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Long-Term Bisphosphonate Treatment of Bone Metastases From Renal Cell Carcinoma

Massachusetts General Hospital, Boston, MA

To the Editor:

About one third of patients with metastatic renal cell carcinoma (RCC) suffer from bone metastases.¹ Skeletal complications include pain, pathologic fractures, impending fractures requiring surgical intervention or radiation, hypercalcemia, and spinal cord compression. Recently, the potent bisphosphonate zoledronic acid was shown to reduce skeletal complications from RCC.² In this letter, we report on a patient with dramatic clinical and radiographic improvement in bone metastases from bisphosphonate therapy.

A 66-year-old man with a medical history of obesity and type 2 diabetes mellitus underwent radical nephrectomy for a stage pT3bN0M0 clear-cell RCC in May 1999. In January 2001, he presented with pain and immobility in his right thigh and left arm, and was found to have multiple new bone metastases with pathologic fractures of the distal right femur and the left humeral head. There was marked osteopenia in the bone adjacent to the metastases. He was treated with palliative external-beam radiation therapy to both fracture sites and narcotic analgesics. Concurrently, monthly intravenous therapy with pamidronate was started. Therapy was changed to 4 mg zoledronic acid every 4 weeks after use of this agent was approved. There was dramatic improvement in the patient’s symptoms and functional capacity during the next 12 months. At the time of initial diagnosis of metastases, he was completely confined to a wheelchair due to pain in the right leg. After 9 months of therapy, he regained the ability to walk short distances and was able to navigate around his home without the use of a wheelchair. Narcotics were no longer required for pain control.

Cross-sectional imaging of the bone metastases 6 months after initiation of bisphosphonate therapy demonstrated interval sclerosis of the bone lesions. Since that time, the clinical and radiographic benefit has continued (Fig 1), and the patient remains stable on bisphosphonate therapy nearly 3 years later. Osteopenia in neighboring bone has resolved. He was not treated at any point with other forms of systemic therapy. Plain x-ray films of the femur and humerus have demonstrated healing fractures, and no new sites of skeletal metastases have been identified since January 2001.

View larger version (83K): [in this window] [in a new window]   Fig 1. A lytic lesion in the right ischium (arrow) first seen in January 2001 (A), demonstrates marked interval sclerosis by March 2003 (B). This lesion was not treated with radiation or any form of therapy other than bisphosphonates. Adjacent areas of bone demonstrate similar improvement in osteopenia.

Authors’ Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Zekri J, Ahmed N, Coleman RE, et al: The skeletal metastatic complications of renal cell carcinoma. Int J Oncol 19: 379-382, 2001[Medline]

2. Lipton A, Zheng M, Seaman J: Zoledronic acid delays the onset of skeletal-related events and progression of skeletal disease in patients with advanced renal cell carcinoma. Cancer 98: 962-969, 2003[CrossRef][Medline]

3. Negrier S, Escudier B, Gomez F, et al: Prognostic factors of survival and rapid progression in 782 patients with metastatic renal carcinomas treated by cytokines: A report from the Groupe Francais d’Immunotherapie. Ann Oncol 13: 1460-1468, 2002[Abstract/Free Full Text]

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Michaelson, M. D. Articles by Smith, M. R. Search for Related Content PubMed PubMed Citation Articles by Michaelson, M. D. Articles by Smith, M. R. Social Bookmarking                            What's this?