Expression profiles of mRNAs for osteoblast and osteoclast proteins as indicators of bone loss in mouse immobilization osteopenia model

An experimental mouse model for disuse osteopenia was developed using unila teral cast immobilization. Analysis of the distal femurs and proximal tibia s by quantitative histomorphometry revealed significant osteopenia within 1 0-21 days of immobilization, At 3 weeks, bone loss was also demonstrated wi th peripheral quantitative computed tomography as diminished bone mineral c ontent and as concomitant reduction in the cross-sectional moment of inerti a. These structural and geometrical alterations resulted in decreased stren gth of the distal femurs tested by cantilever bending. Analysis of the unde rlying cellular and molecular mechanisms of bone loss revealed a rapid incr ease in bone resorption within 3 days of immobilization, The mRNA levels fo r cathepsin K, matrix: metalloproteinase-9, and tartrate resistant acid pho sphatase were all significantly increased during the 21-day immobilization period, but with different expression profiles. These increases were parall eled by an increased number of osteoclasts as measured by histomorphometry. By day 6 of immobilization, the balance of bone turnover was further shift ed toward net bone loss as the mRNA levels for major bone components (type I collagen and osteocalcin) were decreased. In histomorphometric analysis t his was observed as reduced rates of mineral apposition and bone formation after 10 days of immobilization, The results of this study demonstrate that immobilization has a dual negative effect on bone turnover involving both depressed bone formation and enhanced bone resorption.