Treating osteoporosis by targeting parathyroid hormone to bone
by Ponnapakkam, T.; Katikaneni, R.; Sakon, J.; Stratford, R.; Gensure, R. C.
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.
- Journal
- Drug Discovery Today
- Volume
- 19
- Issue
- 3
- Year
- 2014
- Start Page
- 204-208
- URL
- https://dx.doi.org/10.1016/j.drudis.2013.07.015
- ISBN/ISSN
- 1878-5832; 1359-6446
- DOI
- 10.1016/j.drudis.2013.07.015