The Risk and Prognostic Factors of Osteonecrosis of the Jaws in Taiwanese Osteoporotic Patients Treated with Oral Alendronate- A Hospital-Based Study
Jang-Jaer Lee
School of Dentistry, National Taiwan University, Taiwan.
Graduate Institute of Clinical Dentistry, National Taiwan University, Taiwan.
Department of Oral and Maxillofacial Surgery, National Taiwan University Hospital, Taiwan.
Background
Although the risk of osteonecrosis of jaws (ONJ) with oral BPs for osteoporosis was very low, the true incidence still remained uncertain. In the past, little studies were focused on the issue for Asian populations. A retrospective study conducted by Sedghizadeh in US showing that most reported ONJ patients on oral alendronate as a treatment for osteoporosis were Asian Americans, which raises concern about the higher prevalence of ONJ in Asians compared with Western populations receiving oral BPs. In addition, compared with risk factors for the occurrence of ONJ, researches on prognostic indicators of the disease are relatively rare, especially in patients receiving oral BPs. We also found that the range of time required for healing of ONJ was quite large according to past studies.Thus I will report the results of my studies on the possible association between ONJ and oral alendronate used for osteoporosis and its absolute and attributable risks in the Taiwanese population. The prognostic factors of ONJ following treatment will also be further surveyed.
Methods
Using an electronic medical records system and manual confirmation of ONJ, we identified patients who began taking alendronate for osteoporosis and developed ONJ between 2000 and 2012 in National Taiwan University Hospital. We further surveyed a cohort of 100 osteoporotic patients with 111 alendronate- related ONJ lesions treated during a 4-year period from 2008 to 2011. Prognostic values of clinical variables and serum markers ofbone turnover were assessed by univariate and multivariate analyses.
Results
The incidence of ONJ associated with alendronate for the management of osteoporosis began after 1 year of drug exposure and progressively increased with longer durations of therapy, specifically from 0.23% to 0.92% as the duration of treatment went from 2 years to 10 years. The overall frequency of ONJ related to alendronate over a 12-year period was 0.55%. The incidence rate of ONJ attributed to alendronate exposure was 283 per 100 000 persons per year. On multivariate Cox proportional analysis, adjusting for the potential confounders, alendronate remains an independent predictor for ONJ occurrence [hazard ratio 7.42 (1.02–54.09)] compared with raloxifene. Advanced age, drug duration, and coexisting diabetes and rheumatoid arthritis are contributing factors to the development of alendronate-related ONJ. Following treatment of alendronate-related ONJ, the cumulativecomplete response rate at 6 months was 48.65%. Serum bone-specific alkaline phosphatase (BSAP) level >10 μg/L, lesion depth≦10 mm, and lesions in anterior regions denoted a better chance of healing within 6 months and the adjusted hazard ratios were 2.48 (95% confidence interval [CI], 1.41–4.37), 2.71 (95% CI, 1.57–4.70), and 3.94 (95% CI, 1.87–8.30), respectively.
Conclusions
We provided the evidence to support the association of ONJ with alendronate used in the treatment or prevention of osteoporosis and the high prevalence of alendronate-related ONJ in Taiwanese population was also found. Early discovery of lesions and prevention of their deeper extension are crucial for improving the prognosis of alendronate-related ONJ. A higher pretreatment level of BSAP indicates a better prognosis.
