Bone turnover disorders

Bone is primarily made up of collagen matrix containing calcium and phosphate which are deposited as hydroxyapatite. The adult skeleton comprises 2 main types of bone: cortical and trabecular.

Cortical bone is responsible for the bone's main function to support the whole body, protect organs, provide levers for movement and to store and release chemical elements. Conversely, trabecular bone is the metabolically active portion and found at the end of long bones, near joints and in the interior of vertebrae.

Bone turnover, or remodelling, is a dynamic, lifelong process in which old bone is removed (resorption) from the skeleton and new bone is added (formation). It is the way in which bone grows and becomes repaired following injuries such as fractures and micro-damage which can occur during normal activities. It also responds to functional demands of mechanical load. The process is tightly regulated through the action of various systemic hormones (including parathyroid hormone (PTH), vitamin D) and local mediators (such as cytokines and growth factors).

Within a child’s first year, its entire skeleton is resorbed and replaced, and this process continues at a rate of approx. 10 – 20 % per year until the age of around 30 whereby the peak bone mass is reached.

After the attainment of peak bone mass, bone remodelling is a balanced process, with bone mass remaining stable for around a decade, following which increased resorptive activity and reduced bone formation are observed, and age-related bone loss begins.

During the bone remodelling process, compounds are released either from bone or from the cells involved (osteoblasts and osteoclasts). These compounds are referred to as bone turnover markers (BTMs) which are grouped into two categories based on the metabolic phase during which they are produced as markers of formation and resorption. 

Bone resorption markers are all related to osteoclast resorption of the bone matrix – i. e. the dissolution of the mineralised matrix (tartrate-resistant acid phosphatase 5b [TRAcP 5b]) and degradation of the protein matrix (especially telopeptides of collagen type I (CTX-I and NTX-I). Conversely, bone formation markers reflect different aspects of osteoblast function and of bone formation – for example the deposition of protein matrix (osteocalcin and propeptides of type I collagen (PINP)) and mineralisation of the matrix (bone-specific alkaline phosphatase (BAP)). 

Disorders of the remodelling process, e. g. excessive resorption of bone tissue result in metabolic bone diseases, most frequently osteoporosis, osteomalacia and Paget’s disease of bone.