983, 0.988 and 0.972 for PINP, b-ALP and t-ALP, respectively. Correlations between PINP and BMD response Table 4 presents the Spearman correlation coefficients between CHIR98014 mw absolute levels of PINP and their changes at 1 and 6 months, and the change in BMD at 24 months of teriparatide therapy. Bone turnover status at baseline correlated significantly with subsequent BMD responses at 24 months. The highest coefficient value was for the correlation between PINP concentration at 1 month and the change in LS BMD to 24 months (r = 0.365; p < 0.0001) (Table 4). This

coefficient was slightly higher in the subgroup of osteoporosis treatment-naïve patients (r = 0.405; p < 0.0001) (data not shown). The coefficient values were lower for the changes in total hip and femoral neck BMD (Table 4). Table 4 Spearman correlation coefficients (p-values) between absolute levels of PINP or PINP changes at 1 and 6 months, and the change in BMD at 24 months of teriparatide therapy.   Time point (month) Change from baseline in BMD (24 months) Lumbar spine (n = 414) Total hip (n = 401) Femoral neck (n = 401) PINP Baseline 0.301 (<0.0001) 0.218 (<0.0001) 0.116 (<0.05) 1 0.365 (<0.0001) check details 0.141 (<0.005) 0.081 (n.s.) 6 0.219 (<0.0001) 0.111 (<0.05) 0.107 (<0.05) ΔPINP Δ1 0.213 (<0.0001) 0.000 (n.s.) 0.081 (n.s.) Δ6 0.117 (<0.05) 0.035 (n.s) 0.070 (n.s.) BMD, bone mineral density; PINP, procollagen

Type 1 N-terminal propeptide n.s., not significant (p > 0.05) The best-fit model for predicting change from baseline in LS BMD for all patients contained prior duration of antiresorptive treatment, increases in PINP after 1 month, and PINP concentrations at 1 and 6 months, and accounted for 17.4% of the total EGFR cancer variation in change

in LS BMD to 24 months. In this model, prior duration of antiresorptive treatment was negatively associated with BMD Parvulin changes at the LS, as previously described [21]. The different models explored for predicting change from baseline in total hip or femoral neck BMD to 24 months accounted for a maximum of 5.6% of the total variation in the best-fit model which included duration of prior antiresorptive treatment and PINP concentration at 1 month. Forty-nine subjects experienced an incident fracture during follow-up. No relationship between baseline levels or changes in PINP concentrations after 1 and 6 months of treatment with teriparatide and the overall risk of clinical fractures was found (p > 0.05). Discussion Our results showed that teriparatide 20 μg/day was associated with significant early increases in biochemical markers of bone formation at 1 month, and that these changes were increased further after 6 months of therapy. The increases in bone markers occurred regardless of previous antiresorptive therapy, although the absolute values after 1 month of teriparatide treatment were lower in subjects who had received previous antiresorptive therapy than in treatment-naïve subjects.