Dissociation of bone formation from resorption during 2-week treatment with human parathyroid hormone-related peptide-(1-36) in humans: potential as an anabolic therapy for osteoporosis.

Abstract

PTH administration increases bone mass in rodents and in humans. PTH-related protein (PTHrP) binds to and signals via the skeletal PTH receptor. Administration of PTHrP on a once daily basis increases bone mineral content in rats. In humans, PTHrP-(1-36) is equipotent to PTH-(1-34) and is active when administered s.c. These findings suggest that PTHrP might have therapeutic benefit in the treatment of osteoporosis. In this study, 13 postmenopausal estrogen-deficient women received a single daily s.c. dose of PTHrP-(1-36) for a 14-day period to determine whether PTHrP-(1-36) 1) could be given in doses that do not alter systemic mineral homeostasis, but increase markers of bone turnover; and 2) is tolerated without adverse effects. Daily s.c. PTHrP-(1-36) administration caused no significant changes in serum calcium or phosphorus concentrations, fractional calcium excretion, the tubular maximum for phosphorus, fractional calcium excretion, or plasma 1,25-dihydroxyvitamin D concentrations. Nephrogenous cAMP and endogenous PTH-(1-84) declined. Importantly, markers of bone formation trended upward, as reported in subjects treated with PTH. In marked contrast to findings in PTH-treated subjects, in PTHrP-treated subjects, markers of bone resorption declined in a highly significant fashion. These observations indicate that PTHrP-(1-36) treatment uncouples bone formation from resorption, in favor of formation. This uncoupling, if it were to continue over the longer term, would predict that PTHrP-(1-36) might be a potent anabolic therapeutic agent for osteoporosis.

• Authors: H Plotkin, C Gundberg, M Mitnick, A F Stewart
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 83 Issue 8 Pg. 2786-91 (Aug 1998) ISSN: 0021-972X [Print] United States
• PMID: 9709948 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Parathyroid Hormone
• Parathyroid Hormone-Related Protein
• Peptide Fragments
• Proteins
• parathyroid hormone-related peptide (1-36)
• Phosphorus
• Cyclic AMP
• Calcitriol
• Calcium

Topics

• Bone Development (physiology)
• Bone Remodeling
• Bone Resorption
• Calcitriol (blood)
• Calcium (blood, urine)
• Cyclic AMP (metabolism)
• Female
• Glomerular Filtration Rate
• Humans
• Middle Aged
• Osteoporosis (drug therapy)
• Parathyroid Hormone (blood)
• Parathyroid Hormone-Related Protein
• Peptide Fragments (administration & dosage, pharmacology, therapeutic use)
• Phosphorus (blood)
• Postmenopause
• Proteins (administration & dosage, pharmacology, therapeutic use)