Amelioration of type I diabetes-induced osteoporosis by parathyroid hormone is associated with improved osteoblast survival

J Cell Physiol. 2012 Apr;227(4):1326-34. doi: 10.1002/jcp.22844.

Abstract

Type 1 diabetic osteoporosis results from impaired osteoblast activity and death. Therefore, anti-resorptive treatments may not effectively treat bone loss in this patient population. Intermittent parathyroid hormone (PTH) treatment stimulates bone remodeling and increases bone density in healthy subjects. However, PTH effects may be limited in patients with diseases that interfere with its signaling. Here, we examined the ability of 8 and 40 µg/kg intermittent PTH to counteract diabetic bone loss. PTH treatment reduced fat pad mass and blood glucose levels in non-diabetic PTH-treated mice, consistent with PTH-affecting glucose homeostasis. However, PTH treatment did not significantly affect general body parameters, including the blood glucose levels, of type 1 diabetic mice. We found that the high dose of PTH significantly increased tibial trabecular bone density parameters in control and diabetic mice, and the lower dose elevated trabecular bone parameters in diabetic mice. The increased bone density was due to increased mineral apposition and osteoblast surface, all of which are defective in type 1 diabetes. PTH treatment suppressed osteoblast apoptosis in diabetic bone, which could further contribute to the bone-enhancing effects. In addition, PTH treatment (40 µg/kg) reversed preexisting bone loss from diabetes. We conclude that intermittent PTH may increase type 1 diabetic trabecular bone volume through its anabolic effects on osteoblasts.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Phosphatase / genetics
  • Animals
  • Bone Density / drug effects
  • Bone Remodeling / drug effects
  • Bone Resorption / drug therapy
  • Bone Resorption / genetics
  • Cell Survival / drug effects
  • Diabetes Complications / drug therapy*
  • Diabetes Complications / metabolism
  • Diabetes Complications / pathology
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 1 / pathology
  • Humans
  • Isoenzymes / genetics
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Osteoblasts / drug effects*
  • Osteoblasts / pathology
  • Osteogenesis / drug effects
  • Osteoporosis / drug therapy*
  • Osteoporosis / etiology
  • Osteoporosis / metabolism
  • Osteoporosis / pathology
  • Parathyroid Hormone / administration & dosage
  • Parathyroid Hormone / pharmacology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Tartrate-Resistant Acid Phosphatase

Substances

  • Isoenzymes
  • Parathyroid Hormone
  • RNA, Messenger
  • Acid Phosphatase
  • Tartrate-Resistant Acid Phosphatase