Advanced

Osteoclast-derived serum tartrate-resistant acid phosphatase 5b in Albers-Schonberg disease (type II autosomal dominant osteopetrosis)

Alatalo, Sari L; Ivaska, Kaisa LU ; Waguespack, Steven G; Econs, Michael J; Väänänen, H Kalervo and Halleen, Jussi M (2004) In Clinical Chemistry 50(5). p.883-890
Abstract
BACKGROUND: Albers-Schonberg disease, or autosomal dominant osteopetrosis type II (ADO2), is caused by ineffective osteoclastic bone resorption resulting from mutations in the chloride channel 7 (ClCN7) gene. Individuals with ADO2 have increased numbers of large ineffective osteoclasts in addition to increased serum total tartrate-resistant acid phosphatase (TRACP) activity. METHODS: We investigated the serum activity of the osteoclast-derived 5b isoform of TRACP (TRACP 5b) and concentrations of the bone formation marker osteocalcin in clinically affected individuals, unaffected gene carriers, and healthy controls from 10 ADO2 families with known ClCN7 gene mutations. Bone fracture prevalence was studied in association with the serum... (More)
BACKGROUND: Albers-Schonberg disease, or autosomal dominant osteopetrosis type II (ADO2), is caused by ineffective osteoclastic bone resorption resulting from mutations in the chloride channel 7 (ClCN7) gene. Individuals with ADO2 have increased numbers of large ineffective osteoclasts in addition to increased serum total tartrate-resistant acid phosphatase (TRACP) activity. METHODS: We investigated the serum activity of the osteoclast-derived 5b isoform of TRACP (TRACP 5b) and concentrations of the bone formation marker osteocalcin in clinically affected individuals, unaffected gene carriers, and healthy controls from 10 ADO2 families with known ClCN7 gene mutations. Bone fracture prevalence was studied in association with the serum markers. RESULTS: Similar to total TRACP, TRACP 5b was significantly increased in clinically affected individuals compared with age-matched controls. TRACP 5b correlated significantly with total TRACP (r = 0.833; P <0.001), suggesting that most of the TRACP in the serum of ADO2 patients is osteoclast-derived TRACP 5b. Osteocalcin was significantly increased in affected adults and slightly decreased in affected children. TRACP 5b and total TRACP were significantly increased in clinically affected individuals with severe fractures (P <0.05). CONCLUSIONS: The results indicate that in ADO2, serum TRACP 5b reflects the number of osteoclasts and that the extremely high serum TRACP 5b activity is a specific indicator of the disease. Similar to total TRACP, TRACP 5b appears to be a potentially useful marker to stratify individuals with ClCN7 gene mutations into clinically affected and unaffected gene carriers. It may also have a prognostic value in the prediction of fractures in patients with a ClCN7 gene mutation. (Less)
Please use this url to cite or link to this publication:
author
publishing date
type
Contribution to journal
publication status
published
subject
in
Clinical Chemistry
volume
50
issue
5
pages
883 - 890
publisher
American Association for Clinical Chemistry
external identifiers
  • pmid:15016726
  • scopus:2142810972
ISSN
0009-9147
DOI
10.1373/clinchem.2003.029355
language
English
LU publication?
no
id
bba66a4b-1ecb-4e97-bb69-bd328464422e (old id 1130357)
date added to LUP
2008-06-12 11:47:35
date last changed
2017-11-19 03:33:15
@article{bba66a4b-1ecb-4e97-bb69-bd328464422e,
  abstract     = {BACKGROUND: Albers-Schonberg disease, or autosomal dominant osteopetrosis type II (ADO2), is caused by ineffective osteoclastic bone resorption resulting from mutations in the chloride channel 7 (ClCN7) gene. Individuals with ADO2 have increased numbers of large ineffective osteoclasts in addition to increased serum total tartrate-resistant acid phosphatase (TRACP) activity. METHODS: We investigated the serum activity of the osteoclast-derived 5b isoform of TRACP (TRACP 5b) and concentrations of the bone formation marker osteocalcin in clinically affected individuals, unaffected gene carriers, and healthy controls from 10 ADO2 families with known ClCN7 gene mutations. Bone fracture prevalence was studied in association with the serum markers. RESULTS: Similar to total TRACP, TRACP 5b was significantly increased in clinically affected individuals compared with age-matched controls. TRACP 5b correlated significantly with total TRACP (r = 0.833; P &lt;0.001), suggesting that most of the TRACP in the serum of ADO2 patients is osteoclast-derived TRACP 5b. Osteocalcin was significantly increased in affected adults and slightly decreased in affected children. TRACP 5b and total TRACP were significantly increased in clinically affected individuals with severe fractures (P &lt;0.05). CONCLUSIONS: The results indicate that in ADO2, serum TRACP 5b reflects the number of osteoclasts and that the extremely high serum TRACP 5b activity is a specific indicator of the disease. Similar to total TRACP, TRACP 5b appears to be a potentially useful marker to stratify individuals with ClCN7 gene mutations into clinically affected and unaffected gene carriers. It may also have a prognostic value in the prediction of fractures in patients with a ClCN7 gene mutation.},
  author       = {Alatalo, Sari L and Ivaska, Kaisa and Waguespack, Steven G and Econs, Michael J and Väänänen, H Kalervo and Halleen, Jussi M},
  issn         = {0009-9147},
  language     = {eng},
  number       = {5},
  pages        = {883--890},
  publisher    = {American Association for Clinical Chemistry},
  series       = {Clinical Chemistry},
  title        = {Osteoclast-derived serum tartrate-resistant acid phosphatase 5b in Albers-Schonberg disease (type II autosomal dominant osteopetrosis)},
  url          = {http://dx.doi.org/10.1373/clinchem.2003.029355},
  volume       = {50},
  year         = {2004},
}