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Bone Quality determined by Fourier Transform Infrared Imaging Analysis in Mild Primary Hyperparathyroidism

Ludwig Boltzmann Institute of Osteology (R.Z., P.R., E.P.P., K.K.), Hanusch Hospital of WGKK (Social Health Insurance Vienna) and Trauma Centre Meidling of AUVA (Austrian Social Insurance for Occupational Risk), 4th Medical Department, Hanusch Hospital, A-1140 Vienna, Austria; Regional Bone Center (D.W.D., H.Z.), Helen Hayes Hospital, West Haverstraw, New York 10993; and Division of Endocrinology (D.W.D., J.P.B., S.J.S., E.S.), Metabolic Bone Diseases Unit, College of Physicians and Surgeons, Columbia University, New York, New York 10032

Address all correspondence and requests for reprints to: Eleftherios P. Paschalis, Ludwig Boltzmann Institute of Osteology, Hanusch Krankenhaus, Heinrich-Collin Str. 30, A-1140 Vienna, Austria. E-mail: eleftherios.paschalis{at}osteologie.at.

Context: Mild primary hyperparathyroidism (PHPT) is characterized by asymptomatic hypercalcemia, most commonly in the absence of classical signs and symptoms. Hence, there is need to characterize this disorder with particular attention to the skeleton.

Design: We determined the ratio of pyridinium and dehydrodihydroxylysinonorleucine collagen cross-links in 46 iliac crest bone biopsies from patients with PHPT (14 men, aged 28–68 yr; 32 women, aged 26–74 yr) by Fourier transform infrared imaging. The results were compared with previously reported collagen cross-links ratio determined in iliac crest biopsies from normal subjects.

Results: PHPT patients exhibited significantly lower pyridinium to dehydrodihydroxylysinonorleucine collagen cross-links ratio, compared with normal controls. Parathyroidectomy restored values to those comparable with normal controls. Moreover, the differences among PHPT subjects were gender dependent, with female PHPT patients having a statistically significant lower ratio, compared with either male PHPT patients or normal controls. Comparison of the obtained outcomes with histomorphometry showed that the collagen cross-link ratio was strongly correlated with rate of bone formation, and mineralizing surface, in individual patients. This ratio was also correlated with bone mineralization density distribution parameters obtained in the same patients. The strongest correlations were with bone mineralization density distribution variables reflecting heterogeneity of mineralization and primary mineralization parameters.

Conclusions: The results are consistent with the high turnover state manifested in PHPT patients. Reduced collagen cross-link ratio in patients with PHPT would be expected to reduce the stiffness of bone tissue. These observations provide a more complete assessment of bone material properties in this disorder.