Osteoporosis is characterized by the loss of bone mass and strength that leads to fragility fractures in particular during aging. The concept that there are two forms of osteoporosis, one related to estrogen deficiency at the menopause and the other to calcium deficiency and aging of the skeleton has been replaced by the current concept that osteoporosis represents a continuum, in which multiple pathogenetic mechanisms converge to cause loss of bone mass and microarchitectural deterioration of skeletal structure. Epidemiologic studies suggest that sex hormone-binding globulin (SHBG), the major binding protein for sex steroids in plasma, may have an effect on bone loss and fracture risk. While estrogen can act on cells of the osteoblastic lineage, its effects on bone may also be dependent on actions on cells of hematopoietic lineage, including osteoclast precursors, mature osteoclasts, and lymphocytes. Local cytokines and growth factors may mediate these effects.
The concept that stimulation of bone resorption requires an interaction between cells of the osteoblastic and osteoclastic lineages was put forward but its molecular mechanism was only identified recently. Three members of the TNF and TNF receptor superfamily are involved; osteoblasts produced RANKL, a ligand for the receptor activator of NK-kB (RANK) on hematopoietic cells and osteoprotegerin a decoy receptor that can block RANKL/RANK interactions. The RANKL/RANK interaction is critical for both differentiation and maintenance of osteoclast activity and hence represents a final common pathway for any pathogenetic factor in osteoporosis that acts by increasing bone resorption.
The recent discoveries of signal transduction pathways and transcription factors critical for osteoblasts differentiation and function have opened up new approaches to understanding the pathogenesis of osteoporosis. Further, the concept was put forward that locally produced cytokines such as IL-1 and prostaglandins such as prostaglandin E2 (PGE)2 can affect bone. The possibility that these factors might also be involved in the pathogenesis of osteoporosis is based largely on animal studies; however, there is evidence that polymorphisms of IL-1, IL-6, TNF-, and their receptors can influence bone mass in humans.
Prior to the introduction of BMD measurements, the diagnosis of osteoporosis was only made when fragility fractures occurred, BMD helps to diagnose osteoporosis and osteopenia before fractures occur. While low BMD is an important risk factor, many other factors have been identified in epidemiologic studies, including, age, low body weight and smoking.
At present the therapy of osteoporosis is directed at the major pathogenetic mechanisms with a strong emphasis on prevention of bone loss and fractures. Pharmacotherapy for osteoporosis has been focused mainly on interventions that could reverse the second pathogenic mechanisms, excessive bone resorption.
While improvements in diagnosis and therapy are important, it is equally true that tools are developed to assess fracture risk and prevent or treat osteoporosis to reduce that risk.
Sheikh Hamdan Award for Excellence in Medical Research for 2010 will recognize an important achievement in better understanding of pathogenesis and/or significant contribution to diagnosis and therapy of this important disorder.