Diagnosis of Acute or Subacute Avascular Necrosis


Indication Overview

Avascular necrosis (AVN) is also known as osteonecrosis, aseptic necrosis, and ischemic necrosis.1,2 AVN is a sequela of hypoxic (i.e., lack of oxygen delivery or uptake) ischemic cell death.2 AVN can be roughly divided by etiologies, and the most common causes are post-traumatic (most commonly, the femoral head of hip, the humeral head of the upper arm, and the small bones of the wrist — i.e., scaphoid — and ankle — i.e., talus), spontaneous or idiopathic, drug- (steroid) or excessive alcohol consumption–induced, and metabolic/genetic (e.g., sickle cell anemia, Gaucher disease).3 Although spontaneous or traumatic AVN can affect populations spanning from adolescents to the elderly, the underlying trauma or specific pattern of bone involvement does vary with age.2 The most common complaint of patients with AVN is pain that eventually leads to a decrease in range of motion.4

Population: Patients with suspected acute or subacute AVN.

Intervention: Bone scanning (bone scintigraphy) using technetium-99m–labelled methylene diphosphonate (99mTc-MDP).

As with nuclear bone imaging for other indications, the radioisotope-labelled MDP is injected intravenously, and there is increased uptake of 99mTc where there is increased bone turnover or remodelling.1,5 Early-phase AVN is characterized by decreased uptake of radiotracer, producing a "cold area" on the scan.6 Once the reparative process begins, there is increased radiotracer uptake in the area surrounding the cold spot, a pattern commonly referred to as the "donut sign."6 Bone scanning is useful for early diagnosis and follow-up of osteonecrosis.6

Single-photon emission computer tomography (SPECT) is a more advanced imaging technique, again requiring a radioactive tracer (99mTc-MDP) and a gamma camera. With SPECT, a computer constructs detailed two- or three-dimensional images of areas inside the body where the radiotracer is taken up by the cells.7 SPECT/CT hybrid technology, introduced in 1999, provides the functional information of a nuclear scan, and the anatomical detail of CT increases the specificity of bone scans by providing more discrete anatomic localization of identified radioactive tracer abnormalities.7

Comparators: For this report, magnetic resonance imaging (MRI) is considered to be the only alternative to 99mTc-MDP.

Outcomes: Eleven outcomes (referred to as criteria) are considered in this report:

  • Criterion 1: Size of the affected population
  • Criterion 2: Timeliness and urgency of test results in planning patient management
  • Criterion 3: Impact of not performing a diagnostic imaging test on mortality related to the underlying condition
  • Criterion 4: Impact of not performing a diagnostic imaging test on morbidity or quality of life related to the underlying condition
  • Criterion 5: Relative impact on health disparities
  • Criterion 6: Relative acceptability of the test to patients
  • Criterion 7: Relative diagnostic accuracy of the test
  • Criterion 8: Relative risks associated with the test
  • 9. Relative availability of personnel with expertise and experience required for the test
  • 10. Accessibility of alternative tests (equipment and wait times)
  • 11. Relative cost of the test.

Definitions of the criteria are in Appendix 1.

Methods

The literature search was performed by an information specialist using a peer-reviewed search strategy.

Published literature was identified by searching the following bibliographic databases: MEDLINE with In-Process records and daily updates via Ovid; The Cochrane Library via Ovid; and PubMed. The search strategy consisted of both controlled vocabulary, such as the National Library of Medicine's MeSH (Medical Subject Headings), and keywords. The main search concepts were radionuclide imaging and avascular necrosis.

Methodological filters were applied to limit retrieval to health technology assessments, systematic reviews, meta-analyses, randomized controlled trials, non-randomized studies, and diagnostic accuracy studies. No human limits were applied for systematic reviews. For primary studies, human limits were applied. The search was also limited to English language documents. No date limits were applied. Regular alerts were established to update the search until October 2011. See Appendix 2 for the detailed search strategies.

Grey literature (literature that is not commercially published) was identified by searching relevant sections of the CADTH Grey Matters checklist. Google was used to search for additional web-based materials. The searches were supplemented by reviewing the bibliographies of key papers. See Appendix 2 for more information on the grey literature search strategy.

Targeted searches were done as required for the criteria, using the aforementioned databases and Internet search engines. When no literature was identified that addressed specific criteria, experts were consulted.

Search Results

The literature search identified 15 meta-analyses (MA) or systematic reviews (SR) or health technology assessments (HTAs), 18 clinical practice guidelines (CPGs), and 771 primary studies. Three of the MA/SR/HTAs, four CPGs, and 65 primary studies were reviewed in full text. Articles that were excluded based on abstract only did not address diagnostic imaging as it relates to the diagnosis of acute or subacute AVN.

Two of the SRs addressed issues beyond the scope of this report: methods of treatment for concurrent ipsilateral fractures of the hip and femoral shaft8 and screening methods to identify newborns at risk for developmental dysplasia of the hip (DDH).9 The third article, indexed as a SR, was in fact a primary study characterizing bisphosphonate-related osteonecrosis of the jaw (BRONJ) among patients receiving intravenous bisphosphonates and examining bone scanning findings that preceded manifestations of frank osteonecrosis of the jaw (ONJ).10 The four CPGs identified in the database search were published in 2008 and 2009 and addressed BRONJ from a Canadian perspective.11-14 The grey literature search identified a number of guidelines not found in the database search, including those by the American College of Radiology (ACR),15 College of Physicians and Surgeons of Ontario (CPSO),16-19 and the Canadian Protective Chiropractic Association and l'Université du Quebec à Trois-Rivières.20 The ACR Appropriateness Criteria for AVN of the hip can be found in Appendix 3.

Summary table

Table 1: Summary of Criterion Evidence

Domain 1: Criteria Related to the Underlying Health Condition
Criterion Synthesized Information
1 Size of the affected population AVN has been described as a relatively common disease,15,21 but an estimate as to the number of Canadians affected by this affliction has not been found. According to the American Academy of Orthopedic Surgeons, the annual incidence of AVN in the US is estimated at 10,000 to 20,000 (3.26-6.51/100,000).22 A Japanese prognostic study reported that 11,400 patients sought medical care for idiopathic ONFH in 2004 (8.9/100,000).23

Assuming the incidence rate in Canada is similar to that in the US and Japan, this corresponds to more than 1 in 10,000 (0.01%), and less than 1 in 1,000 (0.1%).
2 Timeliness and urgency of test results in planning patient management According to the Saskatchewan Ministry of Health urgency classifications, MRI, a comparator of 99mTc-based bone imaging, should be completed within 2 to 7 days for patients with suspected AVN.24 Early diagnosis and treatment increases the likelihood of joint preservation.25 Imaging results have a moderate impact on the management of the condition or the effective use of health care resources.
3 Impact of not performing a diagnostic imaging test on mortality related to the underlying condition The diagnosis of AVN does not affect patient life expectancy.25 The consequences of not performing imaging tests should have no impact on mortality.
4 Impact of not performing a diagnostic imaging test on morbidity or quality of life related to the underlying condition Delayed diagnosis of AVN can have a serious impact on a patient's quality of life.26 Once radiographic changes occur (stage II), most joints will collapse within 6 to 24 months, if untreated.27 At stage IV, the changes are irreversible.28 Replacement of the femoral head may be considered at stage IV, and by stage V, total hip replacement is required.28 The diagnostic imaging test results can have a moderate impact on morbidity or quality of life.

 

Domain 2: Criteria Comparing 99mTc with an Alternative or Comparing Between Clinical Uses
Criterion Synthesized Information
5 Relative impact on health disparities To be scored locally.
6 Relative acceptability of the test to patients Bone scanning
Patients may have concerns about radiation exposure and the intravenous injection of radiopharmaceutical agent.

MRI
Because of the closed space of an MRI, patients may experience feelings of claustrophobia, as well as be bothered by the noise This may be less of a problem with new MRI machines, if available (MIIMAC expert opinion). It has been reported that up to 30% of patients experience apprehension and 5% to 10% endure some severe psychological distress, panic, or claustrophobia.29,30 Some patients may have difficulty remaining still during the scan. Patients are not exposed to radiation during an MRI scan, which may be more acceptable to some.

Overall, bone scanning with 99mTc-radiolabelled tracers is minimally less acceptable than MRI.
7 Relative diagnostic accuracy of the test In some American centres, MRI has largely replaced radionuclide bone scanning because of its greater sensitivity (up to 100%).15 The generalizability of this finding to Canadian centres is uncertain.

Based on the available evidence, the diagnostic accuracy of bone scanning with 99mTc-radiolabelled tracers is minimally lower than that of MRI.
8 Relative risks associated with the test

Non–radiation-related Risks

Several studies31-34 reported mild adverse events with 99mTc-labelled tracers (e.g., skin reactions).

MRI is often used in conjunction with the contrast agent Gd. Some patients may experience an allergic reaction to the contrast agent (if required), which may worsen with repeated exposure.35 Side effects of Gd include headaches, nausea, and metallic taste. The frequency of severe, life-threatening reactions with Gd is extremely rare (0.001% to 0.01%), and the range in frequency of moderate reactions is also rare (0.004% to 0.7%).36

Radiation-related Risks

Among the modalities to diagnose AVN, bone scanning exposes the patient to ionizing radiation. The average effective dose of radiation delivered with each of these procedures is tabulated.

Effective Doses of Radiation
Procedure Average effective dose (mSv)
Bone scan 4.5-6.337-39
MRI 0
Average background dose of radiation per year 1-3.040-42

In general, bone scanning may be minimally less safe than MRI.

9 Relative availability of personnel with expertise and experience required for the test As of 2006 in Canada, there were 2,034 diagnostic radiologists; 221 nuclear medicine physicians; 12,255 radiological technologists (MRTs); and 1,781 nuclear medicine technologists available across Canada. Yukon, Northwest Territories, and Nunavut do not have the available personnel to perform and interpret tests to image avascular necrosis.

Assuming the necessary equipment is available, it is estimated that 75% to 94% of procedures could be performed in a timely manner using MRI.
10 Accessibility of alternative tests (equipment and wait times) For bone scintigraphy, nuclear medicine facilities with gamma cameras (including SPECT) are required. No nuclear medicine cameras are available in the Yukon, Northwest Territories, or Nunavut.7

No MRI scanners are available in the Yukon, Northwest Territories, or Nunavut.43 According to CIHI's National Survey of Selected Medical Imaging Equipment database, the average number of hours of operation per week for MRI scanners in 2006–2007 ranged from 40 hours in PEI to 99 hours in Ontario, with a national average of 71 hours.7 In 2010, the average wait time for MRI in Canada was 9.8 weeks.44

Depending on the centre and assuming that the necessary personnel and expertise is available, it is estimated that 25% to 74% of procedures could be performed in a timely manner using MRI.
11 Relative cost of the test

According to our estimates, the cost of whole body bone scan with 99mTc-based radioisotopes is $344.016. MRI is a minimally more costly alternative.

Relative costs
Test Total costs ($) Cost of test relative to 99mTc-based test ($)
Bone scan 344.01 Reference
MRI 501.90 +157.89

 

AVN = avascular necrosis; CIHI = Canadian Institute for Health Information; Gd = gadolinium; MRI = magnetic resonance imaging; MRT = radiological technologists; mSv = millisievert; ONFH = osteonecrosis of the femoral head; SPECT = single-photon emission computed tomography.

Criterion 1: Size of affected population (link to definition)

According to a report produced by the Institute for Clinical Evaluative Sciences (ICES), there were 1,008 nuclear bone scans performed per 100,000 population in the province of Ontario in 2005-2006.45 If this rate were applied to the Canadian population, we would expect 345,526 bone scans performed in Canada each year.

AVN has been described as a relatively common disease,15,21 but an estimate as to the number of Canadians affected by this affliction has not been found. According to the American Academy of Orthopedic Surgeons, the annual incidence of AVN in the US is estimated at 10,000 to 20,000 (3.26-6.51/100,000).22 A Japanese prognostic study reported that 11,400 patients sought medical care for idiopathic osteonecrosis of the femoral head (ONFH) in 2004 (8.9/100,000).23 Basic extrapolation of these data to the Canadian setting provides an estimate of 1,098 to 2,197 new cases annually; however, the generalizability of these numbers to the Canadian population is uncertain.

The risk of a completely healthy individual developing AVN is estimated at less than one in 100,000, but there are specific populations who are more affected.25 AVN affects between five and 29 per 100 renal transplant recipients and approximately 15 out of every 100 systemic lupus erythematosus (SLE) patients.26,46 After post-traumatic intracapsular fractures of the femoral neck, the incidence of AVN is 15 to 80 per 100 post-traumatic intracapsular fractors of the femora neck.26

The incidence of specific forms of AVN has also been reported. Legg–Calvé–Perthes (LCP) disease is a form of idiopathic AVN affecting the femoral head in approximately 5.1 to 15.6 per 100,000 preadolescent children.47

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Criterion 2: Timeliness and urgency of test results in planning patient management (link to definition)

Timeliness
Interventions to preserve the joint are associated with better prognoses when the diagnosis of AVN is made early in the course of disease progression.48 In more advanced stages of the disease, when more of the joint is damaged, it becomes less likely that the natural joint can be preserved.25

Urgency
According to the urgency classifications developed by the Saskatchewan Ministry of Health, MRI, a comparator of 99mTc-based bone scanning, should be completed within two to seven days for patients with suspected AVN in any joint or bone. (Patrick Au, Acute and Emergency Services Branch, Saskatchewan Ministry of Health: unpublished data, 2011.)

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Criterion 3: Impact of not performing a diagnostic imaging test on mortality related to the underlying condition (link to definition)

The diagnosis of AVN does not affect patient life expectancy.25 The consequences of not performing imaging tests, or not diagnosing the condition, will affect the patient's quality of life and morbidity, but should have no effect on mortality.

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Criterion 4: Impact of not performing a diagnostic imaging test on morbidity or quality of life related to the underlying condition (link to definition)

Although the natural history of AVN has not been completely determined, it is recognized that delayed diagnosis of AVN can seriously affect patient morbidity and quality of life.26 For example, the average age of diagnosis for AVN of the femoral head is less than 40 years, making preservation of the joints a priority.1,49

Steinberg et al.28 have devised a quantitative system for staging AVN of the femoral head (Table 2). Their evaluation of more than 1,000 hips during a period of 12 years provides evidence that early diagnosis and treatment can greatly improve prognosis and reduce morbidity. Once radiographic changes occur (stage II), most joints will collapse within six to 24 months, if untreated.27 By the time the patient has reached stage IV, the changes are irreversible.28 Replacement of the femoral head may be considered at stage IV, but by stage V, total hip replacement is required.

Table 2: Criteria for Staging AVN of the Femoral Head28

Stage Description
0 Normal or non-diagnostic radiograph, bone scan and MRI
I* Normal radiograph, abnormal bone scan and/or MRI
II* Abnormal radiograph showing "cystic" and sclerotic changes in the femoral head
III* Subchondral collapse producing a crescent sign
IV* Flattening of the femoral head
V* Joint narrowing with or without acetabular involvement
VI Advanced degenerative changes

AVN = avascular necrosis; MRI = magnetic resonance imaging.
*The extent or grade of involvement should also be indicated as A, mild; B, moderate; or C, severe.

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Criterion 5: Relative impact on health disparities (link to definition)

To be scored locally.

AVN affects primarily people with underlying health problems, such as recent trauma and associated fractures, cancer, or recent transplant recipients.25 The risk of a completely healthy individual developing AVN is estimated at less than one in 100,000, but there are specific populations who are more affected.25 AVN affects between five and 29 per 100 renal transplant recipients and approximately 15 out of every 100 SLE patients.26,46 After post-traumatic intracapsular fractures of the femoral neck, the incidence of AVN is 15 to 80 per 100 post-traumatic intracapsular fractures of the femoral neck.26 AVN is more common in men: the male-to-female ratio has been estimated at 8:11; however, it is not clear which etiology this ratio refers to. The unavailability of 99mTc or the replacement with an alternative imaging modality is not expected to worsen these disparities.

Children
Radiography and bone scanning involve exposure to ionizing radiation. This can be a concern in testing pediatric patients, as the risk of radiation-induced cancer is shown to be two to three times greater in children and adolescents than in adult patients.50 The most common form of AVN in children is idiopathic (Perthes disease) and the changes are almost always visible on x-ray by the time the patient presents. For the diagnosis of treatment-induced, multifocal AVN of bone in children, whole-body MRI has been proposed as a safer screening tool.51

Residents of rural and remote areas
When radiographs are normal but AVN is suspected clinically, the ACR recommends MRI to establish or exclude AVN.15 If MRI is not available, as may be the case in smaller centres, bone scan or CT may be appropriate.15 In rural and remote areas without access to these imaging modalities, it may not be possible to confirm the diagnosis of AVN until stage II disease. As later diagnosis is associated with poorer prognosis, residents of rural and remote areas may experience increased morbidity associated with AVN.

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Criterion 6: Relative acceptability of the test to patients(link to definition)

Bone scanning
Patients may have concerns about radiation exposure and the intravenous injection of radiopharmaceutical agent.

MRI
Because of the closed space of an MRI, patients may experience feelings of claustrophobia, as well as be bothered by the noise. This may be less of a problem with new MRI machines, if available (MIIMAC expert opinion). It has been reported that up to 30% of patients experience apprehension with MRIs and 5% to 10% endure some severe psychological distress, panic, or claustrophobia.29,30 Some patients may have difficulty remaining still during the scan. Patients are not exposed to radiation during an MRI scan, which may be more acceptable to some.

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Criterion 7: Relative diagnostic accuracy of the test (link to definition)

Our review of the literature identified seven primary studies on the ability of bone scanning with 99mTc-MDP to correctly diagnose patients with AVN (sensitivity) and without AVN (specificity). No systematic reviews were identified.

Table 3 summarizes the study objectives, interventions compared, study results, and authors' conclusions of those studies published in the past 20 years.46,52,53 All of the studies involved relatively small sample sizes (24 to 107 patients).

Table 3: Diagnostic Accuracy of Bone Scan Versus Comparators (Studies Published 1991–2011)

Author, Date Objective Population Interventions Results Conclusions
Mont et al. 200853 To investigate the utility of bone scanning in the diagnosis or screening of AVN. 48 patients presenting to 2 institutions who underwent simultaneous (within 3 months) radiographs, bone scans, and MRI studies for possible symptomatic AVN of the hip, knee, shoulder, or ankle. Patients with traumatic lesions were excluded. BS vs. MRI

Histological confirmation was obtained for each suspected lesion and this was considered the "gold standard."
163 lesions identified by MRI and histology (sensitivity of 100% for MRI, specificity not reported).

91/163 lesions were identified by bone scan (55.8% sensitivity, specificity not reported).
Bone scanning was observed to have lower sensitivity than MRI in diagnosing symptomatic AVN.

This study does not support the use of bone scans as a diagnostic or screening tool for AVN.
Ryu et al. 200246 To compare the diagnostic sensitivity of bone SPECT and MRI for the detection of early AVN of the femoral head in renal transplant recipients. 24 renal allograft recipients (14 men and 10 women, aged 26-65 y) — 48 femoral heads. SPECT vs. MRI 32 femoral heads were confirmed as having AVN (core decompression in 13 and THR arthroplasty in 14 within 14 months after bone SPECT, 5 confirmed in clinical follow-up).

SPECT detected AVN in all 32 true positives, but also falsely categorized 6 femoral heads as positive (sensitivity of 100%, specificity of 62%).

MRI had a sensitivity of 66% and a specificity of 100%.
Bone SPECT is more sensitive than MRI in the detection of early AVN of the femoral heads after renal transplantation.
Sakai et al. 200152 To determine whether 99mTc-MDP BS is useful for screening of non-traumatic ONK, which was a major affected site, secondary to the femoral head, among multiple AVN, in patients with non-traumatic ONFH. 214 knee joints in 107 patients with ONFH. BS vs. MRI. Sensitivity, specificity, and accuracy of BS in comparison with MRI
 

 

Sens. (%)

Spec. (%)

Accuracy (%)

ONFC (n = 86) 63 71 68
ONFM (n = 32) 3 98 84
ONTP (n = 2) 100 81 81
ONTM (n = 21) 0 99 89
ONP (n = 6) 0 98 95
All ONK lesions showed focal increased bone uptake and did not show "cold in hot pattern," which was specific to ONFH.

The authors concluded their results indicate that BS is useful in screening large ONK in patients with non-traumatic ONFH.

99mTc-MDP = technetium-99m methylene diphosphonate; AUC = area under the curve; AVN = avascular necrosis; BS = bone scanning; MRI = magnetic resonance imaging; ONFC = osteonecrosis of the femoral chondrocyles; ONFH = osteonecrosis of the femoral head; ONFM = osteonecrosis of the distal femoral metaphysis; ONK = osteonecrosis of the knee; ONTP = osteonecrosis of the tibial plateau; ONTM = osteonecrosis of the proximal tibial metaphysis; ONP = osteonecrosis of the patella; ROC = receiver operating characteristic; sens. = sensitivity; spec. = specificity; SPECT = single-photon emission computed tomography; SPECT/CT = single-photon emission computed tomography/computed tomography; THR = total hip replacement; vs. = versus.

Bone scanning using 99mTc-MDP
Bone scanning using 99mTc-MDP has been advocated as a useful diagnostic tool for patients with suspected AVN.27,46,54,55 Particularly before the advent and adoption of MRI, bone scanning was considered a more sensitive diagnostic test than standard radiographs for early disease detection.15,27 A 2008 study by Mont et al. concluded that bone scanning has a low sensitivity for diagnosing symptomatic AVN, particularly for early-stage lesions, and joints other than the hip.53 The 1989 study by Stulberg et al.55 found that SPECT is more sensitive than planar bone scan.

MRI
According to the American College of Radiology,MRI has largely replaced radionuclide bone scanning because of its greater sensitivity (up to 100%).15 The generalizability of these findings to the Canadian health care system is uncertain.

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Criterion 8: Relative risks associated with the test (link to definition)

Non–radiation-related Risks

Bone scanning
Several studies31-34 reported mild adverse events with 99mTc-labelled tracers (e.g., skin reactions).

MRI
MRI is contraindicated in patients with metallic implants including pacemakers.18 MRI is often used in conjunction with the contrast agent gadolinium (Gd). Some patients may experience an allergic reaction to the contrast agent (if required), which may worsen with repeated exposure.35 Side effects of Gd include headaches, nausea, and metallic taste. Gd is contraindicated in patients with renal failure or end stage renal disease, as they are at risk of nephrogenic systemic fibrosis. According to the American College of Radiology Manual on Contrast Media,36 the frequency of severe, life-threatening reactions with Gd is extremely rare (0.001% to 0.01%). Moderate reactions resembling an allergic response (i.e., rash, hives, urticaria) are also very unusual and range in frequency from 0.004% to 0.7%.36

Radiation-Related Risks

Among the modalities to diagnose AVN, only bone scanning exposes the patient to ionizing radiation. The average effective dose of radiation delivered with each of these procedures can be found in Table 5. As the table shows, bone scanning delivers larger doses of radiation than X-ray.

Table 5: Effective Doses of Radiation

Procedure Average Effective Dose (mSv)
Bone scan 4.5-6.337-39
MRI 0
X-ray 0.01-0.738
Average background dose of radiation per year 1-3.040-42

MRI = magnetic resonance imaging; mSv = millisievert.
* Based on 740 MBq injection at 6.1E-03 mSv/MBq

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Criterion 9: Relative availability of personnel with expertise and experience required for the test (equipment and wait times) (link to definition)

Bone scintigraphy
In Canada, physicians involved in the performance, supervision, and interpretation of bone scans should be nuclear medicine physicians or diagnostic radiologists with training or expertise in nuclear imaging.56 Physicians should have a Fellowship of Certification in Nuclear Medicine or Diagnostic Radiology with the Royal College of Physicians and Surgeons of Canada and/or the Collège des médecins du Québec. Nuclear medicine technologists are required to conduct bone scans. Technologists must be certified by the Canadian Association of Medical Radiation Technologists (CAMRT) or an equivalent licensing body.

All alternative imaging modalities
In Canada, physicians involved in the performance, supervision, and interpretation of diagnostic CT scans, MRI, and ultrasound should be diagnostic radiologists7 and must have a Fellowship or Certification in Diagnostic Radiology with the Royal College of Physicians and Surgeons of Canada and/or the Collège des médecins du Québec. Foreign-trained radiologists are also qualified if they are certified by a recognized certifying body and hold a valid provincial licence.56

Medical radiation technologists (MRTs) must be certified by CAMRT or an equivalent licensing body.

Service engineers are needed for system installation, calibration, and preventive maintenance of the imaging equipment at regularly scheduled intervals. The service engineer's qualification will be ensured by the corporation responsible for service and by the manufacturer of the equipment used at the site.

Qualified medical physicists (on site or contracted part time) should be available for the installation, testing, and ongoing quality control of CT scanners, magnetic resonance scanners, and nuclear medicine equipment.56

MRI
Medical technologists must have CAMRT certification in magnetic resonance or be certified by an equivalent licensing body recognized by CAMRT.

Table 6: Medical Imaging Professionals in Canada, 20067

Jurisdiction Diagnostic Radiology Physicians Nuclear Medicine Physicians MRTs Nuclear Medicine Technologists Medical Physicists
NL 46 3 263 15 NR
NS 71 5 403 71 NR
NB 47 3 387 55 NR
PE 7 0 57 3 0
QC 522 90 3,342 460 NR
ON 754 69 4,336 693 NR
MB 58 8 501 42 NR
SK 61 4 359 36 NR
AB 227 18 1,229 193 NR
BC 241 21 1,352 212 NR
YT 0 0 0 0 0
NT 0 0 26 1 0
NU 0 0 0 0 0
Total 2,034 221 12,255 1,781 322*

AB = Alberta; BC = British Columbia; MB = Manitoba; MRTs = Medical radiation technologists; NB = New Brunswick; NL = Newfoundland and Labrador; NR = not reported; NS = Nova Scotia; NT= Northwest Territories; NU = Nunavut; ON = Ontario; PE = Prince Edward Island; QC = Quebec; YT = Yukon.
* this represents a total for all of the jurisdictions

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Criterion 10: Accessibility of alternative tests (equipment and wait times) (link to definition)

There are notable variations in the availability of medical imaging technologies across Canada. Table 7 provides an overview of the availability of equipment required to diagnose AVN. Data for nuclear medicine cameras (including SPECT) are current to January 1, 2007. The number of MRI and SPECT/CT scanners is current to January 1, 2010.

Table 7: Diagnostic Imaging Equipment in Canada7,43

  Nuclear Medicine Cameras MRI Scanners SPECT/CT Scanners
Number of devices 6037 21843 9643
Average number of hours of operation per week (2006-2007)7 40 71 n/a
Provinces and Territories with no devices available YT, NT, NU YT, NT, NU PE, YT, NT, NU

NT = Northwest Territories; NU = Nunavut; PE = Prince Edward Island; YT = Yukon.

Bone scanning
For bone scintigraphy, nuclear medicine facilities with gamma cameras (including SPECT) are required. Three jurisdictions, the Yukon, the Northwest Territories, and Nunavut, do not have any nuclear medicine equipment.7

MRI
No MRI scanners available in the Yukon, Northwest Territories, or Nunavut.43 According to CIHI's National Survey of Selected Medical Imaging Equipment database, the average number of hours of operation per week for MRI scanners in 2006–2007 ranged from 40 hours in PEI to 99 hours in Ontario with a national average of 71 hours.7 In 2010, the average wait time for MR imaging in Canada was 9.8 weeks.44

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Criterion 11: Relative cost of the test (link to definition)

Fee codes from the Ontario Schedule of Benefits were used to estimate the relative costs of bone scanning and its alternatives. Technical fees are intended to cover costs incurred by the hospital (i.e., radiopharmaceutical costs, medical/surgical supplies, and non-physician salaries). Maintenance fees are not billed to OHIP — estimates here were provided by St. Michael's Hospital in Toronto. Certain procedures (i.e., PET scan, CT scan, MRI scan) are paid for, in part, out of the hospital's global budget; these estimates were provided by The Ottawa Hospital. It is understood that the relative costs of imaging will vary from one institution to the next.

According to our estimates (Table 8), the cost of whole body bone scan with 99mTc-based radioisotopes is $344.016. MRI is a minimally more costly alternative.

Table 8: Cost Estimates Based on the Ontario Schedule of Benefits for Physician Services Under the Health Insurance Act (September 2011)57

Fee Code Description Tech. Fees ($) Prof. Fees ($) Total Costs ($)
Bone scan
J867 Blood flow and pool imaging 58.75 29.30 88.05
J851 Bone scintigraphy — single site 87.00 50.95 137.95
J819 Application of tomography (SPECT) 44.60 31.10 75.70
Maintenance fees — global budget 42.31   42.31
TOTAL 232.66 111.35 344.01
MRI
X471C Multislice sequence, one extremity and/or one joint   66.10 66.10
X475C (×3) Repeat (another plane, different pulse sequence; to a maximum of 3 repeats)   33.10 (×3) = 99.30 99.30
Technical cost — from global budget 300.00   300.00
Maintenance fees — from global budget 36.50   36.50
TOTAL 336.50 165.40 501.90

MRI = magnetic resonance imaging; SPECT = single-photon emission computed tomography.

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References

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  49. Steinberg ME. Early diagnosis of avascular necrosis of the femoral head. Instr Course Lect. 1988;37:51-7.
  50. Schembri GP, Miller AE, Smart R. Radiation dosimetry and safety issues in the investigation of pulmonary embolism. Semin Nucl Med. 2010 Nov;40(6):442-54.
  51. Darge K, Jaramillo D, Siegel MJ. Whole-body MRI in children: current status and future applications. Eur J Radiol. 2008 Nov;68(2):289-98.
  52. Sakai T, Sugano N, Nishii T, Haraguchi K, Yoshikawa H, Ohzono K. Bone scintigraphy for osteonecrosis of the knee in patients with non-traumatic osteonecrosis of the femoral head: comparison with magnetic resonance imaging. Ann Rheum Dis [Internet]. 2001 Jan [cited 2011 Apr 13];60(1):14-20. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1753361
  53. Mont MA, Ulrich SD, Seyler TM, Smith JM, Marker DR, McGrath MS, et al. Bone scanning of limited value for diagnosis of symptomatic oligofocal and multifocal osteonecrosis. J Rheumatol. 2008 Aug;35(8):1629-34.
  54. Collier BD, Carrera GF, Johnson RP, Isitman AT, Hellman RS, Knobel J, et al. Detection of femoral head avascular necrosis in adults by SPECT. J Nucl Med. 1985 Sep;26(9):979-87.
  55. Stulberg BN, Levine M, Bauer TW, Belhobek GH, Pflanze W, Feiglin DH, et al. Multimodality approach to osteonecrosis of the femoral head. Clin Orthop Relat Res. 1989 Mar;(240):181-93.
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  57. Ontario Ministry of Health and Long-Term Care. Schedule of benefits for physician services under the Health Insurance Act: effective September 1, 2011 [Internet]. Toronto: OMHLTC; 2011. [cited 2011 Oct 5]. Available from: http://www.health.gov.on.ca/english/providers/program/ohip/sob/physserv/physserv_mn.html

 

Appendix 1: Multi-Criteria Decision Analysis Definitions

Domain 1: Criteria Related to the Underlying Health Condition
Criterion Definition
1. Size of the affected population The estimated size of the patient population that is affected by the underlying health condition and which may potentially undergo the test. The ideal measure is point prevalence, or information on how rare or common the health condition is.
2. Timeliness and urgency of test results in planning patient management The timeliness and urgency of obtaining the test results in terms of their impact on the management of the condition and the effective use of health care resources.
3. Impact of not performing a diagnostic imaging test on mortality related to the underlying condition Impact of not performing the test, in whatever way, on the expected mortality of the underlying condition. Measures could include survival curves showing survival over time, and/or survival at specific time intervals with and without the test.
4. Impact of not performing a diagnostic imaging test on morbidity or quality of life related to the underlying condition Impact of not performing the test, in whatever way, on the expected morbidity or on the quality of life reduction of the underlying condition. Measures of impact may include natural morbidity outcome measures such as events or disease severity, or might be expressed using generic or disease-specific quality of life rating scales with and without the test.
Domain 2: Criteria Comparing 99mTc with an Alternative, or Comparing between Clinical Uses
Criterion Definition
5. Relative impact on health disparities Health disparities are defined as situations where there is a disproportionate burden (e.g., incidence, prevalence, morbidity, or mortality) amongst particular population groups (e.g., gender, age, ethnicity, geography, disability, sexual orientation, socioeconomic status, and special health care needs).

Impact on health disparities is assessed by estimating the proportion of current clients of the 99mTc-based test that are in population groups with disproportionate burdens.

(Explanatory note: The implication of this definition is that, everything else being the same, it is preferable to prioritize those clinical uses that have the greatest proportion of clients in groups with disproportionate burdens.)
6. Relative acceptability of the test to patients Acceptability of the 99mTc-based test from the patient's perspective compared with alternatives. Patient acceptability considerations include discomfort associated with the administration of the test, out-of-pocket expenses or travel costs, factors that may cause great inconvenience to patients, as well as other burdens. This criterion does not include risks of adverse events but is about everything related to the experience of undergoing the test.
7. Relative diagnostic accuracy of the test Ability of the test to correctly diagnose the patients who have the condition (sensitivity) and patients who do not have the condition (specificity) compared with alternatives.
8. Relative risks associated with the test Risks associated with the test (e.g., radiation exposure, side effects, adverse events) compared with alternatives. Risks could include immediate safety concerns from a specific test or long-term cumulative safety concerns from repeat testing or exposure.
9. Relative availability of personnel with expertise and experience required for the test Availability of personnel with the appropriate expertise and experience required to proficiently conduct the test and/or interpret the test findings compared with alternatives.
10. Accessibility of alternatives (equipment and wait times) Availability (supply) of equipment and wait times for alternative tests within the geographic area. Includes consideration of the capacity of the system to accommodate increased demand for the alternatives. Excludes any limitation on accessibility related to human resources considerations.
11. Relative cost of the test Operating cost of test (e.g., consumables, heath care professional reimbursement) compared with alternatives.

99mTc = technetium-99m.

 

Appendix 2: Literature Search Strategy

OVERVIEW
Interface: Ovid
Databases: Database(s): EBM Reviews - ACP Journal Club 1991 to February 2011

EBM Reviews - Cochrane Central Register of Controlled Trials 1st Quarter 2011

EBM Reviews - Cochrane Database of Systematic Reviews 2005 to February 2011

EBM Reviews - Cochrane Methodology Register 1st Quarter 2011

EBM Reviews - Database of Abstracts of Reviews of Effects 1st Quarter 2011

EBM Reviews - Health Technology Assessment 1st Quarter 2011

Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R) 1946 to March 11, 2011

Note: Duplicates between databases were removed in Ovid.
Date of Search: March 11, 2011
Alerts: Monthly search updates began March 11, 2011 and ran until October 2011.
Study Types: Health technology assessments, systematic reviews, meta-analyses, randomized controlled trials, non-randomized studies, and diagnostic accuracy studies.
Limits: English language

Human limit for primary studies
SYNTAX GUIDE
/

MeSH
At the end of a phrase, searches the phrase as a subject heading

Medical subject heading
.fs Floating subheading
exp Explode a subject heading
* Before a word, indicates that the marked subject heading is a primary topic; or, after a word, a truncation symbol (wildcard) to retrieve plurals or varying endings
? Truncation symbol for one or no characters only
ADJ Requires words are adjacent to each other (in any order)
ADJ# Adjacency within # number of words (in any order)
.ti Title
.ab Abstract
.hw Heading word: usually includes subject headings and controlled vocabulary
.tw Text word: searches title, abstract, captions, and full text
.mp Keyword search: includes title, abstract, name of substance word, subject heading word and other text fields
.pt Publication type
.nm Name of substance word: used to search portions of chemical names and includes words from the CAS Registry/EC Number/Name (RN) fields
.jw Journal words: searches words from journal names
/du Diagnostic use
/ri Radionuclide imaging

 

Ovid MEDLINE Strategy
Line # Search Strategy
1 exp Osteonecrosis/
2 (osteonecros* or kienbock* disease* or kienboeck* disease or osteochondritis dissecans or bone infarction* or Perthes* disease).tw.
3 ((avascular or aseptic or ischemic or ischaemic or femur head or femoral head or bone or bones) adj2 (necrosis or necroses)).tw.
4 (ONJ or AVN or SONK).ti,ab.
5 or/1-4
6 Technetium/ or exp Technetium Compounds/ or exp Organotechnetium Compounds/ or exp Radiopharmaceuticals/ or Radionuclide Imaging/ or Perfusion Imaging/
7 (Technetium* or Tc-99 or Tc99 or Tc-99m or Tc99m or 99mTc or 99m-Tc).tw,nm.
8 radionuclide imaging.fs.
9 radioisotope*.mp.
10 ((radionucl* or nuclear or radiotracer*) adj2 (imag* or scan* or test* or diagnos*)).ti,ab.
11 Tomography, Emission-Computed, Single-Photon/
12 (single-photon adj2 emission*).ti,ab.
13 (SPECT or scintigraph* or scintigram* or scintiphotograph*).ti,ab.
14 (medronate or methyl diphosphonate).ti,ab.
15 exp Joints/ri or exp "bone and bones"/ri
16 ((bone or bones or joint or joints or MDP) adj2 (scan* or imag* or scintigraph*)).ti,ab.
17 or/6-16
18 5 and 17
19 ((avascular necrosis or osteonecrosis or asceptic necrosis or ischemic) adj2 (scan* or imag* or scintigraph*)).tw.
20 18 or 19
21 remove duplicates from 20
22 limit 21 to english language [Limit not valid in ACP Journal Club,CCTR,CDSR,CLCMR,DARE; records were retained]
23 meta-analysis.pt.
24 meta-analysis/ or systematic review/ or meta-analysis as topic/ or exp technology assessment, biomedical/
25 ((systematic* adj3 (review* or overview*)) or (methodologic* adj3 (review* or overview*))).ti,ab.
26 ((quantitative adj3 (review* or overview* or synthes*)) or (research adj3 (integrati* or overview*))).ti,ab.
27 ((integrative adj3 (review* or overview*)) or (collaborative adj3 (review* or overview*)) or (pool* adj3 analy*)).ti,ab.
28 (data synthes* or data extraction* or data abstraction*).ti,ab.
29 (handsearch* or hand search*).ti,ab.
30 (mantel haenszel or peto or der simonian or dersimonian or fixed effect* or latin square*).ti,ab.
31 (met analy* or metanaly* or health technology assessment* or HTA or HTAs).ti,ab.
32 (meta regression* or metaregression* or mega regression*).ti,ab.
33 (meta-analy* or metaanaly* or systematic review* or biomedical technology assessment* or bio-medical technology assessment*).mp,hw.
34 (medline or Cochrane or pubmed or medlars).ti,ab,hw.
35 (cochrane or health technology assessment or evidence report).jw.
36 (meta-analysis or systematic review).md.
37 or/23-36
38 22 and 37
39 exp "Sensitivity and Specificity"/
40 False Positive Reactions/
41 False Negative Reactions/
42 du.fs.
43 sensitivit*.tw.
44 (predictive adj4 value*).tw.
45 Comparative Study.pt.
46 (Validation Studies or Evaluation Studies).pt.
47 Randomized Controlled Trial.pt.
48 Controlled Clinical Trial.pt.
49 (Clinical Trial or Clinical Trial, Phase II or Clinical Trial, Phase III or Clinical Trial, Phase IV).pt.
50 Multicenter Study.pt.
51 (random* or sham or placebo*).ti.
52 ((singl* or doubl*) adj (blind* or dumm* or mask*)).ti.
53 ((tripl* or trebl*) adj (blind* or dumm* or mask*)).ti.
54 (control* adj3 (study or studies or trial*)).ti.
55 (non-random* or nonrandom* or quasi-random* or quasirandom*).ti.
56 (allocated adj "to").ti.
57 Cohort Studies/
58 Longitudinal Studies/
59 Prospective Studies/
60 Follow-Up Studies/
61 Retrospective Studies/
62 Case-Control Studies/
63 Cross-Sectional Study/
64 (observational adj3 (study or studies or design or analysis or analyses)).ti.
65 cohort.ti.
66 (prospective adj7 (study or studies or design or analysis or analyses or cohort)).ti.
67 ((follow up or followup) adj7 (study or studies or design or analysis or analyses)).ti.
68 ((longitudinal or longterm or (long adj term)) adj7 (study or studies or design or analysis or analyses or data or cohort)).ti.
69 (retrospective adj7 (study or studies or design or analysis or analyses or cohort or data or review)).ti.
70 ((case adj control) or (case adj comparison) or (case adj controlled)).ti.
71 (case-referent adj3 (study or studies or design or analysis or analyses)).ti.
72 (population adj3 (study or studies or analysis or analyses)).ti.
73 (cross adj sectional adj7 (study or studies or design or research or analysis or analyses or survey or findings)).ti.
74 (distinguish* or differentiat* or enhancement or identif* or detect* or diagnos* or accura* or comparison*).tw.
75 or/39-74
76 75 not case reports.pt.
77 22 and 76
78 exp animals/
79 exp animal experimentation/
80 exp models animal/
81 exp animal experiment/
82 nonhuman/
83 exp vertebrate/
84 animal.po.
85 or/78-84
86 exp humans/
87 exp human experiment/
88 human.po.
89 or/86-88
90 85 not 89
91 77 not 90

 

OTHER DATABASES
PubMed Same MeSH, keywords, limits, and study types used as per Medline search, with appropriate syntax used.

 

GREY LITERATURE SEARCHING
Dates for Search: March 2011
Keywords: Included terms for avascular necrosis and radionuclide imaging
Limits: English language

The following sections of the CADTH grey literature checklist, "Grey matters: a practical search tool for evidence-based medicine" (http://www.cadth.ca/en/resources/grey-matters) were searched:

  • Health Technology Assessment Agencies (selected)
  • Clinical Practice Guidelines
  • Databases (free)
  • Internet Search

 

Appendix 3: ACR Appropriateness Criteria avascular necrosis of the hip 15

The American College of Radiology (ACR) has updated its Relative Radiation Level categories and Rating Scale. The Rating Scale now includes categories (1, 2, 3 = Usually not appropriate; 4, 5, 6 = May be appropriate; 7, 8, 9 = Usually appropriate). See the original guideline document for details.

Clinical Condition: Avascular Necrosis (Osteonecrosis) of the Hip

Variant 1: Initial Study When AVN is Suspected Clinically

Radiologic Procedure Rating Comments Relative Radiation Level
X-ray pelvis 9 For initial evaluation in patients at risk for AVN who present with hip pain. Low
X-ray hips 9 Frog-leg view is necessary to evaluate anterosuperior involvement of the femoral head. Med
CT hips without contrast 1 Not useful for initial evaluation. Med
99mTc bone scan with SPECT hips 1 Sensitive method for detecting AVN, but not indicated before radiographs. Med
MRI hips with or without contrast 1 Most sensitive method for detecting AVN, but not indicated before radiographs. None
Rating Scale: 1 = Least appropriate; 9 = Most appropriate.

Variant 2: AVN with Femoral Head Collapse Detected by Radiographs of the Painful Hip: No Surgery Contemplated at This Time

Radiologic Procedure Rating Comments Relative Radiation Level
MRI hips without contrast 5 May be useful if knowledge of occult AVN in the opposite hip is needed. None
99mTc bone scan with SPECT hips 1 May be useful if knowledge of occult AVN in the opposite hip is needed and MRI is not available. Med
CT hips without contrast 1 Provides no more information than conventional radiographs. Shows subchondral fractures earlier, but not needed. Med
Rating Scale: 1 = Least appropriate; 9 = Most appropriate.

Variant 3: AVN with Femoral Head Collapse by Radiographs in the Painful Hip: Surgery Contemplated

Radiologic Procedure Rating Comments Relative Radiation Level
MRI hips without contrast 5 May be useful if knowledge of occult AVN in the opposite hip is needed or if surgical planning on either hip would be affected. None
99mTc bone scan with SPECT hips 1 May be useful if knowledge of occult AVN in the opposite hip is needed and MRI is not available. Med
CT hips without contrast 1 Provides no more information than conventional radiographs. May be useful if planning osteotomy by defining anatomic localization of the AVN and the extent of bone deformity. Med
Rating Scale: 1 = Least appropriate; 9 = Most appropriate

Variant 4: Radiograph Shows Mottled Femoral Head, Suspicious but Not Definite for AVN in the Painful Hip(s). Further Clinical Evaluation is Needed

Radiologic Procedure Rating Comments Relative Radiation Level
MRI hips without contrast 9 MRI provides definitive diagnosis when radiograph findings are equivocal. None
99mTc bone scan with SPECT hips 6 If MRI is not available or is contraindicated. Med
CT hips without contrast 6 If MRI is not available or is contraindicated. May show subchondral fracture not seen on MRI. Med
Rating Scale: 1 = Least appropriate; 9 = Most appropriate.

Variant 5: AVN Suspected Clinically But Radiographs Are Normal. Further Clinical Evaluation Needed.

Radiologic Procedure Rating Comments Relative Radiation Level
MRI hips without contrast 9 Most sensitive and specific method to establish or exclude AVN. None
99mTc bone scan with SPECT hips 6 If MRI is not available or is contraindicated. Med
CT hips without contrast 6 If MRI is not available or is contraindicated. Med
Rating Scale: 1 = Least appropriate; 9 = Most appropriate

AVN = avascular necrosis; CT = computer tomography; MRI = magnetic resonance imaging; SPECT = single photon emission computer tomography; 99mTc = Technetium-99m.