Regional bone loss after orthotopic liver transplantation in inbred rats: the role of hepatic denervation.
Bone loss and long-term persistence of osteoporosis with increased fracture risk are common after liver transplantation. It is unknown whether transplantation-induced disruption of hepatic nerves, serving numerous regulatory metabolic and sensory functions, is herein involved. To test this possibility, we measured bone mineral density (BMD) by peripheral quantitative computed tomography (pQCT) and studied dynamic histomorphometry, radiocalcium kinetics, and biochemical parameters in 7 liver-transplanted and 7 sham-operated inbred rats. Although liver function was normal in TX rats, trabecular BMD of the first lumbar vertebra and total BMD of the femoral diaphysis were decreased by 13% and 6%, respectively, 9 months postsurgery. The breaking force of the femur was significantly lower by 21%. However, bone mass in the femoral and tibial metaphysis was preserved as evidenced by pQCT measurements and histomorphometry. Trabecular width and wall thickness were significantly decreased in vertebral cancellous bone, whereas indices of bone formation and resorption were normal or slightly reduced. Serum minerals, mineral balance, fractional and net absorption of Ca and Mg, serum calciotropic hormones, IGF-I, leptin, specific activity of 45Ca in bone, 45Ca excretion, and biochemical indices of bone formation and bone resorption remained unchanged. We conclude that liver transplantation-related denervation causes cancellous and cortical bone loss in well-innervated bone sites such as the lumbar spine and the long bone diaphysis. Cancellous bone loss in TX rats is due to an impairment of osteoblast team performance and subsequent trabecular thinning. The mechanism uncovered by our study may contribute to long-term bone loss after liver transplantation.
Division of Experimental Surgery and Endocrine Research Laboratory, Friedrich Alexander University, Erlangen, 91054 Erlangen, Germany. hermann.kissler@stud.uni-erlangen.de
H J
HJ
Kissler
R G
RG
Erben
R
R
Hennig
H
H
Gepp
K
K
Stahr
W
W
Hohenberger
P O
PO
Schwille
D000818:Animals; D015519:Bone Density / Q000502:physiology; D001851:Bone Diseases, Metabolic / Q000209:etiology* / Q000473:pathology; D001842:Bone and Bones / Q000378:metabolism* / Q000503:physiopathology; D003714:Denervation / Q000009:adverse effects*; D005264:Femoral Fractures / Q000503:physiopathology; D005269:Femur / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000294:innervation / Q000601:surgery*; D016031:Liver Transplantation / Q000009:adverse effects* / Q000473:pathology; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D008297:Male; D011183:Postoperative Complications; D011859:Radiography; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D013314:Stress, Mechanical; D013977:Tibia / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology