Serum Vitamin D and Pyridinoline Cross-Linked Carboxyterminal Telopeptide of Type I Collagen in Patients with Ankylosing Spondylitis

Objective. To assess the serum vitamin D and ICTP levels in patients with ankylosing spondylitis (AS) and investigate their relationship with disease activity and bone mineral density (BMD).Method. 150 patients and 168 controls were included. Serum 25(OH)D, ICTP, C-reaction protein (CRP), Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), and Hip BMD were assessed in patients. 25(OH)D and ICTP were detected in controls.Results. The serum 25(OH)D in AS was 57.92 ± 24.42 nmol/L, significantly lower than controls (91.24 ± 42.02 nmol/L). Serum ICTP in AS was 5.72 ± 3.88 ug/L, significantly higher than controls (3.69 ± 1.26 ug/L). ICTP level was higher in men than in women patients (6.07 ± 4.05 versus 3.84 ± 1.96 ug/L,P≤0.01); it was also higher in JAS than in AAS (9.52 ± 3.79 versus 5.27 ± 3.65 ug/L,P≤0.01). Furthermore, 25(OH)D was negatively correlated with ICTP. Low 25(OH)D and high ICTP were one of the reasons of AS patients’ low hip BMD. Besides, a significant relationship was found between serum ICTP and CRP.Conclusion. There was a high incidence of vitamin D inadequacy in AS. Serum ICTP level was elevated in AS, especially in JAS and male patients. 25(OH)D and ICTP seem to be valuable markers to detect bone loss in AS.

Serum carboxyterminal telopeptide (ICTP) as a prognostic marker in bone metastases (BM) treated with bisphosphonates

10107 Background: Biochemical markers of bone turnover, such as N- and C-terminal cross-linking telopeptide of type I collagen have been evaluated as prognostic matkers in patients with BM. In one of such study, we found that ICTP was not affected by bisphosphonate (BP) therapy (Costa, et al., JCO 2002; 20:850–856). In this prospective study we analyzed whether the baseline level of ICTP was predictive of skeletal related events (SREs) as defined by: pathologic fractures (PF), radiation to treat BM (RT) or spinal cord compression (SCC); time to progression (TTP) and overall survival (OS) in patients with BM from solid tumors under BP therapy. Methods: We studied 116 BM patients, median age: 64 years; 67% females; 61% breast cancer; 19% prostate cancer; and 20% other tumor types. The x-ray pattern of BM was lytic in 54% patients, blastic in 23%, and mixed in 21%. At the time of study entry, all patients had serum ICTP levels measured with RIA reagents from Orion Diagnostica (reference range: 2.5–4.0 μg/L). A serum ICTP cutoff of 6.2 μg/L was established using the mean + 2D. The occurrence of SREs was recorded during the study and an objective evaluation of BM status was performed every 4–6 months. During the time period on study, patients received treatment with IV zoledronate (57%), IV pamidronate (28%), or more than one BP. The proportional hazards model was used to investigate the correlation of ICTP baseline level with time to first SRE (TTSRE), TTP, and OS; and Poisson regression with the skeletal morbidity rate (SMR): number of SREs/person/year. Results: The median follow-up was 21 months. 81.9% patients had ICTP level above 6.2 μg/L and the mean value of ICTP was 15.1 (SD 11.9) μg/L. During the time period on study, 38% had PF, 57% had RT, and 9.5% had SCC. Median TTSRE was 20 months and the SMR was 0.84. Median TTP was 12 months and median OS time was 29 months. ICTP levels above 6.2 μg/L were associated with increased mortality risk (hazard ratio (HR) 2.86, 95%CI 1.37–6.00, p=0.005) and increased SMR (incidence rate ratio 1.88, 95%CI 0.98–3.60, p=0.057), but not with TTP (HR 1.18, 95%CI 0.67–2.07, p=0,57) or TTSRE (HR 1.59, 95%CI 0.82–3.08, p=0.17). Conclusions: Elevated serum ICTP levels is associated with decreased survival and increased incidence of SREs in BM patients on BP therapy. No significant financial relationships to disclose.

Biomarkers of bone metabolism in horses: Ante-mortem versus post-mortem correlation in serum and aqueous humour

SummaryThe objective of this study was to determine the correlation between ante-mortem and 24-hour postmortem concentrations of four markers of bone metabolism in equine serum and aqueous humour. The markers evaluated were osteocalcin, bone alkaline phosphatase, carboxyterminal propeptide of type-1 procollagen and carboxyterminal cross-linked telopeptide of type-1 collagen (ICTP). The concentrations of these markers were poorly correlated (P > 0.05) between aqueous humour and serum. ICTP was the only serum marker significantly correlated (r = 0.93) between ante- and post-mortem samples. ICTP is, therefore, a potential marker for evaluating antemortem markers of bone metabolism in dead horses.

Evaluation of markers of bone and collagen turnover in patients with active and preclinical Cushing's syndrome and in patients with adrenal incidentaloma

Although steroid-induced negative effects on bone and collagen have been well described in corticosteroid-treated patients, few studies have extensively evaluated bone and collagen turnover in patients with endogenous Cushing's syndrome. In this work serum bone-Gla protein (BGP), C-terminal cross-linked telopeptide of type I collagen (ICTP) and N-terminal propeptide of type III procollagen (PIIINP) levels were determined in patients with active (n = 12) and preclinical (n = 6) Cushing's syndrome, adrenal incidentalomas (n = 35) and in healthy controls (n = 28). In patients with overt Cushing's syndrome, serum BGP (0.9+/-0.2 ng/ml), ICTP (2.7+/-0.2 ng/ml) and PIIINP (1.9+/-0.2 ng/ml) levels were significantly lower (P < 0.0001) than in controls (5.5+/-0.2, 3.9+/-0.2 and 3.2+/-0.2 ng/ml respectively). In preclinical Cushing's syndrome, serum BGP (2.5+/-0.8 ng/ml), ICTP (2.2+/-0.1 ng/ml) and PIIINP (2.2+/-0.2 ng/ml) levels were significantly lower than in normal subjects (P < 0.0001, P < 0.0001 and P < 0.02 respectively), being similar to those recorded in overt Cushing's syndrome. In patients with adrenal incidentaloma, serum BGP (4.2+/-0.5 ng/ml) and ICTP (2.9+/-0.2 ng/ml) levels were significantly lower than those found in controls (P < 0.05 and P < 0.001 respectively), while serum PIIINP levels (3.6+/-0.2 ng/ml) did not differ from those of normals. In particular, 9/35 patients with adrenal incidentaloma had markedly depressed BGP levels (<2.0 ng/ml; mean 0.8+/-0.1 ng/ml): all patients of this subgroup showed an exaggerated 17-hydroxyprogesterone increase after ACTH administration. In the same patients, serum ICTP (3.0+/-0.4 ng/ml) and PIIINP (3.6+/-0.2 ng/ml) levels did not differ from those found in the incidentaloma group. In conclusion, our study indicates that bone and collagen turnover are markedly affected in patients with overt and preclinical Cushing's syndrome. Although patients with adrenal incidentaloma do not show any signs or symptoms of overt hypercortisolism, the presence of reduced BGP and ICTP levels might be considered a further index of an 'abnormal' pattern of steroid secretion in some of them. As a consequence, the presence of early alterations in markers of bone turnover might be useful for selecting those patients who need more accurate follow-up of the adrenal mass.