Non-steroidal anti-inflammatory drugs and bone healing in animal models—a systematic review and meta-analysis

Table 3 Meta-analysis based on several subgroups showing the effect of NSAID administration on bone volume measurements (histomorphometric analysis) of healing bones after fracture

Histomorphometric NSAID vs control
Subgroup	N	SZ NSAID	SZ C.	SMD	95% CI	P effect(adj. P value)	Q statistic	P within heterog.	I²%	P between heterog.
Overall	33	171	115	− 0.16	[− 0.49, 0.17]	0.341	70.55	< 0.001	54.64	–
Species
Dogs	2	12	12	NA	NA	NA	NA	NA	NA	0.026^a
Rats ^a	19	123	79	− 0.50	[− 0.91, − 0.10]	0.013(0.039)	13.26	0.77	0
Rabbits	12	36	24	0.42	[− 0.14, 0.98]	0.143(0.143)	19.18	0.058	42.65
Sex
Female	6	44	43	− 0.14	[− 0.92, 0.72]	0.723(1.08)	28.42	< 0.001	82.4	0.986
Male	23	106	52	− 0.17	[− 0.60, 0.25]	0.427(0.64)	41.66	0.007	47.19
Not mentioned	4	21	20	− .087	[− 1.01, 0.84]	0.854(0.854)	0.01	1	0
Age/weeks
< 8	0	NA	NA	NA	NA	NA	NA	NA	NA	0.426
8–16	6	24	12	− 0.60	[− 1.43, 0.22]	0.153(0.612)	2.45	0.783	0
> 16	2	12	12	NA	NA	NA	NA	NA	NA
Not mentioned	25	135	91	− 0.09	[− 0.48, 0.29]	0.63(0.63)	38.63	0.03	37.87
Type of NSAID
NS-COX	22	130	87	− 0.25	[− 0.66, 0.14]	0.214(0.428)	50.72	< 0.001	58.6	0.41
S-COX2	11	41	28	0.04	[− 0.55, 0.65]	0.878(0.878)	18.12	0.053	44.81
Time point
< 21 days^a	15	78	46	− 0.50	[− 1.00, − 0.01]	0.042(0.126)	11.97	0.609	0	0.162
21–48 days	15	73	49	0.14	[− 0.36, 0.64]	0.581((0.871)	25.94	0.026	46.04
> 48 days	3	20	20	0.18	[− 0.99, 1,36]	0.758(0.758)	28.07	< 0.001	92.87
Type of fractured bone
Femur	11	89	63	− 0.49	[− 0.99, 0.01]	0.055(0.165)	10.40	0.406	3.869	0.041^a
Tibia	10	46	28	− 0.41	[− 1.03, 0.20]	0.192(0.192)	30.63	< 0.001	70.61
Fibula	12	36	24	0.42	[− 0.14, 0.98]	0.143(0214)	19.18	0.058	42.65

N number of comparisons in analysis, SZ NSAID number of animals in non-steroidal anti-inflammatory drug (NSAID) group, SZ C., number of animals in control group, SMD standardized means of differences (Hedges’ g), CI confidence interval, NS-COX non-selective cyclooxygenase inhibitor, S-COX2 selective cyclooxygenase 2 inhibitor, NA not analyzed because of insufficient data. adj.P value, adjusted P value through Holm-Bonferroni correction
^aNeed to be explained—more details in Tables S23–S28 (supplementary information file)

ISSN: 2046-4053