The biological mechanisms of the antiresorptive therapy of osteoporosis, and the antiresorptive drug related osteonecrosis of jaws
Osteoporosis (OP) is one of the most common debilitating conditions in the population over the age of 50. Its pathomechanism is still not fully understood. Nowadays, in elderly population, the most common approach to control bone loss is blocking osteoclastic activity by administration of antiresorp...
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| Format: | Article |
| Language: | English |
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Hungarian Dental Association
2024-03-01
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| Series: | Fogorvosi Szemle |
| Subjects: | |
| Online Access: | https://ojs3.mtak.hu/index.php/fogorv-szemle/article/view/15294 |
| _version_ | 1827318261134393344 |
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| author | István Gera Nikolette Szücs |
| author_facet | István Gera Nikolette Szücs |
| author_sort | István Gera |
| collection | DOAJ |
| description | Osteoporosis (OP) is one of the most common debilitating conditions in the population over the age of 50. Its pathomechanism
is still not fully understood. Nowadays, in elderly population, the most common approach to control bone loss is
blocking osteoclastic activity by administration of antiresorptive drugs. Such drugs are also used for the management of
metastatic bone cancer, hypercalcemia of malignancy, and other conditions with elevated osteoclastic activity. Bisphosphonate
therapy is the first choice, but recently monoclonal antibody to RANKL (receptor activator for nuclear factorkappa
B ligand), has also been used; each with distinct mechanism of actions. Bisphosphonates irreversibly adhere to
bone minerals, and during bone remodelling, osteoclasts internalise and metabolise matrix-bound bisphosphonates.
Subsequently, they damage cytoskeletal organization and ruffled border integrity, resulting in the eventual osteoclast
apoptosis. On the other hand, denosumab blocks osteoclast neogenesis by neutralizing RANKL, which is necessary for
osteoclast precursor differentiation into mature osteoclasts. Thus, bisphosphonates acts on mature osteoclasts, while
denosumab hinders osteoclast formation from its precursors. Although their antiresorptive actions are different, recent
case reports and controlled clinical studies indicated that administration of either of these may be associated with development
of osteonecrosis of the jaw (ONJ). The fact that ONJ is associated with both bisphosphonates and denosumab
convincingly suggests that osteoclast suppression is essential in the pathomechanism of ONJ. The evidence-based,
cause-related therapy for MRONJ still remains missing. Many alternative therapeutic approaches has recently been tested
and published, amongst them, using recombinant human parathyroid hormone (rh-PTH, teriparatide) may become a
promising treatment modality |
| first_indexed | 2024-04-24T23:55:07Z |
| format | Article |
| id | doaj.art-718dc7702f2d4a128fa0000c07c2a567 |
| institution | Directory Open Access Journal |
| issn | 2498-8170 |
| language | English |
| last_indexed | 2024-04-24T23:55:07Z |
| publishDate | 2024-03-01 |
| publisher | Hungarian Dental Association |
| record_format | Article |
| series | Fogorvosi Szemle |
| spelling | doaj.art-718dc7702f2d4a128fa0000c07c2a5672024-03-14T14:17:03ZengHungarian Dental AssociationFogorvosi Szemle2498-81702024-03-011171112110.33891/FSZ.117.1.11-2115294The biological mechanisms of the antiresorptive therapy of osteoporosis, and the antiresorptive drug related osteonecrosis of jawsIstván Gera0Nikolette Szücs1Semmelweis Egyetem, Fogorvostudományi Kar, Parodontológiai KlinikaSemmelweis Egyetem, Általános Orvostudományi Kar, Belgyógyászati és Onkológiai KlinikaOsteoporosis (OP) is one of the most common debilitating conditions in the population over the age of 50. Its pathomechanism is still not fully understood. Nowadays, in elderly population, the most common approach to control bone loss is blocking osteoclastic activity by administration of antiresorptive drugs. Such drugs are also used for the management of metastatic bone cancer, hypercalcemia of malignancy, and other conditions with elevated osteoclastic activity. Bisphosphonate therapy is the first choice, but recently monoclonal antibody to RANKL (receptor activator for nuclear factorkappa B ligand), has also been used; each with distinct mechanism of actions. Bisphosphonates irreversibly adhere to bone minerals, and during bone remodelling, osteoclasts internalise and metabolise matrix-bound bisphosphonates. Subsequently, they damage cytoskeletal organization and ruffled border integrity, resulting in the eventual osteoclast apoptosis. On the other hand, denosumab blocks osteoclast neogenesis by neutralizing RANKL, which is necessary for osteoclast precursor differentiation into mature osteoclasts. Thus, bisphosphonates acts on mature osteoclasts, while denosumab hinders osteoclast formation from its precursors. Although their antiresorptive actions are different, recent case reports and controlled clinical studies indicated that administration of either of these may be associated with development of osteonecrosis of the jaw (ONJ). The fact that ONJ is associated with both bisphosphonates and denosumab convincingly suggests that osteoclast suppression is essential in the pathomechanism of ONJ. The evidence-based, cause-related therapy for MRONJ still remains missing. Many alternative therapeutic approaches has recently been tested and published, amongst them, using recombinant human parathyroid hormone (rh-PTH, teriparatide) may become a promising treatment modalityhttps://ojs3.mtak.hu/index.php/fogorv-szemle/article/view/15294osteoporosisantirezorptive therapycoupled bone remodellingmedication related osteonecrosis of jaws |
| spellingShingle | István Gera Nikolette Szücs The biological mechanisms of the antiresorptive therapy of osteoporosis, and the antiresorptive drug related osteonecrosis of jaws Fogorvosi Szemle osteoporosis antirezorptive therapy coupled bone remodelling medication related osteonecrosis of jaws |
| title | The biological mechanisms of the antiresorptive therapy of osteoporosis, and the antiresorptive drug related osteonecrosis of jaws |
| title_full | The biological mechanisms of the antiresorptive therapy of osteoporosis, and the antiresorptive drug related osteonecrosis of jaws |
| title_fullStr | The biological mechanisms of the antiresorptive therapy of osteoporosis, and the antiresorptive drug related osteonecrosis of jaws |
| title_full_unstemmed | The biological mechanisms of the antiresorptive therapy of osteoporosis, and the antiresorptive drug related osteonecrosis of jaws |
| title_short | The biological mechanisms of the antiresorptive therapy of osteoporosis, and the antiresorptive drug related osteonecrosis of jaws |
| title_sort | biological mechanisms of the antiresorptive therapy of osteoporosis and the antiresorptive drug related osteonecrosis of jaws |
| topic | osteoporosis antirezorptive therapy coupled bone remodelling medication related osteonecrosis of jaws |
| url | https://ojs3.mtak.hu/index.php/fogorv-szemle/article/view/15294 |
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