RESUMO
BACKGROUND: Osteoporosis is an important cause of morbidity in patients with Crohn's disease. The pathogenesis of reduced bone mineral density (BMD) is multifactorial. A range of genetic factors have been implicated in other populations of patients with osteoporosis. AIM: To investigate the influence of interleukin 6 (IL-6), collagen type 1alpha1 (COL1A1), and vitamin D receptor gene (VDR) single nucleotide polymorphisms (SNP) on BMD in patients with Crohn's disease. PATIENTS: A cohort of 245 well characterised patients with Crohn's disease were recruited from the inflammatory bowel disease register at the Freeman Hospital and Royal Victoria Infirmary, Newcastle upon Tyne, and the Queen Elizabeth Hospital, Gateshead, UK. METHODS: Patients were genotyped for IL-6 C-174G SNP, COL1A1 Sp1 binding site G T SNP, VDR Taq1, and Fok1 SNPs, and CARD15 R702W, G908R, and L1007fs SNPs. BMD was measured at the lumbar spine (LSP) and hip using dual energy x ray absorptiometry. RESULTS: A total of 158 female and 87 male patients, aged 24-70 years (mean 44), were recruited. There were no significant differences in the distribution of the tested SNPs when analysed for age, body mass index, pre/post-menopausal status, smoking, or steroid use. Two hundred and thirteen patients were genotyped for the IL-6 SNP. LSP and total hip BMD was significantly lower in patients with the GG genotype (48%) than the CC genotype (15%) (p = 0.041, p = 0.014). One hundred and eighty patients were genotyped for the COL1A1 SNP. There was no significant difference in BMD at LSP. Hip BMD was significantly lower in heterozygous patients compared with homozygous wild-types (p = 0.034). There were no significant differences in BMD between genotypes for the two VDR SNPs or the CARD15 genotypes examined. CONCLUSION: IL-6 and COL1A1 gene polymorphisms influence BMD in patients with Crohn's disease but the particular VDR gene polymorphisms studied do not have a major effect.
Assuntos
Densidade Óssea/genética , Colágeno Tipo I/genética , Doença de Crohn/genética , Interleucina-6/genética , Receptores de Calcitriol/genética , Corticosteroides/farmacologia , Adulto , Idoso , Densidade Óssea/efeitos dos fármacos , Cadeia alfa 1 do Colágeno Tipo I , Doença de Crohn/tratamento farmacológico , Doença de Crohn/fisiopatologia , Feminino , Genótipo , Articulação do Quadril/fisiopatologia , Humanos , Vértebras Lombares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Osteoporosis is a common complication of Crohn's disease. AIM: To study the effect on the bone mineral density of a bisphosphonate (pamidronate) given intravenously, in combination with oral calcium and vitamin D supplements, compared with oral calcium and vitamin D supplements alone. METHODS: Seventy-four patients with Crohn's disease and low bone mineral density at the lumbar spine and/or hip were randomized to receive either a daily dose of 500 mg of calcium with 400 IU of vitamin D alone or in combination with four three-monthly infusions of 30 mg of intravenous pamidronate over the course of 12 months. The main outcome measure was the change in bone mineral density at the lumbar spine and hip, measured by dual X-ray absorptiometry, at baseline and 12 months. RESULTS: Both groups gained bone mineral density at the lumbar spine and hip after 12 months. There were significant (P < 0.05) changes in the pamidronate group, with gains of + 2.6%[95% confidence interval (CI), 1.4-3.0] at the spine and + 1.6% (95% CI, 0.6-2.5) at the hip, compared with gains of + 1.6% (95% CI, - 0.1-3.2) and + 0.9% (95% CI, - 0.4-2.1) at the spine and hip, respectively, in the group taking vitamin D and calcium supplements alone. CONCLUSIONS: In patients with Crohn's disease and low bone mineral density, intravenous pamidronate significantly increases the bone mineral density at the lumbar spine and hip.
