FORT LAUDERDALE, FLA. — Serum cathepsin K levels could serve as a useful measure in the management of patients with Paget's disease of bone, Dr. Daniela Merlotti said at a meeting sponsored by the Paget Foundation for Paget's Disease of Bone and Related Disorders.
Cathepsin K, a cysteine protease enzyme, is the most abundantly synthesized protein of the resorbing osteoclast, and plays an important role in the degradation of the organic matrix of bone. Recent studies have suggested that the enzyme may serve as a marker for fracture prediction and bone mineral density (J. Lab. Clin. Med. 2005;146:13–7) and as a parameter for bone metabolism in patients with early rheumatoid arthritis (Arthritis Res. Ther. 2005;7:R65–70), noted Dr. Merlotti of the University of Siena, Italy.
Serum cathepsin K levels were assessed before and after bisphosphonate treatment in 60 patients with Paget's disease and in 50 age-matched controls without the disease. Serum total alkaline phosphatase (ALP), carboxyterminal cross-linked telopeptide of type I collagen (sCTX), and bone-specific ALP were also measured.
At baseline, serum cathepsin K levels were significantly higher in the Paget's disease patients, compared with the controls, and were higher in patients with polyostotic disease than in those with monostotic disease. Baseline cathepsin K correlated positively with sCTX and urinary calcium, but not with total or bone-specific ALP. Similar but weaker correlations were seen in the controls, Dr. Merlotti said.
Overall, intravenous bisphosphonate treatment reduced cathepsin K levels by 28% at 3 days, 34% at 30 days, 45% at 3 months, 29% at 6 months, and 32% at 1 year. At each time point, the reduction in cathepsin K was significantly greater among the 20 patients treated with zoledronate than in the 40 who received pamidronate. With pamidronate, serum cathepsin K levels increased between 3 and 6 months, while on zoledronate the levels decreased continuously.
For the group as a whole, serum ALP dropped by 33% at 30 days and 24% at 90 days, then increased slightly thereafter up to 1 year. However, when examined separately, ALP levels in the zoledronate group continued to drop, while they increased after 6 months with pamidronate. At 6 months, serum ALP had normalized in 88% of the zoledronate patients, compared with just 31% of the pamidronate group, Dr. Merlotti reported.
The evaluation of cathepsin K levels at 3 months predicted the response to bisphosphonate treatment: The Paget's disease patients in whom cathepsin K was decreasing at 3 months had an 18% reduction in total serum ALP levels at 6 months, while those in whom cathepsin K was rising at 3 months showed a 5% increase in total serum ALP at 6 months, she said.
ALP levels in the zoledronate group continued to drop after 6 months but increased with pamidronate. DR. MERLOTTI