Bone turnover and type I collagen C-telopeptide isomerization in adult osteogenesis imperfecta: Associations with collagen gene mutations

IntroductionIncreased 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 (αCTX), but with bone matrix maturation αCTX is converted to its isomerized β form (βCTX). Urinary α/βCTX 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 methodsSixty 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 αCTX and urinary and serum βCTX. 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).ResultsCompared 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 αCTX was increased (+ 31%, p = 0.03) whereas urinary (− 15%, p = 0.022) and serum (− 9.9%, p = 0.0056) βCTX were significantly decreased, resulting in a 49% (p < 0.001) higher urinary α/βCTX 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).ConclusionAdults 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.