Clinical, cellular, microscopic, and ultrastructural studies of a case of fibrogenesis imperfecta ossium.

Fibrogenesis imperfecta ossium is a rare disorder of bone usually characterized by marked osteopenia and associated with variable osteoporosis and osteosclerosis, changing over time. Histological examination shows that newly formed collagen is abnormal, lacking birefringence when examined by polarized light. The case presented demonstrates these features and, in addition, a previously undocumented finding of a persistent marked reduction of the serum C3 and C4. Osteoblasts established in culture from a bone biopsy showed abnormal morphology on electron microscopy and increased proliferation when cultured with benzoylbenzoyl-ATP and 1,25-dihydroxyvitamin D, contrasting with findings in normal osteoblasts in culture. A gene microarray study showed marked upregulation of the messenger RNA (mRNA) for G-protein-coupled receptor 128 (GPR 128), an orphan receptor of unknown function and also of osteoprotegerin in the patient's osteoblasts in culture. When normal osteoblasts were cultured with the patient's serum, there was marked upregulation of the mRNA for aquaporin 1. A single pathogenetic factor to account for the features of this disorder has not been defined, but the unique findings described here may facilitate more definitive investigation of the abnormal bone cell function.

Femoral Neck X-Ray Absorptiometry Parameters and Peripheral Quantitative Computer Tomography Tibial Cortical Density Predict Survival in Dialysis Patients.

BACKGROUND: Low bone mineral density (BMD) is a known independent predictor of mortality in the general elderly population. However, studies in patients with end-stage renal disease (ESRD) are limited. The present study evaluated mortality during long-term follow-up in a population of patients having dialysis for ESRD, in whom BMD was also measured. METHODS: Fifty-eight patients with ESRD were recruited consecutively from a dialysis clinic and followed prospectively for 6 years. Baseline BMD of the lumbar spine and femoral neck (FN) were measured by X-ray absorptiometry and by peripheral quantitative CT at the radius and tibia. Serum calcium, phosphate, parathyroid hormone (PTH), and albumin were measured at baseline. RESULTS: During follow-up, 25 patients died. Univariate analysis showed that mortality was significantly associated with FN-BMD: hazards ratio (HR) per 0.1 g/cm2 decrease 1.50 (95% CI 1.07-2.10), p = 0.019; FN-T score: HR per 1-SD decrease 1.84 (95% CI 1.16-2.92), p = 0.009; and tibial cortical density: HR per 10 mg/cm3 decrease 1.08 (95% CI 1.02-1.14), p = 0.010. In multivariate analysis with stepwise adjustment for age, sex, transplant status, albumin, PTH, phosphate, dialysis duration, diabetes, and smoking, FN-T score remained significantly associated with mortality: HR per 1-SD decrease 1.82 (95% CI 1.02-3.24), p = 0.044, whereas the HR for FN-BMD and tibial cortical density were no longer significant. When 4 patients who had peritoneal dialysis were excluded, the HR relating FN-BMD, FN-T score, and tibial cortical density to mortality remained significant but became insignificant when albumin was included in the multivariate analysis. CONCLUSION: Reduced FN-BMD, FN-T score, and tibial cortical density were significantly associated with an increased risk of death in patients with ESRD.

Bone Mineral Density in Postmenopausal Women Heterozygous for the C282Y HFE Mutation.

Mutations in the HFE gene may be associated with increased tissue iron stores reflected in an elevated serum ferritin. With homozygous mutation C282Y, the increase in serum ferritin may be associated with tissue damage in the liver, pancreas, and pituitary and with a reduced bone mineral density. With heterozygous mutation C282Y, the degree of iron retention is less but information relating to how a heterozygous C282Y mutation might impact bone mineral density is uncertain. The present study was undertaken to study the relationships between bone mineral density measured by dual energy X-ray absorptiometry and the serum ferritin and serum iron in postmenopausal women heterozygous for the C282Y mutation. The spinal bone mineral density, L2-4, was significantly less than age matched community controls (P = 0.016). There was no significant change in the femoral neck bone mineral density compared to age matched community controls. The correlation between the spinal bone mineral density, L2-4, the femoral neck bone mineral density, and the serum ferritin was not significant. The serum iron correlated significantly inversely with the femoral neck bone mineral density (P = 0.048). The heterozygous C282Y mutation may be associated with impairment of bone cell function in postmenopausal women when only small increases in the serum iron or serum ferritin have occurred.

Medullary thyroid carcinoma presenting with an initial CEA elevation.

BACKGROUND: Carcinoembryonic antigen (CEA) is a tumour marker commonly associated with gastrointestinal malignancy. Patients presenting with an elevated CEA will therefore often undergo extensive investigations in order to elucidate an underlying gastrointestinal malignancy that may not be clinically apparent. However the GI tract is not the only source of CEA elevation. METHODS: We present a series of patients presenting with raised CEA levels that were initially investigated for a gastrointestinal cause, but after work up were detected to have medullary thyroid cancer. RESULTS: Four patients with raised CEA were evaluated for a gastrointestinal cause for the elevation. We discuss the non gastrointestinal causes for an elevated CEA. CONCLUSION: The paper highlights that in patients presenting with an elevated CEA, in whom a gastrointestinal cause has been ruled out, a tumour of neuroendocrine origin needs to be considered as a cause for the elevated CEA.

Hematologic and urinary excretion anomalies in patients with chronic fatigue syndrome.

Patients with chronic fatigue syndrome (CFS) have a broad and variable spectrum of signs and symptoms with variable onsets. This report outlines the results of a single-blind, cross-sectional research project that extensively investigated a large cohort of 100 CFS patients and 82 non fatigued control subjects with the aim of performing a case-control evaluation of alterations in standard blood parameters and urinary amino and organic acid excretion profiles. Blood biochemistry and full blood counts were unremarkable and fell within normal laboratory ranges. However, the case-control comparison of the blood cell data revealed that CFS patients had a significant decrease in red cell distribution width and increases in mean platelet volume, neutrophil counts, and the neutrophil-lymphocyte ratio. Evaluation of the urine excretion parameters also revealed a number of anomalies. The overnight urine output and rate of amino acid excretion were both reduced in the CFS group (P < 0.01). Significant decreases in the urinary excretion of asparagine (P < 0.0001), phenylalanine (P < 0.003), the branch chain amino acids (P < 0.005), and succinic acid (P < 0.0001), as well as increases in 3-methylhistidine (P < 0.05) and tyrosine (P < 0.05) were observed. It was concluded that the urinary excretion and blood parameters data supported the hypothesis that alterations in physiologic homeostasis exist in CFS patients.

Vitamin D supplementation and bone mineral density in early postmenopausal women.

BACKGROUND: Increased vitamin D intake may preserve or increase bone mineral density (BMD) in older persons. OBJECTIVE: A 2-y double-blind study was undertaken to determine whether weekly administration of 10 000 units of vitamin D(2) maintained or increased BMD in younger postmenopausal women more efficiently than did calcium supplements alone. DESIGN: One hundred eighty-seven women who were >or= 1 y postmenopausal were randomly assigned to take either 1000 mg Ca/d after the evening meal or 1000 mg Ca/d plus 10 000 U vitamin D(2)/wk in a double-blind, placebo-controlled format. The BMD of the proximal forearm, lumbar spine, femoral neck, Ward's triangle, and femoral trochanter was measured at 6-mo intervals by osteodensitometry. RESULTS: During the 2-y period, there was no significant difference in the change in BMD at any site between the subjects taking calcium supplements and those taking calcium plus vitamin D(2). Both groups significantly (P < 0.005) gained BMD in Ward's triangle and the femoral trochanter but significantly (P < 0.005) lost bone in the proximal radius. There was no significant change in the lumbar spine or femoral neck BMD. CONCLUSION: In younger postmenopausal women ( age: 56 y) whose average baseline serum 25-hydroxyvitamin D concentration was well within the normal range, the addition of 10 000 U vitamin D(2)/wk to calcium supplementation at 1000 mg/d did not confer benefits on BMD beyond those achieved with calcium supplementation alone.

Increase in presentations and procedure rates for hyperparathyroidism in Northern Sydney and New South Wales.

OBJECTIVE: To examine changes in presentation of primary hyperparathyroidism and rates of parathyroidectomy in Northern Sydney (the Northern Sydney Area Heath Service) and New South Wales (NSW). DESIGN: Retrospective case series January 1962 - December 2001 and audit of the NSW Department of Health inpatient database (1993-1999). SETTING: University of Sydney Endocrine Surgical Unit, Royal North Shore Hospital. PARTICIPANTS: 1613 patients undergoing parathyroidectomy during the study period. MAIN OUTCOME MEASURES: Age-standardised parathyroidectomy rates and indications for surgical intervention. RESULTS: The age-standardised rates of parathyroidectomy for primary hyperparathyroidism in women have increased significantly in Northern Sydney from 0.14 cases per 100,000 in 1976 to 7.7 cases per 100,000 in 1996 (P < 0.001). In NSW there has been an increase in parathyroidectomy rates in women from 5.1 cases per 100,000 in 1993 to 12.3 cases per 100,000 in 1998 (P < 0.001). Osteoporosis was the most common overall indication for surgery in Northern Sydney, accounting for 27% of all cases. The proportion of cases presenting with osteoporosis increased significantly from 4% in 1962-1980 to 34% over the past decade (P < 0.001). CONCLUSIONS: The rate of parathyroidectomy procedures has increased markedly in Northern Sydney and in NSW. The investigation of osteoporosis has led to the diagnosis of primary hyperparathyroidism in an increasing proportion of cases and has contributed to the growing surgical referral rates.