Intermittent administration of PTH for the treatment of inflammatory bone loss does not enhance entheseal pathological new bone formation

Biochem Biophys Res Commun. 2024 Jun 4:711:149888. doi: 10.1016/j.bbrc.2024.149888. Epub 2024 Apr 4.

Abstract

Objective: To investigate the effect of intermittent parathyroid hormone (iPTH) administration on pathological new bone formation during treatment of ankylosing spondylitis-related osteoporosis.

Methods: Animal models with pathological bone formation caused by hypothetical AS pathogenesis received treatment with iPTH. We determined the effects of iPTH on bone loss and the formation of pathological new bone with micro-computed tomography (micro-CT) and histological examination. In addition, the tamoxifen-inducible conditional knockout mice (CAGGCre-ERTM; PTHflox/flox, PTH-/-) was established to delete PTH and investigate the effect of endogenous PTH on pathological new bone formation.

Results: iPTH treatment significantly improved trabecular bone mass in the modified collagen-induced arthritis (m-CIA) model and unbalanced mechanical loading models. Meanwhile, iPTH treatment did not enhance pathological new bone formation in all types of animal models. Endogenous PTH deficiency had no effects on pathological new bone formation in unbalanced mechanical loading models.

Conclusion: Experimental animal models of AS treated with iPTH show improvement in trabecular bone density, but not entheseal pathological bone formation,indicating it may be a potential treatment for inflammatory bone loss does in AS.

Keywords: Ankylosing spondylitis; Endochondral ossification; Osteoporosis; Parathyroid hormone; Pathological new bone formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental / drug therapy
  • Arthritis, Experimental / pathology
  • Bone Density / drug effects
  • Disease Models, Animal
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Osteogenesis* / drug effects
  • Osteoporosis / drug therapy
  • Osteoporosis / pathology
  • Parathyroid Hormone* / administration & dosage
  • Parathyroid Hormone* / pharmacology
  • Parathyroid Hormone* / therapeutic use
  • Spondylitis, Ankylosing / drug therapy
  • Spondylitis, Ankylosing / pathology
  • X-Ray Microtomography

Substances

  • Parathyroid Hormone