Relationships between Histomorphometric Features of Bone Formation and Bone Cell Characteristicsin Vitroin Renal Osteodystrophy

Abstract

To determine whether abnormal bone cell recruitment or differentiation may be involved in the development of aplastic bone lesion in renal osteodystrophy we have compared histomorphometric parameters of bone formation and in vitro behavior of osteoblastic cells isolated from the trabecular bone surfaces in 37 dialysis patients with osteitis fibrosa, normal bone formation rate, or aplastic bone lesion. The bone cell responses to human PTH-(1-34) (20 nmol/L), as evaluated by intracellular cAMP production, and to 1,25-dihydroxyvitamin D (10 nmol/L), as assessed by osteocalcin synthesis, were not different from normal in patients with low, normal, or high bone formation rates. Osteoblastic cells isolated from patients with a high bone formation rate and markedly elevated serum iPTH and osteocalcin values had a higher than normal DNA replication in primary culture. The peak of [3H]thymidine incorporation, the maximal DNA synthesis, and the area under the growth curve were 4.4- to 6.3-fold increased in osteitis fibrosa compared to those in normal bone cells obtained from age-matched individuals. By contrast, [3H]thymidine incorporation in bone cells from aplastic patients was about 25% of normal and only 5% of the value in osteitis fibrosa. The decreased DNA replication of cultured bone cells in aplastic patients was unrelated to trabecular bone aluminum staining, but was associated with low serum immunoreactive PTH values compared to those in other groups of patients. These results show that high bone formation in uremic osteoitis fibrosa is associated with higher than normal [3H]thymidine incorporation in bone cells in vitro, whereas low bone formation in aplastic patients results from lower than normal DNA replication and suggest that the defective osteoblastic recruitment in aplastic patients may be related to factors other than aluminum, including inappropriate PTH secretion.

Diagnosis of renal osteodystrophy

“…> 40 ng mL − 1 ), independently of the PTH levels. Low levels of BALP in combination with high levels of PTH almost exclude a highturnover bone [39] . On the other hand, higher levels of BALP in combination with normal PTH levels may represent a state of PTH-independent elevated bone resorption [40].…”

Decreased DNA synthesis by cultured osteoblastic cells in eugonadal osteoporotic men with defective bone formation.

“…They were performed with an 8-mm inner diameter trephine in the antero-superior iliac crest. The biopsy was placed in sterile PBS and sectioned longitudinally to separate the biopsy in two symmetric half-cores (15,16). Half of the biopsy was processed for bone histomorphometry; the other halfwas used for bone cell isolation procedures.…”

“…Sections (5 gm thick) were stained with toluidine blue, and IO-,um thick sections were kept unstained for examination under fluorescent illumination. Parameters of bone formation were determined by conventional histomorphometric methods (8,15,16) using an integrator (Zeiss II; Carl Zeiss, Inc., Thornwood, NY) and a semiautomatic image analyzer (Leitz ASM, Rueil, France). The following parameters were measured on the endosteal surface of the trabecular bone: trabecular bone volume, expressed as a percentage ofendosteal bone tissue; osteoblast surface (percentage of trabecular bone surface covered with plump osteoblasts), and mean wall thickness (MWT; micrometers), that is the mean apparent thickness of complete bone packets, obtained by measuring the width of a complete packet perpendicular to the marrow surface (19).…”

“…This can be determined by comparing in vivo bone forming features with in vitro osteoblastic characteristics (15,16). We have therefore evaluated biochemical and histomorphometric parameters of bone formation and determined in vitro characteristics ofosteoblastic cells isolated from a group ofeugonadal men with osteoporosis.…”

The need for a reliable bone biomarker to better assess chronic kidney disease mineral and bone disorder

“…However, the plasma intact PTH concentration mainly reflects the intensity of activity of the parathyroid glands, and given that the uremic condition is often accompanying with a resistance of bone cells to parathyroid actions (8). The relationship between plasma intact PTH levels and bone formation rate is not continuously maintained (9). Additionally, there is a non-PTH truncated fragment, i.e.…”