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Ludwig Boltzmann Institute of Osteology and Fourth Medical Department, Hanusch Hospital and UKH Meidling (B.M.M., P.R., W.T., P.M., K.K.), A-1140 Vienna, Austria; Erich Schmid Institute of Materials Science, Austrian Academy of Sciences and University of Leoben (B.M.M., W.T., P.F.), A-8700 Leoben, Austria; Regional Bone Center, Helen Hayes Hospital (F.C., D.W.D., J.N., R.L.), West Haverstraw, New York 10993; and Columbia University College of Physicians and Surgeons (E.S.K., E.S., J.B.), New York, New York 10032
Address all correspondence and requests for reprints to: Dr. Klaus Klaushofer, Ludwig Boltzmann Institute of Osteology, Hanusch Hospital, Heinrich Collin Strasse 30, A-1140 Wien, Austria. E-mail: klaus.klaushofer{at}univie.ac.at.
Anabolic effects of PTH have been observed at several skeletal sites in humans by dual x-ray absorptiometry without differentiating between an actual increase in bone volume and an increase in mineral content within already established bone. The present study addressed this issue by evaluating the bone mineralization density distribution of iliac crest bone biopsies before and after PTH treatment for 18–36 months in men and women with osteoporosis using quantitative backscattered electron imaging. In cortical bone, pairwise comparison of the two biopsies before and after treatment revealed a reduction in the typical calcium concentration in men (-3.32%; P = 0.02, by paired t test), but no change in women, and the heterogeneity of mineralization increased in both males and females [+18.80% (P = 0.09) and +18.14% (P = 0.005), respectively]. In cancellous bone, there was no change in the typical calcium concentration, but there was a greater heterogeneity of mineralization in both men and women [+19.65% (P = 0.02) and +21.59% (P = 0.056), respectively] due to newly formed bone matrix. Small angle x-ray scattering performed on a subgroup of subjects revealed normal collagen/mineral structure. The findings confirm the observations that PTH stimulates skeletal remodeling, resulting in an increased percentage of newly formed bone matrix of lower mineral density.
Abbreviations: BE, Backscattered electron; BMD, bone mineral density; BMDD, bone mineralization density distribution; CaPeak, typical calcium concentration in the sample; CaWidth, width of the distribution; CLSM, confocal laser scanning microscopy; DXA, dual energy x-ray absorptiometry; FWHM, full width at half maximum; hPTH, human PTH; HRT, hormone replacement therapy; Md. BFR/BS, mineralized bone formation rate/bone surface; qBEI, quantitative backscattered electron imaging; scanning-SAXS, scanning small angle x-ray scattering.
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