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Abstract Number: 2783

Medications Associated with Osteoporotic Fracture Risk in Patients with Rheumatoid Arthritis

Gulsen Ozen1, Sofia Pedro2, Frederick Wolfe2 and Kaleb Michaud1, 1Rheumatology, University of Nebraska Medical Center, Omaha, NE, 2National Data Bank for Rheumatic Diseases, Wichita, KS

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: Anti-depressant, DMARDs, Fracture risk, Opioids and rheumatoid arthritis (RA)

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Session Information

Date: Tuesday, November 7, 2017

Session Title: Rheumatoid Arthritis – Clinical Aspects IV: Medications and Risk

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose: Osteoporotic (OP) fractures are a major cause of disability, cost, and mortality in RA. Besides increased OP fracture risk, chronic inflammation and pain predispose RA patients to several comorbidities including cardiovascular, mental, and gastrointestinal disorders that lead to the frequent use of multiple medications. Some of these medications have been reported to influence OP fracture risk in the general population, but these associations have not been studied in RA patients. We examined the association of DMARDs, statins, antidepressants, proton pump inhibitors (PPI), opioids, NSAIDs, anticonvulsants, and antipsychotics with OP fracture risk in a US-wide observational RA cohort.

Methods: RA patients (≥40 years old) without prior OP fracture from 2001 through 2016 in the National Data Bank for Rheumatic Diseases (NDB) were assessed for OP fractures (fractures resulting from any fall from a standing height or less). DMARDs were categorized into 4 mutually exclusive groups: (1) MTX monotherapy-reference (2) TNF inhibitors (TNFi) (3) Non-TNFi biologics (4) Others; along with a separate glucocorticoid (GC) variable. Statins, antidepressants (selective serotonin reuptake inhibitors [SSRI] and others), PPI, opioids (weak and strong opioids), NSAIDs, anticonvulsants, and antipsychotics were evaluated separately as current use vs. nonuse and based on the treatment duration. Cox proportional hazard models were used to adjust for sociodemographics, comorbidities, BMI, fracture risk by FRAX, and RA severity measures.

Results: During a median (IQR) 5.4 (2.3-9.7) years of followup in 11,002 RA patients, 863 (7.8%) OP fractures were observed. Patients who developed fractures were significantly older, had higher disease duration and activity, GC use, comorbidity and FRAX scores at baseline than who did not. Crude incidence rates (95% CI) in each medication group are presented in the Table. The adjusted models showed a significant OP fracture risk increase with GC use of ≥3 months of any dose, SSRI (HR 1.35 [1.10-1.64], P=0.003), opioids of any strength (weak: HR 1.48 [1.26-1.74]; strong: HR 1.78 [1.41-2.26], P<0.001 for both) (Table). OP fracture risk increase started even after 1-30 days of opioid use (HR 1.99 [1.59-2.48], P<0.001), whereas SSRI-associated risk increase started after 3 months of use (HR 1.25 [0.99-1.59], P= 0.061).

Conclusion: SSRI and opioids were associated with increased OP fracture risk in RA patients. This risk increase might be associated with increased fall risk caused by these medications. Given the frequent occurrence of chronic pain, mood disorders and polypharmacy in RA patients, the necessity of the medications should regularly be reviewed in RA patients, particularly who have high fracture risk and long-term GC use. When managing pain with opioids, even in the short-term, clinicians should be aware of the fracture risk.

 

Table. Crude incidence rates and adjusted hazard ratios associated with mediations in patients with rheumatoid arthritis

 

No. of failures/

No. of exposure

Patient-years

Incidence rates (95% CI) per 1000 patient-years

Adjusted HR¶ (95% CI)

All patients

863/11,002

52,323

16.5 (15.4-17.6)

–

DMARD groups

 

 

 

 

MTX monotherapy

166/3,199

8,886

18.7 (16.0-21.7)

Reference

TNFi

263/4,976

17,449

15.1 (13.4-17.0)

0.81 (0.65-1.02)

Non-TNFi biologics

54/1,201

2,618

20.6 (15.8-26.9)

0.82 (0.58-1.17)

Other DMARDS

380/6,876

23,369

16.3 (14.7-17.9)

0.85 (0.69-1.04)

GC use

 

 

 

 

None

513/8,681

37,946

13.5 (12.4-14.7)

Reference

<7.5mg/d for <3 months

9/792

651

13.8 (7.2-26.5)

1.01 (0.45-2.26)

<7.5mg/d for ≥3 months

209/3,259

9,676

21.6 (18.9-24.7)

1.27 (1.06-1.53)*

≥7.5mg/d for <3 months

15/757

617

24.3 (14.7-40.3)

1.57 (0.84-2.95)

≥7.5mg/d for ≥3 months

117/1,876

3,431

34.1 (28.4-40.9)

1.74 (1.37-2.22)*

Statins

243/4,003

14,391

16.9 (14.9-19.1)

0.96 (0.81-1.13)

Antidepressants

 

 

 

 

SSRIs

173/2,280

6,590

26.3 (22.6-30.5)

1.35 (1.10-1.64)*

Others

76/1,259

3,386

22.4 (17.9-28.1)

1.04 (0.80-1.36)

PPI

319/4,800

15,886

20.1 (18.0-22.4)

0.93 (0.79-1.09)

Opioids

 

 

 

 

Weak opioids

305/4,432

11,609

26.3 (23.5-29.4)

1.48 (1.26-1.74)*

Strong opioids

108/1,417

2,674

40.4 (33.4-48.8)

1.78 (1.41-2.26)*

NSAIDs

 

 

 

 

COX2 inhibitors

113/2,897

7,140

15.8 (13.2-19.0)

0.91 (0.72-1.16)

NonCOX2 inhibitors

289/5,874

18,070

16.0 (14.3-17.9)

1.13 (0.96-1.33)

Anticonvulsants

107/1,949

4,751

22.5 (18.6-27.2)

0.95 (0.75-1.20)

Antipsychotics

29/619

1,279

22.7 (15.8-32.6)

1.05 (0.69-1.58)

¶Stratified by FRAX risk categories for MOF and adjusted for age, sex, ethnicity, disease duration, education level, insurance, , rural residency, smoking, comorbidity index, BMI, HAQ, pain and patient global scores, prior osteoporosis diagnosis, calcium/vitamin D use, HRT,  exercise, prior sDMARD and bDMARD counts, and calendar year

*P<0.05

 

 


Disclosure: G. Ozen, None; S. Pedro, None; F. Wolfe, None; K. Michaud, None.

To cite this abstract in AMA style:

Ozen G, Pedro S, Wolfe F, Michaud K. Medications Associated with Osteoporotic Fracture Risk in Patients with Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/medications-associated-with-osteoporotic-fracture-risk-in-patients-with-rheumatoid-arthritis/. Accessed January 30, 2023.
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