Fluctuation of mineral apposition rate at individual bone-remodeling sites in human iliac cancellous bone: Independent correlations with osteoid width and osteoblastic alkaline phosphatase activity

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Abstract
We investigated the determinants of bone formation at individual remodeling sites (BMUs) in cancellous bone from 8 osteologically normal, sex hormone‐replete women with endometriosis. All were tetracycline double‐ labeled (2, 12, 2, and 4 day regime) before iliac bone biopsy. At each BMU the mineral apposition rate (MAR) was determined conventionally from the distance between label midpoints (MAR 1) and also from the distance between the mineralization front and the trailing edge of the second label (MAR 2). MAR 1 and 2 were compared with within‐BMU measurements of osteoid width (O.Wi) and the activities of osteoblastic alkaline phosphatase (AP) and succinic dehydrogenase (SDH, an enzyme in the Krebs cycle), both quantitated by microdensitometry. A total of 143 BMUs were evaluated, of which 88 were satisfactory for all measurements and 132 were satisfactory for all but SDH. There was a weak correlation (r = 0.34) between MAR 1 and 2 at individual sites, with a mean difference of 0.49 μm/day (mean MAR 0.82 μm/day). The mean MAR of individual subjects tended to be either increasing or decreasing (F = 16.1, p < 0.01). In linear regressions, MAR 2 was statistically dependent on O.Wi, AP, and SDH (73% of the variance accounted for). In contrast, MAR 1 was weakly correlated with O.Wi and only 30% of its variance was accounted for by AP, SDH, and O.Wi. The variance in the MAR 2 data was inversely increased (p < 0.01) compared with MAR 1 as the number of days of bone formation represented. The data are best explained by large within‐BMU variations in MAR over periods of up to a few days and longer term trends affecting all BMUs. Correlations between fluctuation in MAR and osteoblastic AP and SDH activity suggest that bone formation depends partly on AP activity and osteoblast energy balance. Random obliquity of sectioning has considerable theoretical effects on some correlations (e.g., between O.Wi and MAR), but further investigation emphasized the likely biologic importance of the correlations involving enzyme activities.