hydroxylysine and Osteoporosis

Bone collagen cross-links are now widely used to assess bone resorption levels in many metabolic bone diseases. The post-translational modifications of bone and other mineralizing collagens are significantly different from those of other type I collagen matrices, a fact that has been exploited during recent advances in the development of biochemical markers of bone resorption. The enzymatic collagen cross-linking mechanism is based upon aldehyde formation from specific telopeptide lysine or hydroxylysine residues. The immature ketoimine cross-links in bone form via the condensation of a telopeptide aldehyde with a helical lysine or hydroxylysine. Subsequent maturation to the pyridinoline and pyrrole cross-links occur by further reaction of the ketoimines with telopeptide aldehydes. In mineralizing tissues, a relatively low level of lysyl hydroxylation results in low levels of hydroxylysyl pyridinoline, and the occurrence of the largely bone specific lysyl pyridinoline and pyrrolic cross-links. The collagen post-translational modifications appear to play an integral role in matrix mineralization. The matrix of the turkey tendon only mineralizes after a remodeling of the collagen and the subsequent formation of a modified matrix more typical of bone than tendon. Further, disturbances in the post-translational modification of collagen can also affect the mineralization density and crystal structure of the tissue. In addition to their use as a convenient measure of matrix degradation, collagen cross-links are of significant importance for the biomechanical integrity of bone. Recent studies of osteoporotic bone, for example, have demonstrated that subtle perturbations in the pattern of lysine hydroxylation result in changes in the cross-link profile. These alterations, specifically changes in the level of the pyrrolic cross-link, also correlate with the strength of the bone. Further research into the biochemistry of bone collagen cross-links may expand current understanding and their clinical application in metabolic bone disease. This review also demonstrates the potential for further study into this area to provide more subtle information into the mechanisms and etiology of disease and aging of mineralizing tissues.

Topics: Aging; Amino Acids; Animals; Bone and Bones; Bone Development; Calcification, Physiologic; Collagen; Glycosylation; Humans; Hydroxylation; Hydroxylysine; Lysine; Osteoporosis; Protein-Lysine 6-Oxidase

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

Osteoporosis in many countries has reached epidemic proportions. This has stimulated the development of biochemical markers to assist in the assessment of osteoporotic risk and in monitoring the efficacy of treatment. Biochemical markers of bone turnover are products released from osteoblasts and osteoclasts or collagen breakdown products.. Markers of bone formation include bone-specific alkaline phosphatase (BAP), osteocalcin (OC) and procollagen peptides. All of these can be measured easily by immunoassay techniques. Of these markers, OC has been extensively studied. However, OC undergoes in vitro degradation, thus, assay results are variable. BAP, on the other hand, is much more stable and shows less within-person biological variation. Bone resorption markers include tartrate-resistant acid phosphatase (TRAP) and collagen breakdown products, such as pyridinium cross-links, galactosyl hydroxylysine and cross-linked telopeptides, such as CTx and NTx. Of these, deoxypyridinium (DPD) has been extensively studied. DPD shows diurnal variation and the within-individual biological variation is large. Of the newer assays, NTx appear to show large differences at menopause.. Thus, serum BAP and DPD or NTx are the current choice of bone markers.

Topics: Alkaline Phosphatase; Biomarkers; Bone Resorption; Humans; Hydroxylysine; Hydroxyproline; Osteocalcin; Osteoporosis; Procollagen

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

No detailed biochemical analysis has been carried out of the compositional changes in the collagen matrix of avian bone in relation to increased bone fragility in osteoporosis. We have shown that osteoporosis in avian bone is certainly not just a simple loss of apatite and collagen, but involves significant changes in the biochemistry of the collagen molecule and consequently in the physical properties of the fibre. The decreased mechanical strength and the change in the thermal stability can be directly related to changes in post-translational modifications, i.e. lysine hydroxylation and the intermolecular cross-link profile. The increased hydroxylation and change in cross-linking are consistent with increased turnover of the collagen, possibly in an attempt to initiate a repair mechanism which, in fact, leads to an acceleration in the increase in fragility of the bone. Clearly there are post-translational modifications of the newly synthesized collagen in avian osteoporosis, and these changes may play a role in the pathogenesis of the disease.

Topics: Animals; Bird Diseases; Bone and Bones; Chickens; Collagen; Diaphyses; Extracellular Matrix; Female; Hydroxylysine; Osteoporosis; Reference Values; Regression Analysis; Stress, Mechanical

The urinary excretion levels of hydroxylysine glycosides [Hyl-Gs; O-beta-D-Galactopyranosylhydroxylysine (GH) and 2-O-alpha-D-glucopyranosyl-O-beta-D-galactopyranosylhydroxylysine (GGH)], provide a new index of collagen metabolism. The determination of urinary hydroxylysine glycoside excretion levels was applied to 20 osteoporotic patients and 208 healthy control subjects (69 females and 139 males) in order to evaluate the conditions of bone collagen metabolism. Urinary Hyl-Gs were analyzed by the method of pre-column fluorescent derivatized HPLC. Compared to the age and sex-adjusted control, the urinary excretion levels of hydroxylysine glycosides, especially GH, in osteoporotic patients were significantly higher than in the age and sex-adjusted control, and the urinary GGH/GH ratio was lower. Sixteen of the 20 patients whose Hyl-Gs levels we followed exhibited significantly lower values after 200 d compared to the initial levels. These results suggest that clinical therapeutics affected the bone resorption and, therefore, demonstrated the usefulness of determining urinary excretion levels of Hyl-Gs for evaluating the conditions of bone metabolism.

Topics: Adult; Aged; Aged, 80 and over; Bone Resorption; Chromatography, High Pressure Liquid; Collagen; Female; Humans; Hydroxylysine; Male; Middle Aged; Osteoporosis

Glucosyl-galactosyl-hydroxylysine (GGHYL) and galactosyl-hydroxylysine (GHYL) are constituents of collagen protein. The ratio of the two hydroxylysine glycosides varies with the collagen type and, moreover, for a given collagen type, it also varies according to the connective tissue. For example, in type I collagen (the most abundant in the body), the GGHYL/GHYL ratio tends to be greater in soft connective tissues and lower in bone. The hydroxylysine glycosides are not recycled during collagen turnover and are excreted in the urine. Therefore, the urinary GGHYL/GHYL ratio, which reflects the proportion of the two metabolites in the various collagens, may indicate the type of connective tissue affected by pathological turnover, and may thus be a promising marker of bone metabolism. In this paper a method is described for the measurement of urinary hydroxylysine glycosides by reversed-phase liquid chromatography after purification of the sample by solid-phase extraction. The method presented is analytically reliable and suitable for routine use in a clinical laboratory.

Topics: Adult; Biomarkers; Bone and Bones; Chromatography, High Pressure Liquid; Collagen; Female; Humans; Hydroxylysine; Indicators and Reagents; Osteoporosis; Reference Standards; Spectrophotometry, Ultraviolet

Among some patients, regardless of age, the jaw loses bone mass, leading to loosening and falling out of otherwise healthy teeth. This study seeks to establish whether this bone loss is associated with the metabolic manifestations of other forms of localized decalcifications, such as in Paget's disease, or with generalized osteoporosis. Sixteen women being fitted with dental implants to compensate for bone losses provided 24-hour urine samples for the quantitative determination of calcium and galactosyl hydroxylysine, a bone collagen metabolite. These patients provided demographic information, relevant medical, dental, and dietary history, a profile of their current medications, and the status of their smoking and exercise habits. Urinary excretion of galactosyl hydroxylysine, which is increased in the presence of progressive increased bone resorption, remained within normal values in the patients of this study. These results suggest that the thinning of the jaw bones and subsequent tooth loss of these subjects were osteoporotic processes too limited and too localized to produce measurable increases in urinary bone metabolites.

Topics: Adult; Aged; Alveolar Bone Loss; Calcium; Chi-Square Distribution; Creatinine; Estrogens; Female; Humans; Hydroxylysine; Middle Aged; Mouth, Edentulous; Osteoporosis; Regression Analysis; Tooth Loss

No detailed biochemical analysis has been made of the possible compositional changes in the collagen relating to the fragility of osteoporotic bone. We report for the first time significant changes in the compositional properties of the collagen. The major differences were observed in the post-translational modifications, namely, in the hydroxylation of lysine residues and the nature of the stabilizing cross-links of the collagen fibre. The increase in hydroxylation was greater in the head region compared to the neck region of the femoral head, whilst the decrease in the intermediate cross-links was greater in the neck region. Clearly, the collagen is altered in osteoporosis and it is important that these changes are recognised in studies of bone metabolism in osteoporosis since they may play a role in the pathogenesis of the disease.

Topics: Adult; Aged; Amino Acids; Bone and Bones; Collagen; Female; Femur; Humans; Hydroxylation; Hydroxylysine; In Vitro Techniques; Male; Osteoporosis; Protein Processing, Post-Translational; Reference Values

A sensitive and specific method is proposed to follow bone collagen degradation. The procedure consists of the measurement of galactosyl hydroxylysine (GH) in urine by HPLC. The aim of the work is to assess the predictive values of the method for the identification of post-menopausal osteoporotic women. By assuming the value of 12 mumol/g creatinine as the threshold value, the sensitivity of the test is 87% and the specificity 60%. Individuals with a GH/creatinine ratio of 12 or below are not likely to be at risk of bone fractures: an equivalent predictive value is provided by the measurement of bone density by quantitative computed tomography. This biochemical method is however simple and not invasive and may be frequently repeated.

Topics: Adult; Aged; Aged, 80 and over; Aging; Biomarkers; Female; Humans; Hydroxylysine; Middle Aged; Osteoporosis; Predictive Value of Tests

Topics: Administration, Oral; Amino Acids; Animals; Bone and Bones; Bone Resorption; Calcium; Calcium, Dietary; Collagen; Estriol; Femur; Hydroxylysine; Lysine; Male; Osteoporosis; Rats; Tibia

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