The mineralization index--a new approach to the histomorphometric appraisal of osteomalacia

The histomorphometric diagnosis of osteomalacia depends on the conjunction of two or three independent criteria but for several reasons, both clinical and pathophysiologic, it would be useful to have a single index of severity. Accordingly, using an extensive library of normal values in 143 healthy women, we constructed the mineralization index (MI), defined as [osteoid thickness (O.Th) (microm) + osteoid volume/bone volume (OV/BV) (%)] x 1.15 - osteoid mineralization rate (%/day) - [bone formation rate/bone surface (BFR/BS) (microm3/microm2/year) x 0.15]. MI was normally distributed with mean 8.0, SD 3.3, and range 0-15 (arbitrary units); it was unaffected by race, menopausal status, age or bone turnover, and was slightly lower in osteoporotic patients with nontraumatic vertebral fracture than in healthy white postmenopausal women (6.83 vs. 7.95). In hypovitaminosis D osteopathy (HVO) stage I, MI was normal in 18/26 cases (70%; HVOia), demonstrating more rigorously than before that osteoid accumulation is initially due entirely to secondary hyperparathyroidism and increased bone turnover. In the remaining 30% (HVOib), MI was increased, indicating the onset of impaired mineralization while bone formation was still increased and before the appearance of osteomalacia. In secondary hyperparathyroidism due to renal bone disease, 10/20 cases (50%) had normal MI and higher BFR than in HVOia (93 vs. 32), and there was a significant inverse correlation between MI and BFR. In patients with osteomalacia according to current criteria, MI ranged from 29.2 to 166.5; an MI of 30 had high sensitivity and specificity for the diagnosis of osteomalacia. Including all patients with HVO, there was a significant (P < 0.001) inverse correlation between MI and calcium x phosphate product, but the unexplained variance of >70% suggests that vitamin D deficiency impairs mineralization by multiple mechanisms. We conclude that the MI clarifies the early effects of vitamin D deficiency on bone and the relationship between different components of renal bone disease simplifies the histologic diagnosis of osteomalacia and may contribute to its management, and explicates the mechanisms of mineralization.