Basic and patient-oriented research
Serologic Bone Markers for Predicting Development of Osteonecrosis of the Jaw in Patients Receiving Bisphosphonates

https://doi.org/10.1016/j.joms.2010.05.043Get rights and content

Purpose

Osteonecrosis of the jaw is a well-documented side effect of bisphosphonate (BP) use. Attempts have recently been made to predict the development of bisphosphonate-related osteonecrosis of the jaw (BRONJ). We prospectively investigated the predictive value of serum levels of C-terminal telopeptide of collagen I (CTX), bone-specific alkaline phosphatase, and parathyroid hormone for the development of BRONJ.

Patients and Methods

Data on the demographics, comorbidities, and BP treatment were collected from 78 patients scheduled for dentoalveolar surgery. Of the 78 patients, 51 had been treated with oral BPs and 27 had been treated with frequent intravenous infusions of BPs. Blood samples for CTX, bone-specific alkaline phosphatase, and parathyroid hormone measurements were taken preoperatively. Surgery was performed conservatively, and antibiotic medications were prescribed for 7 days.

Results

Of the 78 patients, 4 patients taking oral BPs (7.8%) and 14 receiving intravenous BPs (51.8%) developed BRONJ. A CTX level less than 150 pg/mL was significantly associated with BRONJ development, with an increased odds ratio of 5.268 (P = .004). The bone-specific alkaline phosphatase levels were significantly lower in patients taking oral BPs who developed BRONJ. The parathyroid hormone levels were similar in patients who did and did not develop BRONJ.

Conclusion

The incidence of BRONJ after oral surgery involving bone is greater among patients receiving frequent, intravenous infusions of BPs than among patients taking oral BPs. Although the measurement of serum levels of CTX is not a definitive predictor of the development of BRONJ, it might have an important role in the risk assessment before oral surgery.

Section snippets

Patients

The study population included patients receiving oral or intravenous BP treatment who were referred to the Department of Oral and Maxillofacial Surgery, Sheba Medical Center (Tel Hashomer, Israel) for dentoalveolar surgery from 2007 to 2008. Patients receiving intravenous BPs underwent dentoalveolar surgery only when it was unavoidable. The criteria for study exclusion were a previous diagnosis of BRONJ in the same quadrant of the jaw in which the index surgical procedure was scheduled, a

Patients

A total of 78 consenting patients fulfilled the selection criteria and were included in the present study. Table 1 lists the patient characteristics (gender, age, indication for BP, BP type, and comorbidities).

Bisphosphonate Consumption

Of the 78 patients, 44 (56.4%) had received oral alendronate (70 mg once weekly or 10 mg once daily), 3 (3.9%) had received oral risedronate (35 mg once weekly), and 4 (5.1%) had received the 2 drugs consecutively. The remaining 27 patients had received intravenous BPs: 10 (12.8%),

Discussion

The morbidity of BRONJ, its high incidence among patients receiving frequent intravenous infusions of BPs, and the large number of patients using oral BPs has spurred a vigorous search for predictive and prognostic factors for the development of BRONJ.30, 31 Biochemical markers of bone resorption and bone formation can be used to assess the level of bone turnover.18, 19, 20, 21 Collagen I is an abundant constituent of bone, reaching up to 90% of the organic matrix, and is synthesized primarily

Acknowledgment

The authors thank Prof Amos Buchner for his valuable contribution to the preparation of the manuscript and Mrs Esther Eshkol for editorial assistance.

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