Osteoporosis - Bisphosphonate Therapy
How is the dental care of patients done during and after administering bisphosphonates?
Bisphosphonates (BP) have been used successfully in certain tumor diseases (multiple myeloma) and in the bone metastasis of other tumors, but also in case of osteoporosis and other bone metabolism disorders for more than 20 years. Even quickly progressing diseases can be treated successfully.
Chemically, BP’s are similar to pyrophosphate, which, among other things, plays a significant role as an autologous regulator in bone mineralization.
The big difference between these two substances is the chemic bond between them; pyrophosphate has a phosphorus-oxygen-phosphorus bond (P-O-P bond), while all BP’s have a phosphorus-carbon-phosphorus bond (P-C-P bond). This bond is more resistant to the enzymatic cleavage of osteolytic cells since BP’s are bound to the hydroxylapatite of the bone; this slows down the resorption of bone by osteoclasts (bone-destroying cells).
Depending on the drug, the half-life period may be between a few months and years. BP’s are administered through the vein or the mouth. The side effect profile has been appraised as favorable for years, while it has only been in recent years that osteonecrosis of the jaw, i.e. non-healing wounds of the jawbone, has been brought to the fore.
At first, it was believed that these are normal wound infections, but a pathogenic contamination of the bone (dentogenic infections) or a jaw-related soft tissue bone wound (tooth extractions, jaw surgeries) could not be found in all patients. Since then, case histories have been accumulating, giving the impression of a progressing disease rate. Based on the scientific case collections, there is a generally strengthening view that a relevant risk for a BP-induced osteonecrosis of the jaw exists in patients who are given high doses of an intravenous BP medication over a longer period of time due to a malignant primary disease.
It is interesting to know that similar osteonecroses of the jaw were already found in the 19th and 20th centuries in factory workers who had been breathing in vapors of yellow and white phosphorus over extended periods in the manufacture of match heads. These osteonecroses of the jaw led to suppurations in the bone – including the formation of fistulas. The smell and the inability to eat normally caused the affected persons to be socially isolated, and, in 20-50% of the sufferers, the osteonecrosis of the jaw led to their death, in part, due to suicide. The ban of yellow phosphorus in the production of matches in 1912, led to the extinction of the disease given the nickname, “phossy jaw” and thus, to the extermination of an occupational disease.
The exact reason for the osteonecroses of the jaw caused by bisphosphonate is still unclear. However, there are clues for a multifactorial etiology – in other words, is it assumed that multiple causes are responsible for the occurrence of this disease. Bad oral care, periodontitis, bad root canal treatments and the foci/fistulas frequently associated with them, certain metabolic diseases such as, for example, diabetes mellitus, might promote the development of the osteonecroses of the jaw! Radiation therapy of jaw metastases while being medicated with BP’s constitutes a particularly high risk.
Besides the factors already mentioned, the individual risk profile is substantially influenced by the type of application of the bisphosphonates (intravenously versus orally), the dosage, the duration of the therapy, and the BP type.
So what does an osteonecrosis of the jaw look like? Osteonecroses of the jaw, which are associated with BP’s, show a clinical and radiological resemblance to normal osteoradionecrosis (ORN), which is caused by excessive radiotherapy. In such cases, too, the leading symptom of the exposed bone is the lack of any tendency to heal. A striking feature in BP-associated osteonecroses of the jaw is the often strong mouth odor (halitosis), which may point to an infection.
There may be a total lack of pathological changes in the X-ray. One conspicuous detail is the radiological and intraoperative findings of “persistent alveoles;” normally, new bone develops within 8-12 weeks of a tooth extraction – but this is not the case in osteonecroses of the jaw. Since BP’s reduce the activity of the osteoclasts and osteoblasts, the overall result is decreased bone remodeling, so that the suspension of reparative and resorptive processes in the alveole becomes quite plausible.
Apart from that, there is often a widening of periodontal gaps. If necessary, further diagnostic measures such as a CT, an MRI, or a scintigraphic examination are indicated. The care concept involves prophylaxis prior to and the early detection during/after a BP therapy, as well as the treatment of manifest BP-associated osteonecroses of the jaw.
Prophylaxis before the administration of bisphosphonates: As long as the pathogenesis of the BP-associated osteonecroses of the jaw has not been further clarified, all patients should be clinically and radiologically examined prior to a BP therapy, and chronically inflammatory processes in the area of the mucosa and the jaw should be rehabilitated. To do so, the doctor prescribing BP’s transfers the patient to a dentist and/or a cranio-maxillofacial surgeon. He will evaluate the individual risk profile (taking into account the abovementioned criteria), conduct a radiological examination, and define a rehabilitation plan – which must consider the following issues:
- Consultation and education about the risk of an osteonecrosis of the jaw before and after a bisphosphonate therapy.
- Rehabilitation of potentially inflammatory processes in the area of the jaw and the oral cavity.
- Smoothing of sharp bone edges.
- Restorative measures on teeth worthy of conservation.
- Intensification of the oral hygiene.
- Check of the patient’s dental prosthesis for the risk of pressure points.
- Integration into a continuous recall.
In this process, invasive prophylactic measures, in particular prophylactic tooth extractions, should be limited to patients with a high risk profile. Therefore, a decision for the removal of teeth is subject to different criteria than in a pre-radiotherapeutic tooth restoration. The decisive aspect regarding the prognosis are not carious lesions on predilection areas (tooth neck, cutting edges), but the periodontal condition. While the bacterial flora in the periodontium has largely returned to normal 1-2 years after a radiological therapy, patients with BP-associated osteonecroses of the jaw mention frequent spontaneous losses or removals of loose teeth.
Therefore, teeth with periodontal damages that cannot be restored in the foreseeable future should be removed prior to beginning the administration of BP’s with a relevant risk profile. In high-risk patients, the tooth restoration should be completed prior to the start of the treatment with BP’s. An interval of 14 days between the restoration and the start of the BP treatment would be desirable here; however, there is very few resilient data in medical literature.
Prevention and early detection during an ongoing bisphosphonate therapy
Patients taking BP medication should regularly report to their dentists every 6 months. In case of discomfort, in particular regarding pressure points due to a dental prosthesis or due to progressively loosening teeth, the dentist must be consulted early. With regard to prevention, preference should be given to the conservative therapy, compared to the operative therapy (in particular in case of periodontal diseases). However, necessary surgical interventions should not be delayed and, in high-risk patients, should be conducted under the same conditions as after a radiological treatment of tumors in the cranio-maxillofacial area.
Regarding this issue, the following recommendations may be given:
- Long-term continuation of the recall (at least every 3 months, in particular prior to a renewed BP infusion or in case of need);
- A detailed instruction and sensitization of the patients so that any corresponding symptoms can be subjected early to a targeted diagnosis and therapy;
- Conservative restoration of changes that may potentially be threatened by an infection;
- Conservative therapy including an individually adjusted intensive oral care and cautious tooth cleaning;
- Early exact endodontic therapy of devitalized teeth;
If surgeries are required: As a rule, interventions are to be conducted by a cranio-maxillofacial surgeon, oral surgeon, or a dentist familiar with the disease pattern, subject to the following provisions:
- If possible, an atraumatic surgical technique is to be used;
- Systemic anti-infective prophylaxis;
- No secondary healing, as is otherwise common in dento-alveolar interventions (tooth extractions!!), but a plastic covering of the wound areas;
- Possibly, epiperiostally prepared cloth for a plastic covering in order to prevent a further reduction in the periosteal provision of the jawbone.
Therapy of the osteonecroses of the jaw associated with BP
An osteonecrosis of the jaw caused by bisphosphonates is difficult to treat; the course of the therapy is uncertain. In case of small findings, a therapy may be attempted with a local revision and/or a long-term open after-care. If this is not successful or if there are extensive findings, a bone resection is required. Currently, the following recommendations apply in such cases:
- Therapy through a surgical facility with the possibility of a treatment under general anesthesia, inpatient care, and parenteral, anti-infective therapy, in which the respective therapy indication is determined by the practitioner;
- Gentle, but complete removal of the necrotic bone – insofar as intraoperatively recognizable – and (obligatory!) histological reconditioning (also to exclude metastases and relapse);
- Safe plastic covering under a tension-free mobilization of sufficient soft tissue or – if required – plastic cloth;
- Mechanical rest of the surgery area (liquid to passed food, possibly nasogastric tube or PEG (percutanous endoscopic gastrostomy));
- Since bisphosphonates may remain tied to the hydroxylapatite of the bone for years, there is, according to current knowledge, no evidence for an interruption of the therapy with bisphosphonates.
Dental implant care of patients with a bisphosphonate therapy
To date, there is only isolated data in the medical literature pointing toward an increased risk profile for the development of a BP-related osteonecrosis of the jaw due to dental implants. A patient, with implants that were already inserted prior to the BP therapy, will surely require intensified follow-up care. It is unknown up to what point in time it is possible to implant safely prior to a planned BP therapy. An implantation at the time on an ongoing BP therapy must be determined individually depending on the existing risk profile (primary disease, type, duration of the administration and dosage of the medication, cofactors, etc.).
As long as there are alternatives, sufficient possibilities for a dental provision, high-risk patients receiving an intravenous administration of BP’s due to a malignant primary disease, should currently abstain from getting implants.
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