Bisphosphonates are a drugs which prevent the loss of bone density and used to treat osteoporosis and similar diseases. They are the most commonly prescribed drugs used to treat osteoporosis. They are called bisphosphonates because they have two phosphonate PO(OH)2 groups. They are thus also called diphosphonates.
Evidence shows that they reduce the risk of fracture in post-menopausal women with osteoporosis. Bone tissue undergoes constant remodeling and is kept in balance (homeostasis) by osteoblasts creating bone and osteoclasts destroying bone. Bisphosphonates inhibit the digestion of bone by encouraging osteoclasts to undergo apoptosis or cell death, thereby slowing bone loss.
The uses of bisphosphonates include the prevention and treatment of fibrous dysplasia, Paget's disease of bone, osteoporosis, bone metastasis (with or without hypercalcemia), multiple myeloma, osteogenesis imperfecta, primary hyperparathyroidism, and other conditions that exhibit bone fragility.
There are two modes of administration of bisphosphonates: intravenously (IV) and orally.
There is a lot of difference in potency with both modes as with oral administration only 1% of the dose is absorbed by gastrointestinal tract whereas with IV mode more than 50% of the dose administered is bioavailable, which makes IV dose more potent. Intravenous bisphosphonates are used to reduce bone pain, Paget's disease, hypercalcemia of malignancy, myeloma. Oral bisphosphonates are mainly used for the treatment of osteoporosis, osteogenesis imperfecta.
The main mechanism of their action is explained by the fact that bisphosphonates have a high affinity for bone minerals and bind strongly to hydroxyapatite resulting in selective uptake to the target organ and high local concentration in bone, particularly at the sites of active bone remodeling. They act by inhibiting the osteoclast differentiation, reducing their activity, and inducing osteoclast apoptosis.
Although bisphosphonates have been proved beneficial for many metabolic bone diseases but due to their action on osteoclast, they impair bone healing and remodelling and this has resulted in increased risk of development of osteonecrosis of jaw (ONJ) following surgical dental procedures like extraction or implant placement. The basic mechanism of development of osteonecrosis is that due to osteoclastic inhibition necrotic bone cannot be resorbed by the osteoclast during a normal course of healing and the necrotic bone which remains, affects the blood supply to the area. So, the ONJ becomes the major dental complication in patients on bisphosphonate therapy. The risk of developing ONJ increases with the duration the patient has been taking the drugs. The patients receiving IV bisphosphonates are at more risk for development of ONJ then those getting oral bisphosphonates. So it becomes important to identify the patients who are, or will be placed on bisphosphonate therapy so that appropriate precautions or management can be done prior to any dental procedure.
Complications with the therapy
The most common complication in patients on bisphosphonate therapy is osteonecrosis of jaw which occurs after any surgical dental procedure. Although spontaneous cases of osteonecrosis have been reported in the majority of cases (68.8%), patients had a history of dental disease or treatment. According to the information currently available, the risk for developing bisphosphonate-associated osteonecrosis of jaw is higher in patients on IV bisphosphonate therapy than the patients on oral bisphosphonates as orally they are poorly absorbed.
Clinical presentation of bisphosphonate-associated osteonecrosis of jaw
Osteonecrosis of jaw is also known as avascular necrosis of bone or osteochondritis dissecans. It leads to bone pain, loss of bone function and bone destruction resulting in impairment of blood supply. It usually presents as area of exposed bone along with soft tissue swelling, purulent discharge, loosening of teeth and the lesion do not respond to local debridement and antibiotics. Lesion develops around sharp bony area or previous surgical site including extraction, retrograde apicoectomies, periodontal surgery and dental implant surgery. There also may be feeling of numbness, heaviness or dyesthesia of jaw. However, lesion may remain asymptomatic for weeks or months. Occasionally, pain in jaws may be the only symptom without any evidence of radiological abnormality. The lesion may also become secondary infected with actinomyces.
Management of patients on bisphosphonate therapy
The action of bisphosphonate that is of concern to a dentist is that they destroy osteoclast and without osteoclast, there cannot be bone healing which is very important for surgical dental procedures like extraction or implant placement. So management of patients on bisphosphonate therapy prior to any surgical procedure becomes important.
Guidelines for management of patient on bisphosphonate therapy (preventive measures)
All patients should be asked about the current or past use of bisphosphonate drugs and the mode of administration because IV bisphosphonate have a longer half-life and patients on IV mode are at more risk for development of ONJ than patients on oral bisphosphonate.
Patients yet to start with bisphosphonate therapy should be first examined for the requirement of any surgical dental procedures prior to the therapy, if the risk factors allow. Hopeless teeth should be removed. Subgingival scaling should be performed. Poorly fitting dentures should be replaced to avoid soft tissue trauma. Comprehensive treatment should be performed to minimize the need for future dental treatment.
For patients who have already started with the therapy, any elective procedures should be avoided if possible to avoid the risk of bisphosphonate-induced osteonecrosis of jaw. Root canal treatment should be done rather than dental extraction when possible.
The Patient should be routinely examined radiographically for osteonecrosis and baseline data should be recorded for the patient. A Certain laboratory test may help to monitor markers of bone turnover and can help in diagnosis and risk assessment of developing bisphosphonate-associated osteonecrosis. Patients should be educated about the importance of good oral hygiene, regular dental check-ups and also about the symptoms of osteonecrosis of jaw so that patient can report early if the symptoms develop. Patients in which dental extractions are unavoidable should be first consulted with the prescriber of bisphosphonate therapy for possible temporary interruption of drug if beneficial. Extraction should be done as a-traumatically as possible and flap raising should be avoided. A Sterile technique has to be followed. The Patient should be kept on chlorhexidine mouthwash twice daily for two months and postoperatively 2 months follow up should be done. In some cases, it has been recommended to do root canal of the teeth followed by coronal amputation and leave the roots.
Management of patients who have developed ONJ
- If ONJ is suspected then panoramic radiography is recommended to determine the extent of necrosis and the position of sequestrum or osteomyelitis.
- Microbial cultures from the associated soft tissue swelling or purulent discharge should be done to identify any superinfection and the appropriate antimicrobial therapy.
- Any additional dental trauma should be avoided as it may further delay wound healing.
- ONJ should be properly characterized and staging should be done so that appropriate treatment can be done.
Dental implants and bisphosphonate therapy
Implant placement in patients on bisphosphonate therapy predisposes them to development of osteonecrosis of jaw. So prior to planning implants in such patients it is important to identify the type of bisphosphonate (oral or intravenous) they are taking. Various studies have been done to identify the incidence of osteonecrosis in patients on bisphosphonate therapy. Recent studies showed the incidence of osteonecrosis in patients on bisphosphonate therapy.
From the various studies, it has been seen that patients on oral bisphosphonate therapy do not always result in osteonecrosis of jaw but it also depends on the duration of the therapy. The American Association of oral and maxillofacial surgeons do not contraindicate the dental implant placement in patients taking oral bisphosphonates for fewer than three years prior to surgery provide that they do not present with other risk factors such as medication with steroids or advancing age. If the patient has been taking medicine for more than 3 years it has been recommended to stop the medicine for at least 3 months before carrying out any surgical procedure and once the healing is complete the drug can be taken.
Conclusion
Since the introduction of bisphosphonates they have been used to treat multiple bone disorders and cancers. In routine dental practice clinicians come across many patients who are receiving bisphosphonates as part of their therapy.
Most commonly postmenopausal female patient who are receiving bisphosphonates as a treatment for osteoporosis which is very common for their age group, are encountered.
These patients are at increased risk of developing ONJ when any dental treatment is done or patient is suffering from dental disease. So it becomes important to identify such patients and follow a suggested protocol to avoid complications.
It is also important to identify various risk factors for the patient who might develop bisphosphonate induced ONJ prior to any dental procedure.
