Bone remodeling during alveolar repair is impaired by RANKL antagonist

Post-menopausal osteoporosis is detrimental to bone metabolism as well as alveolar repair. This osteometabolic disorder is an obstacle to the success of maxillofacial rehabilitations, since a large number of patients are carriers of the disease. Denosumab is widely used as a treatment for post menopausal osteoporosis. This drug exerts an antiabsorptive action by inhibiting RANKL, helping to reduce the bone loss caused by osteoporosis. This study aimed to evaluate the repair bone formed after the extraction of the upper incisor of estrogen-deficient rats treated with anti-RANKL monoclonal antibody. The rats (Rattus novergicus albinus, Wistar) were ovariectomized or SHAM operated (n=36). Half of the ovariectomized rats were treated with osteoprotegerin with an Fc fragment (OPG-Fc; 10mg/kg, twice a week), the other half received saline solution as control. After 30 days the rats had their right upper incisor extracted. After 60 days of extraction, the alveoli were evaluated by immunohistochemical, computerized microtomography and confocal microscopy. The OPG-Fc decreased the percentage of bone volume (BV/TV), thickness (Tb.Th) and number of alveolar trabecules (Tb.N) when compared to groups that received saline solution (p<0.005). The OPG-Fc increased the separation between the trabecules (Tb.Sp) and the porosity (Po.tot) of the reparative alveolar bone (p<0.005). The OPG-Fc decreased immunolabelling for RANKL and TRAP when compared to groups that received saline solution. Treatment with OPG-Fc decreased bone neoformation but preserved preexisting bone tissue. This data is supported by the mineral apposition rate, which showed higher values for OVX/OPG-Fc when compared to the OVX group.

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The Effects of Ficus Carica Fruit on Bone Markers and Oestrogen Level of Post-Menopausal Osteoporotic Rats

IIUM Medical Journal Malaysia ◽

10.31436/imjm.v18i1.231 ◽

2020 ◽

Vol 18 (1) ◽

Author(s):

Norfarah Izzaty R ◽

Nur Adlina M ◽

Muhammad Shamsir MA ◽

Nadia ME ◽

Mohd Dzulkhairi MR

Keyword(s):

Aqueous Extract ◽

Ficus Carica ◽

Ovariectomized Rats ◽

Post Menopausal Osteoporosis ◽

Oestrogen Level ◽

Significant Difference ◽

Post Menopausal ◽

Higher Doses ◽

Menopausal Osteoporosis

Introduction: Post-menopausal osteoporosis is the most common type of osteoporosis, which occurs due to a deficiency of oestrogen following menopause. Considering the adverse effects of oestrogen replacement therapy, natural products may serve to replace the current conventional treatment. Ficus carica (FC) which is commonly known as fig may have a potential in treating post-menopausal osteoporosis due to their abundance of important minerals and bioactive compounds such as phenolic, flavonoid and anthocyanins. This study aimed to evaluate the effects of FC on bone metabolism of ovariectomized rats. Materials and Methods: Fifty-six female Spraque-Dawley rats were randomly divided into seven groups; SHAM operated (SHAM), ovariectomized control (OVX), ovariectomized + 64.5 µg/kg oestrogen (ERT), ovariectomized + 50 mg/kg aqueous extract of FC (AQ50), ovariectomized + 100 mg/kg aqueous extract of FC (AQ100), ovariectomized + 50 mg/kg raw FC (RW50), and ovariectomized + 100 mg/kg raw FC (RW100). After eight weeks of treatments, rats were euthanized and femurs were dissected out to measure bone osteocalcin, Ctelopeptide of type 1 collagen and bone estrogen level. Results: RW50 and RW100 showed an increasing trend in osteocalcin levels and also oestrogen level, but no significant difference between all groups. RW50 and RW100 also showed significantly reduced C-telopeptide of type 1 collagen levels compared to OVX group. Conclusion: These findings suggested that raw FC at the doses of 50 mg/kg and 100 mg/kg have potential to improve bone in treating post-menopausal osteoporosis. However, this need to be confirmed with higher doses.

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Inflammation-induced Bone Remodeling in Periodontal Disease and the Influence of Post-menopausal Osteoporosis

Journal of Dental Research ◽

10.1177/154405910608500704 ◽

2006 ◽

Vol 85 (7) ◽

pp. 596-607 ◽

Cited By ~ 177

Author(s):

U.H. Lerner

Keyword(s):

Bone Loss ◽

Bone Formation ◽

Periodontal Disease ◽

Alveolar Bone ◽

Bone Cells ◽

Physiological Conditions ◽

Post Menopausal Osteoporosis ◽

Inflammatory Processes ◽

Post Menopausal ◽

Menopausal Osteoporosis

During physiological conditions, the skeleton is remodeled in so-called bone multi-cellular units. Such units have been estimated to exist at 1–2 x 106 sites in the adult skeleton. The number and activities of these units are regulated by a variety of hormones and cytokines. In post-menopausal osteoporosis, lack of estrogen leads to increased numbers of bone multi-cellular units and to uncoupling of bone formation and bone resorption, resulting in too little bone laid down by osteoblasts compared with the amount of bone resorbed by osteoclasts. Inflammatory processes in the vicinity of the skeleton, e.g., marginal and apical periodontitis, will affect the remodeling of the nearby bone tissue in such a way that, in most patients, the amount of bone resorbed exceeds that being formed, resulting in net bone loss (inflammation-induced osteolysis). In some patients, however, inflammation-induced bone formation exceeds resorption, and a sclerotic lesion will develop. The cellular and molecular pathogenetic mechanisms in inflammation-induced osteolysis and sclerosis are discussed in the present review. The cytokines believed to be involved in inflammation-induced remodeling are very similar to those suggested to play crucial roles in post-menopausal osteoporosis. In patients with periodontal disease and concomitant post-menopausal osteoporosis, the possibility exists that the lack of estrogen influences the activities of bone cells and immune cells in such a way that the progression of alveolar bone loss will be enhanced. In the present paper, the evidence for and against this hypothesis is presented.

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