Evidence for secondary hyperparathyroidism in the osteomalacia associated with chronic liver disease

Previous reports have suggested that secondary hyperparathyroidism is extremely uncommon in hepatic osteomalacia. This, together with other findings, has led to suggestions that in chronic liver disease there may be selective resistance of bone to vitamin D or a specific bone mineralization defect unrelated to Vitamin D. To examine these possibilities, twenty-five patients with chronic liver disease have been studied by bone biopsy, serum calcium and inorganic phosphate, plasma 25-hydroxyvitamin D, plasma immunoreactive parathormone (iPTH), fasting urine cAMP, fasting renal tubular maximal reabsorptive capacity for phosphate (TmP/GFR) and fine grain hand x-rays. Nine of the patients had osteomalacia on bone biopsy, eight of these had subnormal levels of plasma 25-hydroxyvitamin D and the other had a borderline result. Based on the consensus of all the tests, five of these had evidence of secondary hyperparathyroidism. Plasma iPTH was higher in patients with osteomalacia than in patients without osteomalacia (P less than 0.01) or controls (P less than 0.01). Urine cAMP was higher in patients with osteomalacia than in patients without osteomalacia (P less than 0.001) or controls (P less than 0.01). TmP/GFR was significantly lower in patients with osteomalacia than in controls (P less than 0.05) but not significantly different from patients without osteomalacia. The findings of this study indicate that hyperparathyroidism occurs in a substantial proportion of patients with the osteomalacia of chronic liver disease. Moreover, osteomalacia in chronic liver disease is clearly related to reduced levels of plasma 25-hydroxyvitamin D. We conclude that hepatic osteomalacia is a vitamin D deficiency state and there is no need to suggest an unusual aetiology.