Widespread bisphosphonate (BP) use to treat various medical conditions led to increased recognition of their possible association with osteonecrosis (ON) of the jaw.[1] BPs are synthetic pyrophosphate analogs used to treat hypercalcemia secondary to malignancy, osteoporosis, multiple myeloma, Paget disease, osteosclerosis, fibrous dysplasia, and other bone diseases in which bone resorption is involved.[2] Infrequent side effects with BP use include pyrexia, renal function impairment, hypocalcemia, and recently recognized avascular ON of the jaw. The American Society of Bone and Mineral Research defined BP-related jaw ON as current or previous treatment with BPs that leads to exposed bone in the maxillofacial region that does not heal within 8 weeks of identification by a healthcare provider, and the patient has no history of radiation therapy in the craniofacial region.[3] Eight weeks is considered because most surgical and infectious sites heal in this time frame even if complications such as post-surgical infection, chemotherapy, or systemic diseases are present.

We present the case of an 81-year-old woman who was followed up by the Rheumatology Service for osteoporosis and treated with bisphosphonates for more than five years. She reported a fracture of the distal third of the contralateral femur by a low energy mechanism, treated with retrograde intramedullary nailing the previous year. She presented a clinic of cruralgia and left gonalgia, without previous trauma. A scintigraphy and radiographs were performed to support the diagnosis of stress fracture of the distal third of the left femur and osteonecrosis of the left internal femoral condyle. Thinking about the possible complications of performing two interventions in an elderly patient, we decided to complete the treatment in a single time and by the same surgical approach, trying to resolve the osteonecrosis and the fracture at the same time, with the objective of an early rehabilitation and lower morbidity. A femoral retrograde prophylactic nailing was performed to stabilize the stress fracture and a retentive primary knee prosthesis was implanted for the posterior cruciate ligament by the same surgical approach. There were no incidents in the immediate postoperative period, with ambulation beginning with help 48 hours after the intervention. The fracture consolidated and the patient presented a good functional result of the knee, both in the immediate postoperative period and at three years of follow-up.

Bisphosphonates are a group of medicines used in the treatment of oncological osteoporosis, Paget disease and osteogenesis imperfecta. They significantly interfere with the regeneration processes of bone tissue and have a tendency to accumulate in the areas of increased bone remodeling, i.e., the maxilla and the mandible. One of their most serious and problematic side effects is the induction of bisphosphonaterelated osteonecrosis of the jaw (BRONJ), characterized by an exposed, necrotic bone in the maxillofacial area, which lasts longer than 8 weeks, in the case of a patient who is using or was using bisphosphonates and who did not undergo radiotherapy in this anatomical area. Dentistry manipulations are one of the factors which may increase the risk of BRONJ occurrence. The existing recommendations for preventing osteonecrosis are ambiguous. Some authors recommend that the bisphosphonate therapy be discontinued prior to dental procedures, while others say that there is no evidence for the effectiveness of interrupting the therapy. There is also no unequivocal attitude toward antibiotic prophylaxis. According to this research, each case should be considered individually, primarily having regard to the good of a patient.

Bisphosphonate-induced osteonecrosis of the jaw (BIONJ) is a commonly encountered side effect of Bisphosphonates (BPs). Although certain aspects of BIONJ have been studied, the effects of BPs on the proliferation, differentiation, and maintenance of dental stem cells (DSC) in way that might account for development of BIONJ have not been evaluated. In the current study, Dental Pulp Stem Cells (DPSCs), Periodontal Stem Cells (PDLSCs), and human Tooth Germ Stem Cells (hTGSCs) were characterized and then each stem cell type were treated with selected BPs: Zoledronate (ZOL), Alendronate (ALE), and Risedronate (RIS). Negative effect on osteogenesis capacity of DSCs has not been observed after differentiation experiments in vitro. BPs exerted inhibitory effect on the migratory capacities of stem cells confirmed by in vitro scratch assay analysis. Angiogenesis of endothelial cells was blocked by BPs treatment in tube formation analysis. In conclusion, inhibitory effects of BPs on migration capacity of DSCs localized in close proximity to the jaw bone might be the primary reason for the side effects of BPs in the development of BIONJ process. Therefore, further in vivo evidence is required to investigate DSC properties in BP treated animals which might elucidate the importance of DSCs in BIONJ formation.

Recently, drugs targeting the remodelling, vascular circulation and homeostasis of bone are frequently applied with an unquestionable benefit in the therapy of numerous severe medical conditions. Besides bisphosphonates, other antiresorptive and antiangiogenic drugs are also used, however, limited publications are focusing on data of their results. Increasing number of patients arrives the mentioned medication is increasing in the daily dental practice, especially when accurate anamnesis is taken. Our aim is to highlight the preventive considerations that help minimize the occurence of medication-related osteonecrosis of the jaw by presentating a complex dental rehabilitation of a patient at risk. The synchronization of dental surgery, conservative and prosthodontic treatment is essential in the case of an elderly patient having many concomitant disorders. Our aim is also to draw the attention of our colleagues working on different medical fields to the timing of dental procedures. The best and simplest way to prevent jaw necrosis is to achieve good oral health and hygiene before the introduction of antiresorptive therapy. If, however, our patient is already taking this medication, we still have a chance to prevent the appearance of this devastating condition by following the preventive measures. The medication-related necrosis of the jaw is a severe condition leading to a decreased life quality and having a reduced healing expectancy. Orv Hetil. 2018; 159(48): 2031-2036.