Podosome-Driven Defect Development in Lamellar Bone under the Conditions of Senile Osteoporosis Observed at the Nanometer Scale.

Paul Simon,Petr Formanek,Hartmut Worch,Anne Hild,Rüdiger Kniep,Elena Sturm,Wolfgang Pompe,Manfred Bobeth,Sabine Wenisch

doi:10.1021/acsbiomaterials.0c01493

Abstract

The degradation mechanism of human trabecular bone harvested from the central part of the femoral head of a patient with a fragility fracture of the femoral neck under conditions of senile osteoporosis was investigated by high-resolution electron microscopy. As evidenced by light microscopy, there is a disturbance of bone metabolism leading to severe and irreparable damages to the bone structure. These defects are evoked by osteoclasts and thus podosome activity. Podosomes create typical pit marks and holes of about 300–400 nm in diameter on the bone surface. Detailed analysis of the stress field caused by the podosomes in the extracellular bone matrix was performed. The calculations yielded maximum stress in the range of few megapascals resulting in formation of microcracks around the podosomes. Disintegration of hydroxyapatite and free lying collagen fibrils were observed at the edges of the plywood structure of the bone lamella. At the ultimate state, the disintegration of the mineralized collagen fibrils to a gelatinous matrix comes along with a delamination of the apatite nanoplatelets resulting in a brittle, porous bone structure. The nanoplatelets aggregate to big hydroxyapatite plates with a size of up to 10 x 20 μm2. The enhanced plate growth can be explained by the interaction of two mechanisms in the ruffled border zone: the accumulation of delaminated hydroxyapatite nanoplatelets near clusters of podosomes and the accelerated nucleation and random growth of HAP nanoplatelets due to a nonsufficient concentration of process-directing carboxylated osteocalcin cOC.

Highlights

Numerous studies in the literature[1−8] have been devoted to the elucidation of the biochemical and cellular processes causing the senile osteoporosis
There are only few studies devoted to the changes of osteoporotic bone on the nanoscale (1 μm−10 nm).[9−11] Fractures of the femoral neck, vertebrae, and distal radius being the hallmarks of osteoporosis are the results of low energy trauma and occur almost exclusively in the geriatric population (Cummings and Melton,[12] Riggs and Melton,[13] Acros et al.,[14] and McNamara15)
(staining according to Trump[23] and Ito24) the red colored areas of trabecular bone correspond to lamellar bone, appearing bright pink, which is sometimes surrounded by a small edge of osteoid

Summary

Introduction

Numerous studies in the literature[1−8] have been devoted to the elucidation of the biochemical and cellular processes causing the senile osteoporosis. There are only few studies devoted to the changes of osteoporotic bone on the nanoscale (1 μm−10 nm).[9−11] Fractures of the femoral neck, vertebrae, and distal radius being the hallmarks of osteoporosis are the results of low energy trauma and occur almost exclusively in the geriatric population (Cummings and Melton,[12] Riggs and Melton,[13] Acros et al.,[14] and McNamara[15]). Further investigations revealed that the amount of collagen I is decreased.[1,19] it is assumed that a change of the amount of collagen crosslinks, such as homocysteine, lysine, pyrrolidine, glycosylated compounds, and others, may provoke a decrease in the mechanical stability of bone.[16,20]

Results

Discussion

Conclusion