Effects of Indomethacin Administration on Bone Turnover and Bone Mass in Adjuvant-Induced Arthritis in Rats

Abstract

We examined the bone turnover and bone mass in adjuvant-induced arthritis in rats and assessed the effects of indomethacin in this model. One hundred ten SD rats, 6 weeks of age, were assigned to 11 groups and injected with adjuvant or solvent in the right foot. Adjuvant-injected rats were orally administered indomethacin at doses of 0 (vehicle), 0.1 (low), 0.5 (medium), and 1.5 (high) mg/kg body weight from the start (day 0). Animals were sacrificed on days 0, 14 (acute phase), and 28 (chronic phase). In the arthritic-control group, serum osteocalcin level and bone mineral content of the fourth lumbar body (L4) and the femur were significantly reduced on day 14. Serum alkaline-phosphatase was increased on day 28. Trabecular bone volume of L4 was decreased on day 14, and the value was further decreased on day 28. Bone formation rate (BFR/BS) was significantly reduced on day 14, and then osteoclast number (Oc.N/BS) increased on day 28. Indomethacin treatment dose-dependently prevented increases in paw volume and osteoclast number. In the high dose group, these indices were maintained at the same level with those in the normal group. However, indomethacin treatments were not able to maintain the parameters of bone formation such as serum osteocalcin and BFR/BS values, and the trabecular bone mass decrease was only partially prevented. These data clearly indicated both reduced bone formation and increased bone resorption as the causes of bone loss in adjuvant-induced arthritis in rats. Increased bone resorption seemed to be due to the increased activity of prostaglandins, but bone formation defect would be related to other factors in this animal model.

Increased expression of activating factors in large osteoclasts could explain their excessive activity in osteolytic diseases

“…Using an adjuvant arthritis rat model, Xu et al [1996] found that OCs in normal bone express both IL-1R1 and IL-1R2, while OCs in arthritic bone primarily expressed the type I receptor. Assuming that based on the evidence by others [Aota et al, 1996] that OCs in arthritic bone are larger [not reported by Xu et al, 1996], these results would be similar to ours. Our results also parallel those of Wei et al [2005] who showed increased IL-1R1 RNA expression and decreased IL-1R2 expression in bone marrow macrophages differentiated over 4 days of exposure to RANKL.…”

“…Depending on the species, OCs involved in normal bone remodeling contain on average 3-10 nuclei [Piper et al, 1992]. In disease states involving pathological bone loss such as inflammatory arthritis, periodontal disease and Paget's disease, large OCs predominate in the areas of excessive resorption [Arend and Dayer, 1990;Aota et al, 1996;Singer and Roodman, 1996;Smith et al, 1997]. In Paget's disease, OCs have been detected that were 100 mm in diameter and contained up to 100 nuclei [Singer and Roodman, 1996].…”

Anti-Inflammatory and Antioxidant Effects of an Ethanolic Extract of the Aerial Parts of <i>Hilleria latifolia</i> (Lam.) H. Walt. (Phytolaccaceae)

“…The extract, as evidenced from radiological indices (Table 1), at doses of 10 mg kg -1 and 300 mg kg -1 protected against bone loss due to reduced bone formation and increased resorption which are the causes of bone loss in adjuvant-induced arthritis in rats (Aota et al, 1996;Findlay and Haynes, 2005). It is doubtful if this effect is mediated by an immunologic protection of the bones.…”

<i>Trichilia monadelpha</i> Bark Extracts Inhibit Carrageenan-Induced Foot-Oedema in the 7-Day Old Chick and the Oedema Associated with Adjuvant-Induced Arthritis in Rats

“…Also, studies have shown that intraplantar injection of carrageenan in the 7-day-old chick elicits a quantifiable, reliable and relatively short lasting state of oedema, that is differentially attenuated by the administration of typical antiinflammatory compounds (Roach and Sufka, 2003). The rat adjuvant arthritis on the other hand, is the most frequently used model of chronic inflammation for screening NSAIDs, steroids and immunosuppressive drugs (Weichman, 1989;Crofford et al, 1992;Aota et al, 1996).…”