News: Opioids, COX-2 Therapy and ankylosing spondylitis

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[1] Arizona Research and Education Ltd, Phoenix, Arizona, USA

[*]Correspondence and offprints: Sanford H. Roth, Arizona Research and

Education Ltd, 3330 N. 2nd Street Suite 601, Phoenix, AZ 85012, USA.

Abstract:

Arthritis, rheumatic diseases, spinal and peripheral joint disorders share

in common a legacy of chronic pain. At the turn of the millennium,

nonsteroidal anti-inflammatories (NSAIDs) had replaced aspirin as the agents

most commonly used to deal with rheumatic symptoms, including pain.

Paracetamol (acetaminophen) was the most common alternative analgesic for

minor pain. Opioids were most commonly used on an ad-lib basis, usually for

'breakthrough' pain. However, neurobiological research has confirmed the

basis for 24-hour around-the-clock complete suppression of chronic

nonmalignant pain. This avoids the 'wind up' that leads to intractable pain

progression. Proper monitoring, in the absence of the end organ toxicity

seen with NSAIDs, allows a change in direction to opioids for arthritis for

more severe pain. This requires understanding the responsibilities of

maintaining opioids, in properly selected patients, based upon host response

and informed consent. Under such circumstances, evidence-based trials

support the use of stronger opioids in recalcitrant chronic pain of

arthritis. Thus, we endeavour to better fulfill our Oath of Hippocrates: 'to

relieve pain and suffering'.

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Gastroprotective Therapy and Risk of Gastrointestinal Ulcers: Risk Reduction

by COX-2 Therapy

FREDERICK WOLFE, JANICE ANDERSON, THOMAS A. BURKE, LESTER M. ARGUELLES, and

DAN PETTITT

ABSTRACT.

Objective. Proton pump inhibitors (PPI) and misoprostol decrease the risk of

development of nonsteroidal antiinflammatory drug induced gastric ulcers and

aid healing of upper gastrointestinal (GI) ulcers. H2 receptor antagonists

(H2RA) are less effective for this task, but are widely used by patients and

physicians for the treatment of GI symptoms and duodenal ulcers. Sucralfate

is a weaker agent that is sometimes used for prophylaxis or treatment of

upper GI ulcers. We investigated the effect of GI drugs and selective and

nonselective NSAID on the incidence of GI ulcer development in a cohort of

patients immediately after the release of celecoxib and rofecoxib to

investigate the effect of confounding by indication when effective GI agents

and cyclooxygenase 2 (COX-2)-specific inhibitors are prescribed to a high

risk population.

Methods. During a 6 month period of observation 8547 NSAID users were

evaluated by mailed questionnaire concerning NSAID drug use and ulcer

development. In the first half of 1999, patients took 12,177 separate NSAID

courses. GI therapy that followed the development of upper GI ulcers was

excluded from analysis. Ulcer reports were confirmed by followup validation.

Results. GI drugs were used concomitantly in this population by 42% of

patients using an NSAID. GI drugs were associated with an increased risk of

ulcer. But this risk was confined to PPI (OR 4.1, 95% CI 2.95, 5.69), and

not to other GI drugs. Overall, patients using nonselective NSAID compared

to those taking COX-2-specific inhibitors had an increased risk of upper GI

ulcers (OR 2.12, 95% CI 1.43, 3.34). Patients taking nonselective NSAID plus

PPI were also at increased risk for upper GI ulcers compared to those taking

nonselective NSAID alone (OR 5.09, 95% CI 3.88, 6.67). Similarly, the risk

of upper GI ulcers was increased in the nonselective NSAID plus PPI group

(OR 3.83, 95% CI 2.32, 6.31) compared to the COX-2 plus PPI group.

Conclusion. PPI use, but not other GI drug use, is a marker for increased

susceptibility to ulcers among NSAID users. This risk of upper GI ulcers is

increased in PPI users regardless of which NSAID is used (nonselective or

COX-2-specific inhibitor). Although COX-2 use is associated with greater

risk factors for upper GI ulcers due to channeling bias, COX-2 users have

significantly fewer ulcers than equivalent nonselective NSAID users

regardless of concomitant PPI utilization. (J Rheumatol 2002;29:467-73)

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03/11/2002

By Anne MacLennan

Pre- and postmenopausal women with ankylosing spondylitis (AS) have reduced

hip bone mineral density. As well, bone turnover in these patients is

characterised by low serum osteocalcin and bone-specific alkaline

phosphatase.

These are the findings of a study of bone mineral density (BMD), calcaneal

ultrasound and bone turnover markers in women with this condition.

Participants in the study were 50 pre- and 16 postmenopausal women with AS;

132 women of similar age served as controls.

The objective of these researchers was two-fold: 1) to assess BMD using dual

energy x-ray absorptiometry (DEXA) and calcaneal quantitative ultrasound

(QUS) in women with ankylosing spondylitis (AS), and 2) to determine if

there are any relationships between bone turnover markers and disease

activity or severity.

Researchers assessed clinical and radiological status by the Bath AS Disease

Activity Index (BASDAI), Bath AS Functional Index (BASFI), Bath AS Metrology

Index (BASMI) and Bath AS Radiology Index (BASRI). BMD of the hip and spine

was measured by DEXA, and QUS was measured at the heel.

Serum osteocalcin (OC), bone-specific alkaline phosphatase (BALP), urinary

D-pyridinoline crosslinks (D-PYR), and C-reactive protein (CRP) were

assayed.

The 66 women with AS compared with control patients had reduced BMD at the

hip. For pre- and postmenopausal women, mean t scores were -1.1 and -2.0

respectively, and z scores were -0.4 and -0.37. Four of the women (6

percent) had osteoporosis, and 34 (52 percent) had osteopenia by the WHO

definitions.

In further analysis (multiple regression), the authors found femoral neck

BMD to be significantly affected by age, body mass index, and the sacroiliac

radiographic score.

There were no significant correlations of BMD with disease duration or

disease activity. QUS measures did not correlate with DEXA measures of BMD.

Women with AS had significantly lower markers of bone formation, OC and

BALP, and a trend to higher D-PYR than controls. Serum OC levels correlated

negatively with femoral neck BMD, whereas D-PYR correlated with CRP levels.