“
“The publisher regrets that the names of Stefan Unger, Michael Blauth, and Werner Schmoelz

were published incorrectly as Unger Stefan, Blauth Michael, and Schmoelz Werner in the author line. The correct author line appears above. “
“Bisphosphonates play a central role in the management of osteoporosis [1], [2] and [3]. Their major mechanism of action is to suppress osteoclast function and survival [4] and [5]. Due to the normal coupling of bone resorption to formation, one of their effects is to lower bone turnover [6]. Some of these drugs have also recently been demonstrated to protect osteocytes from apoptosis in vivo [7] and [8]. In contrast to the anti-resorptive effects of bisphosphonates, mechanical loading A-1210477 in vivo is the predominant functional osteogenic factor responsible for maintaining structurally appropriate levels of bone mass in adults [9] and [10]. By

suppressing bone resorption, bisphosphonates effectively slow the decline in bone mass due to any cause including decreased mechanical loading [11], [12], [13], [14] and [15]. learn more The question remains as to their effect on the (re)modeling associated with a net osteogenic stimulus such as that derived from a therapeutic regimen of exercise. Some pilot clinical reports have shown an additive effect of bisphosphonates and exercise on areal bone mineral density [16] and [17], but second other trials failed to find such an additive effect [18], [19] and [20]. In experiments involving treadmill exercise in ovariectomized rats, the combination of etidronate, alendronate or risedronate treatment with exercise

had additive or synergistic effects on bones [21], [22] and [23], whereas zoledronic acid and exercise did not show either effect [24]. Since exercise would induce significant changes in cardio-pulmonary and nervous systems as well as skeletal muscle, the effect of combining bisphosphonates with local mechanical stimulation has been studied in a variety of rodent loading models. Again, however, the results are not consistent [25], [26], [27] and [28]. The effect of clodronate on periosteal apposition was increased when combined with mechanical loading in the rat tibia [25], whereas a recent study suggested that zoledronic acid impaired cortical bone’s response to loading in the mouse tibia [28]. In contrast, alendronate, risedronate and zoledronic acid at clinical doses did not influence periosteal expansion induced by loading in the rat ulna [27]. Only one study investigated the effect of combining a bisphosphonate with loading in trabecular bone and showed that pamidronate did not change osteogenesis caused by invasive loading in the rat tail [26].