Introduction: Denosumab is used to treat osteoporosis in postmenopausal women, to increase bone mass in men with osteoporosis, and to treat bone loss in people receiving certain cancer treatments. It works by binding to a protein called RANKL, which is involved in the development and activity of osteoclasts (cells that break down bone tissue), thus reducing bone loss. Denosumab has been approved by the US Food and Drug Administration (FDA) for the treatment of bone loss and skeletal-related events in patients with advanced carcinoma of the breast. This is because breast cancer cells can spread to the bone and cause bone destruction, leading to pain and increased risk of fractures.
Dosage: Denosumab is usually given as a subcutaneous injection every 4 weeks, and treatment may continue as long as it is clinically beneficial.
Uses: Denosumab can help reduce the risk of skeletal-related events in patients with breast cancer, including bone fractures, spinal cord compression, and the need for radiation or surgery to the bone. In addition to its effects on bone, denosumab has also been shown to have anti-tumor effects, although the exact mechanism is not fully understood.
Adverse Effects: Common side effects include back pain, joint pain, muscle pain, and high cholesterol levels. Less common but more serious side effects may include infections, skin rash, and bone damage in the jaw (osteonecrosis).
The most rare complication of denosumab is Gave (0.6%). While the exact mechanism by which denosumab causes GAVE is not fully understood, it is thought to be related to the drug’s effects on bone metabolism and its impact on the regulation of blood vessel growth.
GAVE is a condition characterized by the dilation and enlargement of blood vessels in the stomach lining, leading to chronic gastrointestinal bleeding. It specifically involves abnormally widened small blood vessels in the pyloric antrum, the lower portion of the stomach, which are the primary source of the intestinal bleeding. It is also called watermelon stomach because streaky long red areas that are present in the stomach may resemble the markings on watermelon. GAVE is associated with a number of conditions, including portal hypertension, chronic kidney disease, and cirrhosis of liver. Most patients with GAVE have underlying conditions such as liver cirrhosis, autoimmune disorders, chronic kidney failure, or a history of bone marrow transplantation. Initial symptoms typically range from occult bleeding leading to transfusion-dependent chronic iron-deficiency anemia to episodes of severe acute gastrointestinal bleeding.
Case Discussion: A 67 year-old-female is case of Left Carcinoma of breast stage IV – on chemotherapy – Denosumab – came with complaints of melena for 20 days. Her hemoglobin was 5.9 gms/dl and stool occult blood was positive. Her hemoglobin was grossly dropped from 11.1 gms/dl to 9.3 gms/dl within one month. And further dropped to 5.9 gms/dl within 20 days. She was planned for endoscopy which showed severe Gastric Antral Vascular Angioectasia (GAVE) planned for Argon Plasma Coagulation (APC).
As a complete of the study, her colonoscopy was normal upto terminal ileum. After 1 unit of PRBC transfusion, APC was done along the GAVE and Adrenaline therapy was done along multiple superficial ulcers in D2.
After the endoscopic interventions, she was conservatively managed with octreotide- LAR 30 mg intramuscularly once a month. Portal venous doppler showed normal portal venous flow, no thrombus seen in IVC. After 2 weeks, her stool occult blood was negative.
Hence it is a rare but known complication associated with the use of denosumab. Cases of GAVE have been reported in patients receiving denosumab for the treatment of osteoporosis, as well as in patients with advanced cancer who are receiving denosumab to prevent skeletal-related events. If a patient develops symptoms such as abdominal pain, vomiting, or dark, tarry stools while receiving denosumab, GAVE should be considered as a possible cause and appropriate diagnostic testing and treatment should be initiated.
Dr. S. Vadivel Kumaran Senior Consultant Gastroenterologist Kauvery Hospital Chennai
Miss. Kiruba Nandhini Physician Assistant Kauvery Hospital Chennai
