INCREASED NUCLEOLAR ORGANIZER REGIONS IN OSTEOCLAST NUCLEI OF PAGETS-BONE-DISEASE

The etiology of Paget's disease of bone is still unknown but several s tudies have reported a viral origin, At the electron microscopic level , characteristic nuclear and cytoplasmic inclusions have been found an d mimic paramyxoviral nucleocapsids in osteoclasts (Oc), Sarcomatous d egeneration is observed in 2% of pagetic patients, Nuclear organizer r egions are parts of the nucleolus involved in the synthesis of ribosom es, and they contain nonhistone proteins that can be silver stained (A gNORs) on the interphasic nuclei, AgNOR number is known to correlate w ith the proliferative activity of the cell populations, whether normal or malignant, Cancer cells have an increased demand for (robosomal) r RNA and correlations have been found between AgNORs and proliferative antigens, We have adapted the AgNOR staining method to undecalcified b one biopsies at the light and TEM levels, Bone sections from 10 pageti c patients (without a previous bisphosphonate treatment) were stained for AgNORs, 10 patients having metabolic bone diseases associated with an increased Oc number (i.,e.,, primary and secondary hyperparathyroi dism) were used as controls, AgNORs appeared as black dots within the nucleoli of Oc nuclei and were easily numbered, A maximum of two or th ree dots could be seen in Oc nuclei from control subjects, In pagetic Oc, AgNOR number was greatly increased (6.80 +/- 2.57 dots vs, 2.12 +/ - 1.07 in controls), TEM study also showed AgNOR in the nucleoli of pa getic patients' Cc, The viral inclusions within the nuclei appeared fa intly stained and could not be confused with AgNORs, The large number of AgNORs in the nuclei of pagetic Oc reflects the need for a greater abundance of ribosomes, With the pagetic Cc being highly active, the c ytoplasmic synthesis of proteins is maximized (probably hydrolases inv olved in the matrix breakdown), An increase in AgNORs does not reflect the proliferative activity of the cell because Cc are made by the fus ion of precursors, It is postulated that: (a) other mRNAs (of viral/on cogene origin) could be actively transcribed in pagetic patients and r equire more numerous ribosomes; or (b) a viral genome/oncogene promote s alteration of the nuclear/nucleolar mechanism. (C) 1998 by Elsevier Science Inc, All rights reserved.