images. The injections hurt, but not anywhere near as much as AVN. The injected medication works in three-part stages. First, the initial medication numbs the area relieves the pain within a day or two, but then wears off within a week; several days later, the anti-inflammatory cortisone takes over. The duration of relief is individualistic, ranging from several weeks to many months. A cane should be used during the initial two stages of treatment.

Moving on to more advanced treatments

• Core decompression: Core decompression may be available to you. It involves surgery to remove a portion of the inside layer of the bone, which stimulates growth of new bone tissue.
• Auto-transplant: Rare chronic AVN condition in 15 year old, treated with bone tissue transplanted from one area of the patient to another. Henry Ford Health Systems: When non-operative treatment has failed, proposed treatment options include: simple debridement, curettage with cancellous bone grafting, osteochondral auto graft, arthroplasty, flexion osteotomy, arthrodesis, and replacement. See more at https://scholarlycommons.henryford.com/merf2019caserpt/91/.
• Bilateral Curettage and Impaction Bone Grafting: a medical paper revealed this information: Bisphosponate Therapy failed for a 20-year old man with ALL, diagnosed with AVN in both hips two years post diagnosis of ALL and treatment with chemo and steroids, who then underwent Bilateral Curettage and Impaction Bone Grafting. At an assessment two years after surgery, the patient resumed full weight bearing at 3 months after first surgery, continues to ambulate unrestricted, and remains pain free 3 years post-surgery. See more at: https://www.ncbi.nlm.nih.gov/pubmed/31139921, also published at: https://link.springer.com/article/10.1007/s00256-019-03244-7.
• Regenerative medical treatment encompasses removing dead bone, aspirating bone marrow and combining it with a medical compound that is then inserted where the dead bone was removed. My husband had this done with his back and it was successful. More medical research is likely needed to substantiate this procedure.
• CRFA May Be Effective Treatment For Pain: A pilot case series examined feasibility of anterior radiofrequency approach under combined ultrasound and fluoroscopy guidance to control pain from avascular necrosis of the hip. Patients & methods: Data on 11 consecutive patients were collected on longevity of cooled radiofrequency ablation (CRFA), pain relief and opioid use. Results: The average age was 56 (28–66), BMI 29.5 (16.5–34), in four women and three men. Their average opioids use was 92 mg MS04 equivalents (median 35 mg). The pain score decreased to 3.3 after the CRFA. Five patients claimed more than 50% of pain relief. The average time interval of greater than 50% of pain relief from the CRFA was 70–250 days. Conclusion: CRFA may be an effective treatment of chronic pain from avascular necrosis.
• See more at: Clinical efficacy assessment of cooled radiofrequency ablation of the hip in patients with avascular necrosis, https://www.futuremedicine.com/doi/abs/10.2217/pmt-2018-0083

Avascular Necrosis at other sites than the hip

• Avascular necrosis at sites other than femoral head (AVNOFH)/Non-Femoral AVN is a rare entity. No standard of treatment still exists for treating early stages of AVNOFH with most of the cases eventually progressing to a late arthritic stage needing surgical intervention. That said, Alendronate & Zolendronic Acide May Help - A combination of oral alendronate and intravenous zolendronic acid provides a pragmatic solution to this rare entity of AVNOFH, where no standard treatment exists. See more at: https://josr-online.biomedcentral.com/articles/10.1186/s13018-019-1152-7

Surgery - still undecided?

Surgical intervention results remain significantly successful, even in rare cases of AVN, such as in the shoulder. See more at: https://www.sciencedirect.com/science/article/pii/S1058274618305020.

The successes reportedly continue long term, such as in this report of a hip replacement performed 24 years previous for Avascular Necrosis in a patient with Lupus, an immune disease. See more at: https://www.dl.begellhouse.com/journals/1bef42082d7a0fdf,09743b8d4a5ed3b0,35a4f5a5088b8b7e.html.

Timing of the treatments?

Speaking from the standpoint of underlying life-threatening diseases, if we have learned nothing, we have learned that time waits for no man or woman. You should consult with your doctors to determine the timing of your treatment. If you are however thinking about postponing treatment, think again… consider that you might be so much better off to do all that you can do as soon as you can do it. As well, your life has a very significant probability of improving, and even being free of pain from the necrotic bone tissue. Most people people whom have undergone hip replacements do not regret the surgery, and wish they had done it sooner.

What you can do:

If you have persistent pain in any joint or bone, seek medical attention right away. It may be AVN, but other conditions, including life-threatening conditions, can exist with like symptoms. While AVN is not life threatening, you may be able to extend the life of your bones and ease your pain by seeking medical care.

Is Avascular Necrosis an issue just because you have Graft-versus-Host Disease?

Graft-versus-Host Disease presents issues that must be treated, eliminated or controlled by steroids. Steroids are one of the primary causes of Avascular Necrosis.

Searching For Avascular Necrosis Information

To search for more information, use Google Scholar, https://scholar.google.com. General results in Google search pages contain erroneous information, even from what one might think are reputable pages. Here are some examples:

• Search result says: AVN is caused by a temporary or permanent loss of blood supply. That is not exactly true. The breakdown of bone can be caused by a temporary or permanent loss of blood supply, just as it may also be caused by a diminished blood supply. It is easier to say it that way, but it actually is the death of bone and the lack of new bone because of a lack of good blood flow to the area.
• Search result says: AVN can be cured. Not true. Once bone is dead, it cannot be brought back to life. Bone which has died as a result of Avascular Necrosis can be replaced by artificial devices, which are not bone. Hip replacements, for example, are a treatment, not a cure, and they have a limited shelf life before they, too, must be replaced.

BE A SCHOLAR, USE GOOGLE SCHOLAR (https://scholar.google.com) FOR MEDICAL RESEARCH, or reference Merck Manuals. Merck Manuals are published for doctors and nurses, as well as the public; they are a very reliable source.