Novel Bisphosphonate MPMBP Increases Condylar Bone Mineral Density in Ovariectomized Rats

Objectives: Postmenopausal osteoporosis is prevalent in more than 30% of postmenopausal women. Clinical studies have reported that osteoporosis not only affects long bones but the mandibular condyle as well. The osteoporosis-induced bone resorption can be superimposed upon the subchondral bone resorption associated with temporomandibular disorders.

Bisphosphonates are known to inhibit bone resorption and increase subchondral bone density. However, nitrogen-containing bisphosphonates, such as zoledronate, are also known to induce osteonecrosis of the jaw, gastrointestinal irritation, atypical bone fracture, and ocular inflammation. On the other hand, non-nitrogen-containing bisphosphonates, such as clodronate, do not induce inflammation. The novel bisphosphonate disodium dihydrogen-4-[(methylthio) phenylthio] methanebisphosphonate (MPMBP) is a non-nitrogen-containing bisphosphonate that possesses anti-resorptive, antioxidant and anti-inflammatory properties which give it the potential to treat inflammatory diseases with excessive bone resorption. In this study, the systemic effects of MPMBP on condylar cartilage and bone formation were investigated.
Methods: Fifty 12-week-old Sprague–Dawley rats were subjected to either ovariectomy (OVX; n=40) or Sham operation (n=10). At 24 weeks, the OVX rats were further subdivided into four groups and MPMBP (dosage of 1.2, 6.0, or 30 mg/kg) or normal saline (0.9% NaCl) were administered subcutaneously, once weekly for twelve weeks. At sacrifice, the mandibular condyles were harvested for micro CT, histological and immunohistochemical analyses.
Results: Micro CT revealed that MPMBP significantly (p<0.05) increased cancellous bone mineral density, in the OVX-related osteopenic condyle, dose-dependently, leading to a more dense bone structure and improved mechanical properties. Furthermore, the number of Cathepsin K-positive bone-resorbing osteoclasts significantly (p<0.05) decreased in subchondral bone region, suggesting an inhibition of bone resorption.
Conclusions: With all of these findings, MPMBP may prevent and improve postmenopausal osteoporosis-related temporomandibular disorder and other bone-related disorders.