Supported by PHS Grants HD 00143, LT 32DE007010, DE 04931, and DOE Grant EY76C020119.
General Histology & Cytology
The effect of dichloromethylene diphosphonate, a pyrophosphate analog, on bone and bone cell structure in the growing rat†
Article first published online: 26 JAN 2005
Copyright © 1979 Wiley-Liss, Inc.
The Anatomical Record
Volume 193, Issue 3, pages 439–461, March 1979
How to Cite
Miller, S. C. and Jee, W. S. S. (1979), The effect of dichloromethylene diphosphonate, a pyrophosphate analog, on bone and bone cell structure in the growing rat. Anat. Rec., 193: 439–461. doi: 10.1002/ar.1091930309
- Issue published online: 26 JAN 2005
- Article first published online: 26 JAN 2005
- Manuscript Accepted: 2 OCT 1978
- Manuscript Received: 2 MAY 1978
Dichloromethylene diphosphonate (Cl2MDP) is a synthetic compound related in structure to inorganic pyrophosphate but is resistant to enzymatic and chemical degradation and is known to be a potent inhibitor of bone resorption. The administration of 20 mg/kg/day of Cl2MDP for ten days to growing rats results in marked increases in metaphyseal mineralized tissue mass due to slowed bone resorption. There was an increase in resorption areas covering anorganic bone viewed by scanning electron microscopy (SEM), however, the resorption pits, or Howship's lacunae, in these resorption areas were smaller and less defined than those encountered in controls. The appearance of these large areas of poorly delineated resorption pits is likely due to an inhibition of bone resorption coupled with slowed bone formation. Administration of Cl2MDP to growing rats also results in an increase in the numbers and size of osteoclasts. Because this would appear to be a histological paradox, in view of the ability of Cl2MDP to slow bone resorption, the osteoclasts were examined by transmission electron microscopy (TEM). The ruffled borders and associated cytoplasmic vacuoles were generally less extensive in the Cl2MDP-treated osteoclasts than in controls, even though clear zones were frequently seen. Examination of undecalcified light microscope sections reveal that the area of bone being degraded by adjacent osteoclasts was generally much smaller in the Cl2MDP-treated animals than in controls. Thus the collaborating TEM observations of smaller ruffled borders, with the SEM observations of smaller, less-de-fined resorption pits, with the light microscope observations of smaller bone areas being degraded by individual osteoclasts provide a morphological basis for the observed decreases in bone resorption following Cl2MDP administration.