Journal
DRUG DISCOVERY TODAY
Volume 19, Issue 3, Pages 204-208Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.drudis.2013.07.015
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Funding
- [GM103429]
- [GM103450]
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Osteoporosis is a major public health problem despite widespread use of bisphosphonate therapy. PTH(1-34) is a more effective treatment; but its use has been limited by side effects (hypercalcemia, tumor risk) and inconvenient dosing (daily injection). Long-acting forms of PTH are also effective but cause severe hypercalcemia, presumably from effects in kidney. We hypothesized that targeted delivery of PTH to bone using a collagen binding domain (PTH-CBD) could reduce hypercalcemia. PTH-CBD is cleared from serum within 12 hours after subcutaneous administration. In ovariectomized rats, monthly administration of PTH-CBD increased spinal BMD by 14.2% with no associated hypercalcemia. Such bone-targeted anabolic agents may ultimately allow the superior efficacy of anabolic therapy to be obtained with the dosing convenience of bisphosphonates.
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