Does iron affect osteoblast function? Studies in vitro and in patients with chronic liver disease.
In order to study the role of trace elements as potential osteoblastic toxins, we measured bone aluminum, copper, and iron in 106 ambulant patients with histologically proven liver disease. We used analytical and histochemical methods and we correlated our results with serum biochemistry, forearm and spinal bone density, and dynamic bone histomorphometry. Patients with chronic liver disease had higher iron-stained perimeters than control subjects (P less than 0.001). However, the mean iron-stained perimeter was no greater than 5% of the total mineralized bone perimeter and did not correlate significantly with either the osteoblast perimeters or bone formation rates. The mean concentration of bone iron were 2.5 times (P less than 0.01) greater in the patients than in the controls although 80% of the patients fell within the normal range. There was a weak negative correlation between bone iron and the osteoblast perimeters (R = 0.18, P = ns) and between bone iron and bone formation (R = -0.30, P less than 0.05). There were 57 patients (56% of the total) with diminished bone formation, but only 16 had elevated bone iron concentrations. In a regression analysis, age, hypogonadism, and serum albumin concentrations were the most important predictors of osteoblast perimeters and bone formation rates. In vitro experiments using rat osteoblast-like osteosarcoma cells showed that an iron concentration of 400 mumol/liter was required to diminish cellular proliferation and function. Iron concentrations are elevated in the bones of patients with chronic liver disease. However, there is at present insufficient evidence that this metal is responsible for the osteoblast dysfunction seen in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Diamond
T
T
Department of Endocrinology, Royal North Shore Hospital, St. Leonards, Sydney, Australia.
Pojer
R
R
Stiel
D
D
Alfrey
A
A
Posen
S
S
D000328:Adult; D000375:Aging / Q000378:metabolism / Q000502:physiology; D000535:Aluminum / Q000032:analysis; D000818:Animals; D015519:Bone Density; D002460:Cell Line; D002908:Chronic Disease; D003300:Copper / Q000032:analysis; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D007006:Hypogonadism / Q000503:physiopathology; D007501:Iron / Q000032:analysis / Q000494:pharmacology*; D008099:Liver / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology; D008107:Liver Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010006:Osteoblasts / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D012044:Regression Analysis
D003300:Copper; D000535:Aluminum; D007501:Iron