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.

Testosterone in Older Men: Is Low Normal Too Low?

After attaining peak adult testosterone levels, men experience a continuous decline in testosterone (TST) of about 1% per year. Concomitant changes with aging such as sarcopenia, cognitive decline, reduced strength, and increased abdominal fat mass have been associated with this loss of TST. The definition of "normal" testosterone includes a wide range, and since most late-life males who have TST levels checked do not have an available early-life TST level for comparison, it is difficult to know whether or not low-normal levels represent a significant pathologic contrast from levels in youth.

Emmelot-Vonk et al studied the effects of TST supplementation among Dutch men with low-normal TST levels. Outcomes measured included functional mobility, handgrip strength, leg strength, cognitive function, BMD, lipids, glucose and quality of life (scored by SF-36). In this randomized double-blind trial, men (n=237) received either 80 mg testosterone undecenoate p.o. b.i.d. or placebo for 6 months.

Although TST did produce meaningful increases in lean body mass, and a corresponding decrease in fat mass, there was no concomitant functional mobility or strength change. Of concern, TST was associated with a 20% decline in HDL, without any measurable benefits in QOL or cognitive function.

This study does not support benefit from supplemental TST in men with low-normal TST levels.

Emmelot-Vonk, et al. JAMA. 2008;299(1):39-52.

CT Pulmonary Angiography as Good as Ventilation- perfusion Scanning for Suspected Pulmonary Embolus

Pulmonary embolism (PEM) is responsible for over ¼ million deaths in the US each year, but accurate and timely diagnosis can sometimes prove elusive. The "gold standard" noninvasive test for at least 3 decades has been the ventilation-perfusion scan (VQS), which has an extraordinarily high specificity: a negative VQS essentially excludes PEM. Unfortunately, the majority of VQS results are reported as low-intermediate PEM probability, leaving a great deal of diagnostic uncertainty.

CT pulmonary angiography (CTPA), because it can be read simply as either positive or negative, is not hampered by this same uncertainty. Additionally, it can detect other chest pathology, although historically it has been considered less sensitive than VQS.

In this study, patients suspected of having PEM (n=1417) were randomized to PEM or CTPA. It is critical that PEM diagnostic tests not falsely exclude individuals who actually have the disorder (false negatives). Hence, the primary endpoint of the study was the number of individuals developing symptomatic proximal deep vein thrombosis (DVT) or PEM in the 3 months following an initial negative investigation.

There was no statistically significant difference in the accuracy of PEM vs CTPA. Using standard protocols which employ d-Dimer and leg venous ultrasound, CTPA and VQS have similar predictive value.

Anderson DR, et al. JAMA. 2007;298(23):2743-2753.

Vertebral Fracture Begets Vertebral Fracture

Vertebral fracture may be defined as a decrease of at least 20% in vertebral height, amounting to a height decrement of at least 4 mm. The Study of Osteoporotic Fractures offers a long-term observation of risk of osteoporotic vertebral fracture (VFX) in women with and without VFX at baseline. This study population was comprised of 9,704 midlife Caucasian women (mean age = 68.8, range 65-99 years) recruited within the United States from 1986-1988 and followed for an average of 14.9 years.

At the 15-year follow-up clinic visit, overall 18.2% of women had a new VFX, but the disproportion of incident VFX was markedly skewed towards those had had a prevalent VFX at baseline: 41.4% of the 394 women with baseline VFX at study enrollment had experienced one or more incident VFX, as compared with 14.2% of the 2,286 women without baseline VFX.

Currently recognized risk factors were associated with VFX including low body weight, BMD, smoking history, and age.

Pre-existing VFX was the most potent predictor of future VFX, and was also associated with increased risk for nonvertebral fracture. The predictive capacity of pre-existing VFX was independent of BMD, corroborating the current philosophy that BMD is a major contributor to, but not the only factor involved in, bone fragility.

Cauley JA, et al. JAMA. 2007;298(23)2761-2767.