Introduction
Synonym: Diphosphonates Bisphosphonates are chemical compounds that have two phosphate groups and are used as a medicine 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 treatment of Paget’s disease, 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 mucosa. Of this already low proportion, only 20 to 50% ultimately reach the bone and can accumulate there.
The rest is excreted unchanged via the kidneys and the 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 of up to 40% have been observed.
For this reason, strict regulations 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 the intake of bisphosphonates and other medicines.
To improve the absorption of the active ingredient, bisphosphonates should be swallowed with a glass of tap water (this corresponds to about 200ml). Although bisphosphonates accumulate in the organism in such small doses, their medical use has a number of side effects. A not insignificant number of patients suffer from gastrointestinal complaints when taking bisphosphonates. Above all, nausea, vomiting and severe diarrhoea are among the most common side effects of bisphosphonates.
The following side effects may occur:
Since bisphosphonates form complexes with calcium, drugs containing bisphosphonates can cause side effects. For example: Other possible side effects are gastrointestinal complaints (gastrointestinal side effects) such as:
- Low blood calcium levels (hypocalcemia)
- Mineralization defects of the bones up to bone softening (osteomalacia). – Formation of renal insufficiency, especially if the bisphosphonates are administered intravenously too quickly.
- A dreaded complication in treatment with bisphosphonates is the development of necroses in the area of the jawbone (osteonecrosis). A frequent occurrence of atypical fractures of the femur (femoral shaft fractures) during long-term therapy with bisphosphonates has also been reported. – Nausea
- Vomiting
- Abdominal pain
- Diarrhea (diarrhoea)
- Inflammation of the oesophagus (esophagitis), or
- Development of ulcers (ulcerations)
Many patients also develop symptoms while taking bisphosphonates as rare side effects of bisphosphonates are: The risk of these side effects occurring can be reduced by taking them with plenty of fluids and maintaining an upright posture for some time after taking them.
- Headaches
- Swallowing disorders
- Severe itching
- Hair loss (the exact cause is not yet known)
- Skin rash
- Vertigo and
- Blood count changes
Breast cancer is not a side effect of the bisphosphonate therapy but a field 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 supposed to counteract this. Recent studies have also shown that bisphosphonates might prevent cancer cells from spreading further into the bone marrow. So far, there are no major scientific studies that have confirmed the effect of bisphosphonates in the control of tumours in the bone marrow.
Hair loss is not a symptom that is included in the list of possible adverse effects of bisphosphonates. Bisphosphonate-associated pine necrosis is a dreaded side effect of bisphosphonate therapy. The term jaw necrosis refers to the death of the jawbone and soft tissue.
The interaction between the intake of bisphosphonates and an entry port for bacteria in the mouth (i.e. an open wound, e.g. after tooth removal) should lead to an increased incidence of jaw necrosis. Such entry points can be inflammations, but also fresh surgical wounds or small wounds caused by improperly fitted dentures.
The interaction of medication and bacteria is thought to be a possible trigger for the death of part of the jaw bone, the jaw necrosis. In this case parts of the jawbone are exposed and do not heal for weeks. Symptoms such as severe pain, inflammation, the formation of abscesses and fistulas as well as bad breath occur.
In pronounced cases, fractures of the jawbone may occur. Especially patients with certain types of cancer or bone metastases, who are given bisphosphonates as infusions through the vein, have a significantly increased risk of developing jaw necrosis. Therapeutic options include regular mouthwashes, meticulous oral hygiene and local and systemic (throughout the body) antibiotic therapy, but the healing process is often long.
Usually, surgical removal of the dead bone material under general anaesthetic and suturing of the wound is also necessary. In order to prevent necrosis of the jaw as effectively as possible, the dentist should be consulted before starting therapy with bisphosphonates. The dentist can sanitize possible infection foci in the oral area and thus make it more difficult for bacteria to enter.
Regular and careful oral hygiene also plays an important role. Patients who are given bisphosphonates by infusion should note that dental procedures such as tooth removal or implantation should only be carried out after the end of bisphosphonate therapy. Since bisphosphonates are excreted via the kidney sooner or later, their use is not indicated in cases of severe renal dysfunction.
However, this does not apply to all active ingredients. For some, a dose adjustment for renal insufficiency is sufficient. Some of the bisphosphonates, for example zoledronic acid, are toxic to the kidneys. If this preparation is taken by patients with impaired kidney function, the risk of kidney failure is greatly increased.
