Treating osteoporosis by targeting parathyroid hormone to bone

by Ponnapakkam, Tulasi; Katikaneni, Ranjitha; Sakon, Josh; Stratford, Jr, Robert; Gensure, Robert 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
ISBN/ISSN
1878-5832; 1359-6446
PMID
23932952
DOI
10.1016/j.drudis.2013.07.015