e-book Chapter 15, Biochemical Markers of Bone Metabolism

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Bone Turnover Markers
  1. Pediatric Bone: Biology and Diseases - Google книги
  2. Using biochemical markers of bone turnover in clinical practice
  3. Osteoporosis
  4. Bone Formation Markers
  5. Citation Tools

The second edition of this classic reference deals exclusively with the biology and diseases of bone as they affect children. Rapid advances have been made in our understanding of the mechanisms and factors controlling the growth and development of bone, and these are discussed in detail in this book.

Further, the various diseases of bone that are peculiar to children are highlighted and discussed in the light of our current knowledge with regard to causation, clinical signs and treatment. The book is aimed to provide those clinicians interested in children's diseases and basic scientists with a comprehensive resource covering the various aspects of bone health and disease in children.

Deals exclusively with bone development and diseases of children and each chapter is written by an expert in the field Fully referenced providing an appendix of usually difficult to find information on the investigation of pediatric bone disease and reference values Covers both the physiology of bone and mineral homeostasis in children and diseases in one book. Chapter 2 Bone Matrix and Mineralization. Chapter 3 Prenatal Bone Development.

Chapter 6 Parathyroid Hormone and Calcium Homeostasis. Chapter 7 Phosphate Homeostasis Regulatory Mechanisms. Chapter 8 Vitamin D Biology.

Chapter 18 The Spectrum of Pediatric Osteoporosis. Chapter 19 Osteogenesis Imperfecta.

Pediatric Bone: Biology and Diseases - Google книги

Chapter 20 Sclerosing Bone Dysplasias. Chapter 21 Parathyroid Disorders. Chapter 22 Fibrous Dysplasia. Table 1. Lists of bone markers and required types of samples. Like any other biological markers, sources of variability can be divided into pre-analytical, analytical and post-analytical. In general, bone formation markers are less variable than resorption markers. Urinary markers show more variability than serum markers. Urinary markers concentrations are corrected for creatinine, and thus pre-analytical and analytical variability of creatinine needs to be taken into account.

As for blood samples, the presence of some anticoagulants in plasma can affect OC as mentioned earlier. Table 2. Sources of variability in bone markers. Age and gender : Bone markers concentrations are higher in children than adults, particularly during the first year of life and during puberty when values are 2—10 times higher than in adults.

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In adult men, values remain unchanged after growth is completed until 60 years of age. Subsequently, the changes in bone markers have not been clearly established; although resorption markers have been reported to increase in most studies, bone formation markers were either increased, decreased or unchanged. Ethnicity : Bone markers vary with ethnicity and resorption markers were reported to be lower in Black children than White children. Pregnancy and lactation : Starting from the second trimester of pregnancy, both formation BALP and P1NP and resorption markers cross-links and telopeptides begin to rise and concentrations are significantly higher at term than prior to pregnancy.

Serum OC concentration is decreased during pregnancy which is restored after the delivery. This may be due to placenta clearance of OC or increased renal clearance during pregnancy. Fracture : Bone resorption markers increase during the first four weeks after a fracture, followed by an increase in bone formation markers. Immobility : The bone resorption markers, but not formation markers, tend to increase after 2—4 days of bed rest and return to normal after remobilization. Associated diseases : Non-skeletal diseases affect bone markers by several mechanisms, and it is important to exclude these conditions when interpreting bone marker results.

An increase in BALP is seen in liver diseases due to interference of the assay from liver isoenzymes. Other diseases which affect bone markers are listed in Table 2. Circadian rhythm : Most bone turnover markers concentrations are highest in the early morning between and hours and lowest during afternoon and night between and hours. However, the circadian rhythm of serum BALP is different, with peak concentrations in the afternoon and a nadir in the early morning.

Using biochemical markers of bone turnover in clinical practice

In general, resorption markers show a wider amplitude of circadian changes than formation markers, and urine markers are affected more than serum markers. Therefore, timing of the sample is of utmost importance to minimize the variation. Menstruation : Bone markers vary during the menstrual cycle with an increase in bone formation markers in the luteal phase and an increase in bone resorption markers in the follicular phase. The first 3—7 days of the menstrual cycle is the best time of the cycle for sample collection. However, OHP excretion is increased by ingestion of meat and gelatin.

Serum CTX is also affected by food intake, and patients should be advised to fast overnight before the sample collection. Intrinsic biological variation : In addition to diurnal variations, bone markers also vary from day to day intra-individual variations. Serum markers show less pronounced variations than urine markers. The analytical variability of bone markers has greatly improved with the development of fully automated platforms. However, inter-laboratory variation on the same sample, even using the same method, can be substantial. Thus, it is mandatory to provide information to clinicians that bone marker results may not be comparable between different laboratories.


Ideally, a laboratory should derive its own reference ranges for each specific group of patients to accommodate age, gender and ethnicity variations. Osteoporosis is characterized by low bone mass and increased risk of fractures. It is estimated that one in two women and one in five men over the age of 50 in the UK will sustain a fracture as a result of osteoporosis. BMD is usually measured in the lumbar spine and the hip and occasionally in the forearm. Therefore, T-scores are used, defined as the number of standard deviations from peak bone mass of healthy young adults. Bone markers are currently not recommended for use in the diagnosis of osteoporosis.

However, they have a potential role in the monitoring of treatment as the changes that occur are more rapid, larger and more closely related to fracture reduction when compared to BMD changes. Accelerated bone turnover is associated with higher risk of fracture independent of age, gender or underlying diseases.

Previous studies have demonstrated that increased concentrations of bone markers in postmenopausal women are associated with more rapid bone loss. Bone loss at different sites including the forearm, spine and hip has been studied using a variety of markers. Overall, resorption markers were shown to be more strongly predictive of the rate of bone loss than formation markers. Large population-based studies have demonstrated that high bone turnover is associated with increased risk of osteoporotic fractures and that bone markers may be useful in prediction of fractures independent of BMD.

Bone Formation Markers

The association between fracture risk and bone formation markers is weaker than that for bone resorption markers. Three studies Rotterdam study, EPIDOS and OFELY have established that high levels of resorption markers were associated with increased risk of hip, vertebral and non-vertebral fractures in healthy postmenopausal women. In addition, a greater risk of hip fractures was seen in postmenopausal women with low BMD and high resorption markers than those with high resorption markers alone or low BMD alone.

The association between bone markers and fracture risk in men is less well studied. Increased bone resorption was also found to be associated with increased risk of fracture, independent of BMD, in elderly men in the Dubbo Osteoporosis Epidemiology Study in Australia. Therapeutic options for the treatment of osteoporosis have greatly advanced over the last decade with the development of antiresorptive agents e.

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In theory, it might be desirable to use antiresorptive drugs for patients with high bone turnover and anabolic agents for those with low bone turnover. This concept has not been widely studied, but if shown to be valid, it might be useful for selecting treatment options in clinical practice. Although BMD is used to diagnose osteoporosis, it has limitations in the monitoring of treatment efficacy. First, changes in BMD take longer to occur than bone markers.

Second, interpretation of follow-up DXA scans requires documentation of the reproducibility of measurements and estimation of the least significant change LSC. Last, changes in BMD explain only a small proportion of the fracture reduction in treated patients. Bone turnover markers change in response to antiresorptive agents as early as two weeks and reach a plateau within 3—6 months. At present, there are no consistent recommendations for the calculation LSC for bone markers.

A common aim of antiresorptive therapy in the treatment of postmenopausal osteoporosis is to achieve bone marker concentrations within the premenopausal range. The extent and direction of bone marker changes depend on the therapeutic agent, dose and mode of administration and the sensitivity of the marker.

Ensuring adherence to treatment for osteoporosis is a major challenge. A significant fall in bone markers after starting a treatment indicates that medication is being taken regularly and is absorbed properly. However, to what extent the measurement of bone markers and subsequent feedback to patients improve the compliance is uncertain. It can affect one monostotic or multiple polyostotic bones. The diagnosis can be further confirmed by performing plain X-rays of affected bones and isotope bone scanning.

The type and extent of bone marker changes depend on the extent and severity of disease and level may be normal in monostotic disease. The response to treatment can be monitored by improvement in symptoms, bone markers or radiological appearances. The changes in bone markers can be observed rapidly and are easily detected. BALP changes earlier than total alkaline phosphatase when the disease relapses.