Table 2.

JNJ-28312141 inhibited MRMT-1 tumor–induced bone erosions and osteoclastogenesis

Treatment*JNJ-28312141 plasma levels, ng/mLMicroradiograph scoreTrabecular bone volume score§Osteoclast countsTumor volume score§
No cells002.29 ± 0.31--
MRMT + vehicle03.88 ± 0.240.88 ± 0.1358.0 ± 5.63.00 ± 0
MRMT + JNJ-28312141, 20 mpk822 ± 90.75 ± 0.172.00 ± 0.0.23.7 ± 0.71.75 ± 0.48**
MRMT + JNJ-28312141, 60 mpk2470 ± 4430.83 ± 0.182.33 ± 0.232.6 ± 1.51.50 ± 0.55**
MRMT + zoledronate, 0.03 mpk00.38 ± 0.202.63 ± 0.2021.0 ± 3.21.63 ± 0.20

NOTE: Values represent means ± SEM (n = 8).

  • *On day 0, saline (no cells) or saline containing 3 × 104 MRMT-1 rat mammary gland carcinoma cells was injected into the medullary cavity of the right proximal tibia. Twice-daily oral dosing with vehicle or with 20 or 60 mg/kg JNJ-28312141 or once every other day s.c. dosing with 0.03 mg/kg zoledronate commenced on day 3 until sacrifice on day 17.

  • Plasma levels of JNJ-28312141 were determined 2 h after the final dose administration.

  • Values based on five-point visual score described in Materials and Methods.

  • §Values based on three-point visual score described in Materials and Methods.

  • Mean number of TRAP+ cells in three 200× fields where numbers of tumor-associated osteoclasts were greatest.

  • P < 0.01 versus control.

  • **P < 0.05 versus control.