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Bone turnover and type I collagen C-telopeptide isomerization in adult osteogenesis imperfecta: associations with collagen gene mutations.
Bone. 2009 Mar; 44(3):461-6.BONE

Abstract

INTRODUCTION

Increased bone fragility in osteogenesis imperfecta (OI) is not totally accounted for by decreased bone mineral density (BMD), and alterations of type I collagen (Col I) are believed to play a role. Newly synthesized Col I comprises non isomerized C-telopeptide (alphaCTX), but with bone matrix maturation alphaCTX is converted to its isomerized beta form (betaCTX). Urinary alpha/betaCTX ratio has been proposed to reflect collagen maturation. We investigated changes in bone turnover and Col I isomerization in adult patients with OI and their relationship with Col I gene mutations.

PATIENTS AND METHODS

Sixty four adult patients [25 women, 39 men mean age (SD): 36.2 (11.6) years] with OI participating in a randomized study and 64 healthy controls of similar age and gender distribution were investigated. In patients with OI and controls, we measured the following biochemical markers of bone metabolism: serum type I collagen N-propeptide (PINP) an index of Col I synthesis, osteocalcin a marker of osteoblastic activity, urinary Col I helical peptide, a marker reflecting the degradation of the helical portion of Col I, urinary alphaCTX and urinary and serum betaCTX. Based on the putative functional effects of Col I gene mutations which were identified in 56 OI subjects, patients were divided in those with haploinsufficiency (n=29), patients presenting with helical domain alterations (n=17) and others (n=10).

RESULTS

Compared to healthy controls, patients with OI had decreased levels of PINP (-22.7%, p<0.0001), increased osteocalcin (+73%, p<0.0001) and increased Col I helical peptide (+58%, p=0.0007). Urinary alphaCTX was increased (+31%, p=0.03) whereas urinary (-15%, p=0.022) and serum (-9.9%, p=0.0056) betaCTX were significantly decreased, resulting in a 49% (p<0.001) higher urinary alpha/betaCTX ratio. Patients with Col I gene mutations resulting in haploinsufficiency had lower PINP levels than patients with helical domain alterations (26.4+/-15.3 vs 41.6+/-27.4 ng/ml, p=0.0043) and controls (p<0.01).

CONCLUSION

Adults with OI are characterized by decreased Col I synthesis - especially those with haploinsufficiency mutations - increased Col I degradation and decreased Col I C-telopeptide isomerization.

Authors+Show Affiliations

INSERM Research Unit 664, Lyon, France. patrick.garnero@synarc.comNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19071236

Citation

Garnero, Patrick, et al. "Bone Turnover and Type I Collagen C-telopeptide Isomerization in Adult Osteogenesis Imperfecta: Associations With Collagen Gene Mutations." Bone, vol. 44, no. 3, 2009, pp. 461-6.
Garnero P, Schott AM, Prockop D, et al. Bone turnover and type I collagen C-telopeptide isomerization in adult osteogenesis imperfecta: associations with collagen gene mutations. Bone. 2009;44(3):461-6.
Garnero, P., Schott, A. M., Prockop, D., & Chevrel, G. (2009). Bone turnover and type I collagen C-telopeptide isomerization in adult osteogenesis imperfecta: associations with collagen gene mutations. Bone, 44(3), 461-6. https://doi.org/10.1016/j.bone.2008.11.006
Garnero P, et al. Bone Turnover and Type I Collagen C-telopeptide Isomerization in Adult Osteogenesis Imperfecta: Associations With Collagen Gene Mutations. Bone. 2009;44(3):461-6. PubMed PMID: 19071236.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bone turnover and type I collagen C-telopeptide isomerization in adult osteogenesis imperfecta: associations with collagen gene mutations. AU - Garnero,Patrick, AU - Schott,Anne-Marie, AU - Prockop,Darwin, AU - Chevrel,Guillaume, Y1 - 2008/11/21/ PY - 2008/01/02/received PY - 2008/09/10/revised PY - 2008/11/06/accepted PY - 2008/12/17/entrez PY - 2008/12/17/pubmed PY - 2009/4/7/medline SP - 461 EP - 6 JF - Bone JO - Bone VL - 44 IS - 3 N2 - INTRODUCTION: Increased bone fragility in osteogenesis imperfecta (OI) is not totally accounted for by decreased bone mineral density (BMD), and alterations of type I collagen (Col I) are believed to play a role. Newly synthesized Col I comprises non isomerized C-telopeptide (alphaCTX), but with bone matrix maturation alphaCTX is converted to its isomerized beta form (betaCTX). Urinary alpha/betaCTX ratio has been proposed to reflect collagen maturation. We investigated changes in bone turnover and Col I isomerization in adult patients with OI and their relationship with Col I gene mutations. PATIENTS AND METHODS: Sixty four adult patients [25 women, 39 men mean age (SD): 36.2 (11.6) years] with OI participating in a randomized study and 64 healthy controls of similar age and gender distribution were investigated. In patients with OI and controls, we measured the following biochemical markers of bone metabolism: serum type I collagen N-propeptide (PINP) an index of Col I synthesis, osteocalcin a marker of osteoblastic activity, urinary Col I helical peptide, a marker reflecting the degradation of the helical portion of Col I, urinary alphaCTX and urinary and serum betaCTX. Based on the putative functional effects of Col I gene mutations which were identified in 56 OI subjects, patients were divided in those with haploinsufficiency (n=29), patients presenting with helical domain alterations (n=17) and others (n=10). RESULTS: Compared to healthy controls, patients with OI had decreased levels of PINP (-22.7%, p<0.0001), increased osteocalcin (+73%, p<0.0001) and increased Col I helical peptide (+58%, p=0.0007). Urinary alphaCTX was increased (+31%, p=0.03) whereas urinary (-15%, p=0.022) and serum (-9.9%, p=0.0056) betaCTX were significantly decreased, resulting in a 49% (p<0.001) higher urinary alpha/betaCTX ratio. Patients with Col I gene mutations resulting in haploinsufficiency had lower PINP levels than patients with helical domain alterations (26.4+/-15.3 vs 41.6+/-27.4 ng/ml, p=0.0043) and controls (p<0.01). CONCLUSION: Adults with OI are characterized by decreased Col I synthesis - especially those with haploinsufficiency mutations - increased Col I degradation and decreased Col I C-telopeptide isomerization. SN - 1873-2763 UR - https://www.unboundmedicine.com/medline/citation/19071236/Bone_turnover_and_type_I_collagen_C_telopeptide_isomerization_in_adult_osteogenesis_imperfecta:_associations_with_collagen_gene_mutations_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S8756-3282(08)00897-1 DB - PRIME DP - Unbound Medicine ER -