Relationship between insulin-like growth factor I, dehydroepiandrosterone sulfate and proresorptive cytokines and bone density in cystic fibrosis

Introduction Patients with cystic fibrosis (CF) are known to be at risk for early osteoporosis, and the mechanisms that mediate bone loss are still being delineated. The aim of the present investigation was to investigate if a correlation exists in these patients between skeletal measurements by dual-energy x-ray absorptiometry (DXA) and two anabolic factors, dehydroepiandrosterone (DHEA) and insulin-like growth factor I (IGF-I), and proresorptive factors such as the cytokines interleukin-1β, tumor necrosis factor α, and interleukin-6. Methods We studied 32 outpatients (18 females; mean age: 26.2 ± 7.9 years) at a tertiary care medical center. The subjects had venous samples obtained, underwent anthropometric and bone mineral density (BMD) measurements, and completed a health survey. Serum IGF-I concentrations were below the age-adjusted mean in 78% of the participants, and DHEA sulfate (DHEAS) concentrations were low in 72%. Serum concentrations of all cytokines were on the low side of normal; nonetheless, there was a modest inverse correlation between IL-1β and BMD at all sites. Results In univariate analyses, IGF-I and DHEAS were significant correlates of BMD or bone mineral content. In final multivariate models controlling for anthropometric and other variables of relevance to bone density, only IGF-I was identified as a significant independent skeletal predictor. While alterations in DHEAS, IGF-I, and specific cytokines may contribute to skeletal deficits in patients with CF, of these factors a low IGF-I concentration appears to be most strongly correlated with BMD. Conclusions These findings may have therapeutic implications for enhancing bone density in these patients.     

Bone Mineral Density Determinations by Dual-Energy x-ray Absorptiometry in the Management of Patients with Marfan Syndrome—Some Factors Which Affect the Measurement

Reduced bone mineral density (BMD) was sporadically reported in patients with Marfan syndrome. This may or may not place the Marfan patient at increased risk for bone fracture. In comparing the BMDs of our patients with those reported in the literature, it seemed that agreement between values, and hence the degree of osteoporosis or osteopenia reported, was dependent on the instrumentation used. The objective of this study was to statistically assess this impression. Bone mineral density measurements from our previously published study of 30 adults with Marfan syndrome performed on a Lunar DPXL machine were compared with studies published between 1993–2000 measured using either Lunar or Hologic bone densitometry instruments. The differences of our measurements compared with those made on other Lunar machines were not statistically significant, but did differ significantly with published results from Hologic machines (P < 0.001). Before progress can be made in the assessment of BMD and fracture risk in Marfan patients and in the evidence-based orthopedic management of these patients, standardization of instrumental bone density determinations will be required along with considerations of height, obesity, age, and sex.     

新生儿骨矿质含量及影响因素的研究

应用双光子及单光子吸收测定技术，检测了９２名出生３ｄ内的新生儿骨矿质含量，其中巨大儿３０名，正常体重儿３２名，低出生体重儿３０名，其孕龄分别是４０．１±０．７、３９．１±１．５和３７．４±１．２孕周。结果表明，巨大儿、正常体重儿、低出生体重儿的全身骨矿质含量分别是１０１．６±２８．８、８５．２±１９．８、５９．９±２７．２ｇ／ｃｍ２，巨大儿骨矿质含量最高，正常体重儿次之，低出生体重儿最低，差异有显著性（Ｐ＜０．０１）。颅骨、肱骨、股骨的骨矿质含量与全身的骨矿质含量有高度的相关性，相关系数分别是０．９４３、０．８７９和０．７４５（Ｐ＜０．０１）。全身的骨矿质含量与出生体重、孕龄及头围有高度相关性，相关系数分别是０．７５５、０．５９６和０．５５６（Ｐ＜０．０１）。提示颅骨、肱骨及股骨的任一部位均可代表全身的骨矿质含量，肱骨是确定全身骨矿质含量较好的部位，新生儿骨矿质含量受出生体重、孕龄及头围的影响较大。     

Effect of calcitonin on total body bone mineral contents of experimental osteoporotic rats determined by dual photon absorptiometry

Summary Total body bone mineral (TBBM) content in rats was measured by dual photon absorptiometry (DPA). TBBM showed significant increases over 4 weeks in control groups with significant bone loss over the same time in prednisolone-injected rats on low calcium feed. Daily injections of calcitonin significantly reduced loss of bone mass. Both prednisolone- and prednisolone-calcitonin-injected groups showed significantly elevated serum alkaline phosphatase with the prednisolone-calcitonin group also exhibiting elevated serum calcium and phosphate levels, confirming the impact of the experimental protocol. TBBM measured by DPA in all groups correlated well (r=0.928,P<0.001 n=20) with the total ash weight suggesting that the method reflects total skeletal mineral content in the small animal. TBBM measurement by DPA proves well-suited to monitoring bone mineral in a small animal experimental setting.     

Precision of dual-photon absorptiometry

Summary Precision of dual-photon absorptiometry (DPA) measurements was determined in a lumbar spine phantom and in humans. Approximately half of the measurements were made before and half after a¹⁵³gadolinium source change. The phantom was measured with different amounts of acrylic, which simulates human soft tissue, in order to evaluate the influence of body thickness on bone mineral density (BMD). Results of scans analyzed with two software versions from Lunar Radiation Corp., the widely used 08B and a prototype 08C, are compared. DPA with a cold source significantly overestimated BMD in the phantom in the presence of large amounts (more than 25 cm) of soft tissue equivalent with version 08B but not with the newer version 08C. Similiarly, in nine subjects, there was a significant decrease in spine BMD after a source change when scans were analyzed with version 08B (mean difference 0.026 g/cm²,P=0.002) but not with 08C (0.01 g/cm²,P=0.234). No systematic effect of source change on femoral BMD measurements was observed. The SD of the mean difference of two measurements of the nine subjects was 0.019 g/cm² (1.6% of the mean value) for the spine with software version 08B and 0.024 g/cm² (2.0%) with version 08C, 0.03 g/cm² (3.3%) for the femur neck, 0.03 g/cm² (4.0%) for the greater trochanter, and 0.04 g/cm² (4.9%) for Ward's triangle region of the proximal femur. The spine phanton was scanned on two other commercial bone densitometers in order to assess inter-instrument variation. Phantom measurements of L2-4 BMD made on two Lunar Radiation Corp model DP3 scanners which differed by 2% were 10 and 12% higher than those with a Norland Corp. model 2600 scanner.     

Relationship Among MRTA, DXA, and QUS

Dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound (QUS) are the accepted modalities for the evaluation of fracture risk in the clinical setting. However, neither method provides a direct measurement of bone mechanics. In this study, we investigated a prototype device, known as a mechanical response tissue analyzer (MRTA), which provides direct mechanical measurements of mechanical properties of bone. A total of 56 healthy volunteers (20 men and 36 women) between the ages of 18 and 83 were recruited. The MRTA was used to measure the cross-sectional bending stiffness (EI) of the ulna bone. Axial speed of sound (SOS) at the ulna bone was determined by QUS; bone mineral content (BMC) and bone mineral density (BMD) were determined by DXA. Correlations, regression analysis, and analyses of variance (ANOVAs) were used to compare the three modalities. These analyses revealed that although there are strong linear relationships among the data collected by the various technologies, the bone properties reflected by MRTA are not fully explained by DXA and QUS. We conclude that the total information conveyed by MRTA measurements is unique. Further research is needed to delineate the different qualities of bone strength that are captured by MRTA, but not by DXA or QUS.     

Discrimination of spinal fracture with various bone mineral measurements

For several different bone mineral measurements and various skeletal sites, we compared capability to discriminate between women in various age decades with and without spinal fracture, and attempted to identify the most effective cutoff level in discrimination of spinal fracture. The subjects were 88 women aged 50–59 years (including 32 with fracture), 95 women aged 60–69 years (including 54 with fracture), and 34 women aged 70–79 years (including 18 with fracture). Spinal trabecular and cortical bone mineral density (BMD) were measured using quantitative computed tomography (CT), and spinal, radial (ultra-distal, 10% distal and 33% distal), and calcaneal BMD were measured by dual X-ray absorptiometry. These BMD values were obtained in each subject on the same day. Three statistical techniques—Student's t-test, the logistic regression analysis, and the receiver operating characteristics (ROC) analysis— were applied and accuracy was calculated using the various cutoff values. The capability to discriminate between women with and those without fracture using these BMD values was different among the three age groups. In women aged 50–59 and 60–69 years, all measurements showed good capabilities for discriminating women with fracture. In women aged 70–79 years, these measurements showed lower capability than in those aged 50–59 and 60–69 years, but among them, the calcaneal and ultradistal radial BMD showed relatively good capability. The 10% and 33% distal radial BMD values were not useful in the detection of the high risk women with fracture. The cutoff BMD values for discrimination of women with fracture varied according to the sites and methods of measurement. For each specific age group, the most suitable measurement methods and the appropriate skeletal sites should be considered, and the effective cutoff values to discriminate those with fracture may differ according to the measurement methods, the skeletal sites examined, and age. Received: 5 February 1996 / Accepted: 18 June 1996