Fingolimod Suppresses Bone Resorption in Patients with Multiple Sclerosis (P2.072)

Objective: To elucidate the effect of fingolimod on bone metabolism in patients with multiple sclerosis (MS). Background: MS patients have an increased risk of osteoporosis, which is based on multiple factors including physical inactivity, glucocorticoid treatment, and inflammatory milieu of the disease. Fingolimod is a sphingosine-1-phosphate receptor agonist used to inhibit the inflammatory disease activity of MS. Interestingly, fingolimod has been shown to suppress bone resorption in a mouse model of osteoporosis by inhibiting the recruitment of osteoclast precursors to the bone. However, its effect on bone metabolism in humans has not been shown. Methods: Serum and urine samples were collected from 29 fingolimod-treated MS patients (fingolimod-MS), 29 untreated MS patients (UT-MS), and 25 healthy controls (HC), and the levels of bone resorption markers [urinary type I collagen cross-linked N-telopeptide (uNTx) and serum tartrate-resistant acid phosphatase (TRACP)-5b] and bone formation markers in serum [bone-specific alkaline phosphatase (BAP) and procollagen type 1 amino-terminal propeptide (P1NP)] were quantified. In addition, changes in bone turnover markers during fingolimod treatment (6.1±4.1 months) were analyzed in 13 MS patients. Results: Fingolimod-MS had a significant lower level of uNTx compared with HC and UT-MS (p<0.05). The levels of TRACP-5b, BAP, and P1NP were comparable among HC, UT-MS, and fingolimod-MS. In the longitudinal study, the level of uNTx decreased by fingolimod except for 3 patients in whom the level of uNTx increased after starting fingolimod. The reduction rate of uNTx after starting fingolimod had a positive correlation with its baseline level (p=0.0029), suggesting that patients with elevated bone resorption responded preferentially to fingolimod. The level of TRACP-5b, BAP, and P1NP did not change after starting fingolimod. Conclusions: Fingolimod suppressed bone resorption in patients with MS; thus, it may have a beneficial effect on bone mass reduction especially in those with increased bone resorption. Disclosure: Dr. Miyazaki has received personal compensation for activities with Mitsubishi Tanabe Pharmaceuticals. Dr. Niino has received personal compensation for activities with Biogen Idec, Bayer Schering Pharma, Asahi Kasei Kuraray Medical Co., Ltd., and Novartis. Dr. Kanazawa has nothing to disclose. Dr. Suzuki has nothing to disclose. Dr. Mizuno has nothing to disclose. Dr. Hisahara has nothing to disclose. Dr. Fukazawa has received personal compensation for activities with Bayer Schering, Biogen Idec, Mitsubishi Tanabe Pharma Corporation, and Novartis. Dr. Takahashi has nothing to disclose. Dr. Amino has nothing to disclose. Dr. Ochi has nothing to disclose. Dr. Minami has nothing to disclose. Dr. Fujiki has nothing to disclose. Dr. Doi has nothing to disclose. Dr. Kikuchi received personal compensation for activities with Novartis Pharma, Boehringer Ingelheim, Kyowa Hakko Kirin, Dainippon Sumitomo Pharma, and FP Pharmaceutical Corporation.