Department of Rheumatology, South Cleveland Hospital, Middlesbrough, UK
SIR, The biochemical abnormalities of osteomalacia can easily be overlooked in patients with primary biliary cirrhosis (PBC). This may develop as a consequence of renal tubular acidosis (RTA), which can be associated with PBC. A 47-yr-old lady with a history of nephrotic syndrome resulting from a minimal-change nephropathy, was referred for a liver biopsy because of elevated serum alkaline phosphatase. She was positive for the anti-mitochondrial antibody (AMA), which had first been identified when she had presented with nephrotic syndrome 4 yr earlier. This had been treated successfully with prednisolone and the serum creatinine had stabilized around 150 µmol/l on a maintenance dose of prednisolone 5 mg on alternate days. Although there were no specific histological features of PBC on the liver biopsy, there was evidence of mild chronic hepatitis, and she was given a trial of antioxidants [Bioantox and BioQuinone Q10; both from PharmaNord, Vojens, Denmark] as treatment for PBC.
Over the next 2 yr she developed rib pain and proximal muscle pain, which progressed to the point where her mobility was severely restricted. On referral to the rheumatology department she was found to have a waddling gait with proximal muscle weakness and rib tenderness. The serum bicarbonate was low at 16 mmol/l (normal range 2229 mmol/l) and the urine pH 6.0. The serum phosphate was 0.6 mmol/l (normal range 0.81.4 mmol/l) and the serum alkaline phosphatase 270 IU/l (normal range 30120 IU/l). Glycosuria (++++) was found on urinalysis with a normal blood glucose. There were Looser's zones on radiographs of the femoral neck bilaterally, and a bone scan showed marked uptake at these areas and also numerous hot spots in the ribs, consistent with rib fractures. The serum vitamin D, 25-hydroxyvitamin D, parathyroid hormone and urinary calcium excretion were all within the normal range. The AMA was positive at a titre of 1/40 but the anti-M2 antibody was negative on ELISA. A tetracycline-labelled bone biopsy confirmed severe osteomalacia. The trabecular bone volume was normal but the osteoid was dramatically increased (Fig. 1), and absence of tetracycline labelling indicated failure to mineralize. She was treated with bicarbonate, potassium and phosphate supplements (sodium bicarbonate 9 g daily, Sandoz phosphate 3 tablets daily) together with calcitriol 250 ng daily. Her symptoms resolved over a 9-month period, with an associated reduction in serum alkaline phosphatase concentration and correction of the hypophosphataemia.
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Although an elevated alkaline phosphatase in a patient who is AMA-positive will usually be due to PBC, osteomalacia should be considered, especially when the M2 antibody is negative or the liver biopsy is non-specific.
Notes
Correspondence to: B. K. S. Davidson, Musculoskeletal Unit, Freeman Hospital, High Heaton, Newcastle upon Tyne, NE7 7DN, UK.
References