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Drug Discov Today. 2014 Mar;19(3):204-8. doi: 10.1016/j.drudis.2013.07.015. Epub 2013 Aug 6.

Treating osteoporosis by targeting parathyroid hormone to bone.

Author information

1
Pediatric Endocrinology, Children's Hospital at Montefiore and Albert Einstein College of Medicine, Bronx, NY, USA. Electronic address: tponnapa@montefiore.org.
2
Pediatric Endocrinology, Children's Hospital at Montefiore and Albert Einstein College of Medicine, Bronx, NY, USA.
3
Chemistry, University of Arkansas, Fayetteville, AR, USA.
4
College of Pharmacy, Xavier University of Louisiana, New Orleans, LA, USA.

Abstract

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 12hours 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.

PMID:
23932952
PMCID:
PMC3979969
DOI:
10.1016/j.drudis.2013.07.015
[Indexed for MEDLINE]
Free PMC Article

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