Osteoporosis: recent physiopatologic acquisitions and new therapeutic perspectives.
The World Health Organization (WHO) declared osteoporosis "social disease". The present revision of the literature will focus on the recent acquisitions in bone pathophysiology and the efforts in the formulation of new molecules able to change successfully the course of the disease. Osteocyte cell is now thought to be the main biomechanical transducer of bones, able to release sclerostin that produces inhibition on osteosynthesis and on the other hand to release substances like nitrid oxide and prostaglandins that provide a stimulus to osteosynthesis through direct or indirect activation of osteoblasts. In this work the authors analyze the most important clinical trials involving the use of new molecules, like denosumab, integrin avb3 inhibitor, cathepsin k inhibitors, able to interfere in the new osteometabolic pathways. Two trials, phase I and II, have been conducted using denosumab. The endpoint of the first phase was the evaluation of the markers of resorption and bone formation, while the second phase II trial focused on the use of this molecule in double-blind matching placebo and open alendronate with the evaluation of bone mass density (BMD) over one year in lumbar area. Another clinical trial in double-blind versus placebo was carried on and published on the use of a competitive integrin avb3 inhibitor in various dosages for the evaluation of bone mass modification in the lumbar and femoral area and of bone markers modification. Many studies focus on the use of cathepsin k inhibitors. Odanacatib has demonstrated to have worked on dose-dependent increase of densitometric value and to have reduced the bone turnover.
Operative Unit of Internal Medicine, "S.M. Goretti" Hospital, Latina, Rome, Italy.
R
R
Cesareo
C
C
Napoletano
M
M
Iozzino
B
B
De Rosa
G
G
Iarussi
M
M
Scona
F
F
Romitelli
D000818:Animals; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D004195:Disease Models, Animal; D006801:Humans; D010024:Osteoporosis / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy*
D050071:Bone Density Conservation Agents