Zoledronic acid and bone cellular respiration

AbstractPhosphorescence O2 analyzer was used to measure calvarial bone cellular respiration (cellular mitochondrial O2 consumption) in Taylor Outbred mice in the presence and absence of zoledronic acid. This potent bisphosphonate inhibits osteoclast-mediated calcium resorption, and its effects on bone respiration have not been previously investigated. The change of O2 concentration with time was measured in closed vials containing phosphate-buffered saline (PBS), 5  mM glucose and 5–25 mg calvarial bone fragments, and it was complex fort = 0–30 h. Cyanide (specific inhibitor of cytochrome oxidase) halted O2 consumption, confirming the oxidation occurred in the respiratory chain. Initial rate of respiration was estimated from the zero-order plots d[O2]/dt fort = 0–4 h. For untreated specimens, the rate (mean ± SD) was 2.0 ± 1.2 µM O2 h−1 mg−1 (n = 6). This value was 7–10 times lower than that of other murine organs, but similar to that reported for rat and Guinea pig calvaria (averaging, 2.7 nmol O2 h−1 mg−1). The corresponding rate in the presence of 10 –100 µM zoledronic acid was 2.7 ± 0.7 µM O2 h−1 mg−1 (n = 11),p = 0.216. The first-order plots ln ([O2]t ÷ [O2]t=0) versus time fort = 0–30 h were also used to compare treated and untreated specimens. The rate (h−1 mg−1 103) for specimens incubated in PBS without glucose was 1.3  ± 0.6 (n = 3,p = 0.007), in PBS + glucose it was 10.7 ± 6.9 (n ...
Source: Journal of Bone and Mineral Metabolism - Category: Orthopaedics Source Type: research