Cyclosporin A increases the biochemical markers of bone remodeling in primary biliary cirrhosis.
To assess whether cyclosporin A has any influence on the bones of patients with primary biliary cirrhosis, bone mineral density, vertebral fractures and biochemical and hormonal parameters of bone mineral metabolism were evaluated in 38 female patients with primary biliary cirrhosis who, 7 to 47 months previously, had been randomized to receive cyclosporin A (n = 18) or placebo (n = 20). Bone mineral density and vertebral fractures were reevaluated after 12 to 47 months in 19 of these patients (ten with cyclosporin and nine with placebo). Serum osteocalcin levels in patients taking cyclosporin (median, range: 7.8, 4.2-16 ng/ml) were similar to healthy female controls (6.0, 4.7-9.5 ng/ml), and significantly higher than in patients receiving placebo (5.4, 1.0-8.6 ng/ml, p < 0.02). Patients treated with cyclosporin showed a higher urinary hydroxyproline/creatinine ratio (0.097, 0.025-0.138) than patients with placebo (0.031, 0.022-0.044) (0.05 > p < 0.1), and healthy controls (0.032, 0.021-0.048) (p < 0.001). Urinary hydroxyproline was above normal levels in six of nine patients treated with cyclosporin. Circulating parathyroid hormone levels were also higher in patients treated with cyclosporin (4.3, 2.0-9.0 pmol/l) than in those with placebo (3.1, 1.1-5.1 pmol/l) (p < 0.001), and healthy controls (2.9, 1.1-6.9 pmol/l) (p < 0.001). In four patients treated with cyclosporin the parathyroid hormone levels were above normal values. No patient had renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)
Metabolic Bone Diseases Units, Hospital Clínic i Provincial, Barcelona, Spain.
N
N
Guañabens
A
A
Parés
M
M
Navasa
M J
MJ
Martínez de Osaba
M E
ME
Hernández
J
J
Muñoz
J
J
Rodés
D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects*; D002112:Calcifediol / Q000097:blood; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000097:blood; D003404:Creatinine / Q000097:blood / Q000652:urine; D016572:Cyclosporine / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006909:Hydroxyproline / Q000652:urine; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D008593:Menopause; D008875:Middle Aged; D010710:Phosphates / Q000097:blood; D010919:Placebos; D011446:Prospective Studies; D011517:Prothrombin Time; D012016:Reference Values; D013131:Spine / Q000187:drug effects / Q000473:pathology*; D005723:gamma-Glutamyltransferase / Q000097:blood
D015415:Biomarkers; D010710:Phosphates; D010919:Placebos; D016572:Cyclosporine; D003404:Creatinine; D005723:gamma-Glutamyltransferase; D000469:Alkaline Phosphatase; D002117:Calcitriol; D002112:Calcifediol; D001663:Bilirubin; D006909:Hydroxyproline; D002118:Calcium