Table 3.

Summary of human RCTs on NSAIDs effect on bone healing, used in this meta-analysis.

Study	No.	Bone type and management	NSAID	Length of exposure	Dose	Nonunion diagnosis	Conclusion
Adolphson et al (1993)[53]	42	Displaced Colles fracture Closed reduction	Piroxicam RD: Paracetamol	8 weeks	20 mg /d	Xray	No difference in radial shortening Small but no significant reduction in osteopenia in the piroxicam group after 8 weeks
Brattwall et al (2010)[54]	100	Elective hallux valgus surgery	COX-2 inhibitors RD: paracetamol, oxycodone	7 days	Etoricoxib 120 mg for 4 days then 90 mg for 3 days	CT scan + Clinical evaluation	None of the CT scans showed limited bone healing
Burd et al (2003)[55]	112	Prophylaxis post acetabular fracture ORIF + long bone fracture	Indomethacin	6 weeks	25 mg TID	X-ray	Risk of nonunion significant for indomethacin to control, 5.32 to 1
Davis et al (1988)[56]	100	Colles’ fractures	Flurbiprofen RD∗: paracetamol	14 days	50 mg x 3–6 daily	X-ray	No significant difference with placebo for anatomic position
Drendel et al (2009)[57]	336	Simple Arm fracture in pediatrics (radius, ulna, or humerus)	Ibuprofen	Variable <2 weeks	Avg. 4 doses of 10 mg/kg	Telephone follow-up and file review	No association between refracture or nonunion No direct endpoint related to bone healing
Sagi et al (2014)[58]	98	Acute acetabular fracture treated operatively	Indomethacin	3 days to 6 weeks	75 mg daily	CT scan	Tx 1 week of indomethacin may be beneficial for healing, without increase of nonunion Tx 6 weeks of indomethacin increases the incidence of nonunion

No. = number of patients, ORIF = open reduction internal fixation, RD = rescue drug; Tx, treatment.