ATC Group: M05B Drugs affecting bone structure and mineralization

Anatomical Therapeutic Chemical Classification System

Hierarchical position in ATC classification

Level
Code
Title
1
Musculo-skeletal system
2
Drugs for treatment of bone diseases
3
M05B
Drugs affecting bone structure and mineralization

ATC group contents

Code
Title
Bisphosphonates
Bisphosphonates, combinations
Bone morphogenetic proteins
Other drugs affecting bone structure and mineralization

Active ingredients

Active Ingredient
Description

Alendronic acid is a bisphosphonate that inhibits osteoclastic bone resorption with no direct effect on bone formation. The bone formed during treatment with alendronic acid is of normal quality.

Burosumab is a recombinant human monoclonal antibody (IgG1) that binds to and inhibits the activity of fibroblast growth factor 23 (FGF23). By inhibiting FGF23, burosumab increases tubular reabsorption of phosphate from the kidney and increases serum concentration of 1, 25 dihydroxy-Vitamin D.

Clodronic acid is a bisphosphonate, (formerly diphosphonates), a group of analogues of pyrophosphate, which have been shown, in vitro, to inhibit the formation and dissolution of calcium phosphate (hydroxyapatite). In vivo, they have been shown to inhibit bone resorption to a greater or lesser extent, depending on the compound, and clodronate is one of the most effective in this respect.

Denosumab is a human monoclonal antibody (IgG2) that targets and binds with high affinity and specificity to RANKL, preventing activation of its receptor, RANK, on the surface of osteoclast precursors and osteoclasts. Prevention of the RANKL/RANK interaction inhibits osteoclast formation, function and survival, thereby decreasing bone resorption in cortical and trabecular bone.

Dibotermin alfa is an osteoinductive protein that results in the induction of new bone tissue at the site of implantation. Dibotermin alfa binds to receptors on the surface of mesenchymal cells and causes cells to differentiate into cartilage- and bone-forming cells. The differentiated cells form trabecular bone as the matrix is degraded, with vascular invasion evident at the same time.

Eptotermin alfa, the active substance, initiates bone formation through the induction of cellular differentiation in mesenchymal cells, which are recruited to the implant site from bone marrow, periosteum and muscle. Once bound at the cell surface, the active substance induces a cascade of cellular events leading to the formation of chondroblasts and osteoblasts, which play a key role in the bone formation process.

Etidronate acts primarily on bone. It can inhibit the formation, growth, and dissolution of hydroxyapatite crystals and their amorphous precursors by chemisorption to calcium phosphate surfaces.

Ibandronic acid belongs to the bisphosphonate group of compounds which act specifically on bone. Their selective action on bone tissue is based on the high affinity of bisphosphonates for bone mineral. Bisphosphonates act by inhibiting osteoclast activity, although the precise mechanism is still not clear. In vivo, ibandronic acid prevents experimentally-induced bone destruction caused by cessation of gonadal function, retinoids, tumours or tumour extracts.

The principal pharmacologic action of pamidronic acid is inhibition of bone resorption. Although the mechanism of antiresorptive action is not completely understood, several factors are thought to contribute to this action. Pamidronic acid adsorbs to calcium phosphate (hydroxyapatite) crystals in bone and may directly block dissolution of this mineral component of bone.

Risedronic acid is a pyridinyl bisphosphonate that binds to bone hydroxyapatite and inhibits osteoclast-mediated bone resorption. The bone turnover is reduced while the osteoblast activity and bone mineralisation is preserved.

Romosozumab is a humanized monoclonal antibody (IgG2) that binds and inhibits sclerostin, thereby increasing bone formation, bone matrix production and recruitment of osteoprogenitor cells. Additionally, romosozumab results in changes to expression of osteoclast mediators, thereby decreasing bone resorption. It is indicated in treatment of severe osteoporosis in postmenopausal women at high risk of fracture.

In vitro, strontium ranelate increases bone formation in bone tissue culture as well as osteoblast precursor replication and collagen synthesis in bone cell culture and reduces bone resorption by decreasing osteoclast differentiation and resorbing activity. This results in a rebalance of bone turnover in favour of bone formation.

Vosoritide is a modified type C natriuretic peptide (CNP). In patients with achondroplasia, endochondral bone growth is negatively regulated due to a gain of function mutation in fibroblast growth factor receptor 3 (FGFR3). Binding of vosoritide to natriuretic peptide receptor-B (NPR-B) antagonises FGFR3 downstream signalling. As a result, vosoritide, like CNP, acts as a positive regulator of endochondral bone growth as it promotes chondrocyte proliferation and differentiation.

Zoledronic acid belongs to the class of bisphosphonates and acts primarily on bone. It is an inhibitor of osteoclastic bone resorption.

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