Bone-Resorption Markers Galactosyl Hydroxylysine, Pyridinium Crosslinks, and Hydroxyproline Compared

Bettica, Paolo; Moro, Luigi; Robins, Simon P.; Taylor, A.; Talbot, J. R.; Singer, Frank; Baylink, David J.

doi:10.1093/clinchem/38.11.2313

Cited by 81 publications

(24 citation statements)

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“…Although Pyr is known to occur in a variety of connective tissues, Dpyr is thought to be more specific for the type I collagen present in bone. Both compounds are likely to be more specific biochemical markers of bone resorption than serum tartrate-resistant acid phosphatase (TRAP) and urinary Hypro, and of similar specificity to galactosylhydroxylysine [1,2]. They are excreted in the urine in the free and conjugated form and are usually measured by high-performance liquid chromatography (HPLC) [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

To determine the effects of ultraviolet light, natural light and ionizing radiation on pyridinium cross‐links in bone and urine using high‐performance liquid chromatography

Colwell¹,

Hamer

Blumsohn³

et al. 1996

Eur J Clin Investigation

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The aims of the study were to characterize the denaturation of urinary free and conjugated pyridinoline (Pyr) and deoxypyridinoline (Dpyr) on exposure to ultraviolet (UV) and natural light at different pH levels and to study the effects of X- and gamma-irradiation on Pyr and Dpyr in urine and in the mineralized and non-mineralized compartments of human bone. Urine samples from six normal subjects, adjusted to pH 3.0, 7.0 and 9.0 were exposed to UV light for up to 3 days. Urine collections (2 mL and 24 h) from three subjects, pH adjusted to 1.0, 2.0, 3.0, 4.0 and 5.0, were exposed to natural light for up to 1 day. Urine samples and bone slices from seven human cadaveric femurs were irradiated with increasing doses of X-rays (0-100 Gy) and high-dose gamma-radiation (28 kGy). Mineralized and non-mineralized bone were separated using a modification of a published method employing heat denaturation followed by trypsin hydrolysis and analysed for Pyr, Dpyr and hydroxyproline (Hypro). The rate of UV photolysis of urinary Pyr and Dpyr increased with pH and was faster in the free fraction (after 3 days' exposure: free Pyr and Dpyr at pH 7.0 vs. 9.0, P < 0.05, conjugated pH 3.0 vs. 9.0, P < 0.05). Exposure to natural light for 3 h did not significantly decrease urinary Pyr and Dpyr in either sample collections, but levels were reduced in the 2-mL aliquots after exposure for 1 day (P < 0.05). X-irradiation of urine and bone did not affect Pyr and Dpyr. Pyr content was similar in both bone compartments (Pyr/ Hypro = 0.12 +/- 0.004), but Dpyr was higher in the non-mineralized compartment (Dpyr/Hypro = 0.047 +/- 0.002 vs. 0.038 +/- 0.002, P < 0.001). UV light and gamma-irradiation result in denaturation of pyridinium cross-links in urine. These cross-links are present in both the mineralized and non-mineralized bone compartments but are not affected by the doses of gamma-irradiation that denature these cross-links in urine.

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Section: Introductionmentioning

confidence: 99%

To determine the effects of ultraviolet light, natural light and ionizing radiation on pyridinium cross‐links in bone and urine using high‐performance liquid chromatography

Colwell¹,

Hamer

Blumsohn³

et al. 1996

Eur J Clin Investigation

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“…A number of markers of bone collagen analysed in serum and urine samples have been used in the clinical evaluation of patients with osteoporosis [1][2][3][4][5][6]. However, the sensitivity and specificity of these markers in assessing bone formation and resorption in relation to bone structure and quality in elderly subjects remain unclear.…”

Section: Introductionmentioning

confidence: 99%

“…Skin, as an important source of type I collagen, does not contain either of these cross-links [18]. Recent studies have shown that the urine concentrations of Pyr and Dpyr increase in patients with primary hyperparathyroidism, Paget's disease [19][20][21], postmenopausal osteoporosis [1][2][3]22] and fractures [23,24], all of which may involve an increased rate of bone turnover.…”

Section: Introductionmentioning

confidence: 99%

Serum and urine markers of type I collagen metabolism in elderly women with high and low bone mineral density

Cheng¹,

Kovanen²,

Heikkinen³

et al. 1996

Eur J Clin Investigation

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Abstract. The serum markers of bone formation (carboxy-terminal propeptide of type I collagen, PICP) and resorption (pyridinoline cross-links containing telopeptide of type I collagen, ICTP), as well as urinary resorption markers, pyridinoline (Pyr) and deoxypyridinoline (Dpyr), were studied in 78-year-old women with high (n 18) and low (n 17) bone mineral density (BMD) measured from the calcaneus and tibia. The low-BMD group had higher values for PICP (P 0 : 025), Pyr (P 0 : 001) and Dpyr (P < 0 : 001) than the high-BMD group. No inverse relationship between these markers and BMD was, however, observed within the study groups. ICTP, Pyr and Dpyr correlated with each other in both groups and with PICP in the high-BMD group. Higher levels of both the formation and resorption markers of type I collagen suggest an increased rate of bone turnover and remodelling in osteopenic elderly women.

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“…As bone is resorbed by osteoclastic activity, the degraded crosslinks of mature collagen, termed pyridinium crosslinks, are excreted in the urine. The urinary pyridinium crosslinks, pyridinoline (Pyd) and deoxypyridinoline (Dpd), provide an excellent framework to infer bone resorption (38)(39)(40)(41)(42)(43)(44)(45)(46). Pyd and Dpd are found in bone and cartilage, but bone has the highest content of Dpd (42,43,46).…”

mentioning

confidence: 99%

“…The urinary pyridinium crosslinks, pyridinoline (Pyd) and deoxypyridinoline (Dpd), provide an excellent framework to infer bone resorption (38)(39)(40)(41)(42)(43)(44)(45)(46). Pyd and Dpd are found in bone and cartilage, but bone has the highest content of Dpd (42,43,46). We previously reported that individuals with NF1 have increased markers of bone resorption (47) and osteoclasts have been shown to be hyperactive in NF1 (10,48).…”

mentioning

confidence: 99%

Bone resorption in syndromes of the Ras/MAPK pathway

et al. 2011

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Background Disorders of the Ras/MAPK pathway have an overlapping skeletal phenotype (eg. scoliosis, osteopenia). The Ras proteins regulate cell proliferation and differentiation and NF1 individuals have osteoclast hyperactivity and increased bone resorption as measured by urine pyridinium crosslinks [pyridinoline (Pyd) and deoxypyridinoline (Dpd)]. Pyd and Dpd are hydroxylysine derived cross-links of collagen found in bone and cartilage and excreted in the urine. Dpd is most abundant in bone. The aim of this study was to evaluate if other syndromes of the Ras/MAPK pathway have increased bone resorption, which may impact the skeletal phenotype. Methods and Results Participants: [Noonan syndrome (n=14), Costello syndrome (n=21), and cardiofaciocutaneous (CFC) syndrome (n=14)]. Pyridinium cross-links from two consecutive first morning urines were extracted after acid hydrolysis and analyzed by High Performance Liquid Chromotography. Three separate analyses of covariance (ANCOVA) were performed to compare Pyd, Dpd, and Dpd/Pyd ratio of each group to controls after controlling for age. Data were compared to 99 healthy controls. Conclusions The Dpd and the Dpd/Pyd ratio were elevated (p<0.0001) in all 3 conditions compared to controls suggesting that collagen degradation was predominantly from bone. The data suggest that the Ras/MAPK signal transduction pathway is important in bone homeostasis.

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Bone-Resorption Markers Galactosyl Hydroxylysine, Pyridinium Crosslinks, and Hydroxyproline Compared

Cited by 81 publications

References 0 publications

To determine the effects of ultraviolet light, natural light and ionizing radiation on pyridinium cross‐links in bone and urine using high‐performance liquid chromatography

To determine the effects of ultraviolet light, natural light and ionizing radiation on pyridinium cross‐links in bone and urine using high‐performance liquid chromatography

Serum and urine markers of type I collagen metabolism in elderly women with high and low bone mineral density

Bone resorption in syndromes of the Ras/MAPK pathway

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