Bone density measurements in pediatric patients with renal osteodystrophy.

Peripheral quantitative computed tomography (pQCT) can selectively measure the densities of cortical and trabecular bone, but there is limited information about its use in patients with renal osteodystrophy. Thus pQCT (Norland XCT-2000, Stratec, Pforzheim, Germany) was performed at the ultradistal radius in 21 patients aged 16+/-3.6 (SD) years on continuous cycling peritoneal dialysis. Trabecular bone density (TBD) was higher in patients, 206+/-16 mg/cm(3), than in controls, 182.7+/-24.8 mg/cm(3) ( P<0.0001), whereas cortical bone density (CBD) was lower in patients, 946.5+/-147.5 mg/cm(3), than in controls, 1,153+/-25.4 mg/cm(3) ( P<0.001). TBD was inversely correlated with age ( r=-0.59, P=0.05), height ( r=-0.59, P<0.01), and weight ( r=-0.51, P<0.05). In contrast, CBD was positively correlated with age ( r=0.53, P<0.05), height ( r=0.56, P<0.05), and weight ( r=0.53, P<0.05). CBD was inversely related to serum alkaline phosphatase ( r=-0.71, P<0.001) and parathyroid hormone levels ( r=-0.50, P<0.05). In patients with adynamic bone, TBD was less, 192+/-9 mg/cm(3), than in those with high-turnover lesions, 215+/-13 mg/cm(3), P<0.001. CBD, however, was lower in patients with high-turnover lesions, 900+/-151 mg/cm(3), than in those with low turnover, 1,022+/-111 mg/cm(3), P<0.05. Compared with controls, in patients with high-turnover lesions, CBD was lower ( P<0.0001) and TBD higher ( P<0.0001). These findings suggest that pQCT may be an additional tool in the assessment of renal osteodystrophy.

Progression of coronary artery calcification in patients taking alendronate for osteoporosis.

RATIONALE AND OBJECTIVES: As with their actions on bone, bisphosphonates may play a role in coronary artery calcification (CAC) by inhibiting calcium resorption from plaque. The objective of this study was to determine whether the osteoporosis treatment agent alendronate accelerates the rate of CAC. MATERIALS AND METHODS: The study was a pilot comparative analysis of 56 alendronate-treated patients with osteoporosis compared with 56 control subjects matched for age, sex, risk factors, and CAC scores and with a reference cohort that included 213 control subjects. Patients received alendronate sodium (10 mg daily) for a mean of 24 months and underwent annual assessment of CAC with electron-beam computed tomography and bone mineral density with dual x-ray absorptiometry. The principal outcome measure was the rate of change in CAC score in patients and control populations. RESULTS: There was significant progression of CAC in both alendronate-treated and matched-control groups (paired t test, P = .004 and .006, respectively) but no difference in the rates of CAC progression between the alendronate-treated patients and either the matched or reference control cohort. CONCLUSIONS: This small pilot study indicates that oral alendronate administration does not accelerate the rate of CAC, but a larger cohort should be studied to confirm these findings.

Calcium begets calcium: progression of coronary artery calcification in asymptomatic subjects.

PURPOSE: To test the hypothesis that the rate of coronary artery calcium progression is sex specific, namely, that it is greater in men than in women, and that it is age related, particularly in women. MATERIALS AND METHODS: This was a retrospective study of the progression of coronary artery calcium in 217 consecutive asymptomatic subjects who underwent at least two electron-beam computed tomographic studies of the heart. Calcium in the distribution of the epicardial arteries was quantified by using both the conventional coronary artery calcium score (CCS) and the calcium volume score (CVS). Linear regression models were used to judge the joint influence of various risk factors, including sex and age, on rates of coronary artery calcium progression. RESULTS: This study included 103 women and 114 men. The mean interval between the subjects' first and last studies was 25 months +/- 11 (SD). Regression analyses clearly demonstrated that the amount of coronary artery calcium present at the initial study was the most important determinant of calcium progression. This was true when coronary artery calcium was quantified by using the conventional CCS (P <.001) or CVS (P <.001). Neither sex nor age was a significant predictor of coronary artery calcium progression. Among traditional risk factors, only hypertension (P =.02) and diabetes (P =.01) were significant independent factors for calcium progression. CONCLUSION: In asymptomatic subjects, the initial CCS and CVS were the most important factors that affected rate of coronary artery calcium progression. Neither age nor sex was as important as these factors in determination of coronary artery calcium progression.

A pilot study of all-trans-retinoic acid for the treatment of human emphysema.

Emphysema results from progressive destruction of alveolar septae and was considered irreversible until all-trans-retinoic acid (ATRA) was shown to reverse anatomic and physiologic signs of emphysema in a rat model. To evaluate the feasibility of ATRA as a clinical therapy, 20 patients with severe emphysema were enrolled into a randomized, double-blind, placebo-controlled pilot study. Participants included 16 male and 4 female former smokers, two with alpha(1)-antitrypsin deficiency. Patients were treated with either 3 mo of ATRA (50 mg/m(2)/d) or 3 mo of placebo, followed by a 3-mo crossover phase. Plasma drug levels were followed and outcome measures included serial pulmonary function tests, blood gases, lung compliance, computed tomography (CT) imaging, and quality of life questionnaires. In general, treatment was well tolerated and associated with only mild side effects including skin changes, transient headache, hyperlipidemia, transaminites, and musculoskeletal pains. Plasma drug levels varied considerably between subjects and decreased significantly over time in 35% of the participants. Physiologic and CT measurements did not change appreciably in response to therapy. We conclude that ATRA is well tolerated in patients with emphysema, and trials evaluating higher doses, longer treatment, or different dosing schedules are feasible.