Effects of bisphosphonates on mandibular condyle of ovariectomized osteoporotic rats using micro‐ct and histomorphometric analysis

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The growth and remodeling of condyle cartilage play an important role in the development of the mandible and occlusal balance 1. It is influenced by genetic changes, endocrine factors, paracrine mediators, and mechanical stress 2. Previous studies have shown that estrogen receptor (ER) is expressed in the chondroclastic and hypertrophic layers in condylar cartilage which makes condyle sensitive to changes in estrogen levels after birth or during adolescence 3. Indeed, estrogen has been shown to alter the expression of extracellular matrix, the thickness, morphology, and function of condylar cartilage 5.
Postmenopausal osteoporosis is a common debilitating bone disorder due to estrogen deficiency, which causes excessive bone remodeling leading to loss of bone microarchitecture 6. Some researchers have reported osteoporosis not only affects long bones such as femur, but the mandibular condyle as well 7. During bone remodeling, estrogen level and activity could affect subchondral bone remodeling, and alter bone mineralization and mechanical properties, which is considered as main reason for osteoarthritic cartilage or bone process 8. Previous in vivo studies have shown that estrogen signaling through ER inhibits mandibular condylar cartilage growth 9. The researchers infer there is a possible link between temporomandibular (TMJ) disease and estrogen according to the gender and age distribution of TMJ disease 10. However, the correlation of postmenopausal osteoporosis with the health of condylar cartilage is little studied.
Bisphosphonates (BPs) are the traditional antiresorptive agents in treating osteoporosis that primarily acts by inhibiting osteoclastogenesis that may also have positive feedback effect on osteoblast proliferation and activity 11. Some reports indicate that bisphosphonates have a pharmacological effect on inhibiting articular cartilage turnover and related structural alterations in ovariectomy‐induced rodents 12. Thus, BP treatment for osteoarthritis is appealing. However, what is the effect of BP treatment on condylar cartilage due to cartilage‐specific differences needs to be further studied. In addition, bisphosphonate‐related osteonecrosis of the jaws (BRONJ) in patients have been reported under systemic BP treatment in recent years. With regard to mandible, dental specialists expect whether BPs have a possible negative side effect or a positive treatment effect on the condylar subchondral bone due to their bone‐specific differences. To our knowledge, there were only three published papers in which the effect of BPs (alendronate and zoledronic acid) on condylar cartilage of normal growing rats was assessed 14. The effect of BPs on the mandibular condyle remains largely unknown.
In this study, we aimed to determine the effect of postmenopausal osteoporosis and BP treatment on structural integrity of mandibular condyle using ovariectomized (OVX) rat model. For bisphosphonate treatment, a third‐generation nitrogen‐containing BP risedronate was used 17. In addition, we used histochemical and immunohistochemical techniques to understand the cellular mechanisms involved.
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