Description:
Vertebral fracture assessment (VFA) with densitometry is a technique to assess vertebral fractures at the same time as bone mineral density, using additional software with dual-energy X-ray absorptiometry. The addition of VFA to bone mineral density may augment diagnostic information on fracture risk.

For individuals who are at risk of having vertebral fractures but are not known to have them who receive VFA with densitometry by dual-energy X-ray absorptiometry, the evidence includes diagnostic accuracy studies and subgroup reanalyses of treatment studies. Relevant outcomes are test accuracy, test validity, and morbid events. There is a lack of direct evidence from screening trials that use densitometry with and without VFA improves health outcomes. Because direct evidence was not available, a chain of evidence was sought. Evidence was examined on the diagnostic accuracy of VFA in nonosteoporotic patients (i.e., those not already eligible for treatment), the ability of VFA to identify patients for treatment who would not otherwise be identified, and the effectiveness of treatment in this population. Diagnostic accuracy studies have reported variable findings; recent studies have suggested higher diagnostic accuracy of VFA overall compared with standard radiographs than older studies. Studies have found that VFA can identify patients without osteoporosis who may be appropriate candidates for treatment according to recommendations from the National Osteoporosis Foundation. However, there is limited evidence on the effectiveness of treatment in this population. No treatment data have been published in patients whose vertebral fracture had been identified using VFA software with densitometry. The evidence is insufficient to determine the effects of the technology on health outcomes.  

Background  
Diagnosis
Only 20% to 30% of vertebral fractures are recognized clinically; the rest are discovered incidentally on lateral spine radiographs. Lateral spine radiographs have not been recommended as a component of risk assessment for osteoporosis because of the cost, radiation exposure, and the fact that the radiograph would require a separate procedure in addition to the bone mineral density study using dual-energy X-ray absorptiometry. However, several densitometers with specialized software can perform vertebral fracture assessment (VFA) in conjunction with dual-energy x-ray absorptiometry. The lateral spine scan is performed by using a rotating arm; depending on the densitometer used, the patient can either stay in the supine position after the bone density study or is required to move to the left decubitus position.

VFA differs from radiologic detection of fractures because VFA uses a lower radiation exposure and can detect only fractures, while traditional radiograph images can detect other bone and soft tissue abnormalities in addition to spinal fractures. Manufacturers have also referred to this procedure as instant vertebral assessment, radiographic vertebral assessment, dual-energy vertebral assessment, or lateral vertebral assessment.

For both lateral spine radiographs and images with densitometry, vertebral fractures are assessed visually. A number of grading systems have been proposed, and the Genant semiquantitative method is commonly used. This system grades deformities from I to III, with grade I (mild) representing a 20% to 24% reduction in vertebral height, grade II (moderate) representing a 25% to 39% reduction in height, and grade III (severe) representing a 40% or greater reduction in height. The location of the deformity within the vertebrae may also be noted. For example, if only the mid-height of the vertebrae is affected, the deformity is defined as an endplate deformity; if both the anterior and mid-heights are deformed, it is a wedge deformity; and if the entire vertebrae is deformed, it is classed as a crush deformity. A vertebral deformity of at least 20% loss in height is typically considered a fracture. Accurate interpretation of both lateral spine radiographs and VFA imaging depends on radiologic training. Thus, device location and availability of appropriately trained personnel may influence diagnostic accuracy.

Regulatory Status
Additional software is needed to perform VFA with a densitometer, and it must be cleared for marketing by the U.S. Food and Drug Administration through the 510(k) process. Products cleared for marketing are shown in Table 1 below. Food and Drug Administration product code KGI. 

Table 1. Densitometry Devices Cleared by the US Food and Drug Administration 

Device	Manufacturer	Date Cleared	510(k) No.	Indication
GEHC DXA Bone Densitometers with enCORE version 18	GE Medical Systems Ultrasound & Primary Care Diagnostics LLC	9/19/2019	K191112	For use in vertebral fracture assessment
Aria	GE Medical Systems Ultrasound & Primary Care Diagnostics LLC	4/20/2018	K180782	For use in vertebral fracture assessment
GE Lunar DXA Bone Densitometers with enCORE version 17	GE Medical Systems Ultrasound & Primary Care Diagnostics LLC	12/2/2016	K161682	For use in vertebral fracture assessment
TBS iNsight	MEDIMAPS GROUP SA	4/29/2016	K152299	For use in vertebral fracture assessment
QCT PRO ASYNCHRONOUS CALIBRATION MODULE CLINIQCT™	MINDWAYS SOFTWARE INC.	8/29/2014	K140342	For use in vertebral fracture assessment
ENCORE VERSION 16 SOFTWARE FOR GE LUNAR DXA BONE DENSITOMETERS	GE MEDICAL SYSTEMS ULTRASOUND & PRIMARY CARE DIAGN	5/15/2014	K133664	For use in vertebral fracture assessment

Related Policies
60101 Bone Mineral Density Studies
60140 Whole Body Dual X-Ray Absorptiometry (DEXA) to Determine Body Composition

Policy:
Screening for vertebral fractures using dural x-ray absorptiometry (DEXA or DXA) is investigational and/or unproven and is therefore considered NOT MEDICALLY NECESSARY.

Policy Guidelines
Coding
Diagnostic codes in the Codes table related to screening and conditions without fracture would be considered investigational.

The CPT coding for this procedure depends on whether it is performed with dual-energy X-ray absorptiometry.

Please see the Codes table for details.

Benefit Application
BlueCard^®/National Account Issues
State or federal mandates (e.g., FEP) may dictate that all devices approved by the U.S. Food and Drug Administration (FDA) may not be considered investigational, and thus these devices may be assessed only on the basis of their medical necessity.

Although the primary benefit of vertebral fracture assessment is in individuals with osteopenia, because densitometry and vertebral fracture assessment are done simultaneously, it is not possible to use the findings from BMD testing to determine eligibility for VFA during a particular testing session.

Rationale 
Evidence reviews assess whether a medical test is clinically useful. A useful test provides information to make a clinical management decision that improves the net health outcome. That is, the balance of benefits and harms is better when the test is used to manage the condition than when another test or no test is used to manage the condition.

The first step in assessing a medical test is to formulate the clinical context and purpose of the test. The test must be technically reliable, clinically valid, and clinically useful for that purpose. Evidence reviews assess the evidence on whether a test is clinically valid and clinically useful. Technical reliability is outside the scope of these reviews, and credible information on technical reliability is available from other sources.

Promotion of greater diversity and inclusion in clinical research of historically marginalized groups (e.g., people of color [African-American, Asian, Black, Latino and Native American]; LGBTQIA (lesbian, gay, bisexual, transgender, queer, intersex, asexual); women; and people with disabilities [physical and invisible]) allows policy populations to be more reflective of and findings more applicable to our diverse members. While we also strive to use inclusive language related to these groups in our policies, use of gender-specific nouns (e.g., women, men, sisters, etc.) will continue when reflective of language used in publications describing study populations.

Vertebral Fracture Assessment
Clinical Context and Test Purpose
Vertebral fractures are highly prevalent in the elderly population, and epidemiologic studies have found that these fractures are associated with an increased risk of future spine or hip fractures independent of bone mineral density (BMD).

The purpose of performing vertebral fracture assessment (VFA) using densitometry by dual-energy X-ray absorptiometry (DXA) is to diagnose whether the patient has a vertebral fracture.

The question addressed in this evidence review is whether there is sufficient evidence that screening for VFA using DXA improves the net health outcome in patients at risk of having vertebral fractures compared with alternative approaches.

The following PICO was used to select literature to inform this review.

Populations
The relevant population of interest is individuals at risk of vertebral fractures who are not known to have a fracture at the time of assessment.

Interventions
The relevant intervention of interest is VFA with densitometry using DXA.

Comparators
The following tools and tests are currently being used to make decisions about managing patients at risk for vertebral fracture: Dual-energy X-ray absorptiometry alone for the assessment of BMD as well as spine radiography. Radiography is used to confirm the occurrence of vertebral fractures but is not recommended as a routine component of osteoporosis assessment because of radiation exposure.

Outcomes
Outcomes of interest for diagnostic accuracy include test accuracy and test validity (e.g., sensitivity, specificity). The primary outcome of interest for clinical utility is morbid events, specifically the incidence of future clinical fractures.

Vertebral fracture assessment with densitometry by DXA would occur at the time of osteoporosis screening. The recommended age at which to start screening with DXA and the frequency of screening is addressed in national guidelines.

Study Selection Criteria
For the evaluation of clinical validity of VFA with densitometry, studies that meet the following eligibility criteria were considered:

• Reported on the accuracy of the marketed version of the technology (including any algorithms used to calculate scores)
• Included a suitable reference standard (e.g., spine radiography)
• Patient/sample clinical characteristics were described
• Patient/sample selection criteria were described

Clinically Valid
A test must detect the presence or absence of a condition, the risk of developing a condition in the future, or treatment response (beneficial or adverse).

Review of Evidence
Systematic Reviews
Malgo et al. (2017) compared VFA with DXA to conventional spine radiography and published evidence comparing VFA with DXA to conventional spine radiography from a fracture liaison service (FLS) and meta-analysis of comparative studies.¹ The FLS retrospective diagnostic study included 542 consecutive subjects (25% male) aged 50 years or older assessed for vertebral fractures and osteoporosis between 2012 and 2014 with both VFA and conventional radiography. The diagnostic accuracy of VFA was calculated using conventional radiography as a reference, and observers were blinded to the VFA findings. Normal BMD was reported in 11% of subjects. The sensitivity of VFA with DXA to detect a vertebral fracture greater or equal to Genant grade 2 was 77% and its specificity was 80%. A meta-analysis of 16 studies including 3,238 subjects (19% male) with low to intermediate risk of bias revealed a pooled sensitivity of 84% (95% confidence interval [CI], 72% to 92%) and specificity of 90% (95% CI, 84% to 94%). Reviewers did not report separate analyses for the diagnostic accuracy of VFA with DXA in patients at low- versus high-risk of osteoporosis. While the meta-analysis suggests adequate diagnostic performance of VFA with DXA for the detection of vertebral fractures, the study authors caution that these findings could not be replicated in their FLS center.

A systematic review of studies was published by Lee et al. (2016).³ The authors included studies with postmenopausal women and/or men 50 years and older that compared the diagnostic accuracy of VFA with DXA with spinal radiography. Seventeen studies met selection criteria; 5 were excluded because of an inadequate description of methods or results. Of the remaining 12 studies, 4 examined postmenopausal women, 5 included osteoporotic patients (men and women), and 2 included both populations. Studies were heterogeneous, and thus reviewers did not pool study findings. Among the 8 studies that reported findings on a per-vertebral level, the sensitivity of VFA with DXA ranged from 70% to 93% and the specificity ranged from 95% to 100%. Nine studies reported findings on a per-patient level. Sensitivity ranged from 65% to 100% and specificity from 74% to 100%. Reviewers did not report separate analyses for the diagnostic accuracy of VFA with DXA in osteoporotic versus non-osteoporotic patients.

Nonrandomized Trials
One study included in the systematic review and judged to have a low-risk of bias was published by Domiciano et al. (2013).⁴ The authors reported on 429 adults at least 65 years old who had VFA with densitometry and spine radiography on the same day. On VFA, vertebral fractures were identified in 77 (29.7%) of 259 women and in 48 (28.2%) of 170 men. Comparable numbers on spine radiographs were 74 (28.6%) of 259 women and 52 (30.6%) of 170 men. Compared with spine radiography, the sensitivity of VFA was 81.7% (95% CI, 73.9% to 88.1%) and the specificity was 92.7% (95% CI, 89.2% to 95.4%).

The diagnostic performance of VFA with DXA has tended to be lower in older studies. For example, Ferrar et al. (2008) evaluated the performance of vertebral assessment using a visual algorithm-based approach.⁵ Subjects in the low-risk group were women ages 55 to 79 years who were randomly selected from their general practitioners' offices. Most had a normal BMD or were osteopenic. Subjects in the high-risk group were recruited after a low-trauma fracture to the hip, forearm, or humerus. Most high-risk patients had osteopenia or osteoporosis. In the per-patient analysis and including all poor or unreadable images, the sensitivity of VFA was 60% in the low-risk group and 81% in the high-risk group; specificity was 97% in both groups. Also, Binkley et al. (2005) compared VFA (GE Lunar densitometer) with radiography in 27 osteoporotic, 38 osteopenic, and 15 normal women.⁶ Blinded analysis correctly identified 17 of 18 radiographically evident grade 2 to 3 fractures (false-negative rate, 6%). The study did not describe whether the grade 2 or 3 fractures were found in women with osteoporosis, osteopenia, or normal BMD. Also, only 11 (50%) of 22 grade 1 fractures were identified. Thirty vertebrae were classified as fractured when no fractures were present (38% false-positive), 29 of these were grade 1 fractures by VFA with normal radiography. Also, VFA identified 40 grade 1 fractures, but only 11 (28%) were true-positive results. Also problematic is that results were compared only in vertebrae evaluable by VFA; 1 patient could not be evaluated due to poor image quality, and 66% of T4 to T6 vertebrae in other subjects could not be adequately visualized.

Clinically Useful
A test is clinically useful if the use of the results informs management decisions that improve the net health outcome of care. The net health outcome can be improved if patients receive correct therapy, more effective therapy, or avoid unnecessary therapy or testing.

Direct Evidence
Direct evidence of clinical utility is provided by studies that have compared health outcomes for patients managed with and without the test. Because these are intervention studies, the preferred evidence would be from randomized controlled trials (RCTs).

No RCTs comparing health outcomes in individuals screened with VFA plus bone densitometry using DXA with those screened with bone densitometry using DXA alone were identified.

Chain of Evidence
Indirect evidence on clinical utility rests on clinical validity. If the evidence is insufficient to demonstrate test performance, no inferences can be made about clinical utility.

A chain of evidence for the clinical utility of VFA screening is based on evidence that VFA identifies appropriate candidates for treatment who would not otherwise be identified, and there is evidence that treatment in this population is beneficial. The chain involves evaluating: (1) evidence that VFA is accurate, (2) evidence that VFA identifies appropriate candidates for treatment who would not otherwise be identified, and (3) evidence that treatment in this population is actually beneficial.

In its 2022 clinician's guide, the Bone Health and Osteoporosis Foundation, formerly the National Osteoporosis Foundation, recommends to consider initiating pharmacologic treatment in:⁷

• "Postmenopausal women and men ≥ 50 years who have the following:
  • Primary fracture prevention:
    • T-score ≤ -2.5 at the femoral neck, total hip, lumbar spine, 33% radius by DXA
    • Low bone mass (osteopenia: T-score between -1.0 and -2.5) at the femoral neck or total hip by DXA with a 10-year hip fracture risk ≥ 3% or a 10-year major osteoporosis-related fracture risk ≥ 20% based on the US-adapted FRAX^® model
  • Secondary fracture prevention:
    • Fracture of the hip or vertebra regardless of BMD
    • Fracture of the proximal humerus, pelvis, or distal forearm in persons with low bone mass (osteopenia: T-score between -1.0 and -2.5). The decision to treat should be individualized in persons with a fracture of the proximal humerus, pelvis, or distal forearm who do not have osteopenia or low BMD."

Because patients with osteoporosis (T score, ≤ -2.5) diagnosed by DXA and patients with low bone mass and other risk factors for fracture would be treated regardless of vertebral fractures, any incremental benefit using a VFA-inclusive strategy would accrue in the population without osteoporosis.

Vertebral Fracture Assessment to Identify Candidates Who Would Not Otherwise Be Identified
As stated above, the Bone Health and Osteoporosis Foundation (2022) guidelines have recommended treating patients with osteoporosis, osteopenia, and other risk factors as well as those with hip or vertebral fractures (clinical or asymptomatic).

Vertebral fracture assessment has been used to identify candidates for treatment when patients with vertebral fractures do not fall into 1 of the other established categories. Few studies were identified that specifically dealt with whether VFA could identify candidates for medication treatment who would not otherwise have been identified but several studies are somewhat informative. Representative studies with larger sample sizes are described next.
 
Gill et al. (2023) published a single-center retrospective study of adults who underwent DXA with VFA for any reason over a 1-year period.⁸ The authors identified 479 eligible scans; 54 patients (11%) had a vertebral fracture, of which 47 (10%) were previously undiagnosed. Among patients with new vertebral fractures, approximately 23% had normal BMD, while approximately 40% and 36% met BMD criteria for osteopenia or osteoporosis, respectively. The mean 10-year probability of major osteoporotic or hip fractures when calculated via FRAX without a documented history of fracture (i.e., prior to detection of vertebral fracture) was 7.1% and 2.8%, respectively; when recalculated to incorporate the detected vertebral fracture, these probabilities increased to 12.4% and 4.8%, respectively (p < .01 for each). Indications for DXA with VFA were not reported.

Yang et al. (2020) conducted a systematic review and meta-analysis of 28 studies evaluating detection of vertebral fractures via VFA with DXA in asymptomatic postmenopausal women.⁹ Study sample sizes ranged from 63 to 5156 and mean age ranged from 59.5 to 86.2 years. Among women who had prevalent vertebral fractures, 11.1% to 43% had osteopenia and 3.6% to 32% had normal BMD. The weighted pooled prevalence of VFA-detected vertebral fractures was 28% (95% CI, 23% to 32%) with a high degree of heterogeneity (I2 = 98.89%; p < .001). A separate subgroup analysis for women with normal bone density was not conducted.

Kanterewicz et al. (2014) in Spain collected data on a population-based cohort of 2,968 postmenopausal women between the ages of 59 and 70 years.¹⁰ A total of 127 (4.3%) women had a vertebral fracture according to VFA. Among them, 48.0% had osteoporosis, and 42.5% had osteopenia. Moreover, 42.5% had previous fragility fractures, and 34.6% had a first-degree family history of fractures. Thus, VFA could identify women who would be eligible for fracture prevention therapy according to Bone Health and Osteoporosis Foundation guidelines (i.e., women who did not have osteoporosis, osteopenia plus a 10 year fracture risk, or other risk factors). The authors did not attempt to define this subgroup of women with normal BMD and other risk factors.

Mrgan et al. (2013) in Denmark published a retrospective study evaluating VFA with BMD in 3,275 patients presenting for osteoporosis screening or evaluation of anti-osteoporotic medication; 85% were women.¹¹ Vertebral fractures were found using VFA in 260 (7.9%) patients. Of them, 156 patients (4.8% of the total sample) had osteoporosis (i.e., BMD at least -2.5) and 104 (3.2% of the total sample) did not, according to BMD. The data suggested that up to 40% (104/250) of patients with vertebral fractures identified would be eligible for treatment by Bone Health and Osteoporosis Foundation guidelines and might not have been identified were DXA alone used. Some patients, however, might have had osteopenia and other risk factors that would have led to their eligibility for treatment.

El Maghraoui et al. (2012) published a prospective study evaluating VFA with BMD in 791 asymptomatic men aged between 45 and 89 years with no prior osteoporotic fracture or known diagnosis of osteoporosis in Morocco.¹² In men with normal BMD, a grade 1 to 3 vertebral fracture was identified in 85/262 (32.4%) men. Grade 2 to 3 vertebral fractures were identified in 6.9% of these subjects. Vertebral fractures were also identified in 144/402 (35.8%) men with osteopenia (11.7% grade 2 to 3) and 89/124 (71.8%) men with osteoporosis (37.9% grade 2 to 3). Stepwise regression analysis indicated that prevalence of vertebral fractures was independently related to osteoporotic status (odds ratio [OR], 4.761; 95% CI, 2.956 to 7.668) and smoking status (OR, 1.717; 95% CI, 1.268 to 2.323).

A similar study by El Maghraoui et al. (2013) in 908 asymptomatic postmenopausal women aged between 50 and 91 years identified vertebral fractures in 63 (28.3%) women with normal BMD (8.5% grade 2 to 3).¹³ Stepwise regression analysis indicated that the presence of vertebral fractures was independently related to age, low body mass index, multiparity, history of peripheral fracture, and low BMD. It is unclear whether patients were consecutively enrolled in the El Maghraoui studies.

Jager et al. (2011) reported on 2,424 consecutive patients (65% female) referred for BMD for a variety of reasons at a single-center in the Netherlands.¹⁴ Participants underwent VFA with BMD during the same session. Vertebral fractures (reduction in the height of at least 20%) were detected in 541 (22%) patients. The prevalence of vertebral fractures was 14% (97/678) in patients with normal BMD and 21% (229/1100) in patients with osteopenia. Thus, 60.5% (326/541) of the patients with vertebral fracture did not have osteoporosis and would have been eligible for treatment based on Bone Health and Osteoporosis Foundation guidelines if they did not fall into another eligibility category (e.g., osteopenia with other risk factors). Most fractures had not been identified in the past. The vertebral fractures were previously unknown in 74% of patients with normal BMD and 71% of patients with osteopenia.

Pharmacologic Treatment for Vertebral Fracture and Low Bone Mass
Bisphosphonates decrease bone resorption and are the major class of drugs now used to treat osteoporosis.

Several subgroup analyses of large RCTs evaluating the efficacy of bisphosphonates in patients with low bone mass and/or baseline vertebral fractures have been published. The trials were not designed a priori to assess efficacy according to baseline vertebral fracture status or BMD categories. The Fracture Intervention Trial (FIT) study group was the first large multicenter study comparing the effects of treatment between osteoporotic women and women with low bone mass without existing vertebral fractures using the revised National Health and Nutrition Examination Survey cutoffs.15, This trial randomized 4432 women to alendronate or placebo and analyzed the treatment group in 3 BMD categories (< -2.5 SD, -2.0 to -2.5 SD; -1.6 to -2.0 SD below the mean). Women with a BMD less than -2.5 SD had a statistically significant reduction in clinical and vertebral fractures over 4 years. The relative risk (RR) for all clinical fractures among patients with a BMD less than -2.5 SD was 0.6 (95% CI, 0.5 to 0.8). There was no significant reduction in all clinical fractures for women with higher BMD values (RR, 1.1; 95% CI, 0.9 to 1.4), suggesting no benefit among patients with low bone mass or normal BMD.

Quandt et al. (2005) reanalyzed FIT study data for the outcome of clinical vertebral fractures (symptomatic and diagnosed by a physician) and radiographically detected (assessed at surveillance intervals) vertebral fractures.¹⁶ A total of 3,737 women at least 2 years postmenopausal with low bone mass (T score between -1.6 and -2.5) were included in the analysis. Among the women with low bone mass and existing radiographically detected vertebral fractures (n = 940), the rate of subsequent clinical vertebral fractures was 6 (a rate of 43/10000 person-years of risk) in the alendronate group and 16 (124/10,000 person-years of risk) in the placebo group. Alendronate treatment compared with placebo was accompanied by an RR of 0.3 (95% CI, 0.1 to 0.8) for clinical vertebral fractures and an RR of 0.5 (95% CI, 0.3 to 0.8) for radiographically detected fractures. Similar risk estimates were found for women having low bone mass without vertebral fractures, but absolute risks were lower (12 vs. 81 fractures per 10,000 person-years for those without and with baseline fractures, respectively).

Kanis et al. (2005) reanalyzed data on 1802 women at least 5 years postmenopausal from the Vertebral Efficacy with Risedronate Therapy (VERT) trials who were identified on the basis of a prior radiographically detected vertebral fracture regardless of BMD and had radiographs available at baseline and 3 years.¹⁷ Overall, there was a significantly lower rate of a new vertebral fracture in women with prior vertebral fracture randomized to treatment with risedronate (14.5%) than to placebo (22.3%; p < .001). In the group with a T score greater than -2.5, the rate of new femoral neck fractures was 50 (11%) of 519 in the risedronate group and 71 (15.5%) of 537 in the placebo group (p = .049). In the osteoporotic group, for those with a T score of -2.5 or lower, the rate of new femoral neck fracture was 53 (18.7%) of 355 in the risedronate group and 92 (33.4%) of 318 in the placebo group (p < .001). Findings were similar when the T score at the most severe skeletal site (femoral neck or lumbar spine) was used for stratification.
 
No RCTs were identified that evaluated the efficacy of bisphosphonate treatment in men with vertebral fractures and low bone density. Several trials have evaluated whether bisphosphonate treatment increases BMD in men at risk for bone loss (eg, on androgen deprivation therapy).^18,19 However, vertebral fractures were not assessed and, therefore, conclusions cannot be drawn about the potential benefit of VFA added to densitometry in at-risk men.

Section Summary: Vertebral Fracture Assessment
Several studies have compared VFA with radiography, including in a 2016 systematic review. The sensitivity of VFA compared with standard radiography reported in these studies varied. More recent studies have also reported higher diagnostic accuracy than older studies (ie, sensitivities in the 80% to 99% range and specificities over 90%). Routine use of VFA with DXA will identify substantial numbers of patients with previously unrecognized vertebral fractures. Many of these vertebral fractures are found in patients without osteoporosis. Data are limited on how many of the vertebral fractures in non- osteoporotic patients were in patients who would not otherwise be eligible for treatment (ie, those with osteopenia and other risk factors for fracture).

Evidence from the FIT and VERT studies has suggested that treatment of patients with low bone mass (but not osteoporosis) reduces further fractures. However, the FIT and VERT studies were post hoc subgroup analyses, which are considered to be exploratory. Also, vertebral fracture screening was done using radiography rather than VFA software. Advantages of the studies are that the 2 subgroup re-analyses had large sample sizes and used data from well-conducted randomized trials.

Currently, this chain of evidence is insufficient to determine whether treatment of patients with low bone density and vertebral fractures improves outcomes.

The purpose of the following information is to provide reference material. Inclusion does not imply endorsement or alignment with the evidence review conclusions.

Clinical Input From Physician Specialty Societies and Academic Medical Centers
While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process, through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted.

2014 Input
In response to requests, input was received from 5 physician specialty societies and 6 academic medical centers when this policy was under review in 2014. One of the 5 specialty societies only submitted a practice statement and did not respond to questions. Input was mixed on whether vertebral fracture assessment (VFA) using dual-energy X-ray absorptiometry (DXA) is considered investigational. Input was also mixed on whether the diagnostic accuracy of VFA using DXA is sufficiently high to justify its use as an alternative to plain radiographs. There was a near-consensus agreement with National Osteoporosis Foundation recommendations regarding imaging to evaluate for vertebral fractures. Responders did not cite published literature to support the National Osteoporosis Foundation recommendations. Also, there was near-consensus that patients with vertebral fracture alone (i.e., no low bone mineral density and no other signs of osteoporosis) should be treated with medications to reduce fracture risk.

Practice Guidelines and Position Statements
Guidelines or position statements will be considered for inclusion in Supplemental Information if they were issued by, or jointly by, a U.S. professional society, an international society with U.S. representation, or National Institute for Health and Care Excellence (NICE). Priority will be given to guidelines that are informed by a systematic review, include strength of evidence ratings, and include a description of management of conflict of interest.

American Association of Clinical Endocrinologists and the American College of Endocrinology
The joint guidelines from the American Association of Clinical Endocrinologists and American College of Endocrinology (2016)²⁰ on the diagnosis and treatment of postmenopausal osteoporosis included VFA recommendations similar to those of the International Society for Clinical Densitometry (below). An update to the guidelines in 2020²¹ includes stratification of women with osteoporosis into high-risk and very-high-risk features to drive choice and duration of initial therapy. The guidelines also introduce romosozumab into the treatment algorithm and elucidate treatment transitions from agents such as denosumab.

American College of Physicians
The American College of Physicians' guidelines (2017) on the treatment of low bone density or osteoporosis include the following recommendations (Table 2).²²

Table 2. Guidelines on the Treatment of Low Bone Density or Osteoporosis

Recommendation	GOE	QOE
"ACP recommends that clinicians offer pharmacologic treatment with bisphosphonates to reduce the risk for vertebral fracture in men who have clinically recognized osteoporosis."	Weak	Low
"ACP recommends that clinicians should make the decision whether to treat osteopenic women 65 years of age or older who are at a high risk for fracture based on a discussion of patient preferences, fracture risk profile, and benefits, harms, and costs of medications."	Weak	Low

ACP: American College of Physicians; GOE: grade of evidence; QOE: quality of evidence.

American College of Radiology
The American College of Radiology (ACR) published updated appropriateness criteria for osteoporosis and bone mineral density (BMD) in 2022.²³ DXA VFA is not mentioned among imaging studies in patients undergoing osteoporosis screening or initial imaging of clinically suspected low BMD. For follow-up imaging of patients demonstrated to have risk for fracture or surveillance of established low BMD, DXA VFA is usually not appropriate by ACR criteria. Conversely, for follow-up imaging of patients with T-scores less than -1.0 by DXA, DXA VFA is usually appropriate by ACR criteria in patients who meet 1 or more of the following criteria:

• Females ≥ 70 years of age or males ≥ 80 years of age;
• Historical height loss > 4 cm (> 1.5 inches);
• Self-reported but undocumented prior vertebral fracture;
• Glucocorticoid therapy equivalent to ≥ 5 mg prednisone equivalent per day for ≥ 3 months.

Bone Health and Osteoporosis Foundation
The Bone Health and Osteoporosis Foundation, formerly the National Osteoporosis Foundation, published an updated clinician's guide to the prevention and treatment of osteoporosis in 2022.⁷ Per the guide, "a vertebral fracture in an adult ≥ 50 years is diagnostic of osteoporosis, even in the absence of a bone density diagnosis. Unfortunately, most vertebral fractures are subclinical or completely asymptomatic. As a result, they may go undiagnosed for many years. At the same time, a high proportion of women with asymptomatic vertebral fractures have BMD levels that would not warrant treatment based on BMD alone. The finding of a previously unrecognized vertebral fracture may change a patient's diagnostic classification, alter fracture risk calculations, and determine treatment decisions. Proactive investigation is required to detect these fractures so that further bone damage can be prevented."

Traditionally, conventional lateral thoracic/lumbar spine X-ray has been considered the gold standard for identification of vertebral fractures; however, the guide notes that "DXA-assisted VFA is emerging as an alternative to radiograph for its convenience, low cost, and minimal radiation exposure."⁷ The guide recommends that "to detect subclinical vertebral fractures," clinicians should perform vertebral fracture imaging (X-ray or DXA VFA) in the following:

• Women aged ≥ 65 years if T-score is ≤ -1.0 at the femoral neck;
• Women ≥ 70 years and men ≥ 80 years if T-score is ≤ -1.0 at the lumbar spine, total hip, or femoral neck;  
• Men aged 70 to 79 years if T-score is ≤ -1.5 at the lumbar spine, total hip, or femoral neck;
• Postmenopausal women and men ≥ 50 years with the following specific risk factors:  
  • Fracture(s) during adulthood (any cause).
  • Historical height loss of ≥ 1.5 inches (defined as the difference between the current height and peak height).
  • Prospective height loss of ≥ 0.8 inches (defined as the difference between the current height and last documented height measurement).  
  • Recent or ongoing long-term glucocorticoid treatment.
  • Diagnosis of hyperparathyroidism.

International Society for Clinical Densitometry
The International Society for Clinical Densitometry (2019) updated its recommendations for selecting patients for VFA;²⁴ these recommendations remain the same as in a 2015 update.²⁵ Lateral spine imaging with either standard radiography or densitometric VFA is indicated for patients with a T score of less than -1.0 when at least 1 of the following factors are present:

• "Women age ≥ 70 years or men ≥ 80 years
• Historical height loss greater than 4 cm (1.5 inches)
• Self-reported but undocumented prior vertebral fracture
• Glucocorticoid therapy equivalent to ≥ 5 mg of prednisone or equivalent per day for ≥ 3 months."

An update to the International Society for Clinical Densitometry official positions is in progress.

Endocrine Society
The Endocrine Society Clinical Practice Guideline (2019) on pharmacological management of osteoporosis in postmenopausal women states 4 management principles:²⁶

“(i)    The risk of future fractures in postmenopausal women should be determined using country-specific assessment tools to guide decision-making.

(ii)    Patient preferences should be incorporated into treatment planning.

(iii)   Nutritional and lifestyle interventions and fall prevention should accompany all pharmacologic regimens to reduce fracture risk.

(iv)   Multiple pharmacologic therapies are capable of reducing fracture rates in postmenopausal women at risk with acceptable risk-benefit and safety profiles.”

North American Menopause Society
The North American Menopause Society updated its position statement on the management of osteoporosis in postmenopausal women in 2021.²⁷ The society states that in order to identify asymptomatic compression vertebral fractures, "evaluation by a lateral thoracolumbar radiograph or VFA by DXA" may be used.

U.S. Preventive Services Task Force Recommendations
The U.S. Preventive Services Task Force (2018) updated its recommendations on screening for osteoporosis to prevent fractures.²⁸ The recommendations included: "Most treatment guidelines recommend using BMD, as measured by central DXA, to define osteoporosis and the treatment threshold to prevent osteoporotic fractures." Peripheral DXA and quantitative ultrasound are also described as common bone measurement screening tests for osteoporosis. Vertebral fracture assessment was not specifically mentioned. An update of this topic is currently in progress with plans to address vertebral fracture assessment per the draft research plan.²⁹

Ongoing and Unpublished Clinical Trials
A search of ClinicalTrials.gov in August 2023 did not identify any ongoing or unpublished trials that would likely influence this review.

References:   

1. Alsoof D, Anderson G, McDonald CL, et al. Diagnosis and Management of Vertebral Compression Fracture. Am J Med. Jul 2022; 135(7): 815-821. PMID 35307360
2. Malgo F, Hamdy NAT, Ticheler CHJM, et al. Value and potential limitations of vertebral fracture assessment (VFA) compared to conventional spine radiography: experience from a fracture liaison service (FLS) and a meta-analysis. Osteoporos Int. Oct 2017; 28(10): 2955-2965. PMID 28842721
3. Lee JH, Lee YK, Oh SH, et al. A systematic review of diagnostic accuracy of vertebral fracture assessment (VFA) in postmenopausal women and elderly men. Osteoporos Int. May 2016; 27(5): 1691-9. PMID 26782682
4. Domiciano DS, Figueiredo CP, Lopes JB, et al. Vertebral fracture assessment by dual X-ray absorptiometry: a valid tool to detect vertebral fractures in community-dwelling older adults in a population-based survey. Arthritis Care Res (Hoboken). May 2013; 65(5): 809-15. PMID 23212896
5. Ferrar L, Jiang G, Clowes JA, et al. Comparison of densitometric and radiographic vertebral fracture assessment using the algorithm-based qualitative (ABQ) method in postmenopausal women at low and high risk of fracture. J Bone Miner Res. Jan 2008; 23(1): 103-11. PMID 17892377
6. Binkley N, Krueger D, Gangnon R, et al. Lateral vertebral assessment: a valuable technique to detect clinically significant vertebral fractures. Osteoporos Int. Dec 2005; 16(12): 1513-8. PMID 15834512
7. LeBoff MS, Greenspan SL, Insogna KL, et al. The clinician's guide to prevention and treatment of osteoporosis. Osteoporos Int. Oct 2022; 33(10): 2049-2102. PMID 35478046
8. Gill SM, Hassan A. Routine Use of Lateral Vertebral Assessment With DXA Scan for Detection of Silent But Debilitating Vertebral Fractures. Clin Nucl Med. Feb 01 2023; 48(2): 107-111. PMID 36607360
9. Yang J, Mao Y, Nieves JW. Identification of prevalent vertebral fractures using Vertebral Fracture Assessment (VFA) in asymptomatic postmenopausal women: A systematic review and meta-analysis. Bone. Jul 2020; 136: 115358. PMID 32268210
10. Kanterewicz E, Puigoriol E, García-Barrionuevo J, et al. Prevalence of vertebral fractures and minor vertebral deformities evaluated by DXA- assisted vertebral fracture assessment (VFA) in a population-based study of postmenopausal women: the FRODOS study. Osteoporos Int. May 2014; 25(5): 1455-64. PMID 24599272
11. Mrgan M, Mohammed A, Gram J. Combined vertebral assessment and bone densitometry increases the prevalence and severity of osteoporosis in patients referred to DXA scanning. J Clin Densitom. 2013; 16(4): 549-53. PMID 23769657
12. El Maghraoui A, Mounach A, Rezqi A, et al. Vertebral fracture assessment in asymptomatic men and its impact on management. Bone. Apr 2012; 50(4): 853-7. PMID 22240446
13. El Maghraoui A, Rezqi A, Mounach A, et al. Systematic vertebral fracture assessment in asymptomatic postmenopausal women. Bone. Jan 2013; 52(1): 176-80. PMID 23017663
14. Jager PL, Jonkman S, Koolhaas W, et al. Combined vertebral fracture assessment and bone mineral density measurement: a new standard in the diagnosis of osteoporosis in academic populations. Osteoporos Int. Apr 2011; 22(4): 1059-68. PMID 20571773
15. Cummings SR, Black DM, Thompson DE, et al. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. JAMA. Dec 1998; 280(24): 2077-82. PMID 9875874
16. Quandt SA, Thompson DE, Schneider DL, et al. Effect of alendronate on vertebral fracture risk in women with bone mineral density T scores of-1.6 to -2.5 at the femoral neck: the Fracture Intervention Trial. Mayo Clin Proc. Mar 2005; 80(3): 343-9. PMID 15757015
17. Kanis JA, Barton IP, Johnell O. Risedronate decreases fracture risk in patients selected solely on the basis of prior vertebral fracture. Osteoporos Int. May 2005; 16(5): 475-82. PMID 15875093
18. Bhoopalam N, Campbell SC, Moritz T, et al. Intravenous zoledronic acid to prevent osteoporosis in a veteran population with multiple risk factors for bone loss on androgen deprivation therapy. J Urol. Nov 2009; 182(5): 2257-64. PMID 19758618
19. Greenspan SL, Nelson JB, Trump DL, et al. Effect of once-weekly oral alendronate on bone loss in men receiving androgen deprivation therapy for prostate cancer: a randomized trial. Ann Intern Med. Mar 20 2007; 146(6): 416-24. PMID 17371886
20. Camacho PM, Petak SM, Binkley N, et al. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY CLINICAL PRACTICE GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS - 2016. Endocr Pract. Sep 02 2016; 22(Suppl 4): 1-42. PMID 27662240
21. Camacho PM, Petak SM, Binkley N, et al. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS/AMERICAN COLLEGE OF ENDOCRINOLOGY CLINICAL PRACTICE GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS-2020 UPDATE. Endocr Pract. May 2020; 26(Suppl 1): 1-46. PMID 32427503
22. Qaseem A, Forciea MA, McLean RM, et al. Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update From the American College of Physicians. Ann Intern Med. Jun 06 2017; 166(11): 818-839. PMID 28492856
23. American College of Radiology. ACR Appropriateness Criteria, Osteoporosis and Bone Mineral Density. 2022; https://acsearch.acr.org/docs/69358/Narrative/. Accessed July 25, 2023
24. International Society for Clinical Densitometry. 2019 ISCD Official Positions Adult. 2019; https://iscd.org/wp-content/uploads/2021/09/2019- Official-Positions-Adult-1.pdf. Accessed August 4, 2023.
25. Shepherd JA, Schousboe JT, Broy SB, et al. Executive Summary of the 2015 ISCD Position Development Conference on Advanced Measures From DXA and QCT: Fracture Prediction Beyond BMD. J Clin Densitom. 2015; 18(3): 274-86. PMID 26277847
26. Eastell R, Rosen CJ, Black DM, et al. Pharmacological management of osteoporosis in postmenopausal women: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. May 2019;104(5):1595-1622.
27. Management of osteoporosis in postmenopausal women: the 2021 position statement of The North American Menopause Society. Menopause. Sep 01 2021; 28(9): 973-997. PMID 34448749
28. Curry SJ, Krist AH, Owens DK, et al. Screening for Osteoporosis to Prevent Fractures: US Preventive Services Task Force Recommendation Statement. JAMA. Jun 26 2018; 319(24): 2521-2531. PMID 29946735
29. U.S. Preventive Services Task Force (USPSTF). Draft Research Plan. Osteoporosis to Prevent Fractures: Screening. August 12, 2021; https://www.uspreventiveservicestaskforce.org/uspstf/document/draft-research-plan/osteoporosis-screening-prevent-fractures.

Coding Section

Codes	Number	Description
CPT	0691T (effective 01/01/2022)	Automated analysis of an existing computed tomography study for vertebral fracture(s), including assessment of bone density when performed, data preparation, interpretation, and report
CPT	77085	Dual-energy X-ray absorptiometry (DXA), bone density study, 1 or more sites; axial skeleton (e.g., hips, pelvis, spine), including vertebral fracture assessment
	77086	Vertebral fracture assessment via dual-energy X-ray absorptiometry (DXA)
ICD-10-CM		Investigational for all relevant diagnoses
	M80.08	Age-related osteoporosis with current pathological fracture, vertebra(e)
	M80.88	Other osteoporosis with current pathological fracture, vertebra(e)
	M81.0	Age-related osteoporosis without current pathological fracture
	M81.6	Localized osteoporosis
	M81.8	Other osteoporosis without current pathological fracture
	Z13.820	Encounter for screening for osteoporosis
	Z13.828	Encounter for screening for other musculoskeletal disorder
ICD-10-PCS		ICD-10-PCS codes are only used for inpatient services
	BR00ZZ1, BR07ZZ1, BR09ZZ1, BR0GZZ1	Imaging, axial skeleton, plain radiography, densitometry, code by body part
Type of service	Radiology
Place of service	Outpatient/inpatient

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross Blue Shield Association technology assessment program (TEC) and other nonaffiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

"Current Procedural Terminology © American Medical Association.  All Rights Reserved" 

History From 2013 Forward     

02/21/2024	Corrected date on Last review date and next review date. Changed last review to 02/01/2024 and next review to 02/01/2025. No other changes.
02/07/2024	Annual review, no change to policy intent. Updating regulatory status,rationale and references.
02/02/2023	Annual review, no change to policy intent. Updating rationale and references.
02/07/2022	Annual review, no change to policy intent. Updating rationale and references.
11/23/2021	Updating policy with 2022 coding. Adding code 0691T. No other change made.
02/01/2021	Annual review, no change to policy intent. Updating guidelines, coding, rationale and references.
02/06/2020	Annual review, no change to policy intent. Updating background, regulatory status, rationale and references.
02/20/2019	Annual review, no change to policy intent. Updating rationale, references and coding.
02/27/2018	Annual review, no change to policy intent. Updating background, description, regulatory status, rationale and references. Also removed coding from prior to 2015 from guidelines.
02/01/2017	Annual review, no change to policy intent. Updating background, description, rationale and references.
02/15/2016	Annual review, no change to policy intent. Updating background, description, rationale and references.
02/24/2015	Annual review, no change to policy intent. Updated rationale and references, added guidlines, coding and appendix A.
02/10/2014	Annual review. Updated rationale and references. Added related policies. No change to policy intent.