Assessment Of Metabolic Bone Disease Research Articles

Metabolic Bone Disease of Prematurity: Diagnosis and Management.

Metabolic Bone Disease (MBD) of prematurity is a multifactorial disorder commonly observed in very low birth weight (VLBW, <1,500 g) newborns, with a greater incidence in those extremely low birth weight (ELBW, <1,000 g). MBD is characterized by biochemical and radiological findings related to bone demineralization. Several antenatal and postnatal risk factors have been associated to MBD of prematurity, although the main pathogenetic mechanism is represented by the reduced placental transfer of calcium and phosphate related to preterm birth. The diagnosis of MBD of prematurity requires the assessment of several biochemical markers, radiological, and ultrasonographic findings. However, the best approach is the prevention of the symptomatic disease, based on the screening of subjects exposed to the risks of developing MBD. Regarding the subjects who need to be screened, there is a substantial agreement on the potential risk factors for MBD. On the contrary, different recommendations exist on the diagnosis, management and treatment of this disorder of bone metabolism. This review was aimed at: (1) identifying the subjects at risk for MBD of prematurity; (2) indicating the biochemical findings to take in consideration for the prevention of MBD of prematurity; (3) suggesting practical recommendations on nutritional intake and supplementation in these subjects. We searched for papers which report the current recommendations for biochemical assessment of MBD of prematurity and for its prevention and treatment. The majority of the authors suggest that MBD of prematurity is a disease which tends to normalize overtime, thus it is not mandatory to mimic the rate of mineral fetal accretion through parenteral or enteral supplementation. The optimization of total parenteral nutrition (TPN) and the early achievement of a full enteral feeding are important goals for the prevention and management of MBD of prematurity.

Determination of Serum and Plasma Sclerostin Concentrations by Enzyme-Linked Immunoassays

Sclerostin alters bone formation. The precise and reproducible measurement of sclerostin concentrations in biological samples is important for assessment of metabolic bone disease. We determined sclerostin concentrations in serum and plasma using two commercially available ELISA. We measured sclerostin concentrations in serum or heparin-plasma obtained from 25 normal human subjects using two commercial ELISA available from Biomedica Medizinprodukte GmbH and TECOmedical AG. With the Biomedica assay, serum sclerostin concentrations were 0.99 ± 0.12 ng/ml (mean ± sem), and plasma concentrations were 1.47 ± 0.13 ng/ml (paired t test, P < 0.001). With the TECO assay, serum sclerostin levels were 0.71 ± 0.05 ng/ml, and plasma sclerostin concentrations were 0.80 ± 0.06 ng/ml (paired t test, P < 0.001). Serum and plasma sclerostin concentrations were significantly different when determined by the two assays (serum, P = 0.015; plasma, P < 0.001). Recovery of added recombinant sclerostin to serum was less than expected with both Biomedica and TECO assays (P < 0.001, paired t test). The concentrations of sclerostin in serum and plasma are different when determined by the two assays. Serum or plasma sclerostin concentrations with current assays should be interpreted with caution. The data suggest that the same assay should be used for comparing groups of patients or patients being followed longitudinally. Standardization of sclerostin assays is required before being introduced into general clinical laboratory use.

Clinical application of biochemical markers of bone turnover

With the ageing population in most countries, disorders of bone and mineral metabolism are becoming increasingly relevant to every day clinical practice. Consequently, the interest in, and the need for effective measures to be used in the screening, diagnosis and follow-up of such pathologies have markedly grown. Together with clinical and imaging techniques, biochemical tests play an important role in the assessment and differential diagnosis of metabolic bone disease. In recent years, the isolation and characterisation of cellular and extracellular components of the skeletal matrix have resulted in the development of molecular markers that are considered to reflect either bone formation or bone resorption. These biochemical indices are non-invasive, comparatively inexpensive and, when applied and interpreted correctly, helpful tools in the diagnostic and therapeutic assessment of metabolic bone disease. This review provides an overview of the current evidence regarding the clinical use of biochemical markers of bone remodelling in bone disease, with an emphasis on osteoporosis.

Tibial Speed of Sound in Term and Preterm Infants

The tibial speed of sound (SOS) was measured in 91 healthy singleton infants between 31 and 42 weeks of gestation and 12 sick preterm infants. In healthy infants, the tibial SOS was associated with corrected gestational age (r = 0.40, p < 0.001) but not birth weight. The median tibial SOS in 12 sick preterm infants (2,772, range 2,566–2,934 m/s), whose corrected gestational age was between 31 and 42 weeks, was lower (p < 0.001) than that of 69 healthy gestation-matched healthy infants (3,100, range 2,870–3,381 m/s). Tibial SOS measurements may allow radiation-free assessment of metabolic bone disease of prematurity.

Basic principles and clinical applications of biochemical markers of bone metabolism: biochemical and technical aspects.

The interest in and the need for effective measures to be used in the screening, diagnosis, and follow-up of disorders of connective tissue, bone, and mineral metabolism has markedly grown. Next to clinical and imaging techniques, indices of bone turnover have come to play an important role in the assessment of metabolic bone disease. In osteoporosis, recent research has shown that bone markers may also be used to predict future bone loss and hip fractures (in larger cohorts of older patients), identify individuals at risk for osteoporosis, select therapy, and predict and monitor the therapeutic response in individual patients. The development of new markers of bone metabolism has greatly enriched the spectrum of serum and urine analytes used in the assessment of skeletal pathologies. Besides total alkaline phosphatase, other markers such as bone-specific alkaline phosphatase, osteocalcin, or the collagen propeptides are being used to measure bone formation. Bone resorption, previously assessed only by the measurement of urinary calcium and hydroxyproline, may now be detected more precisely by a number of new serum and urine markers. Among these, the pyridinium crosslinks and the telopeptides of collagen type I are presently considered the most specific markers of bone resorption. More recently, bone sialoprotein has also been suggested as a marker of bone resorption in serum. Tartrate-resistant acid phosphatase is now measurable by immunoassay. This article surveys the biochemistry and relevant technical aspects of the currently available markers of bone metabolism.

Assessment of metabolic bone disease in infants

Assessment of metabolic bone disease in infants

A thionin stain for visualizing bone cells, mineralizing fronts and cement lines in undecalcified bone sections.

A staining method is described using thionin, for undecalcified deacrylated bone sections. RNA is stained purplish violet, allowing still active osteoblasts to be distinguished from lining cells. Staining intensity of mineralized bone is related to the degree of mineralization. Mineralizing fronts and cement lines are visualized clearly. Lamellae show an alternate pattern. Histomorphometric parameters such as osteon thickness and interstitial bone thickness can be measured without using polarized light. The mineralizing front can be assessed and expressed as a percentage of the osteoblast-covered interface between osteoid and mineralized bone. The stain is also useful for qualitative assessment of metabolic bone disease. Thionin stained sections can be kept for at least one year when stored in the dark at 7 C.

Biochemical Markers of Bone Turnover for the Clinical Assessment of Metabolic Bone Disease

There is not yet an ideal marker of bone formation, but circulating BGP is the most satisfactory at present. New developments include the use of sheep BGP64 and human BGP85 as an immunogen and monoclonal antibodies, which may recognize fragments of BGP released during resorption. The specific measurement of bone alkaline phosphatase and the assay of procollagen fragments and of other noncollagenous bone-related proteins will allow a more precise assessment of the complex osteoblastic functions in normal and pathologic conditions. Finding a sensitive and specific marker of resorption is a challenge because all constituents of bone matrix are likely to be degraded into minute peptides during osteoclastic bone resorption. The measurement of pyridinium crosslinks and possibly of tartrate-resistant acid phosphate by a bone-specific monoclonal antibody are the most tangible improvements in this area. These markers need to be validated by comparison with data obtained by direct measurement of bone turnover on iliac crest biopsy. It should be remembered, however, that circulating markers reflect the overall activity of the whole skeleton, including the cortical, subcortical, and trabecular envelopes, which have different remodeling rates in normal and abnormal states. A circulating marker will not detect a specific defect of the cellular activity of one compartment of bone if the summated turnover of the skeleton is unchanged. Conversely, bone histomorphometry is limited to a small area of the trabecular envelope but allows detection of a specific defect at the cellular level. These differences should be kept in mind, as there is growing evidence that, for example, bone mass and bone turnover of osteoporotic patients before and during treatment vary in different appendicular/axial and cortical/trabecular compartments. Finally, a single marker might be valuable in some diseases and not in others (such as serum BGP in Paget's disease of bone). Despite these difficulties, significant advances have been made in the last few years in the bone marker field. In the future, the development of a battery of several bone-specific markers that indicate various aspects of the complex mechanisms of bone formation, resorption, and mineralization is likely to provide new tools for the diagnosis and management of bone diseases.

Assessment of Metabolic Bone Disease: Review of New Nuclear Medicine Procedures

In the management of patients with metabolic bone disease, nuclear medicine laboratories offer two nontraumatic procedures of potential clinical importance: bone mineral measurements and bone scintigraphy. Bone mineral measurements from the radius, lumbar spine, and hip obtained with use of absorptiometry or computed tomography can be used to predict the risk of fracture at these skeletal sites, can determine the severity of bone loss for the assessment of a benefit-versus-risk ratio on which appropriate therapy can be based, and can substantiate the effectiveness of therapy over time. Bone scintigraphy with use of labeled diphosphonate allows assessment of focal and, in defined circumstances, of total skeletal bone turnover in patients with normal kidney function. Both of these techniques have been used successfully in studies of population groups for the evaluation of trends. Their application to the management of individual patients is currently being evaluated.

Two recent advances in the assessment of metabolic bone disease

Two recent advances in the assessment of metabolic bone disease