Introduction:
The most prevalent metabolic bone illness, osteoporosis, is characterized by a structural breakdown of bone structure that increases the risk of fracture. It is a significant public health issue for the elderly and is predicted to worsen as people live longer.
One in two Indian women over 50 and one in five Indian males over 65 are in danger of developing osteoporosis, making India one of the top nations impacted by the disease. Since osteoporosis is frequently a silent disease, it may manifest as a terrifying complication like a hip fracture, related to increased morbidity and four times the death rate in the senior population.
Throughout a person's lifetime, the tissue of the bone is constantly being remodeled. Bone remodeling occurs continuously as a result of the constant coupling of bone resorption and creation at different rates. The kinetics of bone resorption in several metabolic bone illnesses can be gained from research on bone resorption markers.
Despite low bone mineral density (BMD), the degeneration of bone microarchitecture brought on by aging and pathological conditions such as osteoporosis causes a rise in the risk of fracture. BTMs (bone turnover marker or bone resorption marker) complement BMD in evaluating fracture risk since they can measure these microarchitectural changes impacting bone quality. For the treatment of osteoporosis, numerous trustworthy, quick, and affordable automated tests of BTMs with high sensitivity are available.
What Physiological Basis Exists for the Bone Resorption Marker?
As a metabolically active structure, the bone changes continuously over the course of a person's lifetime. The fundamental multicellular unit of bone, known as the "bone remodeling unit" is the first multicellular unit that begins sequential development after reaching peak bone mass. BTMs are a variety of macromolecules that are released into the bloodstream during bone growth and resorption. Bone resorption occurs in roughly ten days under ideal physiological conditions, and bone creation takes about three months. Every year, remodeling may replace up to 20 % of the skeleton.
What Are Bone Markers, and What Are the Types?
Chemicals created during the remodeling of bone can be identified in the blood and urine and serve as a marker.
In the metabolic phase in which they are formed, the BTMs are divided into two types as follows:
- Markers for bone formation.
- Markers of bone resorption.
To assess fracture risk and track treatment in clinical settings, the International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry and Laboratory Medicine have suggested using serum CTX-1 (sCTX) and serum P1NP, respectively, as reference markers of bone resorption and formation.
What Are the Markers of Bone Formation?
During various stages of bone growth, active osteoblasts produce markers of bone formation, which are thought to reflect various facets of osteoblast function and bone formation. Serum or plasma is used to measure all bone-formation markers.
Bone formation indicators can be divided into:
- By-products of collagen synthesis include type 1 collagen propeptides (C-terminal: P1CP, N-terminal: P1NP)
- Alkaline phosphatase (ALP), an osteoblast enzyme (total and bone-specific)
- Osteocalcin is a protein in a matrix (OC).
What Are the Markers of Bone Resorption?
By-products of osteoclast activity generated during bone resorption are among the indicators that are formed during the bone resorption process of bone remodeling.
Following are the several types of bone resorption markers:
Collagen Breakdown Products:
- Teopeptides of type 1 cola (C-terminal: CTX-1 and CTX-matrix. Metalloproteinases [MMP], N-terminal: NTX-1).
- Hydroxyproline.
- Crosslinks between Pyridium (pyridinoline [PYD], deoxypyridinoline [DPD]).
Non-Collagenous Proteins:
- Bone sialyl protein.
Osteoclast-Forming Enzymes:
- Acid phosphatase that can withstand tartrates.
- A cathepsin K.
Indicators of Osteoclast Activity:
- Ligand for the nuclear factor kappa-B receptor (RANKL).
- Osteoprotegerin (OPG) (OPG).
- Dickkopf-associated protein 1.
- Sclerostin.
How Are Bone Markers Used to Determine Fracture Risk?
In postmenopausal women, increased BTMs may predict osteoporotic fracture risk independently of BMD. In addition to poor BMD, increasing bone resorption causes the bone microarchitecture to deteriorate, increasing the fracture risk. BTMs can measure this microarchitectural change that affects bone quality, making them a helpful complement to BMD, which can only measure bone mass for determining fracture risk. As newly generated bone may be a less mineralized and post-translational modification, such as decreasing beta crosslinks and beta isomerization of type 1 collagen, may be reduced, increased BTMs are a sign of loss in the structural integrity of bone.
What Function Does a Bone Marker Have In Monitoring the Treatment of Osteoporosis?
BTMs aid in improving therapy by providing pharmacodynamic data on an individual's treatment response to osteoporosis medication and information on ongoing bone remodeling. They are most helpful in assessing a patient's adherence to medication in chronic, asymptomatic conditions like osteoporosis, when medication adherence can be a big problem.
Monitoring treatment compliance and adherence is a highly practical application of BTMs, particularly for bone resorption inhibitors. Oral medication adherence is notoriously poor and is one of the most significant challenges to reducing the risk of fractures in the elderly. This is especially true for oral bisphosphonates, which must be taken according to a strict dosing regimen.
The emergence of weekly and monthly oral formulations has slightly better adherence or persistence. Thus, BTMs could be useful in identifying a less-than-expected suppression of bone turnover with a given treatment, which could indicate either persistence failure (i.e., the patient has discontinued treatment) or a patient who has not been fully compliant with the drug dosing regimen. As a result, BTMs could be used to monitor biological efficacy or adherence to treatment. However, this would imply that BTMs be calculated before the start of treatment and during subsequent follow-up.
What Are the Barriers to the Bone Resorption Marker?
-
Variability in pre and post-analysis.
-
Inadequate understanding of the sources of variability in each BTM.
-
Assays for BTMs are not standardized.
-
BTM ethnic variations and the absence of ethnicity-based recommended limits for each population.
-
Data on the response of various BTMs to different osteoporosis treatments and comparisons between them are unavailable.
Conclusion:
BTMs are powerful components for osteoporosis management that are gaining attraction in clinical practice around the world. The most useful feature of BTMs is estimating the risk of fracture based on bone remodeling rates and monitoring adherence and treatment response. BTMs have been identified as an independent contributor to fracture risk in extensive epidemiologic studies. Understanding biological variations and the availability of trusted, rapid, cost-effective, and standardized BTMs immunoassay may aid in better use of BTMS in monitoring osteoporosis.
