Side effects of bisphosphonates

introduction

Synonym: diphosphonates

Bisphosphonates are chemical compounds that have two phosphate groups and are used as a drug to be taken in tablet form or as an infusion solution.

In everyday clinical practice, bisphosphonates are currently the most frequently prescribed drugs for the treatment of osteoporotic bone changes.

In addition to this classic indication area, bisphosphonate-containing drugs, such as alendronic acid or etidronic acid, are used in the therapy of Paget's disease and the treatment of bone metastases and multiple myeloma.

Bisphosphonates generally have a very low bioavailability. After oral administration, only 1 to 10% of the active ingredient is absorbed through the intestinal mucous membranes. Of this already small proportion, ultimately only 20 to 50% reach the bone and can accumulate there. The rest is excreted unchanged via the kidneys and intestines.

In addition, various foods and pharmaceutical substances cause an additional reduction in the amount of bisphosphonate available. In extensive studies, reductions in the bisphosphonate concentration in the range of up to 40% have been observed. For this reason, strict requirements must be observed when taking alendronic acid. Bisphosphonates must be taken on an empty stomach half an hour before breakfast.
In addition, there should be a break of at least 30 to 60 minutes between taking bisphosphonates and other drugs. To improve the absorption of the active ingredient, bisphosphonates should be swallowed with a glass of tap water (this corresponds to about 200 ml).

Although bisphosphonates accumulate in the body in such a small dose, their medical use has a number of side effects. A not insignificant number of patients suffer from discomfort of the gastrointestinal tract when taking bisphosphonates. Above all, nausea, vomiting and severe diarrhea are among the most common side effects of bisphosphonates.

The following side effects could occur:

Because bisphosphonates form complexes with calcium, drugs containing bisphosphonates can cause side effects. For example:

• low blood calcium levels (Hypocalcemia)
• Mineralization defects of the bones up to a softening of the bones (osteomalacia).
• Development of renal insufficiency, especially when the bisphosphonates are administered intravenously too quickly.
• A dreaded complication of treatment with bisphosphonates is the development of necrosis in the area of ​​the jawbone (Osteonecrosis). An increased incidence of atypical thigh fractures (Femoral shaft fractures) reported during long-term therapy with bisphosphonates.

Other possible side effects are gastrointestinal complaints (gastrointestinal side effects) how:

• nausea
• Vomit
• stomach pain
• Diarrhea (Diarrhea)
• Esophagitis (Esophagitis) or
• Formation of ulcers (ulcerations)

Many patients also develop symptoms like while taking bisphosphonates

• a headache
• Difficulty swallowing
• severe itching
• Hair loss (the exact cause is not yet known)

Rare side effects of bisphosphonates are:

• skin rash
• Dizziness and
• Changes in blood count

The risk of these side effects occurring can be reduced by taking with plenty of fluids and maintaining an upright posture for some time after ingestion.

Breast cancer and bisphosphonates

Breast cancer is not a side effect of bisphosphonate therapy but an area of ​​application. Bisphosphonates are often used in patients with breast cancer. Primarily because many women with breast cancer have to undergo hormone treatment, which, however, significantly reduces bone stability. Bisphosphonates are said to counteract this.

Recent studies also provide initial indications that bisphosphonates may prevent cancer cells from spreading further in the bone marrow. So far, however, there are no major scientific studies that have definitely confirmed the effect of bisphosphonates for containing tumors in the bone marrow.

Hair loss with bisphosphonates?

Hair loss is not a symptom on the list of possible adverse effects of bisphosphonates.

Pine necrosis as a side effect of bisphosphonates

Bisphosphonate-associated jaw necrosis is a feared side effect of therapy with bisphosphonates. A jaw necrosis is the death of the jawbone and soft tissue.
The interaction between the intake of bisphosphonates and an entry point for bacteria in the mouth (i.e. an open wound, for example after a tooth was removed) should lead to an increased incidence of pine necrosis. Such entry points can be inflammation, but also fresh surgical wounds or small wounds caused by incorrectly fitting dentures.The interaction between drug and bacterium is believed to be a possible trigger for the death of part of the jawbone, called jaw necrosis.

Here parts of the jawbone are exposed and do not heal for weeks. Symptoms include severe pain, inflammation, abscesses and fistulas, and bad breath. In pronounced cases, fractures of the jawbone can occur.

Especially in patients with certain types of cancer or bone metastases who are given bisphosphonates as infusions through the vein, the risk of developing jaw necrosis is significantly increased.

The main therapeutic options are regular mouthwashes, meticulous oral hygiene and local and systemic (throughout the body) antibiotic therapy, but the healing process is often lengthy. Surgical removal of the dead bone material under general anesthesia and suturing of the wound are usually necessary.
In order to prevent jaw necrosis as effectively as possible, the dentist should be consulted before starting therapy with bisphosphonates. This can clean up any foci of infection in the mouth area and thus make the entry of bacteria more difficult. Regular and careful oral hygiene also plays an important role.

Patients who receive bisphosphonates via infusion should note that dental interventions such as tooth extraction or implantation should only be carried out after the bisphosphonate therapy has ended.

Side effects on the kidney

As bisphosphonates are sooner or later excreted via the kidneys, their use in severe renal impairment is not indicated.

However, this does not apply to all active ingredients. For some, a dose adjustment is sufficient in case of renal insufficiency. Some of the bisphosphonates, for example Zoledronic acid, are toxic to the kidney. If this preparation is taken by patients with impaired kidney function, the risk of kidney failure is very much increased.