Treatment of osteomalacia associated with primary biliary cirrhosis with oral 1-alpha-hydroxy vitamin D3.

309 Treatment of osteomalacia associated with primary biliary cirrhosis with oral I-alpha-hydroxy vitamin D3 Osteomalacia sometimes occurs in chronic cholestatic liver disease and is usually treated with large doses of parenteral vitamin D, although oral treatment is also effective.' Treatment with oral lcx-hydroxy vitamin D3 (1ox-OHD,), a synthetic analogue of 1,25-dihydroxy vitamin D3, is of particular interest in liver disease since a therapeutic effect depends on its intestinal absorption and hepatic 25-hydroxylation,' both of which may be impaired in severe chronic cholestasis. We report the biochemical and histological responses to six months' treatment with oral lca-OHD3 in a patient with primary biliary cirrhosis (PBC) and severe osteomalacia. Case history In 1976 a 65-year-old woman presented with pruritus and jaundice. Liver biopsy showed changes consistent with late PBC, and antimitochondrial antibodies were present. Subsequently the serum bilirubin concentration remained between 50 and 103 4smol/l (2-9 and 6 0 mg/100 ml) (normal 3-20 ,umol/l; 0-2-1-2 mg/100 ml) and oesophageal varices developed. In April 1978 transiliac biopsy showed severe osteomnalacia, and in June treatment began with oral 1 oc-OHD3 2 ,ug daily. Serum calcium concentration was measured monthlyand a repeat bone biopsywas performed in December 1978. Renal function was normal throughout. She was also receiving frusemide 80 mg twice daily, potassium supplements, diphenoxylate, and parenteral vitamins A and K. Fasting serum alkaline phosphatase activity and calcium, albumin, phosphate, and bilirubin concentrations were measured on an autoanalyser (SMA 12/60), the serum calcium concentration being corrected for serum albumin value.3 Plasma immunoreactive parathyroid hormone (PTH) values were measured by radioimmunoassay4 (MRC antiserum code BW 211/41). Undecalcified sections of transiliac biopsy specimens (8 ILm) were quantified with a Zeiss 25-point eyepiece graticule. Calcification fronts were shown both by 1 % toluidine-blue staining and by fluorescence microscopy of unstained sections after giving 900 mg demethylchlortetracycline by mouth 48 hours before biopsy. Hyperparathyroidism was assessed qualitatively. Control values were obtained in biopsy specimens from seven women aged 54-73 years (mean 61-8); three were from healthy women and four from women who had died suddenly with no previous immobilisation or history of metabolic bone disease. After treatment with 1 oc-OHD3 the serum calcium and phosphate concentrations increased and the serum alkaline phosphatase activity lessened (see table). The plasma PTH concentration, which was high before treatment , was normal six months later. Liver function, as judged from serum bilirubin and albumin concentrations, remained stable during treatment. Hypercalcaemia was never encountered …