Randomized controlled studies on the efficacy of antiarthritic agents in inhibiting cartilage degeneration and pain associated with progression of osteoarthritis in the rat

Table 4 Summary of in vivo results using the MMT/MCLT rat model

	MMT/MCLT model			Results
	Trial 1: systemic delivery (n = 8)			Weight bearing (significant effects; h; p < 0.05)			Histopathology (n = 8)
	Drug (daily)	Dose	Route (1 ml.)	7 days	14 days	21 days	Cartilage degeneration score		Total joint score
1	Saline control	n.a.	i.p.				1.83 ± 0.31		12.29 ± 0.62
2	Morphine	10 mg/kg	i.p.	1	1,3,5	3,5	2.33 ± 0.66		12.96 ± 0.89
3	Tacrolimus	0.3 mg/kg	i.p.	3	0,1,3,5,24	3	0.5 ± 0.15^a		7.13 ± 0.69^b
4	Tacrolimus	0.6 mg/kg	i.p.	–	1	–	0.96 ± 0.27^c		6.96 ± 0.65^b
5	Fluocinolone	0.005 mg/kg	i.p.	5	1,3	1	1.33 ± 0.14		10.75 ± 0.61
6	Fluocinolone	0.010 mg/kg	i.p.	1, 24	1,3,5,24	–	1.96 ± 0.77		10.54 ± 0.88
7	Clonidine	0.100 mg/kg	i.p.	1	1,3,5	3,5,24	1.29 ± 0.20		11.33 ± 0.55
8	Alendronate	10 μg/kg	i.p.	5	1	–	1.79 ± 0.60		11.55 ± 0.72
9	Curcumin	50 mg/kg	p.o.	–	0,1,3,5,24	0, 3	2.21 ± 0.60		12.96 ± 0.62
10	Withaferin	50 mg/kg	p.o.	1	3	–	1.83 ± 0.52		11.83 ± 0.61
	Trial 2: intraarticular delivery (n = 10)			Weight bearing (significant effects)			Histopathology (n = 10)
	Drug (weekly)	Dose	Route (30 μl)	7 days	14 days	21 days	Synovium	Cartilage degeneration score	Total joint score
1	Saline control	n.a.	i.a.			–	–	1.07 ± 0.24	10.23 ± 0.85
2	Clonidine	100 μg/kg	s.c.	+/−	+/−	+/−	+/−	0.77 ± 0.28	11.03 ± 0.61
3	Clonidine	4.5 μg	i.a.	–	–	–	–	0.67 ± 0.23	9.13 ± 0.54
4	Triamcinolone H	0.15 mg	i.a.	–	–	–	+	2.03 ± 0.52	11.30 ± 1.21
5	Tacrolimus	15 ng	i.a.	–	–	–	–	0.87 ± 0.36	8.60 ± 0.63
6	Tacrolimus	30 ng	i.a.	–	–	–	–	0.8 ± 0.19	8.90 ± 0.66
7	Fluocinolone	15 ng	i.a.	–	–	–	–	0.8 ± 0.25	9.80 ± 0.51
8	Curcumin	30 μg	i.a.	–	–	–	–	1.63 ± 0.61	9.57 ± 0.91

n.a. not applicable, i.a. intraarticular, s.c. subcutaneous, MMT/MCLT medial meniscal tear/medial collateral ligament tear. −24 = worse at 24 h; “Pretrt” refers to an effect on pain that is measurable before dosing
The details of the related studies and results are provided in Additional file 1. In trial 1, drug administration was prophylactic in that test articles were administered subcutaneously daily for 3 weeks beginning 1 day before surgery. In trial 2, drug administration was therapeutic in that drugs were administered weekly beginning 1 week after surgery. For weight bearing, shown are hours after drug delivery when a statistically measurable effect (p ≤ 0.05) was observed compared with the pretreatment baseline of that day, unless noted otherwise. With regard to histopathological measurements, medial femur cartilage degeneration and total joint score are noted. The scores approach 0 with improvement. The mean osteophyte score for each joint was added to the total cartilage degeneration score to create a total joint score. Additional measures of tibial cartilage, bone and synovial changes as well as details of statistical analysis are provided in Additional file 1
^a p ≤ 0.005 compared with vehicle alone
^b p ≤ 0.001 compared with vehicle alone
^c p ≤ 0.05 compared with vehicle alone

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