Space Flight Is Associated with Rapid Decreases of Undercarboxylated Osteocalcin and Increases of Markers of Bone Resorption without Changes in Their Circadian Variation: Observations in Two Cosmonauts

Abstract Background: Microgravity induces bone loss by mechanism(s) that remain largely unknown. Methods: We measured biochemical markers related to bone remodeling in two cosmonauts before, during, and after 21- and 180-day space flights, respectively. Results: During both flights, type I procollagen propeptide and bone alkaline phosphatase decreased as early as 8 days after launch. Undercarboxylated osteocalcin percentage increased early and remained high during both flights. Vitamin K supplementation restored carboxylation of osteocalcin during the long-term flight. Urinary and serum C-telopeptide of type I collagen (CTX) increased as early as day 8 of the flights; the increase was greater in serum than in urine. Pyridinoline, free deoxypyridinoline, and N-telopeptide increased less than CTX during the short-term space flight. The circadian rhythm of bone resorption assessed by urine CTX and free deoxypyridinoline was not altered by microgravity. Conclusion: Vitamin K metabolism or action and bone remodeling may be altered in cosmonauts.

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Bone Remodelling Markers in Rheumatoid Arthritis

Mediators of Inflammation ◽

10.1155/2014/484280 ◽

2014 ◽

Vol 2014 ◽

pp. 1-5 ◽

Cited By ~ 35

Author(s):

Patrice Fardellone ◽

Alice Séjourné ◽

Julien Paccou ◽

Vincent Goëb

Keyword(s):

Rheumatoid Arthritis ◽

Bone Resorption ◽

Bone Remodeling ◽

Type I Collagen ◽

Bone Alkaline Phosphatase ◽

Collagen I ◽

Tartrate Resistant Acid Phosphatase ◽

Type I ◽

Bone Remodeling Markers

Bone loss in rheumatoid arthritis (RA) patients results from chronic inflammation and can lead to osteoporosis and fractures. A few bone remodeling markers have been studied in RA witnessing bone formation (osteocalcin), serum aminoterminal propeptide of type I collagen (PINP), serum carboxyterminal propeptide of type I collagen (ICTP), bone alkaline phosphatase (BAP), osteocalcin (OC), and bone resorption: C-terminal telopeptide of type 1 collagen (I-CTX), N-terminal telopeptide of type 1 collagen (I-NTX), pyridinolines (DPD and PYD), and tartrate-resistant acid phosphatase (TRAP). Bone resorption can be seen either in periarticular bone (demineralization and erosion) or in the total skeleton (osteoporosis). Whatever the location, bone resorption results from activation of osteoclasts when the ratio between osteoprotegerin and receptor activator of nuclear factor kappa-B ligand (OPG/RANKL) is decreased under influence of various proinflammatory cytokines. Bone remodeling markers also allow physicians to evaluate the effect of drugs used in RA like biologic agents, which reduce inflammation and exert a protecting effect on bone. We will discuss in this review changes in bone markers remodeling in patients with RA treated with biologics.

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Serum Bone Resorption Markers after Parathyroidectomy for Renal Hyperparathyroidism: Correlation Analyses for the Cross-Linked N-telopeptide of Collagen I and Tartrate-Resistant Acid Phosphatase

The Scientific World JOURNAL ◽

10.1100/2012/503945 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Kuo-Chin Hung ◽

Chung-Yu Huang ◽

Chuan-Chieh Liu ◽

Chih-Jen Wu ◽

Shao-Yuan Chen ◽

...

Keyword(s):

Acid Phosphatase ◽

Bone Resorption ◽

Type I Collagen ◽

Bone Alkaline Phosphatase ◽

Tartrate Resistant Acid Phosphatase ◽

Type I ◽

Bone Resorption Markers ◽

Correlation Analyses ◽

Serum Trap ◽

The Cross

Patients on long-term dialysis may develop secondary hyperparathyroidism (SHPT) with increased serum concentrations of bone resorption markers such as the cross-linked N-telopeptide of type I collagen (NTX) and type-5b tartrate-resistant acid phosphatase (TRAP). When SHPT proves refractory to treatment, parathyroidectomy (PTX) may be needed. Renal patients on maintenance HD who received PTX for refractory SHPT (n=23) or who did not develop refractory SHPT (control subjects;n=25) were followed prospectively for 4 weeks. Serum intact parathyroid hormone (iPTH), NTX, TRAP, and bone alkaline phosphatase (BAP) concentrations were measured serially and correlation analyses were performed. iPTH values decreased rapidly and dramatically. BAP values increased progressively with peak increases observed at 2 weeks after surgery. NTX and TRAP values decreased concurrently and progressively through 4 weeks following PTX. A significant correlation between TRAP and NTX values was observed before PTX but not at 4 weeks after PTX. Additionally, the fractional changes in serum TRAP were larger than those in serum NTX at all times examined after PTX. Serum iPTH, TRAP, and NTX values declined rapidly following PTX for SHPT. Serum TRAP values declined to greater degrees than serum NTX values throughout the 4-week period following PTX.

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Serum Concentrations of Cross-Linked N-Telopeptides of Type I Collagen: New Marker for Bone Resorption in Hemodialysis Patients

Clinical Chemistry ◽

10.1373/clinchem.2005.051524 ◽

2005 ◽

Vol 51 (12) ◽

pp. 2312-2317 ◽

Cited By ~ 42

Author(s):

Yoshifumi Maeno ◽

Masaaki Inaba ◽

Senji Okuno ◽

Tomoyuki Yamakawa ◽

Eiji Ishimura ◽

...

Keyword(s):

Bone Resorption ◽

Bone Loss ◽

Type I Collagen ◽

Bone Alkaline Phosphatase ◽

Bone Resorption Marker ◽

Type I ◽

Serum Concentrations ◽

Mineral Density ◽

Intact Osteocalcin ◽

Bone Formation Markers

Abstract Background: Urinary cross-linked N-telopeptide of type I collagen (NTX) is a reliable bone resorption marker in patients with metabolic bone disease. We assessed a clinically available serum NTX assay suitable for anuric patients on hemodialysis (HD). Methods: Serum concentrations of NTX, C-terminal telopeptide of type I collagen (β-CTX), pyridinoline (PYD), and deoxypyridinoline (DPD) were determined as bone resorption markers, and those of bone alkaline phosphatase (BAP) and intact osteocalcin (OC) as bone formation markers, in 113 male HD patients (mean age, 59.3 years; mean HD duration, 67.7 months). Each patient’s bone mineral density (BMD) in the distal third of the radius was measured twice, with a 2-year interval between measurements, by dual-energy x-ray absorptiometry. Results: Serum NTX correlated significantly with β-CTX, PYD, DPD, BAP, and intact OC. NTX, as well as β-CTX, PYD, DPD, BAP, and intact OC, correlated significantly with BMD at the time of measurement. NTX, β-CTX, and DPD correlated significantly with the annual change in BMD during the 2-year period thereafter, in contrast to PYD, BAP, and intact OC. Patients in the highest quartile of serum NTX concentrations showed the fastest rate of bone loss. The sensitivity and specificity for detecting rapid bone loss were 48% and 83%, respectively, for serum NTX. Conclusion: Serum NTX may provide a clinically relevant serum assay to estimate bone turnover in HD patients.

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Effects of seasonal vitamin D deficiency and respiratory acidosis on bone metabolism markers in submarine crewmembers during prolonged patrols

Journal of Applied Physiology ◽

10.1152/japplphysiol.00608.2011 ◽

2012 ◽

Vol 112 (4) ◽

pp. 587-596 ◽

Cited By ~ 10

Author(s):

Xavier Holy ◽

Jean-Marc Collombet ◽

Frédéric Labarthe ◽

Nicolas Granger-Veyron ◽

Laurent Bégot

Keyword(s):

Vitamin D ◽

Alkaline Phosphatase ◽

Bone Metabolism ◽

Bone Remodeling ◽

Type I Collagen ◽

Respiratory Acidosis ◽

Bone Alkaline Phosphatase ◽

Type I ◽

Vitamin D Status ◽

Seasonal Influence

The aim of the study was to determine the seasonal influence of vitamin D status on bone metabolism in French submariners over a 2-mo patrol. Blood samples were collected as follows: prepatrol and patrol days 20, 41, and 58 on crewmembers from both a winter (WP; n = 20) and a summer patrol (SP; n = 20), respectively. Vitamin D status was evaluated for WP and SP. Moreover, extended parameters for acid-base balance (Pco2, pH, and bicarbonate), bone metabolism (bone alkaline phosphatase and COOH-terminal telopeptide of type I collagen), and mineral homeostasis (parathyroid hormone, ionized calcium and phosphorus) were scrutinized. As expected, SP vitamin D status was higher than WP vitamin D status, regardless of the considered experimental time. A mild chronic respiratory acidosis (CRA) was identified in both SP and WP submariners, up to patrol day 41. Such an occurrence paired up with an altered bone remodeling coupling (decreased bone alkaline phosphatase-to-COOH-terminal telopeptide of type I collagen ratio). At the end of the patrol ( day 58), a partial compensation of CRA episode, combined with a recovered normal bone remodeling coupling, was observed in SP, not, however, in WP submariners. The mild CRA episode displayed over the initial 41-day submersion period was mainly induced by a hypercapnia resulting from the submarine-enriched CO2 level. The correlated impaired bone remodeling may imply a physiological attempt to compensate this acidosis via bone buffering. On patrol day 58, the discrepancy observed in terms of CRA compensation between SP and WP may result from the seasonal influence on vitamin D status.

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Increased Concentrations of Prostaglandin D2 During Post-Fracture Bone Remodeling

The Journal of Rheumatology ◽

10.3899/jrheum.090622 ◽

2010 ◽

Vol 37 (3) ◽

pp. 644-649 ◽

Cited By ~ 12

Author(s):

MAXIME A. GALLANT ◽

ESTELLE CHAMOUX ◽

MARTINE BISSON ◽

CATARINA WOLSEN ◽

JEAN-LUC PARENT ◽

...

Keyword(s):

Bone Remodeling ◽

Type I Collagen ◽

Bone Cells ◽

Bone Alkaline Phosphatase ◽

Positive Influence ◽

Fracture Repair ◽

Prostaglandin D2 ◽

Type I ◽

Bone Homeostasis

Objective.To test the hypothesis that increased concentrations of prostaglandin D2 (PGD2) correlate with bone remodeling. Studies using isolated bone cells indicate that PGD2 may be implicated in the regulation of bone homeostasis, with a positive influence on bone anabolism. We studied patients with traumatic fractures and age- and sex-matched healthy controls as an in vivo model of increased bone remodeling.Methods.Thirty-five patients with bone fracture and matched controls were recruited. Urine and sera samples were collected. Urinary 11ß-PGF2α, a PGD2 metabolite, and PGE2 metabolites (PGEM), serum lipocalin-type PGD2 synthase (L-PGDS), bone alkaline phosphatase (bone ALP), and crosslinked C-telopeptides of type I collagen (CTX) were measured.Results.At 5–6 weeks post-fracture, 11ß-PGF2α, L-PGDS, bone ALP, and CTX were significantly increased in the fracture patients compared to controls. PGEM levels were not different between groups. Levels of 11ß-PGF2α and bone ALP were positively correlated, suggesting that PGD2 may be implicated in fracture repair.Conclusion.These results support our working hypothesis that PGD2 could be implicated in the control of bone anabolism in humans.

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Vitamin K promotes mineralization, osteoblast-to-osteocyte transition, and an anticatabolic phenotype by γ-carboxylation-dependent and -independent mechanisms

AJP Cell Physiology ◽

10.1152/ajpcell.00216.2009 ◽

2009 ◽

Vol 297 (6) ◽

pp. C1358-C1367 ◽

Cited By ~ 62

Author(s):

Gerald J. Atkins ◽

Katie J. Welldon ◽

Asiri R. Wijenayaka ◽

Lynda F. Bonewald ◽

David M. Findlay

Keyword(s):

Bone Formation ◽

Vitamin K ◽

Type I Collagen ◽

Vitamin K2 ◽

Type I ◽

Vitamin K1 ◽

Vitamin K3 ◽

Positive Effect

The vitamin K family members phylloquinone (vitamin K1) and the menaquinones (vitamin K2) are under study for their roles in bone metabolism and as potential therapeutic agents for skeletal diseases. We have investigated the effects of two naturally occurring homologs, phytonadione (vitamin K1) and menatetrenone (vitamin K2), and those of the synthetic vitamin K, menadione (vitamin K3), on human primary osteoblasts. All homologs promoted in vitro mineralization by these cells. Vitamin K1-induced mineralization was highly sensitive to warfarin, whereas that induced by vitamins K2 and K3 was less sensitive, implying that γ-carboxylation and other mechanisms, possibly genomic actions through activation of the steroid xenobiotic receptor, are involved in the effect. The positive effect on mineralization was associated with decreased matrix synthesis, evidenced by a decrease from control in expression of type I collagen mRNA, implying a maturational effect. Incubation in the presence of vitamin K2 or K3 in a three-dimensional type I collagen gel culture system resulted in increased numbers of cells with elongated cytoplasmic processes resembling osteocytes. This effect was not warfarin sensitive. Addition of calcein to vitamin K-treated cells revealed vitamin K-dependent deposition of mineral associated with cell processes. These effects are consistent with vitamin K promoting the osteoblast-to-osteocyte transition in humans. To test whether vitamin K may also act on mature osteocytes, we tested the effects of vitamin K on MLO-Y4 cells. Vitamin K reduced receptor activator of NF-κB ligand expression relative to osteoprotegerin by MLO-Y4 cells, an effect also seen in human cultures. Together, our findings suggest that vitamin K promotes the osteoblast-to-osteocyte transition, at the same time decreasing the osteoclastogenic potential of these cells. These may be mechanisms by which vitamin K optimizes bone formation and integrity in vivo and may help explain the net positive effect of vitamin K on bone formation.

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Responses of Markers of Bone and Collagen Turnover to Exercise, Growth Hormone (GH) Administration, and GH Withdrawal in Trained Adult Males1

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.85.1.6262 ◽

2000 ◽

Vol 85 (1) ◽

pp. 124-133 ◽

Cited By ~ 3

Author(s):

Jennifer D. Wallace ◽

Ross C. Cuneo ◽

Per Arne Lundberg ◽

Thord Rosén ◽

Jens Otto Lunde Jørgensen ◽

...

Keyword(s):

Acute Exercise ◽

Type I Collagen ◽

Controlled Study ◽

Bone Resorption Marker ◽

Type I ◽

Serum Osteocalcin ◽

Collagen Turnover ◽

Gh Treatment ◽

Type I Procollagen ◽

Procollagen Iii

To examine the interactions between acute exercise and GH on markers of bone and collagen turnover and to assess the potential for detecting GH abuse in athletes using these markers, we studied 17 aerobically trained males (age, 26.9 ± 1.5 yr). Sequential studies of exercise, GH administration, and GH withdrawal were undertaken. A randomized, controlled study of rest vs. exercise showed that exercise did not change serum osteocalcin; other markers of formation increased transiently (each P < 0.001): bone-specific alkaline phosphatase (+16.1%), carboxyterminal propeptide of type I procollagen (+14.1%), and procollagen III N-terminal extension peptide (+5.0%). The carboxyterminal cross-linked telopeptide of type I collagen, a bone resorption marker, increased 9.7% (P = 0.018) in response to exercise. A randomized, double blind, placebo-controlled, parallel study of recombinant human GH treatment (0.15 IU/kg·day) for 1 week increased serum osteocalcin (net increase preexercise, +10.0%; P = 0.017), carboxyterminal propeptide of type I procollagen (+17.6%; P = 0.002), procollagen III N-terminal extension peptide (+48.4%; P = 0.001), and carboxyterminal cross-linked telopeptide of type I collagen (53.3%; P = 0.009). Disappearance half-times after cessation of recombinant human GH for pre- and postexercise markers ranged from 248–770 h. We conclude 1) endurance exercise transiently activates bone and collagen turnover; 2) brief GH administration results in similar but quantitatively greater augmentation; and 3) these data will assist in designing a GH detection strategy.

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Reduced Serum Levels of Bone Formation Marker P1NP in Psoriasis

Frontiers in Medicine ◽

10.3389/fmed.2021.730164 ◽

2021 ◽

Vol 8 ◽

Author(s):

Julia Mentzel ◽

Tabea Kynast ◽

Johannes Kohlmann ◽

Holger Kirsten ◽

Matthias Blüher ◽

...

Keyword(s):

Bone Formation ◽

Bone Metabolism ◽

Type I Collagen ◽

Skin Inflammation ◽

Serum Levels ◽

Serum Markers ◽

Chronic Inflammatory Disease ◽

Type I ◽

Patient Counseling ◽

Type I Procollagen

Psoriasis is a chronic inflammatory disease of the skin and joints. More recent data emphasize an association with dysregulated glucose and fatty acid metabolism, obesity, elevated blood pressure and cardiac disease, summarized as metabolic syndrome. TNF-α and IL-17, central players in the pathogenesis of psoriasis, are known to impair bone formation. Therefore, the relation between psoriasis and bone metabolism parameters was investigated. Two serum markers of either bone formation—N-terminal propeptide of type I procollagen (P1NP) or bone resorption—C-terminal telopeptide of type I collagen (CTX-I)—were analyzed in a cohort of patients with psoriasis vulgaris. In patients with psoriasis, P1NP serum levels were reduced compared to gender-, age-, and body mass index-matched healthy controls. CTX-I levels were indistinguishable between patients with psoriasis and controls. Consistently, induction of psoriasis-like skin inflammation in mice decreases bone volume and activity of osteoblasts. Moreover, efficient anti-psoriatic treatment improved psoriasis severity, but did not reverse decreased P1NP level suggesting that independent of efficient skin treatment psoriasis did affect bone metabolism and might favor the development of osteoporosis. Taken together, evidence is provided that bone metabolism might be affected by psoriatic inflammation, which may have consequences for future patient counseling and disease monitoring.

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Carboxyterminal propeptide of type I procollagen in cerebrospinal fluid in childhood and in children with leukemia undergoing intrathecal treatment

Clinical Chemistry ◽

10.1093/clinchem/37.8.1365 ◽

1991 ◽

Vol 37 (8) ◽

pp. 1365-1369 ◽

Cited By ~ 5

Author(s):

L Vainionpää ◽

L Risteli ◽

M Lanning ◽

J Risteli

Keyword(s):

Cerebrospinal Fluid ◽

Collagen Synthesis ◽

Type I Collagen ◽

Lymphoblastic Leukemia ◽

Corticosteroid Treatment ◽

Reference Interval ◽

Intrathecal Methotrexate ◽

Intrathecal Therapy ◽

Type I ◽

Type I Procollagen

Abstract We determined the reference interval for the carboxyterminal propeptide of type I procollagen (PICP), an indicator of the synthesis of type I collagen, in cerebrospinal fluid (CSF) by studying 32 infants and children, ages less than or equal to 15 years. The concentration of PICP is age dependent, with particularly high concentrations occurring in children younger than 1.5 years. In older children the concentration is stable (reference interval 20-92 micrograms/L). We also investigated the possibility that PICP in CSF could reflect local fibroproliferative changes in the arachnoid in a cohort of 42 children with acute lymphoblastic leukemia who were monitored by repeated sampling in connection with intrathecal therapy. Initially, there was no difference in PICP between the children with newly diagnosed leukemia and the controls. PICP concentrations were significantly higher (P less than 0.01) during intrathecal methotrexate therapy, with median values above the reference interval. Continuous corticosteroid treatment was associated with a significant decrease in PICP (P less than 0.02 and P less than 0.01, respectively, in two groups treated according to different protocols), close to the lower limit of the reference interval. Intrathecally administered methotrexate and systemic corticosteroid treatment are known to be associated with the development of arachnoiditis and with general repression of collagen synthesis, respectively. We conclude that PICP in CSF is a sensitive indicator of local fibroproliferation and ongoing collagen synthesis.

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Different responses of biochemical markers of bone resorption to bisphosphonate therapy in Paget disease

Clinical Chemistry ◽

10.1093/clinchem/41.11.1592 ◽

1995 ◽

Vol 41 (11) ◽

pp. 1592-1598 ◽

Cited By ~ 53

Author(s):

A Blumsohn ◽

K E Naylor ◽

A M Assiri ◽

R Eastell

Keyword(s):

Bone Resorption ◽

Biochemical Markers ◽

Type I Collagen ◽

Bisphosphonate Therapy ◽

Response To Therapy ◽

Tartrate Resistant Acid Phosphatase ◽

Type I ◽

Paget Disease ◽

Markers Of Bone Resorption ◽

Total Alkaline

Abstract We examined the response of different biochemical markers of bone resorption to bisphosphonate therapy (400 mg of etidronate daily for 6 months) in mild Paget disease (n = 14). Urinary markers included hydroxyproline (OHP), total (T) and free (F) pyridinolines (Pyds) determined by HPLC, immunoreactive FPyds, immunoreactive TPyds, and the N- and C-terminal telopeptides of type I collage (NTx, CL). Serum measurements included tartrate-resistant acid phosphatase (TRAcP) and the C-terminal telopeptide of type I collagen (ICTP). ICTP and TRAcP showed a minimal response to therapy (% change at 6 months, -13.1 +/- 6.8 and -6.7 +/- 3.4, respectively). The response was greatest for urinary telopeptides (NTx and CL; % change -75.7 +/- 7.5 and -73.4 +/- 8.9, respectively). The response was somewhat greater for TPyds than for FPyds. We conclude that: (a) ICTP and TRAcP are unreliable indicators of changes in bone turnover; (b) oligopeptide-bound Pyds and telopeptide fragments of type I collagen in urine show a somewhat greater response to therapy than do FPyds and may be more sensitive indicators of bone resorption; and (c) as yet no evidence suggests that these markers are substantially better predictors of the clinical response to therapy than serum total alkaline phosphatase or urinary OHP. There are several problems with the interpretation of these measurements in Paget disease, and the clinical utility of these measurements remains uncertain.

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