Cell signalling and bone remodelling Part II: Developments in the pathogenesis and principles of management of selected skeletal disease states

EJ Raubenheimer,C Noffke

doi:10.17159/2309-8309/2016/v15n1a11

Abstract

Mapping of the bone remodelling signalling pathways contributed significantly to the establishment of a scientific basis for the development of pharmaceuticals which have the potential to induce or suppress bone formation. Enhancing bone healing and the establishment of a pre-determined skeletal phenotype are now within reach of the medical profession. This manuscript provides practitioners with an overview of recent developments in the quest for uncovering the molecular mechanisms involved in the pathogenesis of selected bone disease states and the role these discoveries play in the future management of bone healing and skeletal health.

Highlights

The study of rare genetic skeletal diseases exposed a wealth of information on the autocrine, paracrine and endocrine control of bone metabolism
Enhancing bone healing and the establishment of a pre-determined skeletal phenotype are within reach of the medical profession. This manuscript provides practitioners with an overview of recent developments in the quest for uncovering the molecular mechanisms involved in the pathogenesis of selected bone disease states and the role these discoveries play in the future management of bone healing and skeletal health
Active antiretroviral therapy (HAART), chronic inflammation, the virus itself and dietary factors contribute to bone loss[23] and the increase in the incidence of fractures reported in AIDS patients.[24]

Summary

Introduction

The study of rare genetic skeletal diseases exposed a wealth of information on the autocrine, paracrine and endocrine control of bone metabolism. Human recombinant BMP7 (available commercially under the brand name OP1) is used to facilitate fusion of vertebrae to prevent neurological trauma.[14] rhBMP2 is more widely used to treat non-union of fractures as it appears to be superior in inducing new bone formation than the other BMPs.[15] BMP7 has a potential future role in the management of chronic kidney disease through its inhibition of fibrosis and restoration of healthy epithelial cell populations.[16,17,18] Mineralisation of the newly formed bone is mediated by bone sialoprotein,[14] carboxylated osteocalcin[19] or other cytokines (see Part I*) Mapping of these pathways exposed specific receptor binding sites on bone cells which can potentially be activated or blocked in order to either limit bone resorption or accelerate bone formation and mineralisation, impacting directly on the process of bone healing. Ceramic microsphere carriers are injectable, biodegradable and can be coated to become osteoinductive[21,22] thereby decreasing the post-infection healing time of bone

HIV and antiretroviral therapy

Generalised bone forming diseases

Malignant disease

Conclusion