Bone Metabolism Effects of Medical Therapy in Advanced Renal Cell Carcinoma

Area of Science:

• Oncology
• Endocrinology
• Bone Metabolism

Background:

• Advanced renal cell carcinoma (RCC) treatment relies on targeted therapies, including tyrosine kinase inhibitors (TKI) and immune-checkpoint inhibitors (ICI).
• While endocrine adverse events of these therapies are known, their effects on bone metabolism are less understood.
• Bone is a frequent site for RCC metastasis, highlighting the importance of understanding treatment-related bone complications.

Purpose of the Study:

• To review the known and potential effects of TKI and ICI therapies on bone metabolism in advanced RCC patients.
• To highlight specific bone-related adverse events associated with common RCC treatments.
• To emphasize the need for clinical awareness and evaluation of bone health in patients undergoing these therapies.

Main Methods:

• Review of existing literature, including case reports and small case series, focusing on TKI and ICI effects on bone.
• Analysis of documented bone metabolism alterations and complications in advanced RCC patients treated with targeted therapies.

Main Results:

• Sunitinib and sorafenib (TKI) can induce hypophosphatemia, elevated parathyroid hormone (PTH), and low-normal serum calcium.
• Nivolumab and ipilimumab (ICI) are associated with an increased risk of hypocalcemia, potentially via an autoimmune mechanism targeting the calcium-sensing receptor.
• Osteonecrosis of the jaw is a reported complication for both TKI and, rarely, ICI therapies.

Conclusions:

• Targeted therapies for advanced RCC can significantly affect bone metabolism and health.
• Clinicians must be vigilant for endocrine and bone-related adverse events, including hypocalcemia, hypophosphatemia, and osteonecrosis of the jaw.
• Concurrent use of antiresorptive agents may further elevate the risk of these complications, necessitating careful patient management.