Relation between Urinary Hydroxyproline and Parathyroid Function*

Abstract

With the exception of small amounts in elastin, all the hydroxyproline (OHPr) in the body is found in collagen. Evidence has been presented that the urinary peptide-bound OHPr reflects the metabolism of collagen (2-5) except when the dietary intake of gelatin or collagen is excessive. Since a major body depot of collagen is the matrix of bone, it might be anticipated that under some conditions the rate of OHPr excretion would furnish an index of the turnover of bone matrix.Parathyroid hormone is known to increase bone resorption (6)(7)(8)(9)(10)(11) received constant diets containing at most 120 g of lean, red meat daily, but no fish, Jello, ice cream, or other gelatin-rich foods. PTE was given intramuscularly at a dosage of 600 U a day for 10 to 12 days. Urine was collected in 24-hour pools under toluene and stored in a cold room at 4°C. Feces were collected in 4-or 6-day pools.2) Four-hour calcium infusion. Calcium glucoheptonate was given to a man (T.W., age, 46 years) and a woman (A.M.S., age, 40 years) with surgically induced hypoparathyroidism, to four normal men (ages, 20 to 42 years), and to five normal women (ages, 18 to 54 years). A.M.S. had been treated with vitamin D and T.W. had not been treated. All these subjects were fed a constant, liquid diet to give a daily intake of 350 mg of calcium (Ca), 980 mg of phosphorus (P), and less than 10 mg of OHPr in the form of protein. The diet was given in five equal feedings daily for 4 days. On day 3 of the diet, Ca, at a dosage of 15 mg per kg, as glucoheptonate in 0.9% sodium chloride solution, was administered intravenously by constant infusion over a 4-hour period starting at 9:00 a.m. Urine was collected in 4-hour samples for the determination of OHPr, P, and creatinine. Blood for determination of Ca, P, creatinine, and OHPr was drawn at appropriate times.3) Prolonged calcium infusions. Calcium glucoheptonate was given by continued iv infusion to three patients with hypoparathyroidism for 4 consecutive days while they were on a balance regimen similar to that used in the first group of experiments. The dosage of calcium averaged 7.5, 12.5, and 22.0 mg per kg per day in the three subjects, respectively. The 8 days before and after the infusion served as control periods. Blood was analyzed daily for Ca and P, and urine was collected daily for the determination of P, OHPr, and creatinine.Chemical assays. Samples of diets, urine, and feces were analyzed for P by the method of Fiske and SubbaRow (17), for total nitrogen by the method of Kjeldahl (18), and for Ca by flame photometry; samples of urine were analyzed for creatinine (19). Total OHPr was determined in hydrolyzed samples of urine and homogenized feces by the method of Prockop and Udenfriend (20). At varying levels of OHPr excretion, less than 3% of the total urinary OHPr was found to be the free amino acid; the remainder is presumed to be peptide-bound. Analysis of samples of fecal homogenate by the method 1073

Actions of parathyroid hormone in the vitamin D-deficient dog.

“…Recent studies by Walker, Lapiere, and Gross (25) have shown that parathyroid extract stimulates a collagenolytic factor in bone, thereby causing the release of hydroxyproline peptides in vitro (25). It has also been shown that parathyroid extract increases excretion of hydroxyproline in human subjects (26). The present studies suggest that parathyroid hormone influences bone collagen turnover despite a deficiency of vitamin D.…”

The relationship of parathyroid activity to pyrophosphate excretion.

“…Hydroxyprolinuria has often been reported in clinical disorders of bone metabolism (1,(15)(16)(17), and an apparent relation between parathyroid activity and urinary hydroxyproline has been defined (17). Recent isotopic data also reveal that hydroxyproline excretion correlates well with bone resorption (18)(19)(20).…”

Metabolic studies of human bone in vitro. II. Changes in hyperparathyroidism.

“…As the disease involves not only hypersecretion of the hormone but also loss of secretory control in the abnormal gland or glands (11,14), this hypothesis may be taken one step further to suggest an explanation for the appearance of two types of bone metabolic response in these patients, an explanation which, incidentally, provided the names "intermittent" and "continuous" used in this work to designate the two groups.…”

“…Moreover, serum Ca and P concentrations were borderline or normal, whereas serum alkaline phosphatase activity was not elevated, and urine hydroxyproline excretion was in the normal range. Indeed, the diagnosis had to be made in these patients on the basis of recurrent kidney stone formation, minimal, often intermittent, hypercalcemia or hypercalciuria, and abnormal response to tests of the control of parathyroid function, or all of these symptoms (11,12). The demonstration of these two distinct patterns of response raises the question of whether the difference between these two groups is a quantitative or a qualitative one, a question made more pertinent by Costello and Dent's recent suggestion that there may exist a separate hormone responsible for the changes of osteitis fibrosa cystica (13).…”

“…The association of the elevation of serum alkaline phosphatase and urinary hydroxyproline (14), and increased urinary hydroxyproline is associated with an increase in either collagen synthesis or breakdown or both (7,11 2) These are interpreted as manifestations of differing degrees of overactivity of the parathyroids, one group reflecting intermittent, and the other continuous, hypersecretion of parathyroid hormone.…”