Treating osteoporosis by targeting parathyroid hormone to bone.
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.
Pediatric Endocrinology, Children's Hospital at Montefiore and Albert Einstein College of Medicine, Bronx, NY, USA. Electronic address: tponnapa@montefiore.org.
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Ponnapakkam
Pediatric Endocrinology, Children's Hospital at Montefiore and Albert Einstein College of Medicine, Bronx, NY, USA.
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Katikaneni
Chemistry, University of Arkansas, Fayetteville, AR, USA.
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J
Sakon
College of Pharmacy, Xavier University of Louisiana, New Orleans, LA, USA.
R
R
Stratford
Pediatric Endocrinology, Children's Hospital at Montefiore and Albert Einstein College of Medicine, Bronx, NY, USA.
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Gensure
D045930:Anabolic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D003692:Delayed-Action Preparations; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use; D016503:Drug Delivery Systems; D006934:Hypercalcemia / Q000139:chemically induced / Q000453:epidemiology; D010024:Osteoporosis / Q000188:drug therapy*; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D051381:Rats
D045930:Anabolic Agents; D003692:Delayed-Action Preparations; D004164:Diphosphonates; D010281:Parathyroid Hormone