Disuse and orchidectomy have additional effects on bone loss in the aged male rat.

INTRODUCTION: A severely osteopenic rat model was obtained by combining orchidectomy (ORX) and disuse (due to local paralysis induced by botulinum toxin [BTX] in the quadriceps muscle).

METHODS: Forty-two aged male rats (5-6 months old) were randomized into three groups: 18 were SHAM operated; 6 were ORX; and 18 were ORX and BTX injected in the right hindlimb. One, two, and three months after surgery, bone mass (BV/TV) and microarchitectural parameters (Tb.Th, Tb.N, Tb.Sp, Tb.Pf, and structure model index [SMI]) were measured by microcomputed tomography (microCT) on the primary and secondary spongiosa of the femur. Osteoid parameters (OS/BS, O.Th), the number of osteoclasts (Nb.Oc), and the mineral apposition rate (Ct.MAR, Cn.MAR) were measured by histology. The serum tartrate-resistant acid phosphatase (TRAcP) 5b activity was measured by immunoassay.

RESULTS: ORX induced a decrease of BV/TV, Tb.N and an increase of Tb.Sp, Tb.Pf, and SMI on both primary and secondary spongiosa. ORX and BTX had cumulative effects on bone loss, since differences were maximized on the right femur. The decrease in BV/TV reached -65%. Osteoid parameters and mineral apposition rate increased during the time course of the study. A peak of serum TRAcP was found at 7 days post-ORX. TRAcP levels reached the highest values in the ORX-BTX groups and the effect lasted longer than in the group with ORX alone. The association of ORX-BTX induced a greater bone resorption, due to the removal of complete trabeculae, compared to ORX alone.

CONCLUSION: This model induced a severe and rapid bone loss and can be used to explore pharmacological- and biomaterial-based countermeasures.