DISPARATE EFFECTS OF MILD, MODERATE, AND SEVERE SECONDARY HYPERPARATHYROIDISM ON CANCELLOUS AND CORTICAL BONE IN RATS WITH CHRONIC RENAL-INSUFFICIENCY

The subtotally nephrectomized rat has often been used to investigate t he etiology and treatment of secondary hyperparathyroidism (2 degrees HPT), but it has been used less frequently to study the effects of 2 d egrees HPT on bone. The recent development of a reliable and specific rat parathyroid hormone (PTH) immunoradiometric assay has provided an opportunity for a thorough investigation of the relationship between c irculating, biologically active PTH, and the skeletal abnormalities th at occur in chronic renal insufficiency (CRI), Rats were 5/6 nephrecto mized (Nx) or sham operated and fed diets with varying levels of Ca an d P for 12-14 weeks to induce differing magnitudes of 2 degrees HPT. P arathyroid gland volume increased by 80%-90% in 5/6 Nx rats in the mil d and moderate 2 degrees HPT groups (2.3- and 7.7-fold higher PTH leve ls, respectively) and by 3.3-fold in the severe 2 degrees HPT group (1 2-fold increase in PTH). The increases in gland volume were caused pri marily by cell hyperplasia. Mild 2 degrees HPT resulted in a 12% decre ase in bone mineral density (BMD) across the entire femur, increased o steoclast numbers (N.Oc), unchanged osteoblast numbers (N.Ob), and dec reased cancellous bone volume (Cn.BV) in the tibial metaphysis but, ap art from increased marrow area, no major changes in cortical bone at t he tibio-fibular junction. Moderate 2 degrees HPT was associated with no changes in femoral BMD, or in tibial Cn.BV, but N.Ob and bone forma tion rate (BFR) were markedly elevated. Increased periosteal, intracor tical, and endocortical BFR and turnover were evident, and contributed to increased cortical porosity (Ct,Po), The changes mere exaggerated in the severe 2 degrees HPT group; BMD was lower in the proximal, but higher in the distal femur, and Cn.BV, N.Ob, N.Oc, and BFR were increa sed by six-, seven-, three-, and 30-fold, respectively, Endocortical B FR was elevated 31-fold and the extensive Ct.Po (10%) decreased bone s trength. However, Ct,Po was not apparent until PTH levels exceeded 500 pg/mL, Thus, in rats with CRI of similar magnitude, progressive 2 deg rees HPT is associated with dramatically different effects on bone. Mi ld 2 degrees HPT caused loss of cancellous and endocortical bone, and moderate 2 degrees HPT tended to maintain both types of osseous tissue , whereas PTH levels >500 pg/mL resulted in substantial cortical bone loss, but cancellous bone gain. (Bone 23:257-266; 1998) (C) 1998 by El sevier Science Inc. All rights reserved.