Bone Abstracts

Hyperthyroidism in mice is associated with a low bone mass, an increased bone turnover and high serum levels of sclerostin, a potent Wnt inhibitor. Here, we explored the effects of either reducing bone turnover with bisphosphonates or increasing bone formation with neutralizing sclerostin antibodies (Scl-Ab) on bone mass and estimated strength in hyperthyroid mice.

Twelve-week-old C57BL/6 male mice were rendered hyperthyroid by adding L-thyroxine (T₄) to the drinking water (1.2 μg/ml). Saline, 20 mg/kg Scl-Ab 2×/weekly or 100 μg/kg zoledronic acid (ZOL) 1×/weekly were administered to hyperthyroid and control mice for 4 weeks.

MicroCT analysis revealed a lower trabecular bone volume at the spine (−27%) and the distal femur (−48%) in hyperthyroid mice compared to euthyroid controls. Scl-Ab treatment of hyperthyroid mice increased the trabecular bone volume at the femur 2.5-fold as compared to PBS-treated hyperthyroid mice and ZOL twofold. Similar trends were seen for the spine. Cortical thickness at the femoral diaphysis was lower in hyperthyroid mice and increased through both treatments, with Scl-Ab having a more potent effect than ZOL (+12%, P<0.05). Bone stiffness estimated using finite element modeling at the lumbar vertebra was 49% lower in hyperthyroid mice and was increased three- and twofold after Scl-Ab and ZOL treatment, respectively. Levels of P1NP were 2.7-fold higher in hyperthyroid mice than in euthyroid controls, and treatment of hyperthyroid mice with Scl-Ab led to a further 13% increase in P1NP, whereas ZOL reduced P1NP concentrations by 23%. CTX levels were likewise 47% higher in hyperthyroid mice as opposed to euthyroid controls, remained unchanged after Scl-Ab treatment and decreased after ZOL treatment (−23%).

Thus, both, anti-resorptive and bone-forming treatments are effective in preventing bone loss in hyperthyroid mice, yet via different mechanisms, and may also be useful for the treatment of patients with hyperthyroidism-induced bone disease.