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In an ovine femur model, proliferative woven bone fills critical sized defects enveloped by periosteum within two weeks of treatment with the one stage bone transport surgery. We hypothesize that mechanical loading modulates this process. Using high-definition optical strain measurements we determined prevailing periosteal strains for normal and surgically treated ovine femora subjected ex vivo to compressive loads simulating in vivo stance shifting (n=3 per group, normal versus treated). We determined spatial distribution of calcein green, a label for bone apposition in first the two weeks after surgery, in 15°, 30°, and 45° sectors of histological cross sections through the middle of the defect zone (n=6 bones, 3–4 sections/bone). Finally, we correlated early bone formation to either the maximal periosteal strain or the net change in maximal periosteal strain. We found that treatment with the one stage bone transport surgery profoundly changes the mechanical environment of cells within the periosteum during stance shift loading. The pattern of early bone formation is repeatable within and between animals and relates significantly to the actual strain magnitude prevailing in the periosteum during stance shift loading. Interestingly, early bone apposition after the surgery correlates more to the maximal net change in strain (above circa 2000–3000 µε, in tension or compression) rather than strain magnitude per se, providing further evidence that changes in cell shape may drive mechanoadaptation by progenitor cells. These important insights regarding mechanobiologic factors that enhance rapid bone generation in critical sized defects can be translated to the tissue and organ scale, providing a basis for the development of best practices for clinical implementation and the definition of movement protocols to enhance the regenerative effect.

This paper studies the effect of oral risedronate on osteoclast precursors, osteoclast formation, and cytokine production in 25 osteoporotic women. Risedronate is effective in reducing the number of osteoclast precursors, their formation, vitality, and activity and the level of RANKL and TNF-␣ in cultures.Introduction: Bisphosphonates inhibit bone resorption by acting against osteoclasts. Some in vitro studies suggest that they induce osteoclast apoptosis; others suggest that they exert an effect on the production of pro-osteoclastogenic cytokines. The effect of risedronate on osteoclastogenesis by peripheral blood mononuclear cells (PBMCs) in postmenopausal osteoporosis has not been previously studied. This paper examined the influence of risedronate on the formation of osteoclast precursors and cytokine production within the compass of osteoclastogenesis in osteoporosis. Materials and Methods: This study was conducted on 38 osteoporotic women; 25 patients were treated with risedronate 5 mg/d, whereas 13 were treated with calcium 1 g/d and vitamin D 800 UI/d. The following parameters were assessed: changes in bone turnover, circulating osteoclast precursors, formation of osteoclasts in PBMC cultures, their activity and vitality, and variations in the production of pro-osteoclastogenic cytokines before and after therapy. Results: After 3 mo of risedronate, there was a significant reduction in the number and degree of differentiation of osteoclast precursors, osteoclast formation, vitality and activity, and in the level of RANKL and TNF in cultures and of TNF and osteoprotegerin (OPG) in serum, whereas in the group treated with calcium and vitamin D, there were no significant changes. Conclusions: Our data show that risedronate is effective in lowering the number of circulating osteoclast precursors, their formation, vitality, and activity in cultures, and in reducing the level of pro-osteoclastogenic cytokines in culture supernatants and in serum.

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