Bone modeling and remodeling are potential therapeutic targets for the treatment of osteoporosis

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Bone modeling and remodeling are potential therapeutic targets for the treatment of osteoporosis

In adults, small amounts of bone minerals are removed naturally through the process resorption. There should be an equal balance between the removal and deposition of new minerals (redeposition) to strengthens the bone. Imbalance to this process weakens the bones making them more prone to the fractures or osteoporosis.

This process of resorption and redeposition is closely related to the pathophysiology of osteoporosis. The comparative value of cortical remodeling increases with the age, as with age, the cellular bone is lost and remodeling activity is increased. In bone modeling process, the bones are shaped or reshaped by the independent activity of osteoblast and osteoclasts. The activities of osteoblasts and osteoclasts are not necessarily coupled anatomically or temporally. Skeletal development and the bone growth has been defined by the bone modeling through the entire life. Modeling based bone formation contributes to the periosteal expansion same as of remodeling-based resorption, which is responsible for the medullary expansion observed with the aging.

Hormones are also possibly the most crucial modulators of the bone formation. For optimal bone development and maintenance, estrogen, parathyroid hormone, and testosterone to some extent are essential. Moreover, estrogen have direct effect on the bone cells which interact with the specific proteins or receptors on the surface of osteoblasts and osteoclasts. Existing and upcoming treatments has impact on remodeling and modeling of the bones. For example, teriparatide stimulates the bone formation, which is 70% remodeling based and 20-30% modeling-based. Denosumab inhibits the bone remodeling but is permissive for modeling at cortex. Odanacatib inhibits the bone resorption by inhibiting the cathepsin K activity. Inhibition of sclerostin helps in the stimulation of bone formation and histomorphometric analysis and it has demonstrated the bone formation, which is predominantly modeling based. The bone mass response to some osteoporosis treatments in humans certainly suggests that non-remodeling mechanisms also contributes to the response and bone modeling. However, only demonstration for teriparatide has been given till date. The rediscovery of the phenomenon that was observed half a century ago possess an important impact on understanding that how new anti-fracture treatments work.


Therapeutic Advances in Musculoskeletal Disease

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Bone modeling and remodeling: potential as therapeutic targets for the treatment of osteoporosis


Bente Langdahl, Serge Ferrari, David W. Dempster

Therapeutic Advances in Musculoskeletal Disease
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