Renal insufficiency-induced bone loss is associated with an increase in bone size and preservation of strength in rat proximal femur.
Chronic renal insufficiency (CRI) results in phosphate retention and secondary hyperparathyroidism, the treatment of which is largely based on the use of calcium salts as phosphate binders. Advanced CRI causes bone fragility, but information about bone geometry and strength in moderate CRI is scarce. We assigned 39 8-week-old male Sprague-Dawley rats to sham-operation (Sham) or 5/6 nephrectomy (NTX). Four weeks later, the rats were randomized to 0.3% calcium (Sham, NTX) or 3.0% calcium diet (Sham + Calcium, NTX + Calcium). After 8 weeks, the animals were sacrificed, plasma samples collected, and femora excised for neck and midshaft analyses: dual-energy X-ray absorptiometry, peripheral quantitative computed tomography, and biomechanical testing. The NTX increased plasma urea and PTH 1.6-fold and 3.6-fold, respectively, whereas high calcium intake suppressed PTH to 30% of controls. Total femoral bone mineral content decreased (-6.3%) in the NTX group, while this deleterious effect was reversed by high calcium diet. In the site-specific analysis of the femoral neck, the volumetric bone density (-6.5%) was decreased in the NTX group but not NTX + Calcium group. However, in the nephrectomized rats, there was also a concomitant increase in the cross-sectional area (+15%), and, despite the decrease in bone density, the mechanical strength of the femoral neck was maintained. In the midshaft, NTX decreased cortical volumetric bone density (-1.2%), but similar to the femoral neck, no differences were found in the mechanical strength. In conclusion, a decrease in bone mass in moderate experimental CRI was associated with a concomitant increase in bone size, and maintenance of mechanical competence. Although high calcium diet suppressed plasma PTH to under normal physiological levels, it prevented the CRI-induced loss of bone mass without an adverse influence on bone strength.
Medical School and the Institute of Medical Technology, University of Tampere, Tampere, Finland.
Jarkko
J
Jokihaara
Teppo L N
TL
Järvinen
Pasi
P
Jolma
Peeter
P
Kööbi
Jarkko
J
Kalliovalkama
Juha
J
Tuukkanen
Heikki
H
Saha
Harri
H
Sievänen
Pekka
P
Kannus
Ilkka
I
Pörsti
D015502:Absorptiometry, Photon; D000818:Animals; D001696:Biomechanical Phenomena; D001806:Blood Urea Nitrogen; D001862:Bone Resorption / Q000000981:diagnostic imaging / Q000209:etiology*; D001842:Bone and Bones / Q000033:anatomy & histology* / Q000000981:diagnostic imaging; D002118:Calcium / Q000097:blood; D002136:Calcium, Dietary / Q000008:administration & dosage / Q000494:pharmacology*; D003404:Creatinine / Q000097:blood; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D009392:Nephrectomy; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D051436:Renal Insufficiency, Chronic / Q000209:etiology* / Q000503:physiopathology; D014057:Tomography, X-Ray Computed
D002136:Calcium, Dietary; D010281:Parathyroid Hormone; D010710:Phosphates; D003404:Creatinine; D002118:Calcium