Broken bones are a common occurrence in the playground but are unfortunately frequent in the elderly too, due to the natural loss of bone mass as we age. Bones that are less dense are less strong and break more easily; individuals with particularly weak bones account for the 200 million osteoporosis sufferers worldwide.
The activity of the cells which continually remodel our bones - the osteoblasts (bone forming cells) and osteoclasts (bone destroying cells) - are normally balanced to uphold healthy skeletal strength. The problem is that as we get older we lose more bone than we are able to make.
So can we recapture this balance in bone remodelling for osteoporosis sufferers? Effective medications exist that slow bone loss but there are few drugs on hand to increase bone formation. One way to push osteoblasts to increase their bone forming activity is to mimic the signals that occur following physical weight-bearing exercises such as running. When we run, bone formation is stimulated and bone loss is reduced to meet the physical demand. Likewise, if bones are not used, which we see encountered by astronauts in a weightless environment, bone loss of up to 1-2% per month can occur.
Osteocyte cells within the bones sense the physical force (or mechanical load) and signal through one another to osteoblasts and osteoclasts at the bone surface. Many signals are involved in this process but one signalling protein that is the target of a current drug in development is Sclerostin. Sclerostin is produced by osteocytes and its production is reduced by mechanical load. This is because it acts to prevent another signalling protein from telling osteoblasts to start multiplying and make more bone. Sclerostin levels in the blood increase naturally with age, coinciding with a decrease in bone mass, although this increase is diminished in physically active adults.
Drugs are being developed by pharmaceutical companies that can recognise sclerostin, bind to it and prevent it from carrying out its normal activities. Published findings from a phase I clinical trial showed that injection of a single dose of the drug could increase multiple markers of bone formation and potentially also reduce bone loss. The trial was conducted on healthy males and post-menopausal woman, but the results do suggest that it may be useful in the future in reducing fracture risk in osteoporotic patients. Further trials of the drug are currently under way and the results are expected to be published later this year.
Cooper, C., et al. Osteoporosis International 2(6) 285-9 (1992)
Lang, T., et al. Journal of Bone and Mineral Research 19 1006-1012 (2004)
Amrein, K., et al. Journal of Clinical Endocrinology and Metabolism 97(1) 148-54 (2012)
Padhi, D., et al. Journal of Bone and Mineral Research 26(1) 19-26 (2011)