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Three Part Question

In [patients with simple fractures] do [NSAIDs compared with convential analgesia] delay [fracture healing]?

Clinical Scenario

A 21 year old man attends the emergency department having sustained an undisplaced, closed fracture of his distal radius. You wonder whether giving the patient a course of NSAIDs will delay fracture healing.

Search Strategy

Medline 1966-04/05 using the OVID interface.
[(exp fractures OR fracture$.mp OR fracture healing.mp) AND (exp anti-inflammatory agents, non-steroidal OR nsaid$.mp OR anti-inflammatory$.mp)], limit to human. References of papers and suitable review articles were scrutinised for further possible articles.

Search Outcome

514 papers were found of which 3 were relevant to the three part question. No further articles were discovered by the reference review.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Davis TR and Ackroyd CE. 1988, UK	100 patients >40 years with a 1st Colles' fracture given flurbiprofen 50/100mg tds or placebo for 2/52	PRCT	Functional recovery.	Some early delay with active treatment (4-6/52) but none at 1 year.	1. High drop out rate (24%). 2. No account made to account for the possibility of self-administered confounding treatments
Adolphson P et al, 1993, Sweden	42 post menopausal women with first Colles' fracture given piroxicam 20mg od or placebo for 8/52.	PRCT	Radiological and functional recovery.	No difference in recovery rate. Up to 12/52.	1. Small study 2. Short follow up 3. No account made to account for the possibility of self-administered confounding treatments 4. The randomisation process was not specified and there were significant differences in the demographics between the groups.
Giannoudis 2000 UK	99 patients who had undergone intramedullary nailing of femoral shaft fractures over a 6 year period. 32 patients had suffered from a non-union while 67 had successful bone healing.	Case-control study	The patients were telephoned with a questionnaire about a number of factors which included NSAID use. Their notes were scrutinised for the type of operative procedure and device used (which was the primary variable under investigation).	A significant difference was found in NSAID use between the non-union (62.5%) and successful healing (13.4%0 groups (p<0.0001). The non-union group tended to use NSAIDs for longer (21 vs 1 week).	1. The authors attributed a causal relationship to the association found between non-union and NSAID use. Prolonged NSAID use may have been the result, rather than the cause, of non-union. 2. There was no data given as to the degree of matching of the control cases. 3. Not a typical ED patient population

Comment(s)

Inflammatory processes are integral to the early stages of fracture healing and there is theoretical concern that this may be inhibited by NSAIDs leading to delayed or even non-union. This worry seems to have been backed up by animal experimentation (primarily on rats); the two small RCTs1,2 did not give any clear evidence to suggest that this is translated into significant clinically adverse effects in humans. The case control study (Giannoudis) has raised a concern about the relationship of NSAIDs to non-union that needs further evaluation. NSAIDs are effective analgesics for musculoskeletal trauma, so until more solid evidence becomes available, their use should not be discouraged.

Clinical Bottom Line

At present, although there are theoretical concerns about the adverse effects of NSAIDs on fracture healing, there is not enough clinical evidence to deny patients with simple fractures their analgesic benefits.

Level of Evidence

Level 2 - Studies considered were neither 1 or 3.

References

1. Davis TR and Ackroyd CE. Non-steroidal anti-inflammatory agents in the management of Colles' fractures. Brit J Clin Prac 1988;42(5):184-9.
2. Adolphson P, Abbaszadegan H, Jonsson U et al. No effects of piroxicam on osteopenia and recovery after Colles' fracture. Arch Orthop Trauma Surg. 1993:112(3):127-30.
3. Giannoudis PV, MacDonald DA, Matthews SJ, Smith RM, Furlong AJ, and De Boer P. Nonunion of the femoral diaphysis: the influence of reaming and non-steroidal anti-inflammatory drugs J Bone Joint Surg (Br). 2000; 82; 655-658.