INTENDED
USE
The Ostase BAP Immunoenzymetric Assay
is an in vitro device indicated for the quantitative measurement of
bone-specific alkaline phosphatase (BAP), an indicator of osteoblastic activity,
in human serum. This device is intended to be used as an aid in the management
of postmenopausal osteoporosis and Paget’s
disease.
SUMMARY AND
EXPLANATION
Bone is a dynamic tissue in which bone
formation and bone removal (also referred to as resorption) continue throughout
life in a process called remodeling. The remodeling process is a function of
complex interactions between two types of bone cells: osteoblasts for the
formation of bone, and osteoclasts for the resorption of bone. Bone formation
and resorption are interdependent processes that are, under normal
circumstances, tightly coupled. This coupled relationship is integral to
maintaining the biochemical competence of the skeleton, thereby preserving the
organization of bone structure, form, and
strength.
Serum levels of BAP are believed to
reflect the metabolic status of osteoblasts. An accurate assessment of bone
metabolism is critical for determining the severity of metabolic bone disease
and responses to therapy. Measurement of serum levels of BAP has been shown to
be useful in evaluating patients with Paget’s disease, osteomalacia, primary
hyperparathyroidism, renal osteodystrophy, osteoporosis and metastases to bone.
Total alkaline phosphatase determinations have been the accepted method for the
diagnosis and monitoring of patients with Paget’s
disease.
Paget’s disease of bone is a common
skeletal disorder in which there is a focal proliferation of the normal cellular
components of bone. Paget’s disease is more prevalent than once thought with the
incidence rate in certain populations at 3%-4% in middle-aged patients and
10%-15% in the elderly . This disease does not affect young individuals. The
majority of patients with Paget’s disease have no symptoms and often go
undiagnosed unless an abnormal X-ray or serum alkaline phosphatase level is
found in the course of a medical evaluation for unrelated reasons. The most
common complaints in symptomatic patients are pain and
deformity.
The risk of osteoporosis, another bone
remodeling disorder, depends in part upon skeletal development,the attainment of
peak bone mass, and in later life, the amount of bone lost. In healthy
children,bone formation is favored over bone resorption, which results in bone
development and normal skeletal growth. In healthy young adults, bone formation
and bone resorption are balanced, resulting in no net increase or decrease in
skeletal mass. With advancing age, men and women experience an imbalance in bone
remodeling in which resorption is slightly greater than formation, resulting in
a continuous net loss of bone mass with time. If this imbalance persists, bone
mass may decline until the skeleton is insufficient to withstand normal
mechanical stresses, and it becomes abnormally susceptible to fractures. The
excessive loss of bone mass with an increased susceptibility to fractures is a
disorder known as osteoporosis.
The most common form of osteoporosis
occurs in postmenopausal women and is the result of
estrogen
deficiency. Rapid bone loss accompanies
the decline of estrogen levels at the onset of menopause or as a result of
surgical removal of the ovaries. Rapid bone loss occurs as a result of the
combined effects of an imbalance in bone remodeling and an increase in bone
turnover. In the
Hormone replacement therapy is
currently the most widely prescribed therapy for the prevention of osteoporotic
fractures in postmenopausal women. However many women cannot, or will not,avail
themselves of hormone replacement therapy because of the potential for the
increased risk of cancer and the resumption of menstrual bleeding. For this
reason, other compounds such as bisphosphonates,a standard treatment for Paget’s
disease of bone, have been developed to treat osteoporosis. The antiresorptive
properties of bisphosphonates decrease bone remodeling and, consequently,
decrease the overall loss of bone.
Biochemical markers are useful in
monitoring metabolic bone disease. Urinary hydroxyproline and total serum
alkaline phosphatase have been used for monitoring the treatment of Paget’s
disease.Osteoporosis, however, represents a more subtle modification of the bone
remodeling process; therefore,more specific and sensitive markers are
needed.
The Ostase BAP assay is an in vitro
device for the quantitative measurement of bone-specific alkaline phosphatase
(BAP) in human serum. Changes in BAP have been shown to be useful in patients
undergoing therapy for metabolic bone
disorders.
PRINCIPLES OF THE
PROCEDURE
The Ostase BAP assay is a solid phase,
monoclonal antibody immunoenzymetric assay. Samples containing BAP are reacted
with a solution containing a biotin-labeled, BAP-specific monoclonal
antibody.The reaction takes place in plastic well strips (solid phase) coated
with streptavidin and enclosed in a plastic frame. Following the formation of a
solid phase/capture antibody/BAP complex, the microplate is washed to remove
unbound BAP and is then incubated with an enzyme substrate. The amount of
substrate turnover is determined colorimetrically by measuring the absorbance of
the quenched reaction at 405 nm in a microplate reader. The absorbance is
proportional to the concentration of BAP present in the test sample. The
calculation of BAP concentration in the sample is based on concurrent testing of
BAP calibrators and Zero Calibrator/Diluent.