Received on November 14, 2003
Accepted on February 24, 2004

Endocrinology and Metabolism

Osteoclast-Derived Serum Tartrate-Resistant Acid Phosphatase 5b in Albers-Schönberg Disease (Type II Autosomal Dominant Osteopetrosis)

¹ Institute of Biomedicine, Department of Anatomy, University of Turku, FIN-20520 Turku, Finland
² Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas M. D. Anderson Cancer Center, Houston, TX
³ Medicine and Medical and Molecular Genetics, Indiana University, Indianapolis, IN
⁴ Institute of Biomedicine, Department of Anatomy, University of Turku, FIN-20520 Turku, Finland, and Pharmatest Services Ltd, Turku, Finland

^* To whom correspondence should be addressed. E-mail: sari.alatalo{at}utu.fi.

Background: Albers-Schönberg 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 concentrations of total tartrate-resistant acid phosphatase (TRACP).

Methods: We investigated the serum concentrations of the osteoclast-derived 5b isoform of TRACP (TRACP 5b) and 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 concentration 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.