Urinary hydroxyproline

Westall first noted the presence of hydroxyproline in normal urine it was present only in peptide form and associated with proline. He concluded that this bound hydroxyproline was a degradation product of collagen (W2), a hypothesis later confirmed by the study of enzymatic digests of collagen (G6). The types of hydroxyproline peptide present in the urine and their relation to growth were reviewed by Smiley and 

In several published studies of urinary hydroxyproline excretion in normal adult subjects, males were noted to excrete larger quantities of total hydroxyproline (Table 2). When absolute hydroxyproline excretion was corrected for either surface area or creatinine excretion, no differences between males and females were noted. This observation suggests that 

The age of the subject is a major factor in the interpretation of urinary hydroxyproline levels (S15). Measurements in subjects during active growth have shown elevations to 15-fold the normal adult level (J9). For this reason, it would seem reasonable to divide subjects under the age of 25 into several groups, each requiring its own growth rate -matched controls. Also, more variability is observed in the urinary hydroxyproline levels of these younger subjects than in those of adults. Consequently, attempts have been made to correct the actual hydroxyproline excretion for some parameter of size, such as body surface area. Table 3 outlines the published normal urinary hydroxyproline levels in infants, children, adolescents, and young adults. Both uncorrected and corrected data are 

The difiSculty in obtaining complete 24-hour urine collections in the pediatric age group has prompted the introduction of a correction based on the concomitant determination of creatinine (W4). This type of determination, i.e., the hydroxyproline/creatinine ratio, might obviate the necessity of 24-hour urine collections in adult studies as well, and, if done on a fasting urine sample, might also eliminate the necessity of dietary restriction. Since creatinine is often determined to assess the completeness of 24-hour collections, the technical load would not be 

Children 1-10 years). There is large variation in normals in this age group, perhaps because of the variable growth rates in children and the early age at which females begin the prepubertal growth spurt. When the data are separately presented, normal female children have a higher urinary hydroxyproline excretion than males of comparable age (Table 2). 

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Diet Fractional Renal Ca Reabsorption (%) Plasma Ultra-filtrable Ca (mg/100 ml) Urinary Cyclic AMP (ymoles/day) Urinary Hydroxyproline (mg/day)... 

Diet Urinary Cyclic AMP (pmoles/day) Urinary Hydroxyproline (mg/day)... 

D5. de la Piedra, C., Toural, V., and Rapado, A., Osteocalcin and urinary hydroxyproline/creatinine ratio in the differential diagnosis of primary hyperparathyroidism and hypercalcaemia of malignancy. Scand. J. Clin. Lab. Invest. 47, 587-592 (1987). 

Chronic intoxication with vitamin A has been reported to cause variously hypercalcemia, hyperglycae-mia, increased alkaline phosphatase, hypoproteinemia, hypoprothrombinemia, increased sulfobromphthalein retention, raised serum transaminases, low serum ascorbic acid, reduced protein content of the cerebrospinal fluid, raised urinary hydroxyproline, and hypercalciuria (SED-8, 800) (14). It is not always clear, however, whether these deviations are a cause or an effect of hypervitaminosis A. 

Excessive doses of vitamin A lead to accelerated resorption of trabecular and cortical bone because of increased osteoclastic activity. A raised alkaline phosphatase, increased urinary hydroxyproline concentrations, and hypercalciuria correlate with these findings (54). One study suggested that high dietary intake of retinol might be associated with osteoporosis (55). 

Paroni R, De Vecchi E, Fremo I, Arcelloni C, Diomede L, Magni F, et al. Total urinary hydroxyproline determined with rapid and simple high-performance liquid chromatography. Clin Chem 1992 38 407-11. 

The first aspect has been overcome by measurement of urinary hydroxyproline in individuals with an inherited deficiency of hydroxyproline oxidase. Such persons excrete... 

Calcitonin is a useful marker for medullary carcinoma of the thyroid, which occurs both sporadically and as a dominantly inherited disease. In this type of tumor, the plasma concentration of calcitonin is 1-1000 mg/mL (normal concentration ranges from undetectable to 0.05 ng/mL). Also, urinary hydroxyproline excretion is decreased. Ectopic secretion of calcitonin also occurs from several types of pulmonary tumor in addition to other hormones. 

Calcitonin is used in the treatment of Paget s disease (osteitis deformans), a chronic disorder characterized by increased bone remodeling, normocalcemia and normophosphatemia, frequent episodes of hypercalciuria leading to stone formation, and elevation of serum alkaline phosphatase and urinary hydroxyproline levels. The disease does not appear to be primarily a derangement of calcium metabolism. Calcitonin reduces the levels of serum alkaline phosphatase and urinary hydroxyproline, and may relieve other symptoms of the disease as well. Diphosphonates, especially etidronate disodium, also reduce bone resorption in this disease. Various cancers are accompanied by hypercalcemia and may respond to treatment with calcitonin. 

An estimated 75 million people are affected by osteoporosis to some degree in the United States, Europe, and Japan. Osteoporosis is a systematic skeletal disease characterized by bone mass and microarchitectural deterioration with a consequent increase in bone fragility and susceptibility to fracture. Operationally, osteoporosis can be defined as a certain level of bone mineral density. The definition of osteoporosis is somewhat arbitrary and is based on epidemiological data relating fracture incidence to bone mass. Uncertainty also is introduced due to variability in bone densitometry measurements. Other clinical measures to assess the skeleton include collagen cross-links (measure of bone resorption) and levels of bone-specific alkaline phosphatase and osteocalcin (bone formation). A list of biochemical markers of bone remodeling is provided in Table 37-3. Measurement of total serum alkaline phosphatase level and urinary hydroxyproline or calcium levels is of limited value. 

Adults 24 years or older). The normal adult level of urinary hydroxyproline is fairly well defined, as shown in Table 2. In 32 studies surveyed, reporting data from 515 normal subjects, 25 studies found no normal adults excreting more than 50 mg/day three studies, no more than 60 mg (A2, B6, L7) three studies, no more than 70 mg (J8, L8, R2) and one study, no more than 90 mg (B20). If three subjects were eliminated from this large group, all normal values would be less than 70 mg/day. In the author s experience, the upper limit of normal urinary hydroxyproline excretion, in adults of age 25 or older on diets free of meat... 

The wide variation in normal urinary hydroxyproline levels in children has been discussed above. The most consistent of the abnormalities of urinary hydroxyproline in children, as shown in Table 4, is the decreased excretion associated with defective growth. Whether the cause of growth retardation is hormonal, genetic, or environmental (malnutrition or chronic disease and/or drug therapy), urinary hydroxyproline excretion is decreased. When the hydroxyproline excretion is corrected for surface area or creatinine excretion, this measurement seems to correlate well with the extent of growth retardation (W4). In spite of the fact that creatinine excretion is also reduced in malnutrition, Whitehead found an... 

Much has been written about the value of urinary hydroxyproline elevations in separating bone formation from bone resorption. Correlations have been attempted clinically between urinary hydroxyproline, on the one hand, and serum alkaline phosphatase, serum and urinary calcium, calculations of calcium turnover such as the bone formation rate and bone resorption rate, bone histology, and bone radiology. Most authors feel that the level of urinary hydroxyproline refiects bone destruction (B6, B16, D8, D9, Gl, K26, L8, SI 6) more than bone formation (H9, K20). This does not seem to be a very useful argument clinically, because bone formation and destruction are usually occurring simultaneously in... 

In spite of these inherent shortcomings, the measurement of urinary hydroxyproline offers a useful index of bone matrix metabolism to add to the spate of techniques of bone mineral measurement used to study the endocrinology and metabolism of bone (B8). 

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