Bone turnover disorders

Clinical information

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. 

Diagnostics

Measurement of bone turnover markers contributes to diagnosis and progression monitoring of some metabolic bone conditions as they represent the rate of bone formation and resorption. The most common use of bone turnover markers is for the monitoring of therapies prescribed for bone conditions such as osteoporosis. Since bone turnover is a dynamic process, the levels of BTMs change very quickly following onset of therapy, allowing a rapid assessment of suitability of the treatment and confirm treatment compliance. In some metabolic conditions such as Paget’s disease and hypophosphatasia, use of BTMs prove useful to support diagnosis. 

In bone resorption, type I collagen from the bones is resorbed by osteoclasts, creating C-terminal telopeptides (β-CrossLaps, cross-linked carboxyterminal telopeptide of type I collagen, CTX-I), which are fragments of type I collagen that then reach the bloodstream. When more osteoclasts than osteoblasts are activated, circulating CTX-I concentration rises. The concentration of CTX-I in serum is therefore an indicator for the assessment of the course and/or therapy of osteoporosis. 

Bone turnover markers that indicate a stronger activation of osteoblasts than osteoclasts, e. g. bone-specific alkaline phosphatase (BAP) or osteocalcin are considered markers of bone formation.  

International guidelines recommend the determination of the bone formation marker procollagen type I N-terminal propeptide (PINP) and of the bone resorption marker C-terminal telopeptide of collagen type I (CTX-I) in blood for monitoring of osteoporosis treatment. 

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Biochemical markers of bone turnover

Bone turnover markers - Beyond osteoporosis