Despite the benefits related to the use of bisphosphonates and denosumab, medication-related osteonecrosis of the jaw (MRONJ) is a serious complication. The purpose of this study was to investigate the utility of 4 biochemical markers including serum c-terminal telopeptide cross-link of type I collagen (s-CTX), serum osteocalcin (s-OC), serum parathormon (s-PTH), and serum bone-specific alkaline phosphatase (s-BAP) as useful clinical tools to help assess the risk for MRONJ prior to invasive oral surgery. Twenty patients diagnosed with MRONJ and 20 controls who have been on antiresorptive therapies with no occurrence of MRONJ were included in this 2-arm cross-sectional study. The s-CTX, s-OC, s-PTH, and s-BAP values were measured. Mann-Whitney U test compared the s-CTX, s-OC, s-PTH, and s-BAP values of the MRONJ group and the controls (P < 0.05). Lower values were observed in the MRONJ group compared with the control group for s-CTX (130.00 pg/mL versus 230.0 pg/mL; P = 0.12) and for s-OC (10.6 ng/mL versus 14.80 ng/mL; P = 0.051) both without significance and for s-BAP (0.23 μkat/L versus 0.31 μkat/L; P = 0.002) with significance. By contrast, the median s-PTH value of the MRONJ group was higher (30.65 ng/L versus 25.50 ng/L; P = 0.89), but without significance. The evaluation of the 4 biochemical markers showed that only the value of s-BAP was significantly decreased in the MRONJ patients compared with the controls. Presently, because of the lack of evidence, a routine check prior to oral surgery for the risk assessment of MRONJ cannot be recommended.