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.