Benefits of the quality assured double and arbitration reading of mammograms in the early diagnosis of breast cancer in symptomatic women.

OBJECTIVES: To address the benefits of double and arbitration reading regarding tumour detection rates, percentage of in situ tumours, and number (of patients) needed to send for expert reading (number needed to treat; NNT) for one additional tumour finding. METHODS: QuaMaDi is a quality assured breast cancer diagnosis programme; with two-view mammography (craniocaudal, mediolateral oblique) and, in case of breast density ACR 3 or 4, routine ultrasound imaging; and with independent double reading of all images. A consecutive sample of symptomatic women, i.e. women at risk for breast cancer, women aged 70 and above, and/or women with preceding BI-RADS III findings, was analysed. RESULTS: 28,558 mammograms were performed (mean age of women: 57.3 [standard deviation: 12.3] years). Discordant findings were present in 3,837 double readings and were sent for arbitration reading. After histopathological assessment, 52 carcinomas were found (thereof 32% in situ). These carcinomas accounted for 1.8 tumours per 1,000 examinations in the total cohort and increased the tumour detection rate up to 16.4/1,000. The NNT in discordant cases was 74. CONCLUSION: Double and arbitration reading appears to be a useful tool to ensure the quality of early detection of breast lesions in symptomatic women during indication-based, standardised mammography. KEY POINTS: • Quality assured breast cancer diagnosis is feasible outside organised screening structures. • Double and arbitration reading is beneficial for populations ineligible for screening. • Double and arbitration reading increases the tumour detection rate. • Double and arbitration reading increases the percentage of in situ cancers.

Intima-media thickness in women with borderline personality disorder.

OBJECTIVE: Patients with borderline personality disorder (BPD) may have a higher risk of developing cardiovascular disease caused by altered endocrine, metabolic, and inflammatory parameters. Increased intima-media thickness (IMT) is considered an early marker of atherosclerosis and is associated with most cardiovascular risk factors. METHODS: The mean IMT of the common carotid arteries was assessed by B-mode ultrasound in 47 women with BPD and 28 age-matched healthy women. Mean (standard deviation) age for BPD participants was 31.2 (10.4) years and 31.9 (11.0) years for the comparison group. In addition, Adult Treatment Panel III criteria for metabolic syndrome and markers of inflammation were measured. The patients were characterized by applying DSM-IV criteria and obtaining self-reports of adverse childhood experiences. RESULTS: Women with BPD had a significantly higher IMT than healthy women (mean [standard deviation] = 0.41 [0.11] versus 0.34 [0.11] mm, p = .02). In linear regression analysis, IMT was significantly associated with BPD even when adjusting for body mass index (ß = 0.27, p = .04) and physical activity (ß = 0.29, p = .02). CONCLUSIONS: The data suggest that women with BPD are at increased risk of developing subsequent cardiovascular disease.

Major depression, borderline personality disorder, and visceral fat content in women.

Major depressive disorder (MDD) is associated with increased volumes of visceral fat and a high prevalence of the metabolic syndrome. In turn, affective disorders are frequently found in patients with borderline personality disorder (BPD). It is therefore unclear whether BPD per se may influence body composition. In order to clarify a potential relationship between BPD and body composition, we measured visceral fat content (VFC) in young depressed women with and without comorbid BPD and related this parameter to various features of the metabolic syndrome. Visceral fat content was measured by magnetic resonance imaging in 22 premenopausal women with MDD only, in 44 women with comorbid MDD and BPD, in 12 female BPD patients without MDD, and in 34 healthy women (CG). Data showed that depressed women without comorbid BPD had a 335% higher VFC and women with comorbid BPD had a 250% higher VFC than the CG women. When controlling for age, data showed significant effects of MDD on VFC (F = 8.4; P = 0.005). However, BPD, with or without MDD, was not related to VFC. Young depressed women with and without comorbid BPD display increased visceral fat content when compared to control subjects and may therefore constitute a risk group for the development of the metabolic syndrome. BPD per se is not an additive risk factor in this context.

Timing and targeting of cell-based VEGF165 gene expression in ischemic tissue.

BACKGROUND: Therapeutic angiogenesis has become a key technology in experimental and clinical medicine. Only few data are available on the effects of timing and targeting of therapeutic proteins after cell-based gene transfer. This work investigates such effects after temporary expression of vascular endothelial growth factor 165 (VEGF(165)), the most commonly used angiogenic protein for therapeutic purposes. METHODS: We established a cell-based gene-transfer model using fibroblasts to temporarily produce VEGF(165). Cells were implanted into 40 rats. Protein expression and angiogenic effects were measured by PCR, immunohistology, and microangiography. To determine an improvement for survival of ischemically challenged tissue, cells were implanted in an ischemic flap model at different locations and time points. RESULTS: After implantation of modified cells, a temporary increase was found in the target tissue for VEGF(165), endothelial cell counts, and capillary network formations. Four wk later, histological alterations in the target tissue area were not different from controls. Implantation of modified cells into flap plus wound margin 1 wk before surgery showed significant improvement of tissue survival demonstrated by planimetric measurements and blood vessels counting in the target tissue. CONCLUSION: In our model, temporary expression of VEGF(165) induces therapeutically relevant angiogenesis and improves blood supply only if applied 1 wk before ischemia. It is essential to include the surrounding area for induction of angiogenesis in this model. In contrast, the angiogenic effects are not effective in the target area and its surrounding tissue, if therapeutic gene expression is started during onset of ischemia or 2 wk before ischemia in this model.

Radiofrequency ablation in breast tissue: experimental study for evaluation of radiofrequency effects in the bovine udder and review of the literature.

PURPOSE: To investigate the radiofrequency (RF) effects on the nonlactating and lactating ex vivo bovine udder as a model for normal breast tissue. MATERIALS AND METHODS: RF ablation in three lactating and three nonlactating ex vivo bovine udders (ie, six udders) was performed. The opening of the electrodes was 3 cm. The temperature was applied in 10 degrees C increasing steps between 60 degrees C and 100 degrees C and each temperature was maintained for 15 minutes. The experiment was repeated three times for each temperature step in the lactating and nonlactating udder. Resected specimens were assessed histologically. The maximum diameter of the ablation zone and maximum width of the transition zone with respect to the temperature applied were measured. RESULTS: In the nonlactating tissue, there was a correlation of the temperature and diameter of tissue damage. There was a narrow transition zone of 0.10 cm in all cases except at 100 degrees C, when it was 0.17 cm. In the lactating udder, no correlation was seen. The transition zone was not well visualized at temperatures less than 80 degrees C, ranging in overall size between 0.15 cm and 0.20 cm. CONCLUSIONS: The results of the study, with clear demarcation of the ablation zones and transition zones in the normal breast tissue, support the potential of breast thermal ablation as a viable treatment for further study. Lactating tissue does not seem ideal for thermal ablation. The discrepancy of the extent of ablation and the length of the electrodes is an important finding in this study. Further in vivo studies in normal glandular tissue and tumor are necessary.

Immunolocalization of defensins and cathelicidin in human glands of Moll.

The human gland of Moll located at the margin of the eyelids is a specialized apocrine gland, the function of which is not exactly known. The presence of antimicrobial proteins was identified in this gland recently, suggesting a function in the external ocular defense barrier against pathogens. In this study, we have demonstrated beta-defensin-1, beta-defensin-2 and cathelicidin (LL-37) in the secretory endpieces of the glands of Moll using immunohistochemical methods. beta-Defensin-1, beta-defensin-2 and cathelicidin (LL-37) showed a weak to moderately intensive staining pattern. The strongest immunolocalization of beta-defensin-1 was observed in the apical protrusions of the gland, which could also be observed but to a lesser extent in the case of beta-defensin-2 and cathelicidin. In active glandular cells, a granular staining pattern could be observed. beta-Defensin-1 and beta-defensin-2 varied in staining intensities, and even within one section strongly and weakly stained cells can coexist side by side. Also cells that, according to morphological criteria, appeared to be inactive still had an apical beta-defensin-1 immunolabeling. We assume that beta-defensin-1, beta-defensin-2 and cathelicidin (LL-37) work together with other antimicrobial peptides and proteins to create a defensive barrier against microbial invasion at the ocular surface.

Bone mineral density, bone turnover, and osteoprotegerin in depressed women with and without borderline personality disorder.

OBJECTIVE: Low bone mineral density has repeatedly been reported in patients with major depressive disorder (MDD), and MDD has been discussed as a risk factor for the development of osteoporosis. MDD in young adults often occurs in the context of borderline personality disorder (BPD), and both MDD and BPD have been associated with a dysregulation of the hypothalamic-pituitary-adrenal system and subsequent hypercortisolemia. To date, it is unclear whether comorbid BPD in depressed patients modulates the extent of bone mass reduction. Therefore, we examined bone density, markers of bone turnover, and proinflammatory cytokines in depressed patients with and without BPD. Patients with BPD alone and healthy women served as comparison groups. METHOD: Twenty-four patients with MDD and 23 patients with comorbid MDD and BPD were included. Sixteen patients with BPD and 20 healthy women of similar body mass index served as the comparison group. BMD was assessed by means of dual-energy x-ray absorptiometry. Markers of bone turnover, endocrine and immune parameters were determined. For data analysis, the group of depressed patients without comorbid BPD was divided according to age into two groups (younger depressed patients with a mean age of 30 years and older patients with a mean age of 42.9 years). RESULTS: BMD at the lumbar spine was significantly reduced in a) depressed women with comorbid BPD (mean age, 28.6 years) and in b) older depressed patients without BPD (mean age, 42.9 years). Osteocalcin, a marker of osteoblastic activity, and crosslaps, a marker of bone loss, were significantly different between the study groups. Tumor necrosis factor-alpha was increased in depressed patients when compared with healthy women. Furthermore, TNF-alpha was positively correlated with serum crosslaps, a marker for osteoclastic activity. CONCLUSION: Depression is associated with reduced bone mass, in particular in patients with comorbid BPD. Possible factors contributing to BMD reduction include endocrine and immune alterations associated with either MDD or BPD. We conclude from our data that a history of MDD with and without comorbid BPD should be considered as a risk factor in clinical assessment instruments for the identification of persons prone to osteoporosis.

Human ceruminous gland: ultrastructure and histochemical analysis of antimicrobial and cytoskeletal components.

The ceruminous glands in the skin of the human external auditory canal are modified apocrine glands, which, together with sebaceous glands, produce the cerumen, the ear wax. Cerumen plays an important role in the protection of the ear canal against physical damage and microbial invasion. We studied the morphology of the glandular cells by light and electronmicroscopy. Antimicrobial and cytoskeletal components of the ceruminous glands were investigated by immunohistochemical methods. Numerous antimicrobial proteins and peptides are present in the ceruminous glandular cells: beta-defensin-1, beta-defensin-2, cathelicidin, lysozyme, lactoferrin, MUC1, secretory component of IgA. These data indicate a crucial role in the innate host defense against diverse pathogens. The apocrine secretion mechanism is a special mode of secretion by which the apical part of the cell cytoplasm surrounded by a membrane is pinched off. We could show that the presence of actin filaments, CK 19 and CK 7, seems to play a role in the pinching-off mechanism. Finally, we showed the secretion of lipid vesicles from the ceruminous gland. We could extend the number of detected antimicrobial peptides and proteins in human ceruminous glandular cells that protect the surface of the external auditory meatus. In addition, we detected proteins involved in the apocrine secretion mode of the ceruminous gland.

Bone mineral density, markers of bone turnover, and cytokines in young women with borderline personality disorder with and without comorbid major depressive disorder.

OBJECTIVE: The pathogenesis of bone loss in major depressive disorder is a matter of debate. Studies of bone loss in nonpsychiatric medical disorders have found an association between the activation of osteoclastic cells and an imbalance of pro- and antiinflammatory cytokines. Since major depressive disorder is also associated with alterations in serum cytokine concentrations, the authors hypothesized that bone loss in patients with major depressive disorder and comorbid borderline personality disorder may be associated with cytokines capable of activating osteoclastic cells. METHOD: Twenty-two patients with borderline personality disorder and comorbid current or lifetime major depressive disorder were compared with 16 patients with borderline personality disorder who did not have major depressive disorder and 20 healthy volunteers. Bone mineral density was assessed by means of dual-energy x-ray absorptiometry. Markers of bone turnover as well as endocrine and immune measures were determined. RESULTS: The bone mineral density of 10 patients with borderline disorder plus current major depressive episode was significantly lower than that of the healthy subjects and the patients with borderline personality disorder without depression. Values of crosslaps, osteocalcin, serum cortisol, tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 were significantly higher in the patients with borderline disorder plus current major depressive episode than in the healthy subjects. Crosslaps correlated positively with TNF-alpha but negatively with bone mineral density at the lumbar spine. Patients with borderline personality disorder who did not have current or lifetime depression displayed no alterations of either bone mineral density or the immunological and hormonal measures examined. CONCLUSIONS: Young women with comorbid borderline personality disorder and major depressive disorder have an elevated risk for osteoporosis. Borderline personality disorder per se is not associated with low bone mineral density. These data suggest that the immune and endocrine disturbances associated with depressive disorders in the context of borderline personality disorder may play a role in the pathophysiological process underlying bone loss in the patients studied.

Visceral fat deposition and insulin sensitivity in depressed women with and without comorbid borderline personality disorder.

OBJECTIVE: Major depressive disorder (MDD) is associated with increased intra-abdominal fat, an important antecedent of noninsulin-dependent diabetes mellitus (NIDDM) and cardiovascular disorders. Furthermore, MDD is commonly accompanied by endocrine and immune dysregulation that has also been discussed in connection with the pathogenesis of NIDDM and ischemic heart disease. In borderline personality disorder (BPD), a dysregulation of the hypothalamic-pituitary-adrenal system has also been described. Therefore, our study aimed at examining visceral fat, insulin resistance, and alterations of cortisol and cytokines in young depressed women with and without comorbid BPD. METHODS: Visceral fat was measured in 18 premenopausal women with MDD and in 18 women comorbid with MDD and BPD by means of magnetic resonance tomography at the level of the first lumbar vertebral body. Twelve BPD patients without MDD and 20 healthy women served as the comparison groups. Concentrations of fasting cortisol, tumor necrosis factor-alpha, and interleukin-6 were measured, and indicators of insulin resistance and beta-cell sensitivity were calculated according to the homeostasis assessment model. RESULTS: We found increased visceral fat in women comorbid with MDD and BPD, and to a lesser extent, in women with MDD but without BPD. Insulin sensitivity was reduced in comorbid patients. Serum interleukin-6 (IL-6) and tumor necrosis factor-alpha concentrations were significantly increased in both groups of depressed patients. Reduced insulin sensitivity correlated with the amount of visceral fat and with serum concentrations of IL-6. CONCLUSION: Young depressed women with and without comorbid BPD display increased visceral fat and may constitute a risk group for the development of NIDDM and the metabolic syndrome. Our data support the hypothesis that the immune and endocrine alterations associated with MDD and BPD may contribute to the pathophysiologic processes associated with NIDDM.

Human glands of Moll: histochemical and ultrastructural characterization of the glands of Moll in the human eyelid.

The function of the human gland of Moll of the eyelid is not exactly known. We studied the secretory and cytoskeletal components of these apocrine glands in males and females by immunohistochemical methods, and the ultrastructural organization of the glandular cells with an electron microscope. The glands of Moll are exclusively located at the margin of the eyelids and their ducts empty into the lash follicle. Immunohistochemical staining for actin and cytokeratins CK19 and CK7 points to the involvement of actin in the pinching-off mechanism of the apical cell protrusion during apocrine secretion and to a stabilizing role for the cytokeratins in this apical region of the glandular cells. The presence of the bacteriolytic enzyme lysozyme, the membrane-associated mucin 1, and the immunoglobulin A and its secretory component within the gland suggest a function in local immune defense. The presence of a variety of sugar components in the secretory product was verified by lectin histochemistry and periodic acid Schiff and Alcian blue stain. We suppose that these apocrine glands are active from birth in producing agents against pathogenic microorganisms in the eyelid shaft and on the ocular surface.

[Perfusion imaging of the kidney using contrast-enhanced phase-inversion ultrasound]. / Renale Perfusionsbildgebung mit kontrastverstärktem Phaseninversionsultraschall.

PURPOSE: We evaluated different techniques of contrast-enhanced phase-inversion ultrasound to visualize renal perfusion. MATERIALS AND METHODS: Levovist contrast-enhanced phase-inversion ultrasound with different levels of mechanical index and frame rate was performed in 20 kidneys. Analysis using a software algorithm for time-resolved perfusion imaging was compared to single-image analysis performed by three independent radiologists. RESULTS: Optimal depiction of renal perfusion was achieved only by using a mechanical index which was high enough to destroy the microbubbles of the contrast agent (burst imaging) combined with a low frame rate (0.5 images/second). Renal cortex and medulla showed a homogeneous enhancement. Computer-assisted time-resolved perfusion analysis was applicable; it did not show additional Information to single-image analysis. CONCLUSION: Renal perfusion can be visualized using contrast-enhanced phase-inversion ultrasound. For depiction of bigger vessels, it is equal to B-mode ultrasound or Doppler mode techniques; however, it is superior for visualization of renal parenchymal perfusion.

[Procedures, spectrum and radiation exposure in CT-fluoroscopy]. / Verfahren, Spektrum und Strahlenexposition der CT-Fluoroskopie.

PURPOSE: To assess the techniques, indications and radiation exposures incurred with CT fluoroscopy. MATERIAL AND METHODS: A 1-year period of use of CT fluoroscopy to guide diagnostic and therapeutic interventional procedures was analyzed. The spectrum of indications, different CT fluoroscopic methods and radiation exposures for the radiologist were assessed. Scatter exposures were measured with and without placement of a lead drape on the patient, with and without use of thin rubber radiation protection gloves. In addition, scattered radiation was determined for a combination of lead drape and radiation protection gloves. RESULTS: There is a wide variety for the use of CT fluoroscopy ranging from diagnostic biopsy procedures to therapeutic interventions such as radiofrequency ablation of liver metastases and CT fluoroscopy-guided osteosynthesis of fractures. Scatter exposure rates to the radiologists hand ranged from 1-320 microSv/case without use of a lead drape and without radiation protection gloves. The lead drape reduced the scattered exposure for the radiologists hand by 72%. Radiation protection gloves reduced scatter radiation by 49%. The combination of both radiation protection devices was most effective in decreasing the dose by 97%. CONCLUSIONS: CT fluoroscopy is a useful targeting method with a wide variety for interventional procedures. However, significant radiation exposures may occur. Therefore, the radiologists should be aware of different techniques of CT fluoroscopy guidance and the methods to reduce scatter radiation.

Magnetic resonance imaging of heterotaxis syndrome.

Failure to establish normal left-right body axis (LRA) formation during embryogenesis results in heterotaxis, a multi-malformation syndrome. We report on a 20-year-old young woman who presented to the emergency room with upper abdominal pain. On chest X-ray, dextrocardia was noted. Ultrasound was inconclusive. Barium studies demonstrated non-rotation of the intestine. Magnetic resonance imaging (MRI) of the abdomen confirmed heterotaxis with abnormal arrangement of abdominal organs and vasculature. This is the first radiographic description of LRA in MRI. It provides a unique contribution to the wide morphological variety of lateralization defects in a single examination within 15 min and without the risks of ionizing radiation. In addition, a literature overview over the genetic aspects, broad morphological spectrum, and possible therapeutic consequences is given.

Malignant hemangiopericytoma of the breast: a case report with a review of the literature.

INTRODUCTION: A hemangiopericytoma of the breast is uncommon, and a hemangiopericytoma of the breast is even rarer. Only a few cases of hemangiopericytoma of the breast have been reported in literature. CASE REPORT: Here, we report a case of a 66-year-old woman who presented with a mass in her left breast. The patient had trauma to her left breast 2 years ago with consecutive hematoma. An ultrasound-guided core biopsy indicated a malignant vascular tumor. Its morphology and immunohistochemical marker profile was characteristic for a malignant hemangiopericytoma. Thus, she underwent a mastectomy and an axilla sampling. DISCUSSION: The mammogram and the ultrasound findings of 2004 are presented in relation to those of 2006. Hemangiopericytoma of the breast is infrequent, so that the characteristics of this lesion are discussed in addition to the review of the previous literature on this unusual neoplasm.

Epidermal cyst of the breast mimicking malignancy: clinical, radiological, and histological correlation.

BACKGROUND: Epidermal cyst of the breast is a rare benign intramammary lesion; however, a common finding in other parts of the body and most often located in the scalp, back, and neck. Only a few cases of epidermal cysts of the breast have been reported in literature. CASE REPORT: The patient presented with a small movable left breast lump. Mammography and ultrasonography did not show features of a benign lesion. Ultrasound-guided core biopsy was undertaken. Histology showed an epidermal cyst. The patient returned with an inflammation at the puncture site and a small abscess seen on ultrasound. The abscess was removed surgically. CONCLUSION: Mammographic and sonographic features of an epidermal cyst may mimick a malignant lesion. Biopsy can result in complications, such as inflammation. In addition, an association between epidermal cyst and squamous carcinoma has been reported. Therefore, it is recommended that these lesions are resected.

Long-term results after primary stenting of distal aortic stenosis.

PURPOSE: To review the long-term results of primary stent placement in the distal aorta above the bifurcation. METHODS: Fourteen patients (8 men; mean age 62 years, range 46-82) underwent primary stent implantation performed by an interdisciplinary radiosurgical team. In 10 patients, a long-term follow-up examination consisting of patient history, clinical examination, and duplex sonography was performed. The ankle-brachial index (ABI) for the posterior tibial artery was calculated on the basis of Doppler pressure measurements. RESULTS: The clinical success rate at the first follow-up examination (mean 2.9 months, range 2.1-4.4) was 100% (n = 14). The mean baseline ABI of 0.64 +/- 0.12 had risen to 1.02 +/- 0.10 (p < 0.0001). At midterm follow-up (mean 22.8 months, range 14-42) in 12 patients, the ABI was 0.96 +/- 0.12 (p < 0.0001 versus baseline). At a mean 86 months (range 51-119) after stent treatment, the ABI in 10 patients was 0.90 +/- 0.20 (p < 0.0001 versus baseline). Over the long term, the clinical success rate was 70%. Deterioration was due to the progression of atherosclerosis distal to the aorta; duplex sonography showed no aortic restenosis or occlusion. CONCLUSION: In view of the excellent long-term results in our small series, primary stent placement in focal abdominal aortic stenosis in properly selected patients is a durable treatment. In addition, the mortality and morbidity risks are markedly reduced compared with open surgery.

Radiation dose to the radiologist's hand during continuous CT fluoroscopy-guided interventions.

Computed tomography fluoroscopy (CT fluoroscopy) enables real-time image control over the entire body with high geometric accuracy and, for the most part, without significant interfering artifacts, resulting in increased target accuracy, reduced intervention times, and improved biopsy specimens [1--4]. Depending on the procedure being used, higher radiation doses than in conventional CT-supported interventions might occur. Because the radiologist is present in the CT room during the intervention, he is exposed to additional radiation, which is an important aspect. Initial experience with CT fluoroscopically guided interventions is from the work of Katada et al. in 1994 [5] and only relatively few reports on radiation aspects in CT fluoroscopy are found in the literature [1, 2, 6--11]. To date, there are no reported injuries to patients and radiologists occurring with CT fluoroscopy. The time interval since the wide use of CT fluoroscopy is too short to have data on late effects to the operator using CT fluoroscopy on a daily basis. In addition, the spectrum of CT fluoroscopically guided interventional procedures will expand and more sophisticated procedures requiring longer fluoroscopy times will be performed. Thus, effective exposure reduction is very important. The purpose of our study was to assess the radiation dose to the operator's hand by using data from phantom measurements. In addition, we investigated the effect of a lead drape on the phantom surface adjacent to the scanning plane, the use of thin radiation protective gloves, and the use of different needle holders.

Decreased osteoprotegerin and increased bone turnover in young female patients with major depressive disorder and a lifetime history of anorexia nervosa.

Low bone mineral density (BMD) is a frequent, often persistent complication in patients with major depressive disorder (MDD) and anorexia nervosa (AN) that increases the risk of pathologic fractures. The pathogenetic process underlying osteopenia in MDD and AN is still unclear, although several factors, including a dysbalance of cytokines, are associated with loss of bone mass. Alterations in the serum levels of cytokines have been observed in patients with MDD, AN, and other psychiatric disorders. Therefore, we examined serum levels of cytokines, markers of bone turnover, and BMD in 13 patients with MDD and a lifetime history of AN. Bone turnover markers (osteocalcin and C-terminal degradation products of type I collagen) and tumor necrosis factor alpha (TNF-alpha) in patients were significantly increased compared with those of the control group. Osteoprotegerin (OPG) in patients was significantly decreased. Eight of 13 patients (62%) displayed osteopenia at the lumbar spine. TNF-alpha correlated significantly with C-terminal degradation products of type I collagen, an osteoclastic marker, but significantly negatively with OPG. Our data suggest that TNF-alpha and OPG may play a role in the pathogenetic process underlying osteopenia in these patients.