The treatment of adult phosphate diabetes and Fanconi syndrome with neutral sodium phosphate

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Two adults with untreated phosphate diabetes and severe osteomalacia as demonstrated by wide osteoid seams on bone biopsy, multiple pseudofractures and marked skeletal rarefaction were studied using metabolic balance technics, radiocalcium kinetics and urinary hydroxyproline excretion. Negative calcium balance with high fecal calcium, low normal rates of deposition of calcium in bone and normal rates of hydroxyproline excretion were found. The acute as well as long-term effects of phosphate supplements as the only therapy were investigated by these methods. Healing of the bone disease resulted, as judged by clinical, roentgenologic and histologic criteria, and was accompanied by a striking increase in bone turnover (increased calcium deposition rate in bone and, to a lesser extent, increased calcium removal rate from bone; increased urinary hydroxyproline excretion and increased levels of serum alkaline phosphatase). This increase in bone turnover was accompanied by increased absorption of calcium and phosphorus from the gastrointestinal tract. There was a good correlation between the radiocalcium kinetics and hydroxyproline excretion, less correlation between these two parameters and the levels of alkaline phosphatase. Acute and long-term withdrawal of phosphate supplements was associated with fall of the first two parameters toward pretreatment levels; long-term withdrawal was accompanied by a decrease in the levels of serum alkaline phosphatase as well. Phosphate therapy also produced changes in skeletal retention of an acute load of sodium fluoride, and in the urinary excretion of hydroxylysine which paralleled those obtained using the other parameters of bone turnover. A similar response to phosphate therapy was observed in a subject with the adult Fanconi syndrome, partially treated with vitamin D. In another subject with normal serum phosphate levels and idiopathic osteoporosis, therapy with phosphate for five months produced only minor changes in the aforementioned parameters although the direction was similar to that in the other subjects. In a patient with mild phosphate diabetes, short-term phosphate supplements elicited responses in the same direction, although of lesser magnitude, as in patients with more severe osteomalacia. It is concluded that phosphate treatment of patients with phosphate diabetes and osteomalacia results in stimulation of initially low-normal rates of bone formation by a mechanism as yet undefined. The stimulation of bone resorption which also accompanied phosphate therapy in these subjects may result in part from secondary hyperparathyroidism.