Alendronate increases bone strength by increasing the mean degree of mineralization of bone tissue in osteoporotic women.

The mean degree of mineralization of bone (MDMB) was measured by quantitative microradiography on transiliac bone biopsies taken from 53 postmenopausal osteoporotic women who had been treated with alendronate (ALN; 10 mg/day) during 2 (9 patients) or 3 years (16 patients) or with placebo (PLA; 15 and 13 patients, respectively). In the same patients, bone mineral density (BMD) values were obtained by dual-energy X-ray absorptiometry of the lumbar spine and femoral neck at the beginning and end of treatment. Histomorphometric parameters and activation frequency of new remodeling units were also measured on the iliac biopsies. After 2 years of ALN, MDMB in compact bone was 9.3% (p = 0.0035) and in cancellous bone was 7.3% (p = 0.0009) higher, respectively, than PLA. After 3 years of ALN, MDMB in compact bone was 11.6% (p = 0.0002) and in cancellous bone was 11.4% (p = 0.0001) higher, respectively, than PLA. After 2 and 3 years of ALN, and compared with the corresponding PLA, the distribution of the degree of mineralization in compact and cancellous bone showed a clear shift toward the highest mineralization values and a decrease in the number of bone structure units having low values of mineralization. The between-group differences in MDMB were similar to those of BMD at the lumbar spine BMD (+8.7% after 2 years and +9.6% after 3 years, respectively), suggesting that MDMB augmentation probably accounted for the majority of the increase in BMD seen with ALN. The data support the hypothesis that the reduction in activation frequency caused by the antiresorptive effect of ALN is followed by a prolonged secondary mineralization that increases the percentage of bone structure units having reached a maximum degree of secondary mineralization and, through this mechanism, MDMB. That these effects contribute to improved bone strength is demonstrated by the reduction in fracture incidence previously demonstrated in these patients.

Low rate of bone formation with or without histologic appearance of osteomalacia in patients with aluminum intoxication.

We analyzed transiliac bone biopsy specimens obtained after tetracycline double labeling from 24 patients with aluminum-related bone disease who had undergone long-term hemodialysis. The specimens were selected by the following criteria: Al deposits at the mineralization fronts, a dramatic reduction in double-labeled surfaces, reflecting a low mineralization rate, and a significant increase in osteoid volume and osteoid surfaces. The bone formation rate at the tissue level and at the basic multicellular unit level was decreased in all patients. Seventeen biopsy specimens (group 1) showed morphologic and dynamic evidence of osteomalacia, as defined by an increase in the osteoid seam thickness and a decreased mineralization rate. In one specimen from group 1, thickened osteoid seams were present only in a small part of the specimen. In seven specimens (group 2), the osteoid seam thickness index was normal, indicating "aplastic bone." Two specimens from group 2, however, showed morphologic and dynamic evidence of focal osteomalacia either in trabecular or in cortical bone. Specimens from group 2 patients differed from those in group 1 in their significantly lower values of osteoid volume and lower levels of serum alkaline phosphatase and parathyroid hormone. These data show that the absence of significant increase in osteoid seam thickness and the focal distribution of thickened osteoid seams in patients with Al overload and low rate of bone formation reflect the marked reduction of bone matrix formation at the cellular level. It is suggested that low parathyroid activity might play a role in the reduction of bone matrix formation.