Treatment effects on bone quality and remodeling was assessed in postmenopausal women with osteoporosis treated with oral alendronate. One transiliac bone biopsy was obtained from 231 women at either 24 mo ( n ϭ 11) or 36 mo ( n ϭ 120) from the start of treatment with alendronate at doses of between 5 and 20 mg/d, or placebo. 64 biopsies at 24 mo (31 from the placebo group and 33 alendronatetreated patients) and 95 biopsies at 36 mo (40 from the placebo group and 55 alendronate-treated patients) provided adequate cancellous tissue, and were analyzed by histomorphometry. Mineral apposition rate was unaffected by treatment. At 24 and 36 mo, osteoid thickness, volume, and surface significantly decreased. At each of the doses studied, mineralizing surface and activation frequency significantly decreased at each time point (e.g., Ϫ 92% and Ϫ 87%, respectively, for the 10 mg daily dose after 2 yr). These diminutions were of the same magnitude for each dose at 24 mo, and for the two highest doses at 36 mo. A significant increase in wall thickness accompanied by a reduction in erosion depth was detected in biopsies obtained at 24 mo. These findings confirm that mineralization is normal, and trabecular bone turnover markedly decreased in patients receiving long-term dosing with alendronate. The findings also suggest that the observed increases in bone mineral density could result both from a reduction in the remodeling space due to a decreased activation frequency and a possible trend to a positive bone balance. In addition, further studies focused on a possible increase in the degree of mineralization of bone are required. (

In early postmenopausal women, alendronate given for 3 years at dosages of 5 mg/d or greater prevented the loss of bone mineral density at the spine and hip and in the total body. Alendronate seems to be a safe and effective nonhormonal option for prevention of postmenopausal bone loss.

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Alendronate, an aminobisphosphonate, is much more potent than etidronate, an older bisphosphonate, in inhibiting osteoclast-mediated bone resorption, and unlike etidronate, therapeutic doses of alendronate are not associated with abnormal mineralization. In the present study, we compared the effectiveness, safety, and tolerability of 6 months of daily oral administration of alendronate (40 mg) with those of etidronate (400 mg) in 89 patients with clinically active Paget's disease. The primary efficacy end point was the percent change in serum alkaline phosphatase. Other end points included changes in urinary deoxypyridinoline excretion, pain, functional impairment scores, and radiological osteolysis. Tetracycline-labeled bone biopsies were obtained for histomorphometric analysis from a subset of 43 patients at the 6-month visit. The alendronate-treated group had significantly greater decreases in both serum alkaline phosphatase (79% vs. 44%) and urinary deoxypyridinoline (75% vs. 51%) than the etidronate-treated group (P < 0.001 in both cases). Normalization of serum alkaline phosphatase was much more frequent in alendronate-treated patients (63.4% vs. 17.0%; P < 0.001). Alendronate was well tolerated and had a safety profile similar to that of etidronate. Histomorphometry revealed decreased bone turnover and no qualitative abnormalities, including no direct negative effects on bone mineralization, with alendronate treatment. One patient receiving etidronate developed frank osteomalacia. Alendronate appears to be a highly effective treatment for Paget's disease of bone that offers an important therapeutic advance over etidronate.

PurposeThe purpose of the study is to validate a method that provides the opportunity to distinguish a balanced translocation carrier embryo from a truly normal embryo in parallel with comprehensive chromosome screening (CCS).MethodsA series of translocation carrier couples that underwent IVF with single nucleotide polymorphism (SNP) array-based CCS on 148 embryos were included. Predictions of balanced or normal status of each embryo were made based upon embryonic SNP genotypes. In one case, microdeletion status was used to designate whether embryos were balanced or normal. In 10 additional cases, conventional karyotyping was performed on newborns in order to establish the true genetic status (balanced or normal) of the original transferred embryo. Finally, implantation potential of balanced or normal embryos was compared.ResultsPhasing SNPs using unbalanced embryos allowed accurate prediction of whether transferred embryos were balanced translocation carriers or truly normal in all cases completed to date (100 % concordance with conventional karyotyping of newborns). No difference in implantation potential of balanced or normal embryos was observed.ConclusionsThis study demonstrates the validity of a CCS method capable of distinguishing normal from balanced translocation carrier embryos. The only prerequisite is the availability of parental DNA and an unbalanced IVF embryo, making the method applicable to the majority of carrier couples. In addition, the SNP array platform allows simultaneous CCS for aneuploidy with the same platform and from the same biopsy. Future work will involve prospective predictions to select normal embryos with subsequent karyotyping of the resulting newborns.