Anabolic parathyroid hormone (PTH) treatment does not alter periosteal bone mineral composition during primary and secondary mineralisation
Christina Vrahnas1,2, Thomas A Pearson1,2, Athena R Brunt3, Mark R Forwood3, Keith R Bambery4, Mark J Tobin4, T John Martin1,2 & Natalie A Sims1,2
Parathyroid hormone (PTH) is used to stimulate bone formation in osteoporotic patients, however concerns have been raised about the quality of the matrix produced since lower levels of total matrix mineral have been reported in osteoporotic and fracture patients treated with PTH. High resolution synchrotron-based Fourier Transform Infrared Microscopy (sFTIRM) was used to determine mineral content in age-matched bone during anabolic PTH treatment, using the simplified lamellar structure of growing murine cortical bone.
Eight week old male mice were treated with vehicle or 50 μg/kg PTH, 5 times/week for 4 weeks (n=79/group). Histomorphometry and 3-point bending tests confirmed increased trabecular and periosteal bone formation and increased femoral strength in PTH treated mice. Dual calcein labels allowed region-based analysis by sFTIRM at the midshaft, in six 15 μm2 regions perpendicular to the most immature bone on the periosteal edge of the medial cortex in the same regions where increased bone formation was measured by histomorphometry. All animal procedures were conducted with approval from the St. Vincents Health Melbourne Animal Ethics Committee.
This sFTIRM method was validated in control bones by detecting the expected progressive increase in mineral:matrix ratio and collagen crosslink content from the periosteal edge (new) to the inner (mature) bone. PTH treatment did not alter the progressive changes in these parameters, nor did it alter crystallinity or carbonate content, within the maturing bone, indicating that bone deposited during PTH treatment has the same composition as age-matched bone deposited during normal periosteal bone growth.
These data confirm that earlier studies detecting lower levels of mineralisation in PTH-treated bone reflected a higher proportion of newly formed bone during modelling, rather than a change in collagen maturation and mineral accrual during PTH treatment.