Decreased bone density, elevated serum osteoprotegerin, and beta-cross-laps in Wilson disease.

First Department of Medicine, Semmelweis University, Budapest, Hungary.
Journal of Bone and Mineral Research (Impact Factor: 6.59). 12/2002; 17(11):1961-7. DOI: 10.1359/jbmr.2002.17.11.1961
Source: PubMed

ABSTRACT Osteopathia has been reported in Wilson disease (WD), but bone density has not been measured; therefore, we performed bone mineral density (BMD), bone mineral content (BMC), and quantitative bone ultrasound (QUS) assessments, as well as measured the serum levels of osteocalcin (OCN), beta-cross-laps (beta-CTx's), and the recently discovered osteoprotegerin (OPG) and its ligand RANKL to investigate the underlying mechanism of osseous disorders. Serum OCN, beta-CTx, OPG, and RANKL levels were measured by ELISA in 21 WD patients and in 20 age- and gender-matched healthy subjects. BMD, BMC, and QUS parameters were also determined. Osteoporosis was present in 9/21 (43%) WD patients. Abnormal QUS parameters were found in 7 (33%) of the patients. Although serum OCN levels were similar in patients and controls (29.93 +/- 24.65 mg/ml vs. 29.84 +/- 6.89 mg/ml), beta-CTx and OPG levels were significantly increased in WD compared with the healthy controls (625.4 +/- 312.3 pg/ml vs. 423.6 +/- 144.3 pg/ml and p = 0.022 and 7.2 +/- 3.4 pM vs. 3.5 +/- 1.0 pM and p < 0.001, respectively). No difference was observed in the RANKL level. There was a positive correlation between OCN and beta-CTx (r = 0.55; p = 0.01). We proved high occurrence of osteoporosis in WD. Negative bone remodeling balance is a consequence of increased bone resorption, which is indicated by elevated beta-CTx. The novel finding of elevated serum OPG may reflect a compensatory reaction to enhanced osteoclast activity, despite the normal OCN level.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Wilson's disease is characterized by copper deposition, especially in the liver and central nervous system. We assessed the prevalent fractures and bone mineral density (BMD) and related risk factors in 85 patients. BMD was normal, but patients with severe neurological involvement, low BMI, and/or amenorrhea are at risk for fractures.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Context: The RANK/RANKL/OPG signalling pathway is important in the regulation of bone turnover, with single nucleotide polymorphisms (SNPs) in genes within this pathway associated with bone phenotypic adaptations. Objective: To determine whether four SNPs associated with genes in the RANK/RANKL/OPG signalling pathway were associated with stress fracture injury in elite athletes. Design, participants, and methods: Radiologically confirmed stress fracture history was reported in 518 elite athletes,forming the Stress Fracture Elite Athlete (SFEA) cohort. Data were analysed for the whole group and were sub-stratified into male and cases of multiple stress fracture groups. Genotypes were determined using proprietary fluorescence-based competitive allele-specific PCR assays. Results: SNPs rs3018362 (RANK) and rs1021188 (RANKL) were associated with stress fracture injury (P b 0.05). 8.1% of the stress fracture group and 2.8% of the non-stress fracture group were homozygote for the rare allele of rs1021188. Allele frequency, heterozygotes and homozygotes for the rare allele of rs3018362 were associated with stress fracture period prevalence (P b 0.05). Analysis of the male only group showed 8.2% of rs1021188 rare allele homozygotes had suffered a stress fracturewhilst 2.5% of the non-stress fracture group were homozygous. In cases of multiple stress fractures, homozygotes for the rare allele of rs1021188 and individuals possessing atleast one copy of the rare allele of rs4355801 (OPG) were shown to be associated with stress fracture injury (P b 0.05). Conclusions: The data support an association between SNPs in the RANK/RANKL/OPG signalling pathway and the development of stress fracture injury. The association of rs3018362 (RANK) and rs1021188 (RANKL) with stress fracture injury susceptibility supports their role in the maintenance of bone health and offers potential targets for therapeutic interventions.
    Bone 10/2014; 71:131-136. · 4.46 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: It is being increasingly recognized that patients with liver disease develop bone loss that can be severe enough to lead to atraumatic fractures and thus markedly diminish life quality and expectancy. The estimated prevalence for liver-related osteoporosis is between 20-420/100000 of the general population, and fractures between 60-880/100000. It should be kept in mind that up to 40% of patients with chronic liver disease may experience a fracture. The pathogenic mediators include fibronectin, insulin like growth factor-I, and various cytokines, but decreased vitamin D and/or treatment with corticosteroids contribute to worsening bone health. Despite the advances in bone biology that have shed some light on the pathogenesis of this bone loss, treatment options remain nonspecific and tightly linked to treatments of other forms of osteoporosis. Thus, treatment should include calcium and vitamin D supplementation in all patients with chronic liver disease. Therapy with bisphosphonates should be considered, especially in patients receiving corticosteroids. This review focuses on the prevalence of this entity as well as the evidence available with regard to the pathogenesis of bone loss in liver disease, the diagnostic steps required in all patients, and the therapeutic options available.
    World journal of gastroenterology : WJG. 07/2014; 20(28):9427-9438.

Full-text (2 Sources)

Available from
May 15, 2014