Effect of Bisphosphonates on Mandibular Bone in Mild Type Hypophosphatasia.

Objectives: Hypophosphatasia (HPP) is the inherited disease caused by a deficiency of tissue-non-specific alkaline phosphatase isoenzyme (TNSALP). HPP characterized by rickets, osteomalacia and premature loss of deciduous teeth due to cementum malformation. It is often HPP is misdiagnosed as osteoporosis with bone volume loss. In addition, there have been reports that bisphosphonates, a common treatment for osteoporosis, administered to HPP have caused atypical femur fracture. Nevertheless, it has not been reported that effect of bisphosphonates on mandibular bone in HPP. Therefore, we purposed to investigate the effect of bisphosphonates on mandibular bone and mandibular condyle using mild type HPP (Akp2 ^+/−) mice by pathological and radiological analysis.
Methods: Female wild type (WT) mice (n = 8) and Akp2 ^+/− mice (n = 8) aged 4 weeks were employed.
Zoledronate acid hydrate or saline was injected subcutaneously into Akp2 ^+/− mice and WT mice once a week for 5 weeks. H-E staining of mandibular bone was performed for pathological analysis. The mandibular bone was also observed by micro-CT for radiological analysis.
Results: H-E staining of mandibular condyle in bisphosphonates-administered mice showed increased thickness of hypertrophic cartilage layer and degeneration of cartilage when compared with control group. Micro-CT analysis of mandibular condyle in bisphosphonates-administered mice showed enlargement of that when compared with control. In addition, a slight decrease in bone volume and thickness of the mandibular neck was observed in Akp2 ^+/− mice by micro-CT.
Conclusions: The administration of bisphosphonates resulted in cartilage degeneration in the mandibular condyle. Furthermore, it is possible that the bone of the mandibular neck in Akp2 ^+/− mice are weaker than that of WT. Thus, HPP may be more susceptible to fracture of the mandibular condyle after administration of bisphosphonates. Atypical mandibular fractures in patients treated with bisphosphonates should be monitored carefully.