Bone turnover disorders

Clinical information

Bone is a type of specialised connective tissue that is hardened through mineralisation with calcium phosphate and is subject to consistent remodelling (“turnover”). This makes bone dynamic enough to react to the mechanical forces it is subjected to.

Bone remodelling, which involves the resorption of old bone tissue by osteoclasts and the formation of new bone tissue by osteoblasts, is regulated by central mechanisms as well as local control of bone-forming and -resorbing cells. The fragments released through the activity of the involved cells are known as bone turnover markers. They are divided into bone formation markers and bone resorption markers depending on their part in the remodelling process.

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

Diagnostics

Measurement of bone turnover markers contributes to diagnostics and progression evaluation of diseases associated with bone turnover disorders as they represent the rate of bone formation and resorption. When performed in addition to bone density measurement, this measurement can also help to evaluate the course of osteoporosis and the success of anti-resorptive therapy.

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), which are fragments of type I collagen that then reach the bloodstream. When more osteoclasts than osteoblasts are activated, the circular CTX concentration rises. The concentration of CTX in serum is therefore a diagnostic criterion for the evaluation 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 collagen type I CTX in blood for the evaluation of fracture risk and monitoring of osteoporosis treatment.