Increased variability of bone tissue mineral density resulting from estrogen deficiency influences creep behavior in a rat vertebral body.

Progressive vertebral deformation increases the fracture risk of a vertebral body in the postmenopausal patient. Many studies have observed that bone can demonstrate creep behavior, defined as continued time-dependent deformation even when mechanical loading is held constant. Creep is a characteristic of viscoelastic behavior, which is common in biological materials. We hypothesized that estrogen deficiency-dependent alteration of the mineral distribution of bone at the tissue level could influence the progressive postmenopausal vertebral deformity that is observed as the creep response at the organ level. The objective of this study was thus to examine whether the creep behavior of vertebral bone is changed by estrogen deficiency, and to determine which bone property parameters are responsible for the creep response of vertebral bone at physiological loading levels using an ovariectomized (OVX) rat model. Correlations of creep parameters with bone mineral density (BMD), tissue mineral density (TMD) and architectural parameters of both OVX and sham surgery vertebral bone were tested. As the vertebral creep was not fully recovered during the post-creep unloading period, there was substantial residual displacement for both the sham and OVX groups. A strong positive correlation between loading creep and residual displacement was found (r=0.868, p<0.001). Of the various parameters studied, TMD variability was the parameter that best predicted the creep behavior of the OVX group (p<0.038). The current results indicated that creep caused progressive, permanent reduction in vertebral height for both the sham and OVX groups. In addition, estrogen deficiency-induced active bone remodeling increased variability of trabecular TMD in the OVX group. Taken together, these results suggest that increased variability of trabecular TMD resulting from high bone turnover influences creep behavior of the OVX vertebrae.

Human umbilical cord blood-derived CD34+ cells reverse osteoporosis in NOD/SCID mice by altering osteoblastic and osteoclastic activities.

BACKGROUND: Osteoporosis is a bone disorder associated with loss of bone mineral density and micro architecture. A balance of osteoblasts and osteoclasts activities maintains bone homeostasis. Increased bone loss due to increased osteoclast and decreased osteoblast activities is considered as an underlying cause of osteoporosis. METHODS AND FINDINGS: The cures for osteoporosis are limited, consequently the potential of CD34+ cell therapies is currently being considered. We developed a nanofiber-based expansion technology to obtain adequate numbers of CD34(+) cells isolated from human umbilical cord blood, for therapeutic applications. Herein, we show that CD34(+) cells could be differentiated into osteoblastic lineage, in vitro. Systemically delivered CD34(+) cells home to the bone marrow and significantly improve bone deposition, bone mineral density and bone micro-architecture in osteoporotic mice. The elevated levels of osteocalcin, IL-10, GM-CSF, and decreased levels of MCP-1 in serum parallel the improvements in bone micro-architecture. Furthermore, CD34(+) cells improved osteoblast activity and concurrently impaired osteoclast differentiation, maturation and functionality. CONCLUSIONS: These findings demonstrate a novel approach utilizing nanofiber-expanded CD34(+) cells as a therapeutic application for the treatment of osteoporosis.