Risedronate Prevents Early Bone Loss Resulting from Whole-Body Irradiation

Osteoporosis is a condition characterized by a reduction in bone strength resulting in an overall increase in the risk of fracture. There are many factors that contribute to the development of this condition, including ionizing radiation exposure. Declines in bone volume and trabecular micro-architecture have been found following exposure to multiple types of radiation. Past research has implicated reduction of osteoblast function and changes to vasculature as the primary sources of bone deterioration. Recently, an early increase in osteoclast number was observed following exposure to low-energy Xrays, identifying an increase in resorption as a possible cause and potential target for treatment. The goals of this research are to further characterize the effects of X-rays on trabecular bone at multiple skeletal sites and time points, and assess the effectiveness of the bisphosphonate risedronate to mitigate the radiation-induced deterioration of the trabecular network.

The results from this research indicate trabecular bone deterioration can occur within the first week following exposure to ionizing radiation, with no effects on cortical bone. Serum markers of bone resorption are elevated at 7 days, indicating an early increase in osteoclast activity. Importantly, bisphosphonate administration prevents the deterioration of trabecular bone volume and architecture at all time points and sites, further supporting earlier findings of osteoclast-mediated bone loss.

In order to fully characterize the mechanisms resulting in bone loss, the radiationinduced changes to bone cells should be studied more closely along with effects on bone formation and resorption rates. Earlier time points within the first week post-irradiation must be examined to determine the timeline when changes to bone cells produce functional declines in bone volume and architecture. Additionally, the effects of these declines need to be correlated with changes in overall bone strength in order to determine the most appropriate dosing regimen for preventative and/or treatment therapies. The data from these studies may be useful in determining the most effective method of preventing fractures following radiotherapy

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Year

Entry

1984

Parfitt AM. The cellular basis of bone remodeling: the quantum concept reexamined in light of recent advances in the cell biology of bone. Calcif Tiss Int. March 1984;36(suppl 1):S37-S45.

1997

Silva MJ, Gibson LJ. Modeling the mechanical behavior of vertebral trabecular bone: effects of age-related changes in microstructure. Bone. 1997;21(2):191-199.

1996

Rodan GA, Fleisch HA. Bisphosphonates: mechanisms of action. J Clin Invest. June 15, 1996;97(12):2692-2696.

2001

NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA. February 14, 2001;285(6):785-795.

2004

Lang T, LeBlanc A, Evans H, Lu Y, Genant H, Yu A. Cortical and trabecular bone mineral loss from the spine and hip in long‐duration spaceflight. J Bone Miner Res. June 2004;19(6):1006-1012.