地诺单抗要注意什么事项？

(denosumab) is a synthetic, fully humanized monoclonal antibody (IgG2 antibody) that can bind to RNAKL. It has high affinity and specificity for human RANKL. It is the first drug to prevent local osteolysis and bone erosion through anti-bone resorption. It is also the only approved antagonist drug targeting RANKL so far.

In 2009, denosumab was approved by the U.S. Food and Drug Administration (FDA) for the treatment of postmenopausal osteoporosis, the treatment of bone destruction caused by bone metastasis of breast cancer, prostate cancer, and multiple myeloma, and the prevention of severe bone pain and skeletal-related events (SREs) caused by bone metastasis of malignant solid tumors, such as pathological fractures, spinal cord compression syndrome, etc.

What should patients pay attention to when using denosumab?

1. Hypocalcemia. Use of denosumab can cause severe hypocalcemia. Correct pre-existing hypocalcemia before denosumab treatment. Monitor calcium levels and administer calcium, magnesium, and vitamin D as necessary. Monitor levels more frequently when denosumab is administered with other drugs that can also reduce calcium levels. Advise patients to seek medical attention for symptoms of hypocalcemia.

2. According to clinical trials using lower doses of denosumab, patients with creatinine clearance less than 30 mL/min or receiving dialysis are at higher risk of severe hypocalcemia than patients with normal renal function. In a trial of 55 patients, free of cancer and with varying degrees of renal impairment, receiving a single dose of 60 mg denosumab, 8/17 patients had a creatinine clearance less than 30 mL/min or underwent dialysis and had a corrected serum calcium level less than 8.0 mg/dL compared with 0/12 patients with normal renal function. The risk of hypocalcemia with the recommended dosing regimen of 120 mg every 4 weeks has not been evaluated in patients with creatinine clearance less than 30 mL/min or receiving dialysis.

3. Osteonecrosis of the jaw (ONJ). Osteonecrosis of the jaw, manifested by jaw pain, osteomyelitis, osteitis, bone erosion, dental or periodontal infection, toothache, gingival ulceration, or gingival erosion, may occur in recipient patients. Persistent pain or slow healing of the back of the mouth or jawbone from dental surgery may also be signs of ONJ. In clinical trials, ONJ occurred in 2.2% of patients receiving denosumab, and of these patients, 79% had a history of tooth extraction, poor oral hygiene, or use of dental instruments. Perform oral examinations and appropriate preventive dentistry before starting denosumab and periodically during denosumab treatment. Remind patients about oral hygiene habits. Avoid invasive dental procedures during treatment with denosumab.