M.R. Wills

MUSCLE WEAKNESS IN OSTEOMALACIA

The muscle weakness that frequently accompanies osteomalacia and rickets may arise from a variety of causes. Particularly in patients with muscle weakness, identification of the metabolic disorder is important, since effective treatment is often possible.

SEASONAL VARIATIONS IN SERUM 25-HYDROXYCHOLECALCIFEROL IN HEALTHY PEOPLE

Abstract The rate of endogenous cholecalciferol synthesis depends on the availability of biologically effective ultraviolet light in solar and sky radiation. There is a striking seasonal variation in the availability of ultraviolet light. In a group of healthy men and women a significant seasonal variation has been demonstrated in serum-25-hydroxy-cholecalciferol (25-H.C.C.) concentration. These findings are of importance in the interpretation of serum-25-H.C.C. values in clinical situations.

Clinical, biochemical, and histological studies of osteomalacia, osteoporosis, and parathyroid function in chronic liver disease.

Twenty of 32 patients with either chronic cholestatic or hepatocellular liver disease had bone pain or recent fractures. On bone biopsy five patients had normal bone, 15 had osteomalacia, five had osteoporosis, and seven had a combination of osteomalacia and osteoporosis. In the presence of osteoporosis, osteomalacia was minimal or absent. There was no biochemical, radiological, or histological evidence of excess parathyroid activity. No significant correlations were demonstrated between the plasma and urinary biochemical findings and the presence of either osteoporosis or osteomalacia and bone biopsy was essential for correct diagnosis. There was no statistical relationship between low serum 25-hydroxy vitamin D values and the presence of osteomalacia. Bone disease was not prevented by regular intramuscular vitamin D2, although biochemical changes were improved. Drugs such as corticosteroids and cholestyramine may be important aetiological factors in hepatic osteodystrophy.

25-Hydroxylation of vitamin D in primary biliary cirrhosis.

The ability to 25-hydroxylate vitamin D was investigated in thirty-nine patients with symptomatic primary biliary cirrhosis (P.B.C.). In seven previously untreated patients serum-25-hydroxy-vitamin-D (25-OHD) concentration increased after regular monthly injections of vitamin D. After a single injection of vitamin D in eight P.B.C. patients serum-25-OHD did not change significantly over 12 days; in contrast there were significant increases in eight normal subjects and in seven patients with nutritional osteomalacia. Twenty-three of twenty-five P.B.C. patients on regular vitamin-D therapy had normal serum-25-OHD values. These results indicate that serum-25-OHD concentrations become normal in P.B.C. if adequate amounts of vitamin D are presented to the liver as substrate.

SEASONAL VARIATION IN SERUM-25-HYDROXYVITAMIN-D IN THE ELDERLY IN BRITAIN

In a group of thirty-six non-housebound normal people aged 70 to 88 years living independently in their homes, mean serum-25-hydroxyvitamin-D (+/- 1 S.D.) was 8-62 +/- 3-08 ng/ml in midwinter and had risen to 14-13 +/- 4-90 ng/ml the following September. These values were lower and the seasonal variation was less than previously found in healthy young British adults.

PHYTIC ACID AND NUTRITIONAL RICKETS IN IMMIGRANTS

Abstract Nutritional rickets is reported in a 15-year-old Indian boy. His diet contained a high content of phytic acid and when this was reduced the rickets healed. Reports of nutritional osteomalacia in adults and rickets in children among the immigrant population of the United Kingdom are essentially confined to Indians or Pakistanis. The high dietary phytic acid among the chapati-eating Asian immigrants may be sufficient to impair calcium absorption and account for the nutritional rickets and osteomalacia in this population group.

SERUM-25-HYDROXY-VITAMIN-D IN UNTREATED PARENCHYMAL AND CHOLESTATIC LIVER DISEASE

Serum-25-hydroxy-vitamin-D (25 OHD) concentration has been measured in 106 patients with untreated parenchymal and cholestatic liver disease. Low mean values were found in groups of patients with alcoholic hepatitis and cirrhosis, non-cirrhotic active chronic hepatitis, lupoid and cryptogenic cirrhosis, symptomatic primary biliary cirrhosis, and acute and chronic biliary disease. In a group of patients with presymptomatic biliary cirrhosis the mean value was not significantly different from normal. It is concluded that in the presence of significant parenchymal or cholestatic liver disease serum-25-OHD concentrations are usually low. The mechanisms for the reduction remain to be clarified, but low serum-25-OHD values may play a contributory role in the aetiology of osteomalacia in chronic liver disease.

HYPOPHOSPHATAEMIC OSTEOMALACIA AFTER CADAVERIC RENAL TRANSPLANTATION

Abstract Seven patients with functioning renal transplants were found to have serum-inorganic-phosphate levels below normal, and five of them had X-ray evidence of osteomalacia Evidence for a phosphate leak came from abnormal high values for phosphate clearance and correspondingly low values for tubular reabsorption of phosphate. There was a slight metabolic acidosis. The cause of the phosphate leak is uncertain, but it could be that in these patients the proximal tubule is unduly sensitive to normal levels of parathyroid hormone.

Intestinal absorption of cholecalciferol in alcoholic liver disease and primary biliary cirrhosis.

The intestinal absorption of (3H)cholecalciferol was studied in five patients with alcoholic liver disease, six patients with primary biliary cirrhosis, and 15 healthy subjects. The rate of appearance in plasma of (3H)cholecalciferol after oral ingestion and the subsequent appearance of (3H) polar metabolites in the alcoholic subjects were similar to those in the healthy subjects. In subjects with primary biliary cirrhosis the rate of appearance in plasma of (3H)cholecalciferol was significantly reduced. The rate of appearance of labelled polar metabolites of cholecalciferol was also lower in this group, suggesting that increased removal of labelled vitamin by conversion into more polar metabolites could not account for the reduced plasma (3H)cholecalciferol response. It is suggested that intestinal absorption of cholecalciferol is usually normal in alcoholic liver disease but impaired in primary biliary cirrhosis. Hepatic 25-hydroxylation is normal in alcoholic liver disease but may be defective in primary biliary cirrhosis.

Serum 25-hydroxyvitamin D assay. Evaluation of chromatographic and non-chromatographic procedures

A competitive protein binding assay for serum 25-hydroxyvitamin D is described in which normal human serum is used as the source of binding protein. A serum sample is extracted with diethyl ether/methanol and then chromatographed using silica gel. Validation of the method is reported. Silica gel chromatography is compared with LH20 chromatography. The method is also compared with extraction techniques using diethyl ether and ethanol without subsequent chromatography. It is concluded that chromatography with either silica gel or LH20 is essential. The non-chromatographic methods investigated, in addition to giving much higher values than chromatographic methods, did not meet validation requirements with respect to accuracy and behaviour of samples on dilution.