Ctx physician brochureSerum C-terminal telopeptide (CTX) A new test for monitoring bone health What is CTX?
CTX is a bone turnover marker (BTM) for monitoring osteoporosis drugs such as denosumab or the bisphosphonates.
On a biochemical level, it is the polypeptide chain linking the three strands of type I collagen at their C-terminus.
The CTX test was developed in the mid-90s and since that time has become the most commonly used serum- or urine-based biomarker for osteoporosis research and clinical drug trials.
What are the applications of this test?
Monitoring osteoporosis patients for compliance with treatment and identifying the presence of
medical conditions that diminish the effectiveness of drug therapy.
Compliance rates for bisphosphonates in general practice are very poor, with 50-75% of patients discontinuing therapy within the first year2,3 and experiencing a significantly increased fracture risk (45% in one study).
A CTX test can not only enhance patient motivation to adhere to therapy but provide objective evidence of a patient's compliance with orally administered medication.
DEXA also offers this information but it will not be available to the physician for nearly two years due to bones slow rate of microarchitectural change.
CTX, by contrast, can provide the answers within weeks.
An independent predictor of fracture risk.
Current BC guidelines for DEXA testing severely restrict its use for a patient 65y who is concerned about their risk of a non-traumatic (i.e.potentially preventable) fracture.
In the absence of co-morbidities or a previous fracture, such a patient is unable to properly inform themselves about their likely risk.
The absence of a BMD measurement, in turn, diminishes the value of risk prediction tools such as FRAX6.
It is this vacant diagnostic space which the CTX test is intended to occupy.
Note that BTMs are not included in FRAX because of insufficient data rather than a clear demonstration of no added value.
It is important to realize that CTX does not replace DEXA or any other diagnostic tool.
Rather, it is meant to provide complementary information about the entire skeleton, as indicated by the graph below:What is the value of measuring CTX to monitor response to bisphosphonates when the clinical trials literature shows such a consistent effect?
Cohorts from the clinical trials literature differ markedly from patients seen in regular practice, making the transferability of the studies conclusions questionable.
One osteoporosis clinic found that the vast majority (80-97%) of its new patients, diagnosed with osteoporosis, would not have been eligible for one of its clinical trials, mainly on the grounds of co-morbidities, age and disease severity.
Moreover, the 80% compliance rates in such trials greatly exceed those encountered by the general practitioner.1 Low hip BMD
-2.5) Elevated CTX Low hip BMD andelevated CTX
2 4 5 0 3 Hip fracture risk (OR) in women 75y (Ref.7)How is LifeLabs serum CTX better than existing bone marker tests?
The serum CTX test provides a more reliable assessment of overall bone resorption by overcoming the limitations of the current urine deoxypyridinoline cross links test, such as high within-patient variability and unreliability in the presence of renal impairment.
Moreover, having this MSP-unlisted test performed locally at LifeLabs provides significant savings to the patient.
Many patients with newly-diagnosed osteoporosis present with a recent fracture.
How will this affect the utility of CTX?
Serum CTX will be elevated for one year following a fracture.
However, levels will not rise significantly within 1 day of the fracture10.
A blood sample collected within this period could still be used to establish a baseline for subsequent investigations.
What is the value of measuring CTX for BRONJ risk?
Serum CTX has been promoted by some11,12 but not all13,14 dental surgeons as a risk marker for bisphosphonate-related osteonecrosis of the jaws (BRONJ).
There is no official position on this matter by either Canadian or American dental associations.
The test is not intended to unambiguously identify patients who will acquire BRONJ following oral surgery: rather, CTX 0.15 ng/mL in a patient on bisphosphonate therapy (especially intravenous) is associated with an increased risk of BRONJ.
In such cases, it has been suggested that the drug be discontinued prior to surgery15.
Can CTX be used to evaluate the risk of subtrochanteric fracture?
No; while there is good evidence from histomorphometric and tetracycline labeling studies suggesting excessive suppression of bone turnover in such fractures, BTM results have been unable to support these findings16,17.
However, this is almost certainly due to samples having been collected well after the initial fracture at a time when bone turnover was increased (see above).Biological and analytical variation have been said to limit the usefulness of bone turnover markers.
How has LifeLabs addressed these issues?
All samples are collected under standardized conditions (e.g.fasting, AM, avoidance of strenuous exercise, stable diet).
For a given patient, the baseline sample is stored until the follow-up sample is collected at 3 months, whereupon both are processed together in a single batch.
This feature eliminates the inherent between-run variability of tests such as urine cross-links and differentiates LifeLabs CTX test from those offered elsewhere.
Rosenquist C et al.(1998) Serum CrossLaps one step ELISA.
Clin.Chem.44 2281.2.Rabenda V et al.
(2008) Adherence to bisphosphonate therapy and hip fracture risk in osteoporotic women.Osteoporosis Int.19 811.3.Weycker D et al.
Ctx patient brochureWhat is osteoporosis? Osteoporosis is a signi cant reduction in bone mass due to loss of proteins and minerals such as calcium.It is often due to aging but can also result from medications, hormonal imbalance,
ciency and other disorders.The consequence of low bone mass is an increased risk of bone fracture.
How widespread is osteoporosis? In menopausal women over the age of 50, 80% of all fractures are due to osteoporosis and related disorders.
Yet, fewer than 20% of women receive therapy to prevent further fractures.How can my physician check my bone health? A basic clinical history is the
rst step according to the most recent osteoporosis guidelines published by the Canadian Medical Association (Oct.12, 2010).Following a clinical history, your physician may request a test for bone mineral density (BMD) as well as blood tests such as those for calcium, thyroid hormones and vitamin D.If you are at increased risk of fracture, a bone turnover marker should be considered.
What is bone turnover? Bone is a dynamic tissue: your skeleton is constantly being broken down and rebuilt.In fact, its been estimated that your skeleton is completely replaced every 1015 years.Bone turnover re ects the relative rates of bone formation and bone degradation.
This process is know as resorption.An imbalance of these two processes may lead to osteoporosis.What is the CTX test? The CTX test measures the amount of degraded bone circulating in the bloodstream.
Speci cally, protein component of bone.
This is the most established test of bone resorption, used in clinical trials of osteoporosis drugs such as Fosamax, Actonel and ProliaHow does CTX differ from BMD? a) Rate vs quantity Think of BMD as the location of a moving car and CTX as its speed and direction.One test tells you where you are; the other tells you where youre going and how fast
Serum C-terminal Telopeptide (ctx) - Lifelabs Medical Laboratory ...
Serum C-terminal telopeptide (CTX) A new test for monitoring bone health What is CTX? CTX is a bone turnover marker (BTM) for monitoring osteoporosis drugs such as ... (lifelabs.com)
What Is Osteoporosis? What Is The Ctx Test? What Will I Learn …
What is osteoporosis? Osteoporosis is a signiﬁ cant reduction in bone mass due to loss of proteins and minerals such as calcium. It is often due to aging but can also (lifelabs.com)
Oral Bisphosphonate-induced Osteonecrosis: Risk Factors ...
osteoporosis as well as the go,lls and treatment chal ... roid use or chemotherapy use, a CTX test is highly recommended. If the ; crx ; test is returned with a (usdentalimplant.com)
b) Faster response While a low BMD is the accepted de nition of osteoporosis, it takes about two years for medical intervention to produce a noticeable BMD change.By contrast, a clinically signi cant change in CTX will be seen within a few weeks.
This ability to provide more immediate feedback can help guide treatment plans.c) Evaluation of complete skeleton Fractures can affect any bone in the body, but BMD is measured at only a few speci c locations.CTX, by contrast, evaluates the rate of bone resorption from the skeleton as a whole.What will I learn from this test?
If you are osteoporosis, an increased level of CTX may indicate a higher risk of bone fracture even if your BMD is not in the level associated with osteoporosis.Only one sample is needed.
If you are about to start osteoporosis medications, a 3555% drop in CTX from the initial (baseline) sample to the follow-up sample at 3 months indicates the drugs are working and likely to improve your BMD as expected.
Two samples are needed.If you are already taking osteoporosis medications, CTX may be helpful if you are considering oral surgery and are concerned about your risk of bisphosphonate-related osteonecrosis of the jaws (BRONJ), a rare but serious side-effect linked to these drugs.CTX values lower than 0.15 ng/mL have been associated with increased risk of BRONJ, though the absolute risk remains very low and most patients with these low CTX values will not experience any complications.Only one What is the view of the Canadian Medical Association (CMA)?
cally recommending the use of CTX and related bone turnover markers for monitoring osteoporosis, the CMA states that increased values for bone turnover markers are associated with an approximately two-fold increased risk of fractures, which is largely independent of bone mineral densitymarkers of bone resorption and bone formation may help to assess and assign fracture risk and to monitor the effects of osteoporosis therapy.Osteoporosis & Bone Turnover Osteoporosis & Bone Turnover A Test to Determine Risk of Bone Fracture and How Your Medications are Affecting Your Bone HealthLifeLabs offers C-telopeptide (CTX), a new test to help in the management of Osteoporosis and bone health.Ask your doctor if it is right for you.How do I get tested? Visit your physician.
If CTX is right for you your physician will give you a standard requisition with CTX or C Terminal Telopeptide written in the section labeled Additional Tests.Take this to any of LifeLabs 83 patient service centers where your baseline blood sample will be collected.
If applicable, you will also be given a notice to return for your second sample in 34 months.If you require 2 samples, your
nal test results will be prepared after you have provided the Is there a charge for the test? Yes, you will be charged $65 for a single sample or $130 for a baseline and follow-up test.Payment must be made before any samples are collected.How do I pay for the service? Payment may be made by Visa, MasterCard, debit, cash or cheque.
The fee must be paid before any sample is collected.
Can I get reimbursed by my insurer? Possibly.All plans are different.Check with your extended healthcare provider to see if a test for measuring bone loss is covered by your plan.
How do I get my results and how long will it take? There are two ways to get your results.
You can make an appointment to discuss your results with your physician (recommended), or you can visit www.myehealth.ca and sign up for electronic lab results.LifeLabs has over 50 years experience serving the healthcare needs of Canadians.Our laboratory testing services help physicians and other healthcare providers in the prevention, diagnosis, treatment and monitoring of disease and illness in patients.
Our tests help to: Determine health risks and preventative steps; Diagnose and detect the onset of disease; Identify suitable treatments and reactions; and Monitor and adjust treatments as required.
Oralbis inducedosteoBASIC AND PATIENT-ORIENTED RESEARCH Oral Bisphosphonate-Induced Osteonecrosis: Risk Factors, Prediction of Risk Using Serum CTX Testing, Prevention, and Treatment Robert E.Marx, DDS, *Joseph E.Cillo, Jr, DDS,f and Juan J Ulloa, DDS! Purpose: To assess the risk and time course of oral bisphosphonate-induced osteonecrosis of the jaws.
Materials and Methods: Detailed data from 30 consecutive cases were compared with 116 cases due to intravenous aminobispbosphonates.
Results: Results in part noted a higher incidence related to alendronate (Fosamax; Merck, Whitehouse Station, N]), a 94.7'X, predilection for the posterior mandible, and a 50% occurrence spontaneously, with the remaining 50% resulting from an oral surgical procedure, mostly tooth removals..Just over 53% of patients were taking their oral bisphosphonate for osteopenia, 33.3% for documented osteoporosis, and 13.4% for steroid-induced osteoporosis related to 4 or more years of prednisone therapy for an autoimmune condition.There was a direct exponential relationship between the size of the exposed bone and the duration of oral bisphosphonate use.There was also a direct correlation between reports of pain and clinical evidence of infection.The morning fasting serum C-terminal telopeptide (CTX) test results were observed to correlate to the duration of oral bisphosphonate use and could indicate a recovery of bone remodeling with increased values if the oral bisphosphonate was discontinued.
A stratification of relative risk was seen as CTX values less than 100 pg/mL representing high risk, CTX values between 100 pg/mL and 150 pg/mL representing moderate risk, and CTX values above 150 pg/mL representing minimal risk.The CTX values were noted to increase between 25.9 pg/mL to 26.4 pg/mL for each month of a drug holiday indicating a rccovery of bone remodeling and a guideline as to when oral surgical procedures can be accomplished with the least risk.In addition, drug holidays associated with CTX values rising above the 150 pg/mL threshold were observed to correlate to either spontaneous bone healing or a completc healing response after an office-based debridement procedure.
Conclusions: Oral bisphosphonate-induced osteonecrosis is a rare but real entity that is less frequent, less severe, more predictable, and more responsive to treatment than intravenous bisphosphonateinduced osteonecrosis.The morning fasting serum C-tenninal telopeptide bone suppression marker is a useful tool for the clinician to assess risks and guide treatment decisions.
2007 American Association of Oral and Maxil/ofacial SU1geons ] Oral
Swg 6'5:2397-2410, 2007 Physicians and dentists are now keenly aware of Oral nitrogen-containing bisphosphonates alendrohisphosphonatc-induced osteonecrosis of the jaws nate (Fosamax; Merck, Whitehouse Station, NJ) and from the intravenous nitrogen-containing bisphosresidronate (Actone!; Procter anel Gamble Pharmaceuphonates pamidronate (Aredia; Novartis, East ticals, Cincinnati, OH) (and possibly more recently Hanover, N.J) and zoledronate (Zometa; Novartis).introduced bisphosphonates such as ibandronate Prof:ssor of SlJl'gery and (:hid.Division of and Maxillofacial Address correspondence and reprint requests to Dr ,\'Iarx: Surgery, University of Miami :'Uller School of Medicine.
!\-tiami, FL.Division of Oral and Maxillofacial Surgery.University of Miami tAm.:nding Surgeon.Oral and Maxillol:'cial Surgery, Alkghany Miller School of YkdiciJle, 93HO SW I '50th St, Suite 190.
(;eneral Hospital.Pittsburgh.Pt\, 331 '57; e-mail: firstname.lastname@example.org :j:Fello\V in TUl110r ano Ikconstructin' Surgery, Division of Oral ,) 2007 "\mellc n A:.wclt,IIOn cI O,a1
!v\oxiliol clol S"'9"';)"' and Maxillofacial Surgery.
University of Miami :''1i.llcr Sehool oi 027 2391/07/6:-' 2-0002$32.00/0 Meoicine, -"Hami.FI..JOi lO rOI6/1.;oms.2007 08 '103 2397.