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Abstract Number: 2232

Risk of Osteoporotic Fractures with Use of Cyclooxygenase-2 Inhibitors

Deepan Dalal1, Devyani Misra2, Christine Peloquin3, Tuhina Neogi4, Yuqing Zhang5, David T. Felson6 and Maureen Dubreuil7, 1Rheumatology, Boston Medical Center, Boston, MA, 2Medicine, Section of, BUSM, Boston, MA, 3Clinical Epidemiology Unit, Boston University School of Medicine, Boston, MA, 4Clinical Epidemiology, BUSM, Boston, MA, 5BUSM, Boston, MA, 6Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, MA, 7Rheumatology, Boston VA HealthCare System, Boston, MA

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: analgesics, fractures and osteoporosis

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Session Information

Date: Tuesday, November 10, 2015

Session Title: Epidemiology and Public Health Poster III (ACR): Gout and Non-Inflammatory Musculoskeletal Conditions

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose:   In animal models, cyclo-oxygenase (COX)-2 stimulates osteoclasts through prostaglandin E2 (PGE2). Therefore, non-steroidal anti-inflammatory drugs (NSAIDs) preferentially inhibiting COX-2 (ie-coxibs) should prevent bone resorption. Withdrawal of COX-2 inhibition leads to a rebound effect and excessive osteoclast stimulation which may cause fractures. There are few human studies assessing the risk of fracture with NSAID use. Thus, we examined the risk of osteoporotic fracture with NSAID use, specifically related to the duration and timing of coxib use.

Methods: We conducted a nested case control study using The Health Improvement Network, a population-based electronic medical records database from the UK. We included persons aged 40-89 with hip or knee osteoarthritis (OA). Individuals with malignancy or metabolic bone disease were excluded. NSAID use, including coxibs, was assessed using detailed prescription records. 

Incident osteoporotic fracture cases were identified using Readcodes, and the date of fracture was considered the index date. Up to 4 controls were matched to each case by age, gender, year of OA diagnosis and index date.

Fracture risk is expected to depend on the cumulative dose and how recent the drug use was. Hence coxib users were categorized as: (A) Current long term users (>6 months use, and prescription within 3 months of the index date), (B) Current short term users (<6 months use and a prescription within 3 months), (C) Remote long term users (>6 months use and no prescription within 3 months), (D) Remote short term users (<6 months use and no prescription within 3 months), (E) non-selective NSAID users and (F) NSAID non-users.  Coxibs included: celecoxib, etorocoxib, lumiracoxib, rofecoxib, and valdecoxib.

Potential confounders included BMI, smoking, alcohol use, history of falls, osteoporosis, other comorbidities and medication use. Conditional logistic regression was conducted to assess the risk associated with each of the coxib exposure categories compared to NSAID non-user. 

Results:  4153 cases and 15040 matching controls were identified.  Fracture cases had a higher prevalence of osteoporosis, anti-osteoporotic drug use and history of falls.  Other baseline demographics were similar between 2 groups (Table). Each of the coxib exposure categories was associated increased risk of fractures.  Current coxib use with <6 months of exposure had the highest risk of fracture (Table).

Conclusion: In this large OA population, risk of fracture was most increased with current use of COX-2 inhibitors.  While confounding by indication cannot be ruled out, fracture risk was also present with remote use. This topic warrants further research. 

 

Table.  Baseline   characteristics of fracture cases and matched controls, and odds of fracture   with coxib exposure

 

 

Fracture Cases

Controls

Subjects (n)

 

4153

15040

Age in years, mean ± SD

 

78.3 ± 7.5

78.0 ± 7.5

Female

 

3334 (80.3%)

11966 (79.6%)

Chronic Kidney Disease

 

690 (16.6%)

2586 (17.2%)

Diabetes

 

594 (14.3%)

2283 (15.2%)

History of falls

 

1435 (34.6%)

3191 (21.2%)

Hyperlipidemia

 

692 (16.7%)

2548 (16.9%)

Hypertension

 

2331 (56.1%)

8791 (58.5%)

Inflammatory Rheumatic   Diseases*

 

349 (8.4%)

1195 (7.9%)

Myocardial   infarction/Stroke

 

820 (19.7%)

2557 (17.0%)

Osteoporosis/osteopenia

 

554 (13.3%)

1165 (7.7%)

Anti-osteporotic drugs*

 

448 (10.8%)

1061 (7.1%)

Glucocorticoids

 

521 (12.5%)

1398 (9.3%)

HRT/SERM

 

39 (0.9%)

282 (1.9%)

Alcohol Use

Non-drinker

1055 (25.4%)

3781 (25.1%)

 

Former drinker

112 (2.7%)

397 (2.6%)

 

Current drinker

2550 (61.4%)

9181 (61.0%)

 

Missing

436 (10.5%)

1681 (11.2%)

Body Mass Index (BMI)

Underweight

107 (2.6%)

276 (1.8%)

 

Normal

1028 (24.8%)

2943 (19.6%)

 

Overweight

1246 (30.0%)

4621 (30.7%)

 

Obese

734 (17.7%)

3218 (21.4%)

 

Missing

1038 (25.0%)

3982 (26.5%)

Smoking

Non-smoker

2428 (58.5%)

9053 (60.2%)

 

Former smoker

1171 (28.2%)

4157 (27.6%)

 

Current smoker

392 (9.4%)

1214 (8.1%)

 

Missing

162 (3.9%)

616 (4.1%)

Adjusted odds of fracture with coxib exposure categories

 

Fracture Cases

Controls

Adjusted odds ratio

A. Current long term coxib use

27

67

1.72 (1.08, 2.74)

B. Current short term coxib use

39

76

2.06 (1.38, 3.08)

C. Remote long term coxib use

103

304

1.31 (1.03, 1.67)

D. Remote short term coxib use

326

991

1.18 (1.02, 1.36)

E. Non-coxib NSAID use

1359

4530

1.17 (1.08, 1.27)

F. No NSAID use

2299

9072

1

Inflammatory rheumatic   diseases included spondyloarthritides, psoriasis, connective tissue diseases,   vasculitidies, and crystal arthropathies; Anti-osteoporotic drugs included   bisophsphenates, denosumab and parathyroid hormone; HRT:  hormone replacement therapy, SERM: selective   estrogen receptor modulator. Coxib: cyclooxygenase-2 inhibitor. NSAID:   non-steroidal anti-inflammatory drug


Disclosure: D. Dalal, None; D. Misra, None; C. Peloquin, None; T. Neogi, None; Y. Zhang, None; D. T. Felson, None; M. Dubreuil, None.

To cite this abstract in AMA style:

Dalal D, Misra D, Peloquin C, Neogi T, Zhang Y, Felson DT, Dubreuil M. Risk of Osteoporotic Fractures with Use of Cyclooxygenase-2 Inhibitors [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/risk-of-osteoporotic-fractures-with-use-of-cyclooxygenase-2-inhibitors/. Accessed March 8, 2021.
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