Use of lanthanum (III) compounds for enhancing bone formation, inhibiting osteoclastic differentiation and/or activating osteoblastic differentiation to treat bone disease such as osteoporosis

摘要

Enhancing bone formation, inhibiting osteoclastic differentiation and/or activating osteoblastic differentiation to manage, treat or achieve prophylaxis of bone disease comprises administering a lanthanum compound (preferably lanthanum (III)) to a human or animal. An independent claim is included for a composition for the treatment of a bone remodeling disorder comprising the lanthanum (III) compound and a bone enhancing agent. ACTIVITY : Osteopathic; Cytostatic; Antiarthritic; Antirheumatic; Antiinflammatory. MECHANISM OF ACTION : Osteoblast differentiation stimulator; Osteoclast differentiation inhibitor. 8-10 week old mice were killed and tibia and femora were dissected free from adhering soft tissues. The bone ends were cut off and the marrow was flushed with alpha -minimal essential medium (alpha -MEM) supplemented with penicillin (100 IU/ml) and streptomycin (100 Microg/ml). Cells were centrifuged for 10 minutes and the cell pellet was resuspended in alpha -MEM containing 10% fetal calf serum. Cells were then incubated for 2 hours at 370[deg]C. Nonadherent cells were duly removed and the attached bone marrow cells were cultured (1 X 10 6cells/well = 1 ml) for 6 days. Half of the media were changed at day 3 and the treatments replaced. At the end of the culture, the plates were fixed with 2% paraformaldehyde in PBS for 20 minutes. To study the effect of the lanthanum (III) ion on Osteoclast differentiation, the following groups were included: (A) baseline (including vehicle); (B) control (baseline without 1,25-dihydroxyvitamin D3); (C) baseline + 100/500/1000/5000/15000 ng/ml lanthanum. Six replicates were included in each group and the test was performed twice. Osteoclast formation was determined by measuring tartrate-resistant acid phosphate (TRAP) activity from the culture media. Combined results of relative TRAP 5b activities in three osteoclast differentiation assay were as follows: Osteoclast number for A) = 18; B) = 18; C) = 18/12/12/12/12 for 100/500/1000/5000/15000 ng/ml lanthanum respectively; Mean +-SD for A) = 1+-0.36; B) 0.15+-0.07; C) = 0.70+-0.27/0.89+-0.29/0.65+-0.23/0.05+-0.20/0.30+-0.19 for 100/500/1000/5000/15000 ng/ml lanthanum respectively. The above data showed that a clear dose-dependent inhibition was observed with lanthanum (500 - 15000 ng/ml) that was statistically significant from lanthanum (1000 - 15000 ng/ml). A statistically significant inhibition was also observed with lanthanum (100 ng/ml). In the control group where vitamin D was omitted, osteoclast differentiation was significantly lower than in the baseline group.