This study was designed to compare efficacy of local administration of a nonsteroidal anti-inflammatory drug with systemic administration in patients with osteoarthritis (OA) of the knee. For this purpose, intra-articular tenoxicam and oral tenoxicam therapies were applied and the improvement in control of pain and physical functioning were evaluated. A total of 69 patients with OA of the knee were randomized into three groups. Patients in the first group (41 knees of 23 patients) were treated for 1-3 weeks with once weekly intra-articular injection of tenoxicam 20 mg. Patients in the second group (45 knees of 26 patients) received 20 mg/day tenoxicam orally for 3 weeks and only physical exercises were applied to the third group (32 knees of 20 patients). Physical examination of the knee joint, Western Ontario and McMaster Universities Index and the Lequesne Algofunctional Index were used as outcome measurements at baseline, and the 1st, 3rd and 6th months. More significant improvement in pain and disability parameters was observed in groups 1 and 2 than group 3 compared with baseline measures. Among the patients' responses a few of the differences were statistically significant, more in favour of tenoxicam, and tenoxicam seemed to be superior to exercise alone especially at the final evaluation. There was no significant difference between the oral and intra-articular tenoxicam treatment regimens. The results of this study showed that treatment of OA of the knee with intra-articular tenoxicam is as effective as that with oral tenoxicam. It can be thought that intra-articular administration can be preferred to oral therapy due to minimal possibility of systemic side effects.

In this prospective study, we aimed to evaluate the effect of simvastatin on bone metabolism and the correlation between changes in bone turnover parameters and serum cytokine levels. For this purpose, 38 postmenopausal subjects with hypercholesterolemia (>240 mg/dl), not on osteoporosis treatment, were studied. Simvastatin was started at a dose of 20 mg daily and continued for 3 months. Six patients were excluded from the study during the follow-up period. Pre- and post-treatment samples were analyzed for bone alkaline phosphatase (BAP) and osteocalcin (OCL), as markers of bone formation; for carboxyterminal telopeptide of collagen I (CTX), as a marker of bone resorption; and for interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) cytokine levels. Total cholesterol level was decreased from 262.1 +/- 30.9 to 210.2 +/- 35.6 mg/dl after simvastatin treatment (P < 0.0001). While no significant change was observed in serum CTX level, BAP and OCL levels were significantly increased (from 120.8 +/- 56.6 to 149.5 +/- 57.6 IU/l [P = 0.008], and from 20.8 +/- 12.6 to 34.7 +/- 18.4 microg/l [P = 0.015], respectively). In the analysis of cytokines, while no significant change was observed in IL-6 levels, the TNF-alpha level was found to be significantly decreased after simvastatin treatment (from 77.9 +/- 31.6 pg/ml to 23.5 +/- 12.6 pg/ml [P = 0.021]). Individual changes in TNF-alpha levels showed a moderate negative correlation with the individual changes in BAP and OCL levels (r = -0.550 [P = 0.001], and r = -0.497 [P = 0.004], respectively). In conclusion; 20-mg daily simvastatin treatment for 3 months significantly increased BAP and OCL levels (markers of bone formation) in hypercholesterolemic postmenopausal subjects, without affecting bone resorption. These findings support the idea that simvastatin has an anabolic effect on bone formation. Additionally, the presence of a negative correlation between TNF-alpha levels and the anabolic bone parameters suggests that a cytokine-lowering effect of simvastatin may also be involved in the remodeling process and could exert some additive beneficial effect on bone metabolism.

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