Bisphosphonate-associated Bone Necrosis: Causes, Symptoms & Treatment

Bisphosphonate-associated bone necrosis is necrosis of bone that occurs as a result of treatment with bisphosphonates. In the majority of cases, bone necrosis occurs after treatment by a dentist or orthodontist after bisphosphonates have been used. Therefore, bisphosphonate-associated bone necrosis of the jaw is particularly common. In addition, spontaneous bisphosphonate-associated bone necrosis is possible.

What is bisphosphonate-associated bone necrosis?

Bisphosphonate-associated bone necrosis results from the medicinal agents in bisphosphonates. Bisphosphonates are substances that inhibit the breakdown of bone. For this reason, they are used, for example, as drugs for osteoporosis or metastases of the bones. They have a strong affinity effect on the surface of the bones and impair the osteoclasts. As a result, the resorption of the bones is reduced. If the breakdown of bone substance is accelerated, for example, by osteoporosis or metastases to the bones, bisphophonates inhibit this breakdown and thus counteract the disease. Therapy with bisphosphonates also briefly increases the density of the bone substance. The half-life of bisphosphonates inside the bone is extraordinarily long, sometimes exceeding ten years. This requires strict standards in the medical use of bisphosphonates. Currently, bisphosphonates are mainly approved for the treatment of metastases to bone and osteoporosis after menopause.

Causes

The exact mechanisms of development of bisphosphonate-associated bone necrosis are currently unclear. Research is also still needed regarding the pathogenesis in people receiving bisphosphonates as part of systemic treatment. Some physicians suspect a connection to the inhibition of osteoclasts and osteoblasts. This may lead to a depression of osteoblasts, so that the bone’s ability to regenerate decreases. Meanwhile, bisphosphonate-associated bone necrosis is a significant problem for medicine. Especially in people with cancer, bisphosphonate-associated bone necrosis develops in nearly 20 percent of cases after intravenous administration of bisphosphonates. In benign conditions such as osteoporosis, the risk of bisphosphonate-associated bone necrosis is only 0.1 percent.

Symptoms, complaints, and signs

In bisphosphonate-associated bone necrosis, necrotic areas develop on the bones of diseased patients. The disease is sometimes severe, and the individual course of bisphosphonate-associated bone necrosis varies widely in each case and also depends on the underlying disease. People suffering from cancer and taking immunosuppressive drugs are at particular risk of bisphosphonate-associated bone necrosis. Basically, bisphosphonate-associated bone necrosis occurs mainly in association with amino-bisphosphonates that are injected intravenously by the physician.

Diagnosis and course

The diagnosis of bisphosphonate-associated bone necrosis is made by a specialist. The history focuses on discussion of the patient’s underlying diseases and any past treatment with bisphosphonates. When making the diagnosis, it should be noted that bisphosphonate-associated

bone necrosis may develop some time after bisphosphonate administration. This fact is due to the long half-life of bisphosphonates in the substance of the bone. For this reason, a thorough history is essential at the beginning of the diagnosis of bisphosphonate-associated bone necrosis. The clinical examination of the diseased person is based on various procedures. For example, the physician measures bone density and uses imaging methods of the bones. X-ray or MRI examinations are possible, for example. In addition, the treating physician may perform punctures on the bone and order a laboratory analysis of the tissue samples obtained. In general, blood analyses also play an important role in the diagnosis of bisphosphonate-associated bone necrosis.

Complications

Bisphosphonate-associated bone necrosis is a very serious disease.The further course and complications depend strongly on the underlying disease. In most cases, a diagnosis can be made relatively quickly so that treatment can be started early. A blood analysis is also performed. Treatment is primarily aimed at adjusting the medication. Thus, the symptoms can be stopped and limited and the disease does not spread any further. If the affected person is expected to undergo another surgical procedure, antibiotics are used instead. In this case, the surgery is done with great care so that there is no trauma to the affected area. Should the disease occur in a cancer patient, the treatment must be discussed with a physician, since the use of bisphospahte inhibits the degradation of the bones, but contributes to the disease. Unfortunately, a direct and causal treatment of this disease is not possible. The life expectancy is greatly reduced. As a rule, this is based on the expectation due to the tumor. During the treatment, the patient does not experience any other complications directly caused by the treatment.

When should you go to the doctor?

In the case of this complaint, a doctor must be consulted immediately. As a rule, self-healing does not occur in this case, so that an improvement of the complaints is only possible by discontinuing or changing the respective medication. However, this should always be done only after a doctor’s instructions. As a rule, the doctor should be consulted when bone necrosis occurs. Above all, the affected person must consult a doctor if there is severe pain or if there are clear restrictions in everyday life and movement. This also applies to patients who have cancer and for this reason take medication that can lead to bone necrosis. In most cases, the diagnosis and treatment of this disease is performed by a specialist. X-rays or MRI scans are necessary for this. The further treatment depends strongly on the basic disease and is also carried out by a specialist. Whether this will result in a completely positive course cannot be universally predicted.

Treatment and therapy

The options for therapy of bisphosphonate-associated bone necrosis have been relatively limited. For now, the most important approach to therapy for bisphosphonate-associated bone necrosis is to discontinue the administration of bisphosphonates. If surgical procedures are required in bisphosphonate-treated patients, individuals receive antibiotics. In addition, doctors try to cause as little trauma as possible in the operated areas. Generally, it is recommended that therapeutic measures and follow-ups of bisphosphonate-associated bone necrosis be performed in appropriate specialized medical centers. If bisphosphonate-associated bone necrosis occurs in cancer patients, further therapy of bone metastases must be weighed against the disease. This is because the use of bisphosphonates inhibits the breakdown of bone substance, but at the same time leads to the development of bisphosphonate-associated bone necrosis. Since the exact causes of the development of bisphosphonate-associated bone necrosis are not yet precisely known, adequate treatment options are also lacking. However, medical researchers are busy developing agents and procedures against bisphosphonate-associated bone necrosis.

Prospect and prognosis

The prospects for cure of bisphosphonate-associated bone necrosis are very low. Despite medical advances, researchers and scientists have not yet succeeded in finding a sufficient treatment to cure the disease. Bisphosphonate-associated bone necrosis has a progressive disease course that cannot be stopped. Without medical care, continuous bone loss occurs in the patient. Further complaints occur, which make the patient’s everyday life very difficult. Medical care is used to try to slow down the progress of the disease. In addition, accompanying symptoms are treated. This significantly increases the well-being of the person affected. A very unfavorable course can be observed in patients with cancer. Due to the treatment as well as the cancer therapy, the organism of the patient is very weakened.This further minimizes the prospects of alleviating the symptoms of bisphosphonate-associated bone necrosis. If the underlying disease is mild, the patient is in good health, and the diagnosis is made early and the treatment of bone necrosis is started as soon as possible, the best chances for an improvement in the state of health exist. The organism can be optimally cared for with various medications in order to contain the progress of the disease as much as possible. Although a cure is not possible, in some patients this succeeds in stopping the deterioration.

Prevention

Medical researchers have identified several risk factors to prevent bisphosphonate-associated bone necrosis. Necrosis of the jaw bones occurs in cancer patients, especially at high doses of the agents. Lesions develop exclusively with drugs containing nitrogen. The risk of bisphosphonate-associated bone necrosis is reduced when individuals take bisphosphonates in the form of tablets rather than injections. In contrast, intravenous administration increases the likelihood of bisphosphonate-associated bone necrosis. Performing highly invasive dental therapy procedures such as implant placement, tooth extraction, or root canal treatments also increase the risk of disease. If dental treatment is required, its completion prior to therapy with intravenous bisphosphonates is prudent.

Follow-up care

Follow-up care is usually not available for this condition. Affected individuals are dependent on therapy, and complete cure of the disease is not possible. Since the symptoms can be limited with the help of antibiotics, the patient should be careful to take the medication regularly and also be aware of possible interactions with other medications. If the disease is caused by a tumor, regular examinations should be performed in order to identify and treat further tumors quickly and at an early stage. The life expectancy of the affected person is very often significantly limited with this disease. Since the disease can often also lead to psychological discomfort, psychological counseling during treatment is very useful. Contact with other sufferers of the disease can also prove useful and lead to an exchange of information. Often, the patient’s relatives also need psychological treatment. If the disease is treated by surgery, care must be taken to ensure that the patient recovers sufficiently after the procedure. Wounds must heal completely, and the surgery itself must not cause other damage to the body to avoid further trauma.

What you can do yourself

Bisphosphonate-associated bone necrosis is a condition that requires treatment. Self-help measures cannot achieve sufficient relief of symptoms. Therefore, the affected person should discuss the symptoms and changes in cooperation with a trusted physician. Since medication is initially administered to alleviate the symptoms, side effects and changes should be taken into account. Under no circumstances should the medication be changed or discontinued on the patient’s own responsibility. Consumption of alcohol should be avoided, as the organism is overtaxed by the active ingredients of the medication and complications arise. These considerably worsen the quality of life and cause delays in the healing process. If surgical intervention is necessary, risk factors should be reduced in advance. Stress should be avoided and well-being should be promoted. A balanced and healthy diet can stabilize the body’s immune system. This is of immense importance in the healing process and especially after surgery. The consumption of harmful substances such as nicotine, drugs or caffeine should be avoided. They delay the recovery of the affected person and also trigger complications. If the bone necrosis appears in the area of the jaw, sufficient dental care must be carried out despite all adversities. Together with a dentist, the optimal care of the mouth should be discussed so that no secondary diseases are triggered.