Effects Of a One-Month Treatment With PTH(1–34) on Bone Formation on Cancellous, Endocortical, and Periosteal Surfaces of the Human Ilium

Authors

  • Robert Lindsay MD, PhD,

    Corresponding author
    1. Clinical Research Center, Helen Hayes Hospital, West Haverstraw, New York, USA
    2. Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA
    • Clinical Research Center, Helen Hayes Hospital, Route 9W, West Haverstraw, NY 10993, USA
    Search for more papers by this author
  • Hua Zhou,

    1. Regional Bone Center, Helen Hayes Hospital, West Haverstraw, New York, USA
    Search for more papers by this author
  • Felicia Cosman,

    1. Clinical Research Center, Helen Hayes Hospital, West Haverstraw, New York, USA
    2. Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA
    Search for more papers by this author
  • Jeri Nieves,

    1. Clinical Research Center, Helen Hayes Hospital, West Haverstraw, New York, USA
    2. Department of Epidemiology, Columbia University College of Physicians and Surgeons, New York, New York, USA
    Search for more papers by this author
  • David W Dempster,

    1. Regional Bone Center, Helen Hayes Hospital, West Haverstraw, New York, USA
    2. Department of Pathology, Columbia University College of Physicians and Surgeons, New York, New York, USA
    Search for more papers by this author
  • Anthony B Hodsman

    1. University of Western Ontario, St Joseph's Health Care, London, Ontario, Canada
    Search for more papers by this author

  • Dr Hodsman is a member of the advisory board for Eli Lilly Canada and NPS Pharmaceuticals. Drs Lindsay and Cosman have received speaker fees from Eli Lilly & Co. Dr Dempster has served as a consultant for and received speaker fees from Eli Lilly & Co. All other authors state that they have no conflicts of interest.

Abstract

Using bone histomorphometry, we found that a 1-month treatment with PTH(1–34) [hPTH(1–34)] stimulated new bone formation on cancellous, endocortical, and periosteal bone surfaces. Enhanced bone formation was associated with an increase in osteoblast apoptosis.

Introduction: The precise mechanisms by which hPTH(1–34) increases bone mass and improves bone structure are unclear. Using bone histomorphometry, we studied the early effects of treating postmenopausal women with osteoporosis with hPTH(1–34).

Materials and Methods: Tetracycline-labeled iliac crest bone biopsies were obtained from 27 postmenopausal women with osteoporosis who were treated for 1 month with hPTH(1–34), 50 μg daily subcutaneously. The results were compared with tetracycline-labeled biopsies from a representative control group of 13 postmenopausal women with osteoporosis.

Results: The bone formation rate on the cancellous and endocortical surfaces was higher in hPTH(1–34)–treated women than in control women by factors of 4.5 and 5.0, respectively. We also showed a 4-fold increase in bone formation rate on the periosteal surface, suggesting that hPTH(1–34) has the potential to increase bone diameter in humans. On the cancellous and endocortical surfaces, the increased bone formation rate was primarily caused by stimulation of formation in ongoing remodeling units, with a modest amount of increased formation on previously quiescent surfaces. hPTH(1–34)–stimulated bone formation was associated with an increase in osteoblast apoptosis, which may reflect enhanced turnover of the osteoblast population and may contribute to the anabolic action of hPTH(1–34).

Conclusions: These findings provide new insight into the cellular basis by which hPTH(1–34) improves cancellous and cortical bone architecture and geometry in patients with osteoporosis.

Ancillary