Spectroscopic markers of bone quality in alendronate-treated postmenopausal women

Abstract

Comparison of infrared spectroscopic images of sections from biopsies of placebo-treated post-menopausal women and women treated for 3 years with 10 mg/day alendronate demonstrated significant increases in cortical bone mineral content, no alterations in other spectroscopic markers of "bone quality," but a decrease in tissue heterogeneity.

Methods: The material properties of thick sections from iliac crest biopsies of seven alendronate-treated women were compared to those from ten comparably aged post-menopausal women without bone disease, using infrared spectroscopic imaging at approximately 7 microm spatial resolution. Parameters evaluated were mineral/matrix ratio, crystallinity, carbonate/amide I ratio, and collagen maturity. The line widths at half maximum of the pixel histograms for each parameter were used as measures of heterogeneity.

Results: The mineral content (mineral/matrix ratio) in the cortical bone of the treated women's biopsies was higher than that in the untreated control women. Crystallinity, carbonate/protein, and collagen maturity indices were not significantly altered; however, the pixel distribution was significantly narrowed for all cortical and trabecular parameters with the exception of collagen maturity in the alendronate treatment group.

Conclusions: The increases in mineral density and decreased fracture risk associated with bisphosphonate treatment may be counterbalanced by a decrease in tissue heterogeneity, which could impair tissue mechanical properties. These consistent data suggest that alendronate treatment, while increasing the bone mass, decreases the tissue heterogeneity.

Fig. 1

Infrared spectrum of healthy adult cortical bone showing regions of interest for the current study. The spectrum has been baseline corrected and the PMMA contribution subtracted

Fig. 2

Mean±SD for each parameter measured from three to five FTIR images of cortical and cancellous bone per biopsy in patients treated with alendronate (ALN) or a placebo. Values shown are mineral/matrix ratio (M/M); carbonate/phosphate ratio (C/P), this value has been multiplied by 100 for ease of presentation; carbonate/amide I ratio (C/Am I) also multiplied by 100; crystallinity (XST); and collagen maturity ratio (XLR). For each parameter, *p<0.05 relative to placebo control

Fig. 3

Typical FTIRI images and pixel histograms for cortical (left) and cancellous (right) bone from one placebo and one ALN-treated case; a mineral/matrix, b carbonate/phosphate

Fig. 4

Heterogeneity was calculated from FWHM of pixel histograms as illustrated in a and b. The mean±SD for FWHM for each parameter in the cortical and cancellous bones of the ALN and placebo groups are shown. Values shown for carbonate/phosphate ratio (C/P) and carbonate/amide I ratio have been multiplied by 100 for ease of presentation, crystallinity (XST), and collagen maturity ratio (XLR) values multiplied by 10. *p<0.05 relative to placebo control