No abstract

Osteoporosis and fractures are increasingly recognized in children and adults with cystic fibrosis. To investigate the prevalence and pathogenesis of osteoporosis and low bone mass in adults with advanced pulmonary disease due to cystic fibrosis, we examined the relationships between bone mineral density (BMD), anthropomorphic variables, pulmonary status, glucocorticoid therapy, and vitamin D concentrations. BMD of the lumbar spine, hip, and proximal radius was measured by dual energy X-ray absorptiometry in 30 white adults (16 women), age 30 +/- 2 yr (mean +/- SEM). Compared with a normal control population, the patients had significantly reduced BMD at the lumbar spine (17 +/- 3%), total hip and femoral neck (24 +/- 3% and 20 +/- 4%, respectively). The radius was significantly less demineralized (4 +/- 2%; p <= 0.003) than the other sites. Moreover, only 21% of patients with cystic fibrosis had normal BMD (T score > -1.0) at the lumbar spine, 23% at the hip sites, and 39% at the radius. Age, weight, and body mass index (BMI) were most strongly correlated with bone mass, whereas glucocorticoid therapy and pulmonary function were not predictive. Despite oral vitamin D (400 to 800 IU daily), the mean serum 25-hydroxyvitamin D (25-OHD) concentration was at the low end of the normal range (16 +/- 2 ng/ml; normal 10 to 52 ng/ml); 8 of 20 patients (40%) had frankly low (<= 10 ng/ml) levels. BMD was significantly lower in patients with low 25-OHD concentrations at the lumbar spine (0.774 +/- 0.02 versus 0.913 +/- 0.04 g/cm2; p = 0.01) and total hip (0.648 +/- 0.04 versus 0.811 +/- 0.04 g/cm2; p = 0.01). Vertebral fractures were present in 19% of subjects and 41% had a confirmed history of previous fracture. In summary, osteoporosis, low bone mass, and fractures are common in adults with advanced cystic fibrosis lung disease. Despite oral supplements, vitamin D deficiency is also common and is associated with more severe demineralization at the lumbar spine and hip. We conclude that the widespread practice of oral supplementation with 400 to 800 units of vitamin D is ineffective in maintaining normal vitamin D stores in many patients with cystic fibrosis. To ensure adequacy of vitamin D stores, measurement of serum 25-OHD should be included in the routine management of patients with cystic fibrosis.

No abstract

Early high-grade acute rejections (pathologic grade A2 or A3) in recipients of lung allografts are a major risk factor for the subsequent development of obliterative bronchiolitis (OB). We analyzed the risk factors for high-grade acute rejections in 152 recipients of single (100) or bilateral (52) lung allografts transplanted at our institution between 1990 and 1996. Using Kaplan-Meier product limit estimate analysis, there was a 50% probability of grade A2 or A3 rejection by 1 yr after transplant. By univariate analysis, the only significant predictor of early high-grade rejections was the presence of one or more mismatches at the HLA-DR locus (p = 0.038). This association was confirmed using the Cox proportional hazards model for multivariable analysis, with HLA-DR locus mismatch being the only risk factor identified for high-grade rejection (p = 0.036). Using repeated rejection analysis, recipients with one or more matches at the HLA-DR locus had a lower cumulative rate of grade A2 or A3 rejections during the first year compared with recipients with no matches at the HLA-DR locus (0.73 versus 1.32). In addition, recipients with one or more HLA-B locus matches had a lower cumulative rate of grade A2 or A3 rejections in the first year than did recipients with no matches at the HLA-B locus (0.59 versus 1.30). These results indicate that mismatches between donors and recipients at the HLA-DR and HLA-B loci are important risk factors for early high-grade rejections after lung transplantation. Immunosuppressive protocols that are more effective in preventing recipient T-cell activation by donor alloantigens are likely to reduce the rate of high-grade acute rejections in recipients of lung transplants, and may directly impact on the time to onset of OB.

We conclude that fractures are a significant problem in the first year after lung transplantation, even in patients who receive therapy to prevent bone loss. Women with low pretransplantation BMD and a history of pretransplantation glucocorticoid therapy are at greatest risk.