COLLAGEN-METABOLISM IN 2 TYPES OF AUTOSOMAL-DOMINANT OSTEOPETROSIS DURING STIMULATION WITH THYROID-HORMONES

In order to investigate collagen metabolism in two different types of autosomal dominant osteopetrosis (ADO), eight patients with type I (ag ed 23-61 years, mean 40.4 years) and nine patients with type II ADO (a ged 20-49 years, mean 32.8 years) were compared with ten normal contro ls (aged 22-54 years, mean 35.4 years). The subjects were treated with 100 mu g of triiodothyronine (T-3) daily for 7 days and followed for a total of 4 weeks. Serum T-3 increased in all subjects and a correspo nding suppression of thyroid-stimulating hormone (TSH) was observed. S erum carboxy-terminal propeptide of type I collagen (S-PICP) in the co ntrol and type I groups showed no difference at baseline, whereas type II was lower than controls (p < 0.01). No significant alterations fol lowing stimulation were observed in any of the groups. Serum BGP (oste ocalcin) values in the two patient groups were insignificantly lower t han controls both at baseline and throughout the study. Following stim ulation, a significant response was seen in the three groups (p < 0.00 1). The increases during the treatment period (delta values) for contr ols, 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 b one-specific alkaline phosphatase (S-ALP) was not different between th e groups and no alterations were observed in relation to treatment. Th e serum N-terminal propeptide of type III collagen (S-PIINP) showed no difference at baseline between type I and controls but was significan tly higher (p < 0.003) in type II than in the controls. After stimulat ion, significant responses were observed in all three groups (p < 0.00 1). Serum PIINP 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 (S-ICTP) did not differ between type I and controls at baseline but was increased in type II(p < 0.04), as i t was throughout the observation period (p < 0.12 and p < 0.02). A sig nificant response was observed in the three groups following stimulati on. The delta values were 69% (p = 0.005), 56% (p < 0.02) and 34% (p < 0.02), respectively. The urinary hydroxyproline (OHP)/creatinine rati o did not differ between the groups either at baseline or following st imulation. 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), re spectively. 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-o sseous collagen turnover, we question the suitability of this paramete r as a sensitive marker of bone resorption.