hydroxylysine and Bone-Diseases--Metabolic

The purpose of this study is to review the urine products of bone breakdown as markers of bone resorption and usefulness of urinary hydroxyproline.. Related researches published in 1985 - 2000 were systematically reviewed.. Bone markers could be used for early diagnosis of bone metabolic diseases. Biochemical markers of bone resorption that reflect osteoclast activity and/or collagen degradation provide a new and potentially important clinical tool for the assessment and monitoring of bone metabolism. Assessment of bone resorption can be achieved with measurement of urinary hydroxylysine glycosides, urinary excretion of the collagen pyridinium cross-links, urinary excretion of type I collagen telopeptide breakdown products (cross-linked telopeptides) and urinary hydroxyproline.. Urinary hydroxyproline has been in use as a marker of bone resorption, but it lacks sensitivity and specificity. It is a modified amino acid that is a metabolic product of collagen breakdown. Hydroxyproline may be released either free or with fragments of the collagen molecule attached during bone resorption, and it is also liberated by the breakdown of complement and nonskeletal collagen.

Topics: Biomarkers; Bone Diseases, Metabolic; Bone Resorption; Collagen; Humans; Hydroxylysine; Hydroxyproline; Pyridinium Compounds

The pyridinium derivatives hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) are intermolecular crosslinking compounds of collagen which are only present in its mature form. Contrasting to the wide distribution of type I and II collagens, HP and LP are absent from skin, ligament and fascia, and their major sources are bone and cartilage. Using a specific HPLC assay, we have determined the 24-h excretion of HP and LP crosslinks in normal adults of both sexes, in patients with primary hyperparathyroidism and in patients with Paget's disease of bone before and after intravenous treatment with amino-propylidene bisphosphonate (APB). Mean adult normal values were 33 +/- 13 pmol/mumol creatinine for HP and 6.3 +/- 3.4 pmol/mumol creatinine for LP. In women, menopause induced a 2-3-fold increase of HP and LP reflecting the well documented postmenopausal increase of bone turnover. In the urine of patients with primary hyperparathyroidism and of patients with active Paget's disease of bone, urinary crosslinks were significantly higher than in age-matched controls, with a mean 3- and 12-fold increase, respectively. Urinary excretion of hydroxyproline is a well recognized but poorly sensitive marker of bone turnover, reflecting resorption. In the same patients, the effect of menopause and disease state on hydroxyproline excretion was much less dramatic than on HP and LP. During intravenous APB treatment of pagetic patients, there was an early decrease of HP and LP, which was significant after 24 h and reached 62% at 4 days, contrasting with a late and milder decrease of urinary hydroxyproline. Because APB is a potent inhibitor of resorption which does not have a direct short-term effect on bone formation, these data also indicate that urinary excretion of HP and LP reflect only collagen degradation occurring during osteoclastic resorption and not the degradation of newly synthesized collagen. We conclude that urinary HP and LP excretion represents the first sensitive and specific marker of bone resorption. Its use should be valuable in the clinical investigation of metabolic bone diseases, especially osteoporosis.

Topics: Adult; Aged; Alkaline Phosphatase; Amino Acids; Bone Diseases, Metabolic; Bone Resorption; Chromatography, High Pressure Liquid; Female; Humans; Hydroxylysine; Hyperparathyroidism; Lysine; Male; Menopause; Middle Aged; Osteitis Deformans; Pyridinium Compounds; Reference Standards

Immediately after the trauma, spinal cord injury patients have an increased rate of collagen synthesis and an even greater increase of collagen degradation. Collagen lost from bone is implicated in the etiology of osteoporosis and heterotopic ossification, and collagen lost from skin might lead to a propensity to develop pressure ulcers. The urinary excretion of two collagen metabolites has been monitored and their fluctuation related to the onset of skin or bone complications in these patients. One metabolite, glucosyl-galactosyl hydroxylysine, is more abundant in skin collagen; the other, galactosyl hydroxylysine, is more abundant in bone collagen. The excretion of both metabolites increases after injury, reaching a peak between three and six months after injury, and declines gradually, reaching control values about a year after injury. If a skin pressure ulcer develops, the urinary excretion of the diglycoside remains elevated instead of gradually decreasing. Similarly, if osteoporosis or heterotopic ossification is diagnosed, the monoglycoside excretion does not return to control values until the bone turnover stabilizes. Monitoring of the urinary excretion of both glycosides might prove helpful in prompting early examination to establish the presence of emerging skin and bone complications. Thus, aggressive preventive therapy could be given sooner.

Topics: Adolescent; Adult; Bone Diseases, Metabolic; Collagen; Humans; Hydroxylysine; Male; Middle Aged; Pressure Ulcer; Spinal Cord Injuries