Metabolic bone disease & related research最新文献

The variations with time in function and morphology at the resorptive site in normal iliac crest trabecular bone were reconstructed from tetracycline double-labeled iliac crest bone biopsies from 20 normal individuals.

Resorption depths below osteoclasts, mononuclear cells, and preosteoblast-like cells were measured by counting the number of lamellae of known thickness eroded. Mean resorption depth below osteoclasts was 19.0 (±4.9) μm. Lacunae containing mononuclear cells were deeper (P < < 0.0001), with a mean resorption depth of 49.1 (±10.2) μm. The deepest lacunae were lacunae containing preosteoblast-like cells, with a mean resorption depth of 62.6 (±12.5) μm. This depth was significantly deeper (P < 0.001) than the resorption depth found below mononuclear cells.

Median total resorption period was 48 days (31–68; 95% confidence interval). Median osteoclastic function period was 8 days (6–12), median mononuclear cell function period was 34 days (24–48), and median period where preosteoblast-like cells were present in lacunae before matrix synthesis started was 9 days (6–13). Distribution curves describing the occurrence of the three cell types in relation to resorption depth showed that osteoclasts occupied the more superior parts of the resorption lacunae, with mononuclear cells and preosteoblast-like cells situated in the deeper parts. The distribution curves support the hypothesis that osteoclasts precede mononuclear cells, which again precede preosteoblast-like cells. Based on this hypothesis, curves showing the variation in resorption depth with time were constructed in duplicate. Resorption rates were calculated for three periods. An initial osteoclastic resorption rate showed a median value of 3.8 μm/day (2.4–6.0), a mixed osteoclastic-mononuclear rate was found to be 1.3 μm/day (1.2–1.6), and the terminal mononuclear resorption rate was 0.7 μm/day (0.3–1.2). Median total resorption rate was 1.4 μm/day (1.2–1.7). No significant differences between the distributions of completed wall thickness and preosteoblast-like cell resorption depths could be demonstrated.

A stereologic procedure for the reconstruction of matrix and mineralized bone growth curves at formative sites in trabecular bone is presented. Iliac crest bone biopsies obtained from twenty normal individuals after tetracycline double-labeling were investigated histomorphometrically. Corresponding values for osteoid width and apparent distance between bone markers and width of mineralized bone walls were classified using a sector plotting system. Observed structure widths were converted to three-dimensional structure thicknesses by a stereologic unfolding procedure. Osteoid thickness, calcification rate, and fractional labeling of osteoid varied characteristically with increasing wall thickness and permitted the construction of curves describing the time-dependent variations in matrix and wall thicknesses.

The mean thickness of completed walls was 61.9 ± 1.5 μm (SE), and the mean bone formation period (Sigma_f) was 145 days (124–168; 95% confidence interval.). The initial appositional rates for bone matrix (2.1 μm³/μm²/day) (1.4–2.9) and bone mineral (1.1 μm³/μm²/day) (0.4–1.9) declined gradually toward zero at the end of Sigma_f. The initial mineralization lag time was 15 days (12–24) and increased to a maximum of 27 days during the first 45% of Sigma_f. Thereafter, it decreased gradually toward zero. The height of the osteoblast nuclei gradually declined from 6.7 ± 0.5 μm at the start of bone formation to 1.2 ± 0.1 μm at the end.

The study demonstrates that it is possible to reconstruct growth curves for trabecular bone walls based on three-dimensional values for structure thicknesses using different sections for light and fluorescence microscopy and avoiding classification according to osteoblastic nuclear morphology. This more detailed description of the bone remodeling sequence is important for the planning of treatment of different metabolic bone diseases. The techniques described make it possible to assess bone mineral balance at the BMU level and may give further insight into the mechanisms by which different hormones and drugs influence bone remodeling.

Examination of bone from chickens infected as 10-day-old embryos with isolates of an avian osteopetrosis virus revealed that MAV-2(O) plaque isolate 32/2/4 caused rapid bone growth, while MAV-2(O) plaque isolate 13 caused a mild form of bone growth. MAV-2(O) plaque isolate 32/2/4 caused anemia when injected into the 8-day-old hatched chick and bone growth in ovo when injected into the 4-day-old embryo. Passive administration of neutralizing antibody protected against MAV-2(O)-induced bone growth when antibody was given to the embryo 1 day after virus. Neutralizing antibody also protected against an acute anemia observed when normal and bursectomized chickens were given MAV-2(O) 32/2/4, but antibody did not prevent the appearance of a chronic anemia or osteopetrosis in bursectomized chickens. Repeated animal passage of a slow onset plaque isolate of MAV-2(O) caused the virus to progressively induce more severe bone growth and anemia.

A 19-year-old Indian girl presenting with intermittent tetany, enamel hypoplasia, bilateral cataracts, and calcification of the basal ganglia is described. Dental evidence suggested a calcification defect had been present from the age of 2–3 years. Hypocalcemia, hyperphosphatemia, and low levels of immunoassayable parathyroid hormone (iPTH), urinary cAMP, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D were documented, suggesting hypoparathyroidism with vitamin D deficiency. A bone biopsy showed osteomalacia. Following ultraviolet irradiation and oral calciferol therapy, a symptomatic and biochemical response typical of privational vitamin D deficiency occurred. iPTH levels rose to normal and remained normal following withdrawal of treatment, indicating that the clinical features were entirely due to long-standing vitamin D deficiency.