68 



L. V. AviOLi, Ph. H. Henneman: Urinary Pyrophosphate in Disorders 



inorganic phosphate according to the method of Fiske and Subbarow (1925). Micro- 

 phosphate determinations on hydrolyzed pyrophosphate eluates were made by a 

 modification of the method of Chen et al. (1956). 



Results 



Urinary pyrophosphate excretion in normal adult subjects and in patients with 

 increased bone turnover are illustrated in Fig. 1. The normal mean pyrophosphate 

 excretion of 3.99 mg P/24 hr. (S.E. ±0.45) was much lower than that observed in 

 Paget's disease (15.48 ± 1.76), metastatic bone disease (24.33 ± 4.61), hyperpara- 

 thyroidism (21.31 ±4.78), and hyperthyroidism (20.79 ± 2.09). The elevated mean 

 values in subjects with increased bone turnover differed significantly from normal 

 with P-<.001 in each case. Urinary hydroxyproline excretion was also elevated in 

 the subjects with bone disease and paralleled the observed pyrophosphaturia in each 

 group (Fig. 2). Despite the marked increments in urinary pyrophosphate in disorders 

 of bone metabolism, no correlated changes were noted in orthophosphate excretion. 



HYDROXYPROLINE 

 mg /24hr 



D 



HYDROXYPROLINE 

 PYROPHOSPHATE 



^ 



PYROPHOSPHATE 

 mg P/24hr 



Fig. 2. Urinary pyrophosphate and total hydroxyproline in normals 



heigh: of the horizontal bar in eadi group represents the respective 



standard error about the meai 



and i 

 mean 



ith bone 

 rs repres 



disease. The 

 nt twice the 



Comments and conclusions 



Recent observations by Fleisch (1964) suggest that the normal 24-hour pyro- 

 phosphate excretion corresponds approximately to the amount of bone resorbed 

 daily. Fiydroxyprolinuria has been repeatedly documented in clinical disorders of bone 

 metabolism and attributed by Dull and Henneman (1963) to an accelerated resorp- 

 tion of collagenous bone matrix. The observation of parallel increments in urinary 

 hydroxyproline and pyrophosphate in the present study suggests that urinary pyro- 

 phosphate is derived primarily from bone dissolution. The significant elevations of 

 urinary pyrophosphate observed in Paget's disease, hyperparathyroidism, metastatic 

 bone disease and hyperthyroidism suggest that pyrophosphate excretion may be as 

 useful an index of bone resorption as is serum alkaline phosphatase for bone for- 

 mation in patients with accelerated bone turnover. 



