Denosumab was the subject of a further MHRA safety alert in February 2013, relating to atypical fractures with long term use
- Drug therapy is only part of osteoporotic fracture management along with Falls assessment, Lifestyle advice and Calcium and Vitamin D supplement
Mode of action
- Denosumab is a human monoclonal antibody (IgG2) that targets RANKL
- Reduces osteoclast activity, and so reduces bone breakdown.
- Osteoporosis in postmenopausal women at increased risk of fractures.
- Metastases to bone usually not prostate cancer where Bisphosphonates would have otherwise been prescribed
- Giant cell tumour of bone.
- Osteoporosis: Denosumab is administered as a single subcutaneous injection into the thigh, abdomen or back of the arm. The recommended dosage is Denosumab 60 mg S/C once every 6 months.
- Bone metastases: Denosumab 120 mg every 4 weeks, supplementation of at least calcium 500 mg and Vitamin D 400 units daily should also be taken unless hypercalcaemia is present, to be administered into the thigh, abdomen or upper arm. Osteonecrosis of the jaw is a well-known and common side-effect in patients receiving Denosumab 120 mg for cancer.
- Supplemental calcium and vitamin D to be given to all patients unless hypercalcaemia is present. Correct pre-existing hypocalcaemia before treatment
- A dental examination and appropriate preventative dentistry before starting treatment are now recommended for all patients having Denosumab 120 mg for cancer-related disease.
- Do not start denosumab in patients with a dental or jaw condition requiring surgery, or in patients who have unhealed lesions from dental or oral surgery
- Monitor for Hypocalcaemia. UTI, upper respiratory tract infection, sciatica, cataracts
- Constipation, rash, pain in extremity and skin infections (predominantly cellulitis).
- Osteonecrosis of the jaw has been reported in patients receiving denosumab or bisphosphonates, with most cases occurring in people with cancer, but some occurred in people with osteoporosis
- During Denosumab treatment, patients should be advised to report new or unusual thigh, hip, or groin pain. Patients presenting with such symptoms should be evaluated for an incomplete femoral fracture. Atypical femoral fractures may occur with little or no trauma in the subtrochanteric and diaphyseal regions of the femur.
- The contralateral femur should be examined in denosumab-treated patients who have sustained a femoral shaft fracture, as atypical femoral fractures are often bilateral (as noted from the bisphosphonates assessment). Discontinuation of denosumab treatment should be considered if an atypical femur fracture is suspected, while the patient is evaluated. An individual assessment of the benefits and risks should be performed