hydroxylysine and Osteitis-Deformans

In inflammatory granuloma, synovial sclerosis or inflammation and in Dupuytren's contracture, the neocollagen contains chains and/or transverse links that are characteristic of rapidly growing immature tissues. In arthrosis, a conversion of collagen synthesis towards a cutaneous type may occur. The destruction of cartilage in rheumatoid arthritis is brought about by a specific collagenase that originates from the inflamed synovial membrane. Finally, certain forms of osteoporosis may be due to alterations of the osseous collagen which impair the mechanism of calcification.

Topics: Animals; Arthritis, Rheumatoid; Bone Diseases; Cartilage, Articular; Collagen; Collagen Diseases; Dupuytren Contracture; Fibroblasts; Granulation Tissue; Granuloma; Humans; Hydroxylysine; Microbial Collagenase; Osteitis Deformans; Osteoarthritis; Osteoporosis; Protein Conformation; Rheumatic Diseases; Sclerosis; Synovial Membrane; Synovitis

Topics: Bone and Bones; Calcitonin; Calcium; Collagen; Etidronic Acid; Humans; Hydroxylysine; Hydroxyproline; Osteitis Deformans; Procollagen

Serum-based biochemical markers of bone resorption may provide better clinical information than urinary markers because direct comparison with serum markers of bone formation is possible and because the within-subject variability of serum markers may be lower. We describe a method for the measurement of free beta-1-galactosyl-O-hydroxylysine (Gal-Hyl) in serum.. The assay used preliminary ultrafiltration of serum, dansylation, and separation by reversed-phase HPLC with fluorescence detection. Healthy subjects were recruited from population-based studies of bone turnover.. The within-run (n = 15) and between-run (n = 15) CVs were 7% and 14%, respectively, at a mean value of 48 nmol/L. In women and pubertal girls, serum free Gal-Hyl correlated with urine free Gal-Hyl (r = 0.84; P <0.001). Serum Gal-Hyl was higher during puberty and increased after menopause. The fractional renal clearance of free Gal-Hyl relative to that of creatinine was 0.90 (95% confidence interval, 0.82-0.98). Serum free Gal-Hyl decreased by 36% (SE = 4%) in 14 patients with mild Paget disease treated with an oral bisphosphonate, and this decrease was significantly (P <0. 001) greater than that seen for either serum tartrate-resistant acid phosphatase (9%; SE = 4%) or serum C-terminal telopeptide of collagen I (19%; SE = 8%).. Serum free Gal-Hyl may be useful as a serum marker of bone resorption.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Biomarkers; Bone Resorption; Child; Diphosphonates; Female; Humans; Hydroxylysine; Menopause; Middle Aged; Osteitis Deformans; Puberty

Urinary galactosyl hydroxylysine/creatinine ratio (GHL) was used to assess rates of bone collagen degradation and the activity of the pagetic lesion as well as for monitoring the rate and degree of suppression of bone resorption over 1 year in patients treated with 30 mg of intravenous pamidronate for 3 consecutive days. The clinical utility of GHL was compared with that of urinary hydroxyproline/creatinine and deoxypyridinoline/creatinine and with bone isoenzyme of serum alkaline phosphatase. The results suggest that GHL is a quantitative marker of the activity of Paget's bone disease. GHL is less sensitive than hydroxyproline, deoxypyridinolone and bone alkaline phosphatase in monitoring treatment of Paget's disease. The assay of GHL is easier, faster and less costly than that of hydroxyproline or deoxypyridinoline and it can be easily standardized.

Topics: Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Biomarkers; Bone and Bones; Bone Resorption; Chromatography, High Pressure Liquid; Creatinine; Female; Humans; Hydroxylysine; Hydroxyproline; Isoenzymes; Male; Middle Aged; Osteitis Deformans; Spectrometry, Fluorescence

Galactosylhydroxylysine (GHL) is released during bone resorption and has been shown to be elevated in subjects with metabolic bone loss. GHL is relatively specific for bone, it is not recycled or significantly metabolized during collagen turnover, and the levels are not influenced by diet. Previous measurements of GHL levels in urine have been performed using reverse-phase high performance liquid chromatography following pre-column derivatization. We produced polyclonal antibodies to GHL using GHL purified from sea sponges and developed an immunoassay that can recognize GHL in urine. The antibodies have minimal cross-reactivity with a physiological mixture of amino acids (< 1%), galactose (< 0.2%), lactose (< 0.3%), and glucosylgalactosylhydroxylysine (< 1%). This competitive immunoassay requires no dilution or pretreatment of the samples and provides a rapid and easy method for the evaluation of GHL in urine. Analysis of clinical samples from normal individuals, post-menopausal women, osteoporotic patients and individuals with Paget's disease show that the assay can discriminate between groups with differing levels of bone resorption as well as deoxypyridinoline (Dpd).

Topics: Adult; Aged; Amino Acids; Animals; Biomarkers; Bone Resorption; Chromatography, High Pressure Liquid; Collagen; Female; Humans; Hydroxylysine; Immunoassay; Male; Middle Aged; Osteitis Deformans; Osteoporosis; Osteoporosis, Postmenopausal; Porifera; Postmenopause; Rabbits; Reference Values; Reproducibility of Results; Sensitivity and Specificity

We compared the clinical performances of four bone-resorption (BR) assays (hydroxyproline, HYP; galactosyl hydroxylysine, GHYL; deoxypyridinoline, DPD; and pyridinoline, PYD) in subjects with different BR rates: normal (adult men and premenopausal women), mildly increased (postmenopausal osteoporotic women), high (Paget disease patients), and very high (children). The discrimination power (Z score) and the accuracy (estimated by receiver-operating characteristic analysis) for GHYL, DPD, and PYD were compared with those for HYP. Discrimination power and accuracy were similar for high- and very-high-BR groups for all four assays. However in the mildly increased-BR group, DPD, GHYL, and PYD showed a higher discrimination power and accuracy than did HYP. The clinical performances of HYP, DPD, GHYL, and PYD are comparable for large changes in BR. For modest changes, DPD, GHYL, and PYD are more accurate and have a higher discrimination power than does HYP.

Topics: Adult; Aged; Amino Acids; Biomarkers; Bone Resorption; Child; Chromatography, High Pressure Liquid; Female; Humans; Hydroxylysine; Hydroxyproline; Male; Middle Aged; Osteitis Deformans; Osteoporosis, Postmenopausal; 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

Patient's with carcinoma metastases in bone and Pagent's disease of bone have different patterns of collagen metabolite excretion. Both forms of bone disease resulted in an increased excretion of total hydroxyproline and the ratio of glucosylgalactosylhydroxylsine to galactosylhydroxylysine was below normal. The excretion of glucosylgalactosylhydroxylysine and galactosylhydroxylysine was increased in all patients with carcinoma metastases in bone while the excretion of glucosylgalactosylhydroxylysine in patients with Paget's disease. The ratio of total hydroxylysine (free hydroxylysine + glycosylated hydroxylysines) to total hydroxyproline was normal in patients with carcinoma metastases in bone and below normal in patients with Paget's disease bosne. The pattern of urinary collagen metabolite excretion is a more specific indicator of the presence of bone disease than is the measurement of the excretion rate of any individual collagen metabolite. Bone diseases of different etiologies may result in different patterns of urinary collagen metabolite excretion.

Topics: Bone Neoplasms; Collagen; Glycosides; Humans; Hydroxylysine; Hydroxyproline; Neoplasm Metastasis; Osteitis Deformans

Urimary excretion of hydroxyprolin (Hyp) is one index of total collagen degradation, from all sources. Since some of the Hyp released from collagen may be further metabolized before it is excreted, other markers are necessary to measure collagen breakdown. Excretion of the glycosides of hydroxylysine (Hyl), glucosyl galactosyl hydroxylysine (Hy1[Gl)cGa1]), and galactosyl hydroxylysine (Hyl[Ga)]), more accurately reflects collagen metabolism since these products occur in specificratios in different tissue collagens and are themselves metabolized only to a minor degree. The ratios of total Hy1/Hyp and Hyl(GlcGal)/Hyl(Ga1) were measured in the urine of norma. subjects and of patients with Paget's disease of bone, hyperphosphatasia, and extensive thermal burns. In patients with extensive thermal burns the pattern of urinary Hy1 and its glycosides was consistent with degradation of collagen in dermis and fascia. When bone collagen degradation was dominant, the pattern of urinary metabolites reflected that source. Pagetic bone collagen has an amino acid composition similar to normal bone and Hy1(G1cGa1/Hyl(G1) of 0.396-0.743,vs. normal of 0.474+/-0.088. In untreated patients with severe Paget's disease of bone or hyperphosphatasia (urinary Hyp greater than 2.0 micronmol/mg creatinine) urinary Hyl/Hyp averaged 0.052+/-0.042 (0.042+/-0.009 in normal bone) and Hy1(G1cGa1)/Hy1(Ga1) 0.601+/-0.017 (0.47+/-0.009 in normal bone). When bone resorption was decreased sufficiently with calcitonin or disodium etidronate in these patients, both the urinary ratios of Hy1/Hyp and Hy1(G1cGa1)/Hyl(Gal) rose. In normal subjects treated with calcitonin and excreting relatively little Hyp, the ratio of Hy1/H)P approached 0.7 and Hy1(G1ycGa1)/Hy1(Ga1) approached 3.5. There increased ratios reveal the existence of a source of collagen breakdown other than skin or bone. The first subcompoent of complement, Clq, which has collagen-like sequences, relatively high amounts of Hy1, and most of the glycosylated Hy1 as Hy1(G1cGa1), could be the source of these metabolites.

Topics: Adolescent; Adult; Amino Acids; Bone and Bones; Burns; Calcitonin; Child; Collagen; Etidronic Acid; Fascia; Female; Glycosides; Humans; Hydroxylysine; Hydroxyproline; Male; Middle Aged; Osteitis Deformans

The urinary excretion of glucosyl-galactosyl-hydroxylysine and of galactosyl-hydroxylysine were studied in Paget's disease of bone and in primary hyperparathyroidism. Both metabolites were increased in these diseases. Although glucosyl-galactosyl-hydroxylysine is not abundant in bone collagen, it is possible that a part of it originates from calcified tissue.

Topics: Alkaline Phosphatase; Bone and Bones; Calcitonin; Collagen; Glycosides; Humans; Hydroxylysine; Hyperparathyroidism; Osteitis Deformans

Topics: Adult; Bone Diseases; Calcitonin; Chromatography, Ion Exchange; Creatinine; Disaccharides; Female; Galactose; Glycosides; Glycosuria; Humans; Hydroxylysine; Hyperparathyroidism; Male; Monosaccharides; Osteitis Deformans; Osteomalacia; Parathyroid Glands; Protein Binding; Skin Diseases

Topics: Bone Diseases; Bone Matrix; Glycosaminoglycans; Humans; Hydroxylysine; Hydroxyproline; Kidney; Lysine; Ossification, Heterotopic; Osteitis Deformans; Osteomalacia; Osteoporosis; Proline; Renal Aminoacidurias