C - Michigan Technological University

low-dose administration of parathyroid hormone (PTH) lengthens the lifetime of matureosteoblasts, thus increasing BFR and bone mineral density (BMD) of the spine and hindlimbsof mice [49, 55]. Low-dose, intermittent administration of PTH abates bone loss inhind-limb suspended mice [56]. Additionally, attenuation of apoptosis by administrationof sex steroids or melatonin abates bone loss in ovariectomized rats [57, 58], indicatingosteoblast and osteocyte apoptosis may play a key role in bone loss due to estrogendeficiency as well.Together, these results suggest that disuse-induced osteocyte and osteoblastapoptosis leads to an uncoupling of bone formation and resorption leading to net boneloss, and that this mechanism can be controlled by hormones. Administration of antiapoptotichormones can counteract the pro-apoptotic signaling from disuse, thusenabling balanced bone formation and resorption. Similarly, if apoptosis of bone cellswere inhibited during hibernation in bears, formation and resorption would remaincoupled, resulting in balanced bone turnover, as observed in grizzly bears [20]. It ispossible that bears maintain balanced bone turnover during hibernation by upregulatinganti-apoptotic serum factors (or by down-regulating pro-apoptoticfactors), thus decreasing osteoblast and osteocyte apoptosis. This study quantifiedserum concentrations of several bone-active hormones and explored the anti-apoptoticpotential of seasonal bear serum on an osteoblast cell line.In contrast to hind-limb unloading models, simulated microgravity does notinduce osteoblast apoptosis, although bone mass is lost during space flight due to anincrease in bone resorption with a decrease in bone formation [31, 59]. Human primaryosteoblasts, mouse primary osteoblasts, and the immortalized pre-osteoblast cell lineMC3T3-E1 do not undergo apoptosis when cultured in simulated microgravity comparedto static controls [60-62]. Thus, microgravity appears to be a unique form of disuse, andcare must be taken not to generalize between the different forms of disuse osteoporosis.1.5 Disuse in humansOsteopenia due to reduced mechanical loading occurs in a variety of clinicalsituations and can therefore be a threat to anybody, regardless of age and current7