Improvement of cancellous bone microstructure in patients on teriparatide following alendronate pretreatment

An increase in procollagen type I amino-terminal propeptide (PINP) early after teriparatide initiation was shown to correlate with increased lumbar spine areal BMD and is a good predictor of the anabolic response to teriparatide. Few data exist correlating PINP and bone microstructure, and no data exist in patients on teriparatide following prior potent antiresorptive treatment. This exploratory analysis aimed to investigate the effects of teriparatide on cancellous bone microstructure and correlations of bone markers with microstructure in alendronate-pretreated patients. This was a post hoc analysis of changes in bone markers and three-dimensional indices of bone microstructure in paired iliac crest biopsies from a prospective teriparatide treatment study in postmenopausal women with osteoporosis who were either treatment-naïve (TN, n = 16) or alendronate-pretreated (ALN, n = 29) at teriparatide initiation. Teriparatide (20 μg/day) was given for 24 months; biopsies were taken at baseline and endpoint, and serum concentrations of PINP and type 1 collagen cross-linked C-telopeptide (βCTX) were measured at intervals up to 24 months. In the TN and ALN groups, respectively, mean (SD) increases in three-dimensional bone volume/tissue volume were 105 (356)% (P = 0.039) and 55 (139)% (P < 0.005) and trabecular thickness 30.4 (30)% (P < 0.001) and 30.8 (53)% (P < 0.001). No significant changes were observed in trabecular number or separation. In the ALN patients, 3-month change of neither PINP nor βCTX correlated with indices of cancellous bone microstructure. However, 12-month changes in biochemical bone markers correlated significantly with improvements in bone volume/tissue volume, r = 0.502 (P < 0.01) and r = 0.378 (P < 0.05), trabecular number, r = 0.559 (P < 0.01) and r = 0.515 (P < 0.01), and reduction of trabecular separation, r = −0.432 (P < 0.05) and r = −0.530 (P < 0.01), for PINP and βCTX, respectively. We conclude that cancellous bone microstructure improved with teriparatide therapy irrespective of prior antiresorptive use

[89Zr]Zr-PSMA-617 PET/CT in biochemical recurrence of prostate cancer : first clinical experience from a pilot study including biodistribution and dose estimates

Purpose Prostate-specific membrane antigen (PSMA)-targeted PET/CT has become increasingly important in the management of prostate cancer, especially in localization of biochemical recurrence (BCR). PSMA-targeted PET/CT imaging with long-lived radionuclides as 89Zr (T1/2=78.4 h) may improve diagnostics by allowing data acquisition on later time points. In this study, we present our frst clinical experience including preliminary biodistribution and dosimetry data of [ 89Zr]Zr-PSMA-617 PET/CT in patients with BCR of prostate cancer. Methods Seven patients with BCR of prostate cancer who revealed no (n =4) or undetermined (n =3) findings on [ 68Ga]Ga-PSMA-11 PET/CT imaging were referred to [ 89Zr]Zr-PSMA-617 PET/CT. PET/CT imaging was performed 1 h, 24 h, 48 h, and 72 h post injection (p.i.) of 111±11 MBq [ 89Zr]Zr-PSMA-617 (mean±standard deviation). Normal organ distribution and dosimetry were determined. Lesions visually considered as suggestive of prostate cancer were quantitatively analyzed. Results Intense physiological uptake was observed in the salivary and lacrimal glands, liver, spleen, kidneys, intestine and urinary tract. The parotid gland received the highest absorbed dose (0.601±0.185 mGy/MBq), followed by the kidneys (0.517±0.125 mGy/MBq). The estimated overall efective dose for the administration of 111 MBq was 10.1 mSv (0.0913±0.0118 mSv/MBq). In 6 patients, and in particular in 3 of 4 patients with negative [ 68Ga]Ga-PSMA-11 PET/CT, at least one prostate cancer lesion was detected in [ 89Zr]Zr-PSMA-617 PET/CT imaging at later time points. The majority of tumor lesions were frst visible at 24 h p.i. with continuously increasing tumor-to-background ratio over time. All tumor lesions were detectable at 48 h and 72 h p.i. Conclusion [ 89Zr]Zr-PSMA-617 PET/CT imaging is a promising new diagnostic tool with acceptable radiation exposure for patients with prostate cancer especially when [ 68Ga]Ga-PSMA-11 PET/CT imaging fails detecting recurrent disease. The long half-life of 89Zr enables late time point imaging (up to 72 h in our study) with increased tracer uptake in tumor lesions and higher tumor-to-background ratios allowing identifcation of lesions non-visible on [ 68Ga]Ga-PSMA-11 PET/CT imaging

Early changes in biochemical markers of bone formation during teriparatide therapy correlate with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis

Summary: Changes of the bone formation marker PINP correlated positively with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis (GIO) who received 18-month treatment with teriparatide, but not with risedronate. These results support the use of PINP as a surrogate marker of bone strength in GIO patients treated with teriparatide. Introduction: To investigate the correlations between biochemical markers of bone turnover and vertebral strength estimated by finite element analysis (FEA) in men with GIO. Methods: A total of 92 men with GIO were included in an 18-month, randomized, open-label trial of teriparatide (20 μg/day, n = 45) and risedronate (35 mg/week, n = 47). High-resolution quantitative computed tomography images of the 12th thoracic vertebra obtained at baseline, 6 and 18 months were converted into digital nonlinear FE models and subjected to anterior bending, axial compression and torsion. Stiffness and strength were computed for each model and loading mode. Serum biochemical markers of bone formation (amino-terminal-propeptide of type I collagen [PINP]) and bone resorption (type I collagen cross-linked C-telopeptide degradation fragments [CTx]) were measured at baseline, 3 months, 6 months and 18 months. A mixed-model of repeated measures analysed changes from baseline and between-group differences. Spearman correlations assessed the relationship between changes from baseline of bone markers with FEA variables. Results: PINP and CTx levels increased in the teriparatide group and decreased in the risedronate group. FEA-derived parameters increased in both groups, but were significantly higher at 18 months in the teriparatide group. Significant positive correlations were found between changes from baseline of PINP at 3, 6 and 18 months with changes in FE strength in the teriparatide-treated group, but not in the risedronate group. Conclusions: Positive correlations between changes in a biochemical marker of bone formation and improvement of biomechanical properties support the use of PINP as a surrogate marker of bone strength in teriparatide-treated GIO patients