Association between bone mineral density and the use of nonsteroidal anti-inflammatory drugs and aspirin: impact of cyclooxygenase selectivity.
BMD was examined in users of NSAIDs (by COX selectivity) and aspirin in the Health ABC cohort (n = 2853). Significantly higher BMD was found in users of relative COX-2 selective NSAIDs with aspirin (COX-2/ASA) compared with nonusers. This suggests a role for COX-2/ASA in osteoporosis.


BACKGROUND
The purpose of this study was to determine the relationship of nonsteroidal anti-inflammatory drug (NSAID) use, by cyclo-oxygenase selectivity (COX), and aspirin use on bone mineral density (BMD) in participants from the Health, Aging, and Body Composition (Health ABC) population-based cohort. It is known that NSAIDs inhibit the COX enzyme and decrease production of prostaglandins, which are involved in regulation of bone turnover. COX has two isoforms, COX-1 and COX-2. Production of prostaglandins associated with bone loss is primarily mediated through the COX-2 pathway. In addition, aspirin may have effects on bone independent of the prostaglandin pathway.


METHODS
NSAID (by COX selectivity) and aspirin use and BMD were assessed in 2853 adults (49.5% women, 50.5% men: 43.1% black, 56.9% white; mean age: 73.6 years) from the Health ABC cohort. For the purposes of this analysis, relative COX-1 selective NSAIDs were defined as having a ratio of COX-1 IC50 to COX-2 IC50 of > 1 in whole blood, and relative COX-2 selective NSAIDs were defined as having a ratio of COX-1 IC50 to COX-2 IC50 of < 1 in whole blood. Analysis of covariance was used to compare BMD across each NSAID use and aspirin use category adjusting for age, race, gender, weight, height, study site, calcium and vitamin D supplementation, Womac score, history of rheumatoid arthritis, history of arthritis other than rheumatoid, and smoking status.


RESULTS
After adjustment for possible confounders, current use of relative COX-2 selective NSAIDs with aspirin was associated with higher BMD at the whole body (4.2%, 1.2-7.3 CI) and total hip (4.6%, 0.5-8.8 CI) by DXA and at both trabecular (34.1%, 15.4-52.7 CI) and cortical spine (12.8%, 2.3-23.3 CI) by quantitative computed tomography.


CONCLUSIONS
Our data suggest that the combination of relative COX-2 selective NSAIDs and aspirin is associated with higher BMD at multiple skeletal sites in men and women.
Carbone
Laura D
LD
Department of Medicine, University of Tennessee Health Sciences Center, Memphis, Tennessee 38163, USA. lcarbone@utmem.edu
Tylavsky
Frances A
FA
Cauley
Jane A
JA
Harris
Tamara B
TB
Lang
Thomas F
TF
Bauer
Douglas C
DC
Barrow
Karen D
KD
Kritchevsky
Stephen B
SB
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism / Q000494:pharmacology*; D001241:Aspirin / Q000378:metabolism / Q000494:pharmacology*; D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects*; D015331:Cohort Studies; D005260:Female; D006615:Hip / Q000473:pathology; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism; D020033:Protein Isoforms; D014057:Tomography, X-Ray Computed
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011453:Prostaglandins; D020033:Protein Isoforms; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin