Bone quality of the newest bone formed after two years of teriparatide therapy in patients who were previously treatment-na < ve or on long-term alendronate therapy
Authors: Hofstetter, B.; Gamsjaeger, S.; Varga, F.; Dobnig, H.; Stepan, J. J.; Petto, H.; Pavo, I.; Klaushofer, K.; Paschalis, E. P.
The results of the present study, involving analysis of biopsies from patients who received teriparatide for 2 years and were previously either treatment-na < ve or on long-term alendronate therapy, suggest that prior alendronate use does not blunt the favorable effects of teriparatide on bone quality. Examine the effect of 2 years of teriparatide (TPTD) treatment on mineral and organic matrix properties of the newest formed bone in patients who were previously treatment-na < ve (TN) or on long-term alendronate (ALN) therapy. Raman and Fourier transform infrared microspectroscopic analyses were used to determine the mineral/matrix (M/M) ratio, the relative proteoglycan (PG) content, and the mineral maturity/crystallinity (MMC; determined by three methods: carbonate content, full width at half height of the v (1) PO4 band [FWHH], and wavelength at maxima of the v (1) PO4 band), as well as collagen maturity (ratio of pyridinoline/divalent cross-links), in paired iliac crest biopsies at trabecular, endosteal, and osteonal surfaces of newly formed bone in postmenopausal osteoporotic women who were previously either TN (n = 16) or receiving long-term ALN treatment (n = 24). Trabecular M/M ratio increased and matrix content decreased significantly in the ALN pretreated group. Collagen maturity decreased in both patient groups. Endosteal M/M ratio increased significantly in the TN group. Trabecular M/M ratio was higher at endpoint in the ALN pretreated group than in the TN group. Overall, no changes from baseline were observed in PG content, except that PG content was higher in the ALN pretreated group than in the TN group at endosteal surfaces at endpoint. The ability of TPTD treatment to reduce MMC in both patient groups and at the different bone surfaces depended on the measurement tool (relative carbonate content or wavelength at maxima of the v (1) PO4 band). None of the changes in MMC were different between the two patient groups. The results suggest some favorable impact of TPTD on bone mineral and organic matrix properties of in situ forming bone in terms of increased initial mineralization and decreased MMC and collagen maturity. Moreover, prior long-term ALN administration may have only limited influence on these properties in bone newly formed after 2 years of TPTD treatment.
Evidence of increased bone resorption in neurofibromatosis type 1 using urinary pyridinium crosslink analysis
Authors: Stevenson, David A.; Schwarz, Elisabeth L.; Viskochil, David H.; Moyer-Mileur, Laurie J.; Murray, Mary; Firth, Sean D.; D'Astous, Jacques L.; Carey, John C.; Pasquali, Marzia
Although neurofibromatosis type 1 (NF1) is a neurocutaneous disorder, skeletal abnormalities such as long-bone dysplasia, scoliosis, sphenoid wing dysplasia, and osteopenia are observed. To investigate the role of bone resorption as a mechanism for the bony abnormalities, we selected urinary pyridinium crosslinks (collagen degradation products excreted in urine) as a measure of bone resorption in NF1. Bone resorption was evaluated by quantitative assessment of the urinary excretion of pyridinium crosslinks [pyridinoline (Pyd) and deoxypyridinoline (Dpd)]. Total (free plus peptide-bound) pyridinium crosslinks from the first morning urines from 59 NF1 children (ages 5-19) were extracted and analyzed (17 children with a localized skeletal dysplasia, and 42 without). The data were compared with a healthy reference population without NF1 (n=99). Multivariate analyses, controlling for age showed statistically significant increases for Dpd (p < 0.001) and the Dpd/Pyd ratio (p < 0.001) in NF1 individuals with and without a skeletal dysplasia. NF1 children have an increase in the urinary excretion of pyridinium crosslinks, reflecting increased,bone resorption. The effects of NF1 haploinsufficiency likely contribute to abnormal bone remodeling, either directly or indirectly by aberrant Ras signaling, potentially predisposing NF1 individuals to localized skeletal defects.