Calcitonin simultaneously regulates both periosteal hyperostosis and trabecular osteopenia in the spinal hyperostotic mouse (twy/twy) in vivo

Calcif Tissue Int. 1999 Mar;64(3):239-47. doi: 10.1007/s002239900610.

Abstract

The twy (tiptoe-walking-Yoshimura) mouse, established in Japan in 1978 by brother-sister mating of ICR strain mice, is a valuable mutant as a model of ossification of the posterior longitudinal ligament (OPLL). OPLL causes severe myelopathy and has been thought to be very similar to ankylosing spinal hyperostosis (ASH) and diffuse idiopathic skeletal hyperostosis (DISH). In the twy mouse, both an increase in vertebral cortical membranous bone formation and a decrease in trabecular bone mass due to accelerated bone resorption occur simultaneously. This process is attributed to an inherited autosomal recessive single gene (twy). Calcitonin's suppression of bone resorption has been well established in the past, whereas the effects of this hormone on bone formation remain to be defined. Of particular interest is the simultaneous action of calcitonin on the abnormally accelerated bone formation and resorption. Thirty twy mice and 14 ICR mice were divided into seven groups, and changes induced by calcitonin on vertebral cortical appositional rate and on trabecular bone mass were investigated histomorphometrically. Results were (1) osteoclastic activity on trabecular surface was clearly suppressed by chicken calcitonin injected subcutaneously for 4 weeks; (2) no significant difference between the lumbar vertebral periosteal bone formation of calcitonin (CA) and vehicle-administrated twy mice groups. However, on the periosteal surface of the cervical vertebrae of the 6-week-old twy mice, the abnormally accelerated bone formation was suppressed by CA administration. This was also true for the elderly twy mice, although the effect was less pronounced. In conclusion, CA suppressed the abnormally hyperactivated periosteal bone formation. Results also suggested a possible therapeutic value of CA for OPLL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Diseases, Metabolic / drug therapy*
  • Bone Remodeling / drug effects
  • Calcitonin / pharmacology
  • Calcitonin / therapeutic use*
  • Cervical Vertebrae / drug effects
  • Cervical Vertebrae / pathology
  • Disease Models, Animal
  • Female
  • Fluoresceins
  • Fluorescent Dyes
  • Hyperostosis, Diffuse Idiopathic Skeletal / drug therapy*
  • Hyperostosis, Diffuse Idiopathic Skeletal / genetics
  • Hyperostosis, Diffuse Idiopathic Skeletal / pathology
  • Lumbar Vertebrae / diagnostic imaging
  • Lumbar Vertebrae / drug effects
  • Male
  • Mice
  • Mice, Inbred ICR
  • Mice, Mutant Strains
  • Ossification of Posterior Longitudinal Ligament / drug therapy*
  • Ossification of Posterior Longitudinal Ligament / genetics
  • Periosteum / drug effects
  • Periosteum / pathology
  • Radiography
  • Tetracycline

Substances

  • Fluoresceins
  • Fluorescent Dyes
  • Calcitonin
  • Tetracycline
  • fluorexon