Collagen metabolism in two types of autosomal dominant osteopetrosis during stimulation with thyroid hormones
Authors: Bollerslev Jens , Thomas Sian , Grodum Ellen , Brixen Kim , Djøseland Ole 
Published: December 2008

Bollerslev J, Thomas S, Grodum E, Brixen K, Djøseland 0. Collagen metabolism in two types of autosomal dominant osteopetrosis during stimulation with thyroid hormones. Eur J Endocrinol 1995;133:557–63. ISSN 0804–4643

In order to investigate collagen metabolism in two different types of autosomal dominant osteopetrosis (ADO), eight patients with type I (aged 23–61 years, mean 40.4 years) and nine patients with type II ADO (aged 20–49 years, mean 32.8 years) were compared with ten normal controls (aged 22–54 years, mean 35.4 years). The subjects were treated with 100 μg of triiodothyronine (T3) daily for 7 days and followed for a total of 4 weeks. Serum T3 increased in all subjects and a corresponding suppression of thyroid-stimulating hormone (TSH) was observed. Serum carboxy-terminal propeptide of type I collagen (S-PICP) in the control and type I groups showed no difference at baseline, whereas type II was lower than controls (p < 0.01). No significant alterations following stimulation were observed in any of the groups. Serum BGP (osteocalcin) values in the two patient groups were insignificantly lower than controls both at baseline and throughout the study. Following stimulation, a significant response was seen in the three groups (p < 0.001). The increases during the treatment period (delta values) for controls, type I and type II were 47.6% (p < 0.01), 51.7% (p = 0.05) and 34.8% (NS), respectively, with no difference between the groups. Serum bone-specific alkaline phosphatase (S-ALP) was not different between the groups and no alterations were observed in relation to treatment. The serum N-terminal propeptide of type III collagen (S-PIIINP) showed no difference at baseline between type I and controls but was significantly higher (p < 0.003) in type II than in the controls. After stimulation, significant responses were observed in all three groups (p < 0.001). Serum PIIINP increased following 1 week of treatment by 64% (p < 0.01), 41% (p < 0.02) and 18% (NS), respectively. Serum carboxy-terminal telopeptide of type I collagen (SICTP) did not differ between type I and controls at baseline but was increased in type II (p < 0.04), as it was throughout the observation period (p < 0.12 and p < 0.02). A significant response was observed in the three groups following stimulation. The delta values were 69% (p = 0.005), 56% (p < 0.02) and 34% (p < 0.02), respectively. The urinary hydroxyproline (OHP)/creatinine ratio did not differ between the groups either at baseline or following stimulation. A significant response (p < 0.001) was observed, with delta values of 44.2% (p < 0.06), 35.9% (p < 0.04) and 34.3% (p < 0.01), respectively. The two bone resorptive markers (S-ICTP and OHP/creatinine ratio) were correlated significantly at baseline for all three groups. It is concluded that collagen metabolism is disturbed in type II ADO, which might reflect an increased turnover of extra-osseous collagen. Because ICTP levels are increased in disorders with increased extra-osseous collagen turnover, we question the suitability of this parameter as a sensitive marker of bone resorption.

Jens Bollerslev, Department of Medical Endocrinology, National University Hospital, N-0027 Oslo, Norway