Abnormal skeletal metabolism and its changes after decopper therapy in patients with Wilson disease

BACKGROUND: Researches indicate that patients with Wilson disease (WD) have abnormal skeletal metabolism, which is induced by various factors. OBJECTIVE: To probe into the changing characteristics of abnormal skeletal metabolism in WD patients and observe the effect of decopper therapy. DESIGN: Case-contrast and self-control study. SETTING: Department of Neurology, Affiliated Hospital of Neurological Institute, Anhui College of Traditional Chinese Medicine. PARTICIPANTS: A total of 35 patients with WD including 21 males and 14 females aged from 10 to 42 years with the mean age of (20±8) years were selected from Department of Neurology, Affiliated Hospital of Neurological Institute, Anhui College of Traditional Chinese Medicine from September 2000 to February 2001. All the patients were in compliance with the diagnostic criteria: history of family heredity; cone symptoms in vitro, physical sign or liver symptoms; positive Kayser-Fleischer ring; serum copper protein < 200 mg/L or A copper oxidase < 0.2; urine copper > 1.6 μmol/24 hours; liver copper > 250 μg/g (dry weight). The control group was selected from 25 cases of health individuals including 13 males and 12 females aged from 16 to 35 years with the mean age of (22±6) years. All patients who participated in the study were informed first and consented. METHODS: Patients in treatment group were treated with venous injection of 1.0 g sodium dimercaptosulfonate, once a day for totally 6 successive days. And then, patients rested for 2 days. This procedure mentioned above was regarded as a course, and the treatment lasted for 4-8 courses. Before and after injection of sodium dimercaptosulfonate, serum calcitonin (CT), osteocalcin (BGP), parathyroid hormone (PTH) and 1,25-(OH)2VitD3 were measured with radio-immunity method; blood, urine calcium, phosphorum and urine creatinine were measured with biochemical analyzer; urine dihydropyrimidine dehydrogenase(DPD) was detected with enzyme-immunity method; bone mineral density (BMD) was checked at the one third from distal end of ulna and radius with single photon absorptiometry (SPA). MAIN OUTCOME MEASURES: Relative indexes of bone metabolism of blood and urine and results of BMD in both two groups before and after treatment. RESULTS: Among 35 patients with WD and 25 healthy subjects, 5 patients were excluded because of uncompleted decopper therapy; therefore, 30 patients with WD and 25 healthy subjects were involved in the final analysis. ① Comparisons between the two groups: Contents of serum calcium, PTH and 1,25-(OH)2VitD3 were lower in treatment group than those in control group [(2.49±0.34) mmol/L vs. (2.69±0.19) mmol/L; (218.7±50.5) ng/L vs. (262.5±88.9) ng/L; (23.53±14.21) ng/L vs. (42.78±14.44) ng/L; P < 0.05-0.01]; however, contents of serum BGP and CT were higher in treatment group than those in control group [(10.22±6.11) μg/L vs. (5.78±4.22) μg/L; (282.8±109.6) ng/L vs. (62.5±37.9) ng/L, P < 0.01]; moreover, there was no significant difference of contents of serum phosphorum, urine calcium, phosphorum and DPD/creatinine between treatment group and control group (P > 0.05). BMD of males and females was lower in treatment group than that in control group [(0.617±0.197) g/cm2 vs. (0.718±0.274) g/cm2; (0.594±0.124) g/cm2 vs. (0.677±0.157) g/cm2, P < 0.05]. ② Comparisons in treatment group before and after treatment: Contents of CT and urine calcium were lower after treatment than those before treatment [(95.3±55.4) ng/L vs. (283.3±96.7) ng/L; (2.38±1.68) mmol/L vs. (3.31±2.30) mmol/L; P < 0.01, 0.05]; however, contents of 1,25-(OH)2VitD3 and DPD/creatinine were higher after treatment than those before treatment [(33.61±19.30) ng/L vs. (24.21±14.47) ng/L; (42.95±19.92) nmol/mmol vs. (19.51±9.96) nmol/mmol, P < 0.05]; moreover, there were no significant differences among other indexes before and after treatment (P > 0.05). Furthermore, there was no significant difference of BMD before and after treatment (P > 0.05). CONCLUSION: WD patients have changes in the related indexes of abnormal skeletal metabolism. In addition, contents of CT and urine calcium are decreased remarkably after decopper therapy; however, value of BMD is not changed obviously.

A novel function of CREG in metabolic disorders

Metabolic disorders are public health problems that require prevention and new efficient drugs for treatment.Cellular repressor of E1A-stimulated genes(CREG)is ubiquitously expressed in mature tissues and cells in mammals and plays a critical role in keeping cells or tissues in a mature,homeostatic state.Recently,CREG turns to be an important mediator in the development of metabolic disorders.Here in this review,we briefly discuss the structure and molecular regulation of CREG along with the therapeutic strategy to combat the metabolic disorders.