Clinical Briefs

By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is a consultant for GlaxoSmithKline and is on the speaker's bureau of GlaxoSmithKline, 3M, Wyeth-Ayerst, Pfizer, Novartis, Bristol-Myers Squibb, AstraZeneca, Jones Pharma, and Boehringer Ingelheim.

Fenofibrate for Diabetic Retinopathy

Clinicians may recall that the FIELD trial (Fenofibrate Intervention and Event Lowering in Diabetes) failed to achieve its primary endpoint: reduction of fatal + nonfatal MI. A substudy of the FIELD trial was comprised of subjects (n=1,012) who underwent standardized retinal photography at baseline and during followup to determine the incidence of new diabetic retinopathy. Subjects were treated with micronized fenofibrate 200 mg QD (or placebo) for 5 years. This substudy trial endpoint was needed for laser treatment of diabetic retinopathy.

A statistically significant relative risk reduction of 31% in the need for first laser retina treatment was seen in the treatment group vs placebo (3.4% vs 4.9%, absolute risk reduction=1.5%). In the group of patients with pre-existing retinopathy at baseline, there was a marked reduction in need for second laser treatment (3.1% vs 14.6%).

The retinal benefits seen in FIELD were in patients who were mostly already receiving standard-of-care interventions such as statins, glucose control, and blood pressure control. The mechanisms by which fibrates provide reductions in progression of diabetic retinopathy are uncertain, although potential effects on apoptosis, inflammation, and oxidation are postulated. The authors suggest that fenofibrate should be considered in the treatment regimen of diabetic eye disease.

Keech AC, et al. Lancet. 2007;370:1687-1697.

Does Obesity Cause A Delay in Diagnosis of Prostate Cancer?

It has been demonstrated in more than one population that obese men have a lower PSA than nonobese men. One explanation of this was that obese men have lower androgens, resulting in lower PSA. However, it has been recently hypothesized that the larger plasma volume seen in obese men might artifactually lower PSA levels by simple hemodilution.

To examine the relationship between obesity and PSA, as well as PSA corrected for plasma volume, three different populations of men (total n= 13,534) who were post-prostatectomy for prostate CA were studied.

There was an inverse association between BMI and PSA level. For instance, men with a BMI over 35 had a PSA that was 11-21% lower than normal weight men; in the Duke population, as an example, the mean PSA at a BMI < 25 was 6.64, vs a PSA of 5.27 for men with BMI > 35. These effects are felt to be due to hemodilution.

Even though the relationship between BMI and PSA has been clarified, these data are retrospective, and represent information from men proven to have prostate cancer. Whether the hemodilution effects on PSA screening are meaningful remains to be prospectively studied.

Banez LL, et al. JAMA. 2007;298(19):2275-2280.

Protecting Bone During Glucocorticoid Treatment

Current guidelines suggest that if patients are receiving long term Glucocorticoid treatment (ie, 5 mg/d of prednisone for 90 days or longer), they should be considered for preventive interventions to forestall the anticipated bone loss, and reduce fracture risk.

Teriperatide (TPT) is a parenteral recombinant parathyroid hormone that has been shown to stimulate osteoblasts, increase bone mass, and reduce fracture risk. The relative efficacy of TPT vs bisphosphonate for prevention of glucocorticoid-induced bone mineral density (BMD) loss has not been previously studied.

Adults with osteoporosis who were receiving glucocorticoid therapy for at least 3 months (n=428) were randomized to TPT or the oral bisphosphonate alendronate (ALN), 10 mg qd orally. The study is intended to extend for 36 months, but this initial report provides interim outcome data at 18 months.

BMD at the lumbar spine increased in both groups, but TPT surpassed ALN (7.2% vs 3.4%). Similarly, fewer new vertebral fractures were seen in the TPT group (0.6% vs 6.1%). There were no serious drug-attributable adverse events in either group, however hypercalcemia was seen substantially more commonly in TPT recipients. Based upon this data, TPT emerges as an equally, if not more effective intervention for prevention of glucocorticoid-induced osteoporosis and fracture compared with ALN.

Saag KG, et al. N Engl J Med. 2007;357:2028-2039.