Pre-emptive, early, and delayed alendronate treatment in a rat model of knee osteoarthritis: effect on subchondral trabecular bone microarchitecture and.

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Presentation transcript:

Pre-emptive, early, and delayed alendronate treatment in a rat model of knee osteoarthritis: effect on subchondral trabecular bone microarchitecture and cartilage degradation of the tibia, bone/cartilage turnover, and joint discomfort G. Mohan, E. Perilli, I.H. Parkinson, J.M. Humphries, N.L. Fazzalari, J.S. Kuliwaba Osteoarthritis and Cartilage Volume 21, Issue 10, Pages 1595-1604 (October 2013) DOI: 10.1016/j.joca.2013.06.020 Copyright © 2013 Osteoarthritis Research Society International Terms and Conditions

Fig. 1 Effect of pre-emptive ALN treatment on tibial subchondral trabecular bone after 2 weeks of ALN treatment initiation. Histomorphometric parameters of the MIA-injected knee from the OA and the ALN groups and the right knee of the control group are shown. Results are reported as mean ± 95% confidence intervals. *P < 0.05, **P < 0.001, and ***P < 0.0001. Osteoarthritis and Cartilage 2013 21, 1595-1604DOI: (10.1016/j.joca.2013.06.020) Copyright © 2013 Osteoarthritis Research Society International Terms and Conditions

Fig. 2 Effect of early ALN treatment (started 2 weeks after OA induction) on tibial subchondral trabecular bone. Histomorphometric parameters of the MIA-injected knee from the OA and the ALN groups and the right knee of the control group are shown. Results are reported as mean ± 95% confidence intervals. # Measurement after ALN treatment initiation. *P < 0.05, **P < 0.001, and ***P < 0.0001. Osteoarthritis and Cartilage 2013 21, 1595-1604DOI: (10.1016/j.joca.2013.06.020) Copyright © 2013 Osteoarthritis Research Society International Terms and Conditions

Fig. 3 Effect of delayed ALN treatment (started 6 weeks after OA induction) on tibial subchondral trabecular bone. Histomorphometric parameters of the MIA-injected knee from the OA and the ALN groups and the right knee of the control group are shown. Results are reported as mean ± 95% confidence intervals. # Measurement after ALN treatment initiation. *P < 0.05, **P < 0.001, and ***P < 0.0001. Osteoarthritis and Cartilage 2013 21, 1595-1604DOI: (10.1016/j.joca.2013.06.020) Copyright © 2013 Osteoarthritis Research Society International Terms and Conditions

Fig. 4 Effect of pre-emptive ALN treatment on rat HLWB. Pre-emptive ALN effectively prevented decreased weight-bearing of the OA knee on day 1, 3 and 5 after MIA injection. Results are reported as mean ± 95% confidence intervals. a = HLWB difference over time compared to baseline value of the OA group (P < 0.001 for day 1 and 3 and P < 0.05 for day 5 and 7 respectively). b = OA vs control (P < 0.05). *P < 0.05 OA vs ALN, ***P < 0.001 OA vs ALN. Osteoarthritis and Cartilage 2013 21, 1595-1604DOI: (10.1016/j.joca.2013.06.020) Copyright © 2013 Osteoarthritis Research Society International Terms and Conditions

Fig. 5 Articular cartilage and subchondral bone of medial tibial plateau from control, OA, and ALN treatment groups after 2, 6, and 10 weeks (right tibia). Progressive cartilage degradation was evident in the OA group. Loss of trabeculae was observed after 2 weeks (square) followed by subchondral bone sclerosis after 6 and 10 weeks. Progressive osteophyte formation (arrow) was evident at 2, 6, and 10 weeks after OA induction. In the pre-emptive ALN treatment group there were less severe proteoglycan loss and less chondrocyte necrosis compared to the OA group. Pre-emptive treatment did not have a significant effect on the cartilage or osteophyte formation; however it prevented loss of subchondral trabeculae. Early ALN treatment (treatment started 2 weeks after OA induction) and delayed ALN treatment (treatment started 6 weeks after OA induction) did not prevent cartilage degradation or subchondral bone sclerosis. However, in the early ALN treatment group the osteophytes were in the form of cartilaginous outgrowths without bony transformation. Original magnification 40×. Osteoarthritis and Cartilage 2013 21, 1595-1604DOI: (10.1016/j.joca.2013.06.020) Copyright © 2013 Osteoarthritis Research Society International Terms and Conditions

Fig. 6 (A) OARSI scores of OA, pre-emptive ALN, early ALN, and delayed ALN groups. ALN treatment did not have a significant effect on OARSI score. Results are reported as mean ± 95% confidence intervals. (B) Tibial subchondral trabecular bone MAR of OA, pre-emptive, early ALN, and delayed ALN groups. In the OA group, MAR was significantly increased at 2 weeks compared to, 6 and 10 weeks after OA induction. Pre-emptive ALN treatment significantly decreased MAR whereas; early ALN and delayed ALN treatment did not have a significant effect on MAR. Results are reported as mean ± 95% confidence intervals. **P < 0.01. Osteoarthritis and Cartilage 2013 21, 1595-1604DOI: (10.1016/j.joca.2013.06.020) Copyright © 2013 Osteoarthritis Research Society International Terms and Conditions

Fig. 7 Serum COMP, CTX-I, and urine CTX-II levels of the OA group, pre-emptive ALN, early ALN, delayed ALN treatment groups and control group. The pre-emptive, early, and delayed ALN treatment did not have a significant effect on serum COMP and urine CTX-II levels. However, they significantly suppressed serum CTX-I levels observed in the OA group. Results are reported as mean ± 95% confidence intervals. *P < 0.05 and **P < 0.01. Osteoarthritis and Cartilage 2013 21, 1595-1604DOI: (10.1016/j.joca.2013.06.020) Copyright © 2013 Osteoarthritis Research Society International Terms and Conditions