Bisphosphonate inhibits bone turnover in OPG(-/-) mice via a depressive effect on both osteoclasts and osteoblasts

Area of Science:

• Bone biology
• Osteoclast and osteoblast interactions
• Pharmacology

Background:

• Osteoclast activity is regulated by osteoblasts via RANKL.
• The reciprocal control of osteoblasts by osteoclasts is not well understood.
• Osteoporosis involves high bone turnover and altered bone remodeling.

Purpose of the Study:

• To investigate the effect of bisphosphonate (BP), an osteoclast inhibitor, on the response of maxillary bone to mechanical stress in an osteoporosis model.
• To explore potential negative control of osteoblasts by osteoclasts.

Main Methods:

• Utilized OPG(-/-) mice, a model for high-turnover osteoporosis.
• Mechanical stress was applied to the maxillary first molar using orthodontic elastics.
• Bisphosphonate (BP) was administered daily prior to and during elastic insertion.
• Evaluated tooth movement, interradicular septum bone resorption, osteoclast counts, serum alkaline phosphatase (ALP), and Runx2 staining.

Main Results:

• OPG(-/-) mice exhibited increased tooth movement, bone resorption, osteoclast counts, and serum ALP compared to wild type (WT).
• BP treatment in OPG(-/-) mice reduced tooth movement, increased interradicular bone volume, decreased osteoclast counts, and lowered serum ALP.
• BP administration altered the timing of peak Runx2 staining in OPG(-/-) mice, normalizing it towards WT levels.
• BP inhibited both osteoclast and osteoblast activity in OPG(-/-) mice.

Conclusions:

• Bisphosphonate administration not only inhibits osteoclast activity but also suppresses osteoblast activity systemically and locally.
• The findings suggest a potential negative regulatory role of osteoclasts on osteoblast function.
• This study provides insights into the complex interplay between osteoclasts and osteoblasts in bone remodeling, particularly under conditions of high turnover.