Clinical Briefs

By Louis Kuritzky, MD

Parathyroid Hormone and Alendronate Alone or in Combination in Postmenopausal Osteoporosis

The prevention and treatment of osteoporosis (OSPS) present formidable public health issues for men and women, especially since the somewhat disconcerting results of the Women’s Health Initiative have dampened enthusiasm for hormone replacement therapy in menopausal women. Bisphosphonates like alendronate (ALN) and risedronate have been demonstrated to have a favorable effect on bone mineral density (BMD) and fracture risk, mediated through decreased bone resorption. Parathyroid hormone (PTH) has been shown to have favorable anabolic effects on BMD, which could theoretically complement benefits accrued through antiresorptive therapy with bisphosphonates.

In this study of postmenopausal women with low BMD (T score = -2.0 or less) patients were randomly assigned to PTH (n = 119), ALN (n = 60), or the PTH + ALN combination (n = 59) for 12 months. PTH was administered as 100 mg SQ QD, ALN 10 mg QD, and all study participants received 500 mg calcium (Tums) and 400 IU of vitamin D.

BMD enhancement in the lumbar spine was similarly attained with PTH, ALN, or PTH + ALN. At the hip, ALN and ALN + PTH improved BMD, but PTH alone did not. Although intellectually appealing, the combination of an anabolic bone agent (ie, PTH) with an antiresorptive agent (ie, ALN) failed to provide meaningful benefit over either agent used alone. Whether these conclusions would apply to other bisphosphonates such as risedronate is uncertain, but these results would not encourage such combination treatment until more edifying results have been obtained.

Black DM, et al. N Engl J Med. 2003; 349:1207-1215.

Evaluation of D-Dimer in the Diagnosis of Suspected Deep-Vein Thrombosis

All strategies currently used for the diagnosis of suspected deep-vein thrombosis (DVT) are imperfect. Since investigative tools are time-consuming, can produce false-positive results leading to unnecessary hospitalizations and treatments, and are responsible for some not-insubstantial costs, refinement of strategies to improve diagnosis without sacrificing accuracy are needed.

In step one of this trial, clinicians used a clinical model for predicting pretest probability of DVT. This model scored DVT probability based upon clinical characteristics such as presence of cancer, recent immobilization, leg swelling, and history of previous DVT.

In one group, patients (n = 601) considered unlikely to have DVT based upon clinical prediction model were randomized to either d-Dimer (DIM) testing or ultrasound imaging (USI). If the DIM was positive, USI was performed, but if negative, DVT was considered ruled out, and no USI was performed. Patients were followed for 3 months after presentation. A second group (n = 495) who scored high on likelihood of having DVT were randomized to DIM + USI vs USI alone. Persons with negative USI but positive DIM underwent follow-up USI for DVT confirmation 1 week later.

Results indicated that in patients identified as low likelihood of DVT based upon a clinical model scoring system, a negative DIM essentially excludes the diagnosis.

Wells PS, et al. N Engl J Med. 2003; 349:1227-1235.

Exercise Testing to Predict Cardiovascular and All-Cause Death in Women

In the mid 1970s almost 3000 asymptomatic women underwent Bruce-protocol exercise treadmill tests (ETT) as part of the Lipid Research Clinics Prevalence study. These women had entered the trial due to elevated lipids, but were free of known cardiovascular disease at the time of their ETT. The short-term prognostic value of ETT in women has suffered some criticism, but little data have been available on long-term prognosis based upon ETT.

The mean follow-up was 20.3 years, during which time 14% of subjects died; cardiovascular deaths comprised 34% of all deaths. Women with highest exercise capacity on ETT had lower overall mortality rates, as well as cardiovascular deaths. For each MET decrease in exercise capacity at baseline, there was a 20% greater hazard ratio for cardiovascular death over the study observation period. On the other hand, ST segment changes did not predict subsequent cardiovascular death, in contradistinction to findings previously demonstrated in male populations. Data from ETT, specifically METs exercise capacity, is predictive of long-term cardiovascular mortality and might prove useful on a more large-scale population basis for risk stratification.

Mora S, et al. JAMA. 2003;290:1600-1607.

Dr. Kuritzky, Clinical Assistant Professor, University of Florida, Gainesville, is Associate Editor of Internal Medicine Alert.