Introduction

Bone and mineral metabolism

Bone and mineral metabolism is regulated by an intricate interplay between systemic hormones and locally produced factors (i.e. growth factors, cytokines and prostaglandins) exerting autocrine and paracrine actions on the bone cells or their precursors (Canalis, 1983; Raisz, 1988; Canalis, McCarthy & Centrella, 1989; Ohlsson et al., 1993; Mundy, 1995). Fine tuning of this complex system ensures normal bone growth and preservation of functional integrity of the adult skeleton, but is equally important for ionic homeostasis.

Adult bone is subject to a continuous remodelling process, characterized by focal renewal of microscopic quanta of bone, which takes place in bone remodelling units scattered throughout the skeleton. Within these microscopic units, bone renewal proceeds according to a highly organized sequence of events, the remodelling cycle, involving bone removal by osteoclasts (bone resorption) followed by deposition and mineralization of new bone matrix by osteoblasts (bone formation). Osteoclast and osteoblast function are tightly regulated and coupled through autocrine/paracrine mechanisms, so that in young adults bone resorption and formation are normally in balance.

Partial uncoupling of resorption and formation, with negative or positive balance of the remodelling cycles, will result in loss or gain of bone mass, respectively. Whether these changes in bone mass occur slowly or rapidly depends mainly on the frequency of activation of new remodelling units, which sets the level of bone turnover (i.e. the summation of the remodelling activity in all active units during a considered period of time) (Eriksen, 1986; Parfitt, 1988; Peck & Woods, 1988; Raisz, 1988; Mundy, 1995).