Microtopography of Immune Cells in Osteoporosis and Bone Lesions by Endocrine Disruptors

Abstract

Osteoporosis stems from an unbalance between bone mineral resorption and deposition. Among the numerous cellular players responsible for this unbalance bone marrow (BM) monocytes/macrophages, mast cells, T and B lymphocytes, and dendritic cells play a key role in regulating osteoclasts, osteoblasts, and their progenitor cells through interactions occurring in the context of the different bone compartments (cancellous and cortical). Therefore, the microtopography of immune cells inside trabecular and compact bone is expected to play a relevant role in setting initial sites of osteoporotic lesion. Indeed, in physiological conditions, each immune cell type preferentially occupies either endosteal, subendosteal, central, and/or perisinusoidal regions of the BM. However, in the presence of an activation, immune cells recirculate throughout these different microanatomical areas giving rise to a specific distribution. As a result, the trabeculae of the cancellous bone and endosteal free edge of the diaphyseal case emerge as the primary anatomical targets of their osteoporotic action. Immune cells may also transit from the BM to the depth of the compact bone, thanks to the efferent venous capillaries coursing in the Haversian and Volkmann canals. Consistently, the innermost parts of the osteons and the periosteum are later involved by their immunomodulatory action, becoming another site of mineral reabsorption in the course of an osteoporotic insult. The novelty of our updating is to highlight the microtopography of bone immune cells in the cancellous and cortical compartments in relation to the most consistent data on their action in bone remodeling, to offer a mechanist perspective useful to dissect their role in the osteoporotic process, including bone damage derived from the immunomodulatory effects of endocrine disrupting chemicals.

Keywords: bone remodeling; endocrine disrupting chemical; immunobiology; immunomodulation; organoid; osteoporosis.

Figure 1

Topographic distribution of bone lesions in the human jaw following classical osteoporotic processes (chronic bacterial inflammation and menopause). (A) Edentulous patient (male, age 74 years) showing osteoporotic vertical resorption (arrow) of the maxilla during severe periodontitis. Surgical displacement of the gum flap revealed consistent porosity of the vast majority of the exposed bone, including complete loss of the cortical bone but more limited destruction of the cancellous trabeculae; (B) loss of central and lateral, inferior incisors in a patient (female, age 74 years) with vertical resorption (arrow) of the jaw as a consequence of severe postmenopausal osteoporosis. Note the presence of bone implants (white bracket) becoming visible after exposing the resorbed bone through a gum flap. Osteoporosis led to a decreased rate of cancellous bone formation in both the implanted socket and interdental bone, thus increasing risk of trabecular microfractures and prosthetic instability (from the Odontostomatological Archive of CMG, San Venanzio di Galliera, BO, Italy, with permission).