Bone Health

Liver & Kidney Health, Bone Health

Serum alkaline phosphatase is a member of a family of zinc metalloprotein enzymes that function to split off a terminal phosphate group from an organic phosphate ester. This enzyme functions in an alkaline environment (optimum pH of 10). Active center of ALP enzymes includes a serine residue. Mg and Zn ions are required for minimal activity. Enzyme activity is localized in the brush border of the proximal convoluted tubule of the kidney, intestinal mucosal epithelial cells, hepatic sinusoidal membranes, vascular endothelial cells and osteoblasts of bone. There are distinctive forms of ALP in the placenta and small intestine; hepatic, renal and osteoblast (bone) ALP are similar molecules.Serum ALP activity of intestinal origin occurs only in individuals of ABO blood type O or A. They are secretors of ABH RBC antigens and also carry the Lewis red cell antigen. Serum intestinal ALP level increases in these individuals about two hours following consumption of a fatty meal.Liver alkaline phosphatase is increased in cholestasis and inflammatory liver disease as well as in infiltrative liver disease. The enzyme is sensitive to obstructive biliary processes, even small secondary bile duct obstruction, and thus may be increased in those patients when the bilirubin is normal due to compensatory bilirubin excretion by the rest of the liver. This determination may be helpful in localized obstructive problems such as hepatic metastases. An electrophoretically slow moving isoenzyme with high relative mass may occur in some patients with bile duct obstruction and hepatic metastases and may result in false elevation of CK-MB.7To confirm biliary abnormality, an additional useful test is GT. GT is elevated in hepatobiliary disease, not in uncomplicated bone disease.Serum ALP is increased during pregnancy. Marked decline of high ALP of pregnancy is seen with placental insufficiency and imminent fetal demise.

Nutrition & Vitamins, Bone Health

In the differential diagnosis of hypercalcemia serum calcium should be measured on at least three occasions. Inprimary hyperparathyroidism(HPT) parathyroid hormone, serum chloride, and urine calcium are increased. Rarely, in HPT the hypercalcemia is accompanied by a low-normal PTH.8In HPT, calcium rises, then phosphorus falls, then alkaline phosphatase rises. Alkaline phosphatase is usually not more than twice its upper limit in HPT. Measured ionized calcium and calculated ionized calcium may be helpful.Twenty-four hour urinary calcium is increased in HPT, low infamilial hypocalciuric hypercalcemia(FHH) which is characterized by hypercalcemia and hypocalciuria. An autosomal dominant, it apparently has no complications. A ratio of renal calcium clearance:creatinine clearance <0.01 suggests this genetic disease. The calcium:creatinine clearance ratio is said to discriminate between FHH and hyperparathyroidism.2Family studies are highly desirable.Hypocalcemia, then hypercalcemia occur with rhabdomyolysis − induced acute renal failure.9,10

Nutrition & Vitamins, Bone Health

Serum calcium is involved in the regulation of neuromuscular and enzyme activity, bone metabolism and blood coagulation. Calcium blood levels are controlled by a complex interaction of parathyroid hormone, vitamin D, calcitonin and adrenal cortical steroids. Calcium measurements are useful in the diagnosis of parathyroid disease, some bone disorders and chronic renal disease. A low level of calcium may result in tetany.

Liver & Kidney Health, Bone Health

Serum alkaline phosphatase levels are of interest in the diagnosis of hepatobiliary disorders and bone disease associated with increased osteoblastic activity. Moderate elevations of alkaline phosphatase may be seen in several conditions that do not involve the liver or bone. Among these are Hodgkin's disease, congestive heart failure, ulcerative colitis, regional enteritis, and intra-abdominal bacterial infections. Elevations are also observed during the third trimester of pregnancy.

Bone Health, Hormone Testing

Offered as part of multiple lab tests

Nutrition & Vitamins, Bone Health

Serum phosphorus (Phosphate) levels alone are of limited diagnostic value and should be correlated with serum calcium levels. An increased phosphorus with decreased calcium suggests either hypoparathyroidism or renal disease. A decreased phosphorus and an increased calcium suggests hyperparathyroidism or sarcoidosis. When both calcium and phosphorus are decreased diagnostic considerations include malabsorption, vitamin D deficiency and renal tubular acidosis. Increased phosphorus and normal or increased calcium suggests Milk-alkali syndrome or hypervitaminosis D.

Autoimmune & Inflammation, Bone Health

Elevated RF is found in collagen vascular diseases such as SLE, rheumatoid arthritis, scleroderma, Sjogren's syndrome, and in other conditions such as leprosy, tuberculosis, syphilis, malignancy, thyroid disease and in a significant percentage of otherwise normal elderly patients.

Nutrition & Vitamins, Bone Health

Measurement of serum 25-OH vitamin D concentrations provide a good index of circulating vitamin D activity in patients not suffering from renal disease. Lower than normal 25-OH vitamin D levels can result from a dietary deficiency, poor absorption of the vitamin or impaired metabolism of the sterol in the liver. A 25-OH vitamin D deficiency can lead to bone diseases such as rickets and osteomalacia. Above normal levels can lead to hypercalcemia

Nutrition & Vitamins, Bone Health

Ionized calcium represents the true "bioavailable" calcium in the circulation. In situations where the total calcium is normal but does not fit the clinical picture, e.g. , hyperparathyroidism, a determination of the ionized calcium will, many times, show an elevation in the "bioavailable" calcium component. This may be due to alterations in protein concentrations, especially albumin, that binds most of the calcium in the circulation.

Nutrition & Vitamins, Bone Health

Measurement of serum 25-OH vitamin D concentrations provide a good index of circulating vitamin D activity in patients not suffering from renal disease. Lower than normal 25-OH vitamin D levels can result from a dietary deficiency, poor absorption of the vitamin or impaired metabolism of the sterol in the liver. A 25-OH vitamin D deficiency can lead to bone diseases such as rickets and osteomalacia. Above normal levels can lead to hypercalcemia. This assay employs liquid chromatography tandem mass spectrometry to independently measure and report the two common forms of 25-hydroxy vitamin D: 25-OH D3- the endogenous form of the vitamin and 25-OH D2- the analog form used to treat 25-OH Vitamin D3deficiency.

Autoimmune & Inflammation, Bone Health

A synthetic circular peptide containing citrulline called CCP IgG (cyclic citrullinated peptide) has been found to be better at discriminating Rheumatoid Arthritis patients from patients with other diseases such as hepatitis C infection. Rheumatoid Arthritis Classification Criteria include CCP IgG Antibody, rheumatoid factor, C-reactive protein and erythrocyte sedimentation rate (ESR). Approximately 70% of patients with Rheumatoid Arthritis are positive for Anti-CCP IgG, while only about 2% of random blood donors and disease controls subjects are positive.

Bone Health, Women's Health

NTx is useful to assess bone resorption in patients with metabolic bone disease. The test is also useful in monitoring therapy to slow or halt osteoporotic bone loss. A decline of 30% or more of NTx over a six-month period suggests effective therapy.

Nutrition & Vitamins, Bone Health

Humans get vitamin D from their normal diet, dietary supplements and from exposure to sunlight.1-5Ultraviolet B irradiation of the skin drives the conversion of 7-dehydrocholesterol to previtamin D3, which is then rapidly converted to vitamin D3.1Vitamin D from the skin and diet is further metabolized in the liver to 25-(OH) vitamin D (or calcidiol).1-5Calcidiol is the principle circulating reservoir of vitamin D in plasma and is generally the best indicator of overall vitamin D status. Calcidiol is further converted by the enzyme 25-(OH) D-1α-hydroxylase (CYP27B1) in the proximal tubules of the kidney to the biologically active form of vitamin D, 1,25-(OH)2 vitamin D (or calcitriol).1-5The renal production of calcitriol is tightly regulated by plasma parathyroid hormone (PTH)1-5and fibroblast growth factor 23 (FGF-23). FGF-23 is a circulating hormone synthesized by osteocytes and osteoblasts.5-8Calcitriol and phosphate intake stimulates the synthesis of FGF-23, which, in turn, suppresses calcitriol synthesis and activates calcitriol conversion to inactive metabolites.1-6Calcitriol is a steroid-like hormone that binds to a specific cytoplasmic vitamin D receptor (VDR) in the cytoplasm of target cells. The calcitriol-VDR complex then migrates into the nucleus, where its effects are mediated at a transcriptional level.5Renal production of calcitriol is important in the regulation of serum calcium homeostasis and in the maintenance of healthy bone.1,2,9-11Calcitriol stimulates the absorption of calcium and phosphate by the intestine and increases calcium and phosphate resorption by the kidney.1-6,12,13Calcitriol also suppresses PTH production and regulates osteoblast function and bone resorption.5It has been suggested that calcitriol has roles beyond the calcium-skeletal axis.1-5,14Vitamin D deficiency can affect the production of calcitriol owing to the lack of substrate. A positive correlation between serum levels of calcidiol and calcitriol was observed during seasonal changes. Treatment with calcidiol can normalize calcitriol concentrations in patients with vitamin D deficiency.12,15,16Calcitriol assessment may be beneficial in patients with chronic kidney failure. Diminished levels of calcitriol can be seen in patients with kidney failure due to reduced 1α-hydroxylase activity and phosphate retention resulting in increased FGF-23 levels.17,18Impaired calcitriol production plays a major role in the development of secondary hyperparathyroidism as calcitriol deficiency promotes parathyroid gland hyperplasia and increased parathyroid hormone (PTH) synthesis due to the loss of the ability to upregulate vitamin D receptor expression within parathyroid cells.19This ultimately results in elevated serum PTH and abnormal calcium and phosphorus balance.Calcitriol measurement may be of use in patients with early-onset rickets or a family history of rickets. Serum calcitriol levels can also be increased in patients with hereditary vitamin D-resistant rickets, a very rare autosomal recessive disorder in which mutations of vitamin D receptor (VDR) impair calcitriol binding to the VDR.20Patients usually present with hypocalcemia, early-onset rickets, alopecia, and other ectodermal anomalies.20Other heritable disorders associated with low calcitriol levels include vitamin D–dependent rickets type 1 (inactivating mutation in the 1-hydroxylase gene),21autosomal-dominant hypophosphatemic rickets (mutation of the gene coding for FGF-23, which prevents its breakdown),22and X-linked hypophosphatemic rickets (mutations that elevate levels of FGF-23).23Individuals treated with glucocorticoids or anticonvulsants are at risk of hypocalcemia associated with a low concentration of calcitriol. HIV protease inhibitors have been reported to markedly suppress calcitriol synthesis24,25In tumor-induced osteomalacia, tumor-secreted FGF-23 inhibits enzyme 1α-hydroxylase and subsequently results in decreased calcitriol synthesis.26Calcitriol may also be helpful in the diagnosis of parathyroid function disorders. A high serum level of calcitriol, for example, may suggest of primary hyperparathyroidism, whereas a normal or low serum level is more likely found in secondary hyperparathyroidism. Increased calcitriol levels can be seen in some individuals with lymphoproliferative disorders and granulomatous disease including, sarcoidosis, tuberculosis, and inflammatory bowel disease where increased macrophage activity is associated with extrarenal 1α-hydroxylase enzyme activity.27However, unlike the kidney, the 1α-hydroxylase activity in the macrophages is not controlled by the usual physiologic regulators.14,28

Nutrition & Vitamins, Bone Health

This test measures the bioactive form of vitamin D. It is used in the differential diagnosis of hypocalcemia and to monitor patients with renal osteodystrophy or chronic renal failure. This test is not suitable for diagnosis of vitamin D deficiency and monitoring supplementation in most patients. The 25-hydroxyvitamin D test is the recommended test for those purposes (N Engl J Med. 2007;357:266-281).

Bone Health, Women's Health

Approximately 90% of the organic matrix of mammalian bone consists of type I collagen that is cross-linked at the N-terminal and C-terminal ends.1This highly cross-linked structure provides for the basic fabric and tensile strength of bone tissue. The collagen infrastructure of bone undergoes a continuous process of remodeling that involves osteoclast-mediated bone resorption and osteoblast-mediated bone formation. Osteoporosis occurs when there is an imbalance between bone formation and bone resorption leading to net bone loss.2-5Certain aspects of this bone composition and structure that contribute to increased bone fragility may not be captured by bone mineral density measurements.5Bone resorption by osteoclasts results in the production of cross-linked N-telopeptides of type I collagen (NTx).1NTx is specific to bone and is found in urine as a stable end product of bone degradation. Levels of NTx correlate with the rate of bone resorption. Bone resorption rates exceeding bone formation results in a net loss of bone and ultimately osteopenia or osteoporosis.2-8Osteoporotic fractures are a major source of morbidity and mortality in older women.2The NTx test is intended for use in predicting skeletal response to hormonal antiresorptive therapy in postmenopausal women. The NTx test can also be used to monitor the efficacy of antiresorptive therapy7in postmenopausal women, women with osteoporosis, and individuals with Paget disease. The NTx test can also be used in monitoring the effect of estrogen-suppressing therapies on the rate of bone resorption. A recent study8supported the use of NTx to identify the probability of a decrease in bone mineral density after one year in postmenopausal women receiving a calcium supplement relative to those treated with hormonal antiresorptive therapy.Several studies have shown that certain biochemical markers of bone turnover, measured in serum or urine, can be used as independent predictors of fractures, especially spine and hip.2,6Bone mineral density (BMD) is often used to monitor the efficacy of osteoporosis treatment and to follow patient compliance. Unfortunately, changes in BMD in response to treatment are slow, and it takes at least one year of treatment before a significant change in BMD can be observed in many cases.2,7As a result, the absence of BMD increase does not necessarily indicate a lack of therapeutic response.2,7The use NTx can be helpful for assessing early changes in BMD (baseline vs post-treatment) revealing a biological effect of the medication and proving patient compliance and persistence.2,7

Liver & Kidney Health, Bone Health

When the Total Alkaline Phosphatase activity is increased, the Isoenzymes are useful in determining the source of the increased activity.

Nutrition & Vitamins, Bone Health

Measurement of serum 25-OH vitamin D concentrations provide a good index of circulating vitamin D activity in patients not suffering from renal disease. Lower than normal 25-OH vitamin D levels can result from a dietary deficiency, poor absorption of the vitamin or impaired metabolism of the sterol in the liver. A 25-OH vitamin D deficiency can lead to bone diseases such as rickets and osteomalacia. Above normal levels can lead hypercalcemia. This assay employs liquid chromatography tandem mass spectrometry to independently measure and report the two common forms of 25-hydroxy vitamin D: 25OH D3- the endogenous form of the vitamin and 25OH D2- the analog form used to treat 25OH Vitamin D3deficiency.

Bone Health, Nutrition & Vitamins

The bone-specific alkaline phosphatase (BSAP) assay provides a general index of bone formation and a specific index of total osteoblast activity. BSAP and osteocalcin are the most effective markers of bone formation and are particularly useful for monitoring bone formation therapies and antiresorptive therapies.

Autoimmune & Inflammation, Bone Health

HLA-B27 is found in 90% of patients with ankylosing spondylitis and 80% in Reiter's disease. Ankylosing spondylitis affects 1 in 1000 caucasians. Ankylosing spondylitis is 10 times more common among individuals with HLA-B27 compared to individuals without this antigen.

Bone Health, Women's Health

Offered as part of multiple lab tests

Bone Health, Women's Health

Offered as part of multiple lab tests

Bone Health

This test is used in the evaluation of genetic risk for Ankylosing Spondylitis, uveitis, and several other autoimmune disorders.

Bone Health, Women's Health

Osteocalcin, the most abundant non-collagen protein in bone matrix, is a bone-specific, calcium binding protein. Serum osteocalcin levels are related to the rate of bone turnover in various disorders of bone metabolism, e.g., osteoporosis, primary and secondary hyperparathyroidism, and Paget's disease.

Autoimmune & Inflammation, Bone Health

The combination of RF and anti-CCP antibodies provide greater specificity for the diagnosis of Rheumatoid Arthritis (RA). CCP antibodies may be present earlier than RF and often indicate increased erosive disease in RA.

Bone Health

Type I collagen, which is synthesized by fibroblasts and osteoblasts, is the most abundant collagen type in the body and the only collagen type found in mineralized bone, where it accounts for more than 90% of the organic matrix. Since bone is the major collagenous organ and metabolically highly active throughout life, the majority of the synthesized type I collagen stems from bone osteoblasts. Bone collagen is derived from a larger protein, type I procollagen, which consists of three amino acid chains that are intertwined to form a rod-like triple helix. Type I procollagen has propeptide extensions at both ends of the molecule, which are removed by specific proteinases before the collagen molecules thus formed are assembled into collagen fibers. Both propeptides can be found in the circulation, where their concentration reflects the synthesis rate of type 1 collagen. The P1NP assay measures the serum concentration of the amino-terminal propeptide of type I procollagen (P1NP).1As the concentration of this extension propeptide is directly proportional to the amount of new collagen laid down in bone, it can be used to assess bone formation. During bone formation, the bone matrix is produced before mineralization occurs; hence P1NP is an early marker of bone formation.Bone tissue is metabolically active and throughout life undergoes constant remodeling. Bone remodeling is achieved by two counteracting processes: bone formation and bone resorption, which under normal conditions are tightly coupled to each other. Metabolic bone diseases are characterized by imbalances in bone turnover and often lead to an uncoupling between bone formation and resorption.2P1NP is a byproduct produced from the bone formation (osteoblast) activity that can be measured in serum as a biomarker reflecting the rate of bone turnover.3,5An indicator of type I collagen turnover, such as P1NP, is useful for investigating skeletal remodeling under normal and abnormal conditions. P1NP has very low circadian and biological variation, is not affected by food intake, and is very stable in serum after venipuncture.6The International Osteoporosis Foundation (IOF) and International Federation of Clinical Chemistry (IFCC) has recommended serum P1NP as bone formation for use in fracture risk prediction and monitoring of osteoporosis treatment.7The National Bone Health Alliance, working in association with the American Association for Clinical Chemistry, established that the preferred bone formation marker is P1NP in clinical studies of bone turnover.8The application of P1NP as a biomarker of bone turnover in various clinical applications has been reviewed extensively.9-13The P1NP assay provides a sensitive tool for assessing increased bone turnover in postmenopausal women.14-19Unlike bone density measurements, P1NP levels can show appreciable, rapid response to changes in turnover rate, supporting its clinically use for monitoring treatment response and adherence in osteoporotic patients from the onset of treatment initiation.13P1NP has been applied for monitoring the effect of antiresorptive and anabolic therapy on bone metabolism20-43and in hormone replacement therapy.31,32,34,44,45The determination of PINP concentrations has also been used to detect increases in type I collagen turnover in disease states such as renal osteodystrophy,46primary hyperparathyroidism47and Paget’s disease of bone.48-51P1NP determination may be useful in assessing bone metastatic activity in malignancy and in predicting survival.52-54When monitoring response to osteoporosis treatment, a change of greater or equal to 21% (Reference Change Value - RCV) from baseline PINP levels (i.e., prior to the start of therapy), three to six months after initiation of therapy indicates an adequate therapeutic response.55

Bone Health

Low levels of fibrinogen are associated with bleeding most commonly secondary to liver disease or disseminated intravascular coagulation (DIC). Fibrinogen is an acute phase reactant and thus elevated levels may be associated with inflammation. Increased concentrations are also associated with increased risk of atherosclerosis.

Nutrition & Vitamins, Bone Health

The biological function of vitamin D is to maintain normal levels of calcium and phosphorus absorption. 25-Hydroxy vitamin D is the storage form of vitamin D. Vitamin D assists in maintaining bone health by facilitating calcium absorption. Vitamin D deficiency can also cause osteomalacia, which frequently affects elderly patients. Vitamin D from sunshine on the skin or from dietary intake is converted predominantly by the liver into 25-hydroxy vitamin D, which has a long half-life and is stored in the adipose tissue. The metabolically active form of vitamin D, 1,25-di-hydroxy vitamin D, which has a short life, is then synthesized in the kidney as needed from circulating 25-hydroxy vitamin D. The reference interval of greater than 30 ng/mL is a target value established by the Endocrine Society.1

Bone Health, Hormone Testing

Fibroblast growth factor 23 (FGF-23), a member of the fibroblast growth factor (FGF) family of proteins, is a phosphaturic hormone predominantly produced by bone osteocytes.2-7Plasma FGF-23 exerts its actions by binding to the FGF receptors on cell membranes. Effective FGF-23 binding to these cell surface receptors requires that the cell membrane also contain the transmembrane protein, Klotho.2,8-11FGF-23 inhibits phosphate reabsorption by suppressing Na/Pi cotransporter activity in the proximal convoluted tubule of the kidney. In addition, FGF-23 suppresses intestinal phosphate absorption by inhibiting 1-α-hydroxylase, the enzyme responsible for the conversion of calcifediol to calcitriol, the biologically active form of vitamin D.2-4FGF-23 also possibly inhibits parathyroid hormone (PTH) synthesis and secretion.1-9In healthy individuals, low levels of FGF-23 are detected in the circulation, and FGF-23 secretion rises with increased phosphorus intake and increased calcitriol levels.12Elevated plasma FGF-23 activity has been associated with several hypophosphatemic diseases characterized by impaired renal phosphate reabsorption and rickets/osteomalacia.5,6,9Mutations in FGF-23 that render the protein resistant to proteolytic cleavage lead to increased FGF-23 activity and the renal phosphate loss found in autosomal-dominant hypophosphatemic rickets (ADHR). X-linked hypophosphatemic rickets (XLH)5,6,9and autosomal-recessive hypophosphatemic rickets (ARHR) are due to mutations in PHEX and dentin matrix protein 1, respectively. Both disorders are characterized by overproduction of FGF-23 by bone osteocytes. In tumor-induced osteomalacia (TIO), an acquired disorder of renal phosphate wasting associated with tumors, typically of mesenchymal origin; phosphatonins produced by the tumor promote renal phosphate wasting. FGF-23 is the most common phosphatonin found in patients with TIO.5Patients with TIO share similar biochemical and skeletal phenotypes with patients who have ADHR, ARHR, and XLH.5FGF-23 levels increase dramatically as renal function declines in chronic kidney disease (CKD) as the body attempts to overcome persistent phosphate retention.2,4FGF-23 elevation is thought to play a role in causing the disordered bone and mineral metabolism seen in CKD patients.2,4FGF-23 levels increase in parallel with the decline in renal function well before a significant increase in serum phosphate concentration or PTH occur.2,4Increased FGF-23 levels lead to reduced renal production of 1,25-dihydroxyvitamin D and to hypersecretion of parathyroid hormone.3Prospective studies have demonstrated that elevated FGF-23 levels predict faster disease progression in CKD patients not on dialysis and increased mortality in patients undergoing maintenance hemodialysis and patients with renal transplants.2,13FGF-23 may predict future development of refractory hyperparathyroidism and cardiovascular events in CKD patients3,14and is thought to play a central role in the pathogenesis of post-transplant hypophosphatemia in kidney transplant recipients.3

Autoimmune & Inflammation, Bone Health

Offered as part of multiple lab tests

Genetic Testing, Bone Health

Offered as part of multiple lab tests