Abstract
The bone mineral deficiency in osteoporosis poses a threat to the long-term outcomes of endosseous implants. The inhibitors of cathepsin K (CatK) significantly affect bone turnover, bone mineral density (BMD) and bone strength in the patients with osteoporosis. Therefore, we hypothesised that the application of a CatK inhibitor (CatKI) could increase the osseointegration of endosseous implants under osteoporotic conditions. Odanacatib (ODN), a highly selective CatKI, was chosen as the experimental drug. Sixteen rats were randomised into 4 groups: sham, ovariectomy (OVX) with vehicle, OVX with low-dose ODN (5 mg/kg) and OVX with high-dose ODN (30 mg/kg). Titanium implants were placed into the distal metaphysis of bilateral femurs of each OVX rat. After 8 weeks of gavaging, CatKI treatment increased the removal torque, BMD and bone-to-implant contact (BIC). Moreover, high-dose CatKI exerted a better influence than low-dose CatKI. Furthermore, CatKI treatment not only robustly suppressed CatK gene (CTSK) expression, but also moderately reduced expression of the osteoblast-related genes Runx2, Collagen-1, BSP, Osterix, OPN, SPP1 and ALP. Thus, CatKI could affect the osteoblast-related genes, although the balance of bone turnover was achieved mainly by CatK inhibition. In conclusion, CatKI prevented bone loss and aided endosseous implantation in osteoporotic conditions.
Highlights
The bone mineral deficiency in osteoporosis poses a threat to the long-term outcomes of endosseous implants
A significant difference was noted between the two CatK inhibitor (CatKI)-treated groups (p < 0.05). These results demonstrated that bone-to-implant contact (BIC) decreased after OVX surgery but significantly increased when CatKI was administered
The number of cases of bisphosphonate-related osteonecrosis increased gradually to an alarming number; CatKI is generally well tolerated without bone necrosis
Summary
The bone mineral deficiency in osteoporosis poses a threat to the long-term outcomes of endosseous implants. The inhibitors of cathepsin K (CatK) significantly affect bone turnover, bone mineral density (BMD) and bone strength in the patients with osteoporosis. We hypothesised that the application of a CatK inhibitor (CatKI) could increase the osseointegration of endosseous implants under osteoporotic conditions. After 8 weeks of gavaging, CatKI treatment increased the removal torque, BMD and bone-to-implant contact (BIC). CatKI could affect the osteoblast-related genes, the balance of bone turnover was achieved mainly by CatK inhibition. CatKI prevented bone loss and aided endosseous implantation in osteoporotic conditions. In order to degrade the bone effectively, osteoclasts secrete acid to demineralise hydroxyapatite and a lysosomal cysteine protease—cathepsin K (CatK)—to degrade the bone matrix proteins[16,20]. Overexpression of CatK gene (CTSK) can increase the bone turnover rate, leading to low bone mass[20,21,22].
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