TBS iNsight is a software provided for use as a complement to both DXA analysis and clinical examination. It computes the antero-posterior spine DXA examination file and calculates a score (Trabecular Bone Score - TBS) that is compared to those of the age matched controls. The TBS is derived from the texture of the DXA image and has been shown to be related to bone microarchitecture.

TBS iNsight provides as an option an assessment of 10-year fracture risk. It provides an estimate of 10-year probability of hip fracture and 10-year probability of a major osteoporotic fracture (clinical spine, forearm, hip or shoulder fracture). This estimate is based on the WHO's FRAX® Fracture Risk Assessment Tool, after adjustment for the TBS. The tool has been validated for Caucasian and Asian men and post-menopausal women between 40 and 90 years old.

TBS provides information independent of BMD value: it is used as a complement to the data obtained from the DXA analysis and the clinical examination (questioning by the clinician about patient history, bioassay of bone resorption markers...).

The results can be used by a physician in conjunction with other clinical risk factors as an aid in the diagnosis of osteoporosis and other medical conditions leading to altered trabecular bone microarchitecture, and ultimately in the assessment of fracture risk.

The TBS score can assist the health care professional in monitoring the effect of treatments on patients across time. Overall fracture risk will depend on many additional factors that should be considered before making diagnostic or therapeutic recommendations. The software does not disease or recommend treatment regimens. Only the health care professional can make these judgments.

Device Description

TBS iNsight is a software application provided for use as a complement to bone mineral density (BMD) acquired from dual energy X-ray absorptiometry (DXA) and other clinical risk factors for osteoporosis and fragility fracture. It calculates a score (Trabecular Bone Score - TBS) derived from the texture of the DXA image of the anterior-posterior (AP) lumbar spine and has been shown to be related to bone microarchitecture. The method analyzes X-ray based images acquired by DXA imaging systems and produces the TBS based on the computation of an Adapted Experimental Variogram (modified fractal-like approach). This variogram is used to measure the degree of spatial variation between pairs of data points in a spatial dimension of a region of a digital image.

The absolute TBS values for the same equivalent tissue thickness vary slightly between GE and Hologic systems. Additionally, within each system, variability in TBS values can be observed across different scan modes. To address these differences, corrections are applied that are both device-specific and mode-specific. For instance, TBS is corrected differently for GE and Hologic systems to account for inherent differences in tissue thickness assessment. Furthermore, corrections are also tailored separately for each scan mode within the same system, ensuring that TBS measurements remain consistent and reliable regardless of the scan mode used. These device-specific and mode-specific corrections are necessitated by differences in the dynamic range of tissue thickness measurements between GE and Hologic devices. The variations arise due to differences in the methodologies used to assess tissue thickness. To harmonize these discrepancies and ensure measurement accuracy, correction fits derived from ex-vivo data are applied individually to each device and scan mode. This approach ensures the accuracy and consistency of TBS measurements across all configurations.

The device is intended to be used for bone health assessment in medical facilities employing one or more DXA system(s) to which the subject device is connected. These facilities are usually hospitals, clinics, healthcare centers, radiology practices and medical imaging centers. The software is designed to be used by qualified clinical professionals (including physicians, radiologists and DXA technicians) and the physicians are solely responsible for making all final patient management decisions.

AI/ML Overview

The provided text does not contain a discrete table of acceptance criteria nor explicit reported device performance metrics against such criteria in a tabular format. However, based on the Performance Testing Summary & Conclusions section (pages 9-10), the acceptance criteria can be inferred from the studies described. The reported performance is woven into the narrative of the study results.

Here's an attempt to derive the information requested:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Inferred from study objectives)	Reported Device Performance (TBS iNsight V4)
Accuracy of TBS V4 in reflecting bone microarchitecture (vs. microCT)	Strong and statistically significant correlations with parameters such as trabecular number and separation. Maintained or exceeded correlations established with the predicate.
Agreement between TBS V4 and Predicate Software	Excellent agreement, with correlation coefficients exceeding 0.99. Bland-Altman statistics confirmed negligible differences between versions across multiple DXA systems.
Reproducibility (Precision and Least Significant Change - LSC) in ex vivo settings	Precision and LSC values comparable to or slightly improved over the predicate, consistent across various DXA systems.
Reproducibility (Precision and LSC) in in vivo settings (clinical conditions with repositioning)	Met or exceeded precision standards established by the International Society for Clinical Densitometry (ISCD), with LSC values within acceptable thresholds.
Validity of Tissue Thickness (TT) Range	Validated in-vivo, establishing a valid tissue thickness range of 7-30 cm, aligning with physiological parameters for TBS calculations.
Applicability across diverse demographic groups (population-specific reference curves)	Generation of population-specific reference curves for age, sex, and ethnicity. Comparisons with the predicate software confirmed statistical equivalence, reinforcing reliability across diverse demographic groups, including multi-ethnic populations in the United States.
Performance in fracture risk assessment (TBS-adjusted FRAX and BMD T-scores)	Demonstrated similar TBS-adjusted FRAX and BMD T-scores for major osteoporotic and hip fractures compared to the predicate, using data from over 17,000 individuals across 14 international cohorts.
Effectiveness for treatment monitoring (TBS-adjusted FRAX and BMD T-scores over time)	Demonstrated effectiveness for accurately outputting TBS-adjusted FRAX and BMD T-scores over time for treatment monitoring, with substantial equivalence to the predicate, in a large cohort of postmenopausal women with osteoporosis.
Software Verification and Validation	Demonstrated specified requirements are met and the software functions as intended.
Cybersecurity Compliance	Controls and processes implemented; documentation and testing demonstrate alignment with FDA guidance ("Cybersecurity in Medical Devices") and Section 524B of the FD&C Act.
Substantial Equivalence (Overall Device Performance)	TBS version 4.0 demonstrates substantially equivalent performance in the assessment of bone quality and TBS-adjusted FRAX and BMD T-scores compared to the predicate device. Standalone validation studies confirm performance, reliability, and utility across diverse populations and DXA systems.

2. Sample Sizes Used for the Test Set and Data Provenance

Clinical Association Study 1 (Correlation with microCT):
- Sample Size: 30 human cadaver lumbar vertebrae.
- Data Provenance: Not explicitly stated, but "human cadaver lumbar vertebrae" implies a laboratory-based, retrospective study.
Clinical Association Study 2 (Agreement between V4 and Predicate):
- Sample Size: 15 human cadaver vertebrae.
- Data Provenance: Not explicitly stated, but "human cadaver vertebrae" implies a laboratory-based, retrospective study. Measurements were performed on "multiple DXA systems."
Analytical Reproducibility (Ex Vivo Study):
- Sample Size: Not explicitly stated, but "dried human lumbar vertebrae," likely similar to the cadaver studies.
- Data Provenance: Retrospective, laboratory-based.
Analytical Reproducibility (In Vivo Study):
- Sample Size: 132 participants.
- Data Provenance: Not explicitly stated, but "scanned on four different DXA systems" with "repositioning between scans" indicates a prospective, controlled clinical study.
Performance and Utility (Fracture Risk Assessment):
- Sample Size: Over 17,000 individuals across 14 international cohorts.
- Data Provenance: International cohorts, implying retrospective data from multiple countries.
Performance and Utility (Treatment Monitoring):
- Sample Size: A "large cohort" of postmenopausal women with osteoporosis. Specific number not provided.
- Data Provenance: Not explicitly stated, but likely retrospective clinical data.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

The document does not specify the number or qualifications of experts used to establish ground truth for the various test sets.

For microCT correlation: Micro-computed tomography (microCT) is an objective imaging technique, so human expert interpretation for ground truth might not be directly applicable in the same way as, for example, image interpretation by radiologists.
For in vivo studies: The ground truth for bone microarchitecture or fracture risk assessment, as implied by the use of ISCD standards and FRAX, are typically established by clinical diagnosis and follow-up, rather than a panel of experts explicitly reviewing the test set images for ground truth.

4. Adjudication Method for the Test Set

The document does not describe any adjudication methods (e.g., 2+1, 3+1) for establishing ground truth from expert readers for the test sets.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve with AI vs. Without AI Assistance

No, an MRMC comparative effectiveness study was not explicitly described in the provided text. The studies focus on the device's standalone performance, its agreement with the predicate device, and its correlation with bone microarchitecture ground truth (microCT), as well as its utility for fracture risk assessment and treatment monitoring.
The text describes the device as a "complement to both DXA analysis and clinical examination" and states that "The results can be used by a physician in conjunction with other clinical risk factors." While it aids physicians, the document does not include a comparative study evaluating how human reader performance (e.g., diagnosis or risk assessment accuracy) improves with TBS iNsight V4 assistance versus without it.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, a standalone performance assessment was conducted. The "Standalone Performance Testing Summary" section (page 9) explicitly states that "Software Verification and Validation demonstrate specified requirements are met and the software functions as intended."
Furthermore, the "Clinical Association" and "Analytical Reproducibility" studies directly evaluate the performance of TBS version 4.0 in calculating TBS values and their correlation with microCT independently, and their agreement/reproducibility compared to the predicate, without human intervention in the calculation process.

7. The Type of Ground Truth Used

Pathology/Objective Measurement: For establishing the relationship between TBS and bone microarchitecture, micro-computed tomography (microCT) measurements were used as the ground truth (e.g., for trabecular number and separation). This is an objective measurement of bone structure.
Clinical Diagnosis/Outcomes Data: For "fracture risk assessment" and "treatment monitoring," the ground truth implicitly refers to the clinically established reference values (e.g., those used in FRAX) and potentially actual fracture outcomes data from the cohorts. The studies confirm that TBS V4 provides "similar TBS-adjusted FRAX and BMD T-scores" and is effective for monitoring, suggesting that it aligns with known clinical indicators and outcomes.
Predicate Device Performance: For demonstrating "agreement" and "substantial equivalence," the performance of the predicate device (TBS iNsight V3) serves as a comparative ground truth or benchmark.

8. The Sample Size for the Training Set

The document does not provide information regarding the sample size used for the training set for the TBS iNsight V4 algorithm.

9. How the Ground Truth for the Training Set Was Established

The document does not provide information on how the ground truth for any training set was established, as the details of algorithm development and training are not included. The focus is on the performance testing of the final device version.

Summary

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Image /page/0/Picture/0 description: The image contains the logos of the Department of Health & Human Services and the Food and Drug Administration (FDA). The Department of Health & Human Services logo is on the left, and the FDA logo is on the right. The FDA logo includes the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text.

January 17, 2025

Medimaps Group SA % Giorgio Zoia Quality and Regulatory VP, Medimaps SA Group Chemin du Champ-des-Filles 36 Plan-les-Ouates, 1228 SWITZERLAND

Re: K243218

Trade/Device Name: TBS iNsight (V4) Regulation Number: 21 CFR 892.1170 Regulation Name: Bone Densitometer Regulatory Class: Class II Product Code: KGI Dated: December 20, 2024 Received: December 20, 2024

Dear Giorgio Zoia:

We have reviewed your section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (the Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

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Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30. Design controls; 21 CFR 820.90. Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rule"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-device-advicecomprehensive-regulatory-assistance/unique-device-identification-system-udi-system.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatory

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assistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Lu Jiang

Lu Jiang, Ph.D. Assistant Director Diagnostic X-Ray Systems Team DHT8B: Division of Radiological Imaging Devices and Electronic Products OHT8: Office of Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K243218

Device Name TBS iNsight (v4)

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)

Prescription Use (Part 21 CFR 801 Subpart D)	区
Over-The-Counter Use (21 CFR 801 Subpart C)

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510(K) SUMMARY

Date:	January 16, 2025
-------	------------------

510(k) Number: K243218

1) Applicant Information

510(k) Owner:	Medimaps Group SA
	Chemin du Champ-des-Filles 36 Plan-les-Ouates
	1228 Switzerland
Contact Person:	Giorgio Zoia, PhD
	Quality and Regulatory VP
	Phone 41 22 515 01 14
	Email regulatory@medimapsgroup.com

1. Device Identification

Trade Name:	TBS iNsight (V4)
Common Name:	Bone densitometer
Regulation Number :	892.1170
Regulation Name:	Bone densitometer
Regulatory Class:	II

KGI

3) Predicate Device

Product Code:

Trade Name:	TBS iNsight
510 (k) Number:	K152299
Common Name:	Bone densitometer
Regulation Number :	892.1170
Regulation Name:	Bone densitometer
Regulatory Class:	==============================================================================================================================================================================
Product Code:	KGI

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Device Description Summary

TBS iNsight is a software application provided for use as a complement to bone mineral density (BMD) acquired from dual energy X-ray absorptiometry (DXA) and other clinical risk factors for osteoporosis and fragility fracture. It calculates a score (Trabecular Bone Score - TBS) derived from the texture of the DXA image of the anterior-posterior (AP) lumbar spine and has been shown to be related to bone microarchitecture. The method analyzes X-ray based images acquired by DXA imaging systems and produces the TBS based on the computation of an Adapted Experimental Variogram (modified fractallike approach). This variogram is used to measure the degree of spatial variation between pairs of data points in a spatial dimension of a region of a digital image.

Intended Use

TBS iNsight is indicated as an adjunct to BMD and other clinical factors, for the assessment of bone health and the management of primary and secondary osteoporosis. Primary osteoporosis can occur in both sexes with aging, and in females due to the menopause and associated estrogen deficiency. Secondary osteoporosis occurs as a result of an underlying disease or condition, which alters bone metabolism leading to a net loss of bone and degradation of bone quality, for example, diabetes, hyperparathyroidism, chronic kidney disease and rheumatological conditions.

Indication for Use

TBS iNsight provides as an option an assessment of 10-year fracture risk. It provides an estimate of 10year probability of hip fracture and 10-year probability of a major osteoporotic fracture (clinical spine, forearm, hip or shoulder fracture). This estimate is based on the WHO's FRAX® Fracture Risk

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Assessment Tool, after adjustment for the TBS. The tool has been validated for Caucasian and Asian men and post-menopausal women between 40 and 90 years old.

TBS provides information independent of BMD value; it is used as a complement to the data obtained from the DXA analysis and the clinical examination (questioning by the clinician about patient history, bioassay of bone resorption markers...).

The TBS score can assist the health care professional in monitoring the effect of treatments on patients across time.

Overall fracture risk will depend on many additional factors that should be considered before making diagnostic or therapeutic recommendations. The software does not diagnose disease or recommend treatment regimens. Only the health care professional can make these judgments.

Technological Comparison

The subject device, TBS iNsight V4, has been designed to maintain identical core functionalities as its predicate, specifically in the computation of Trabecular Bone Score (TBS) from DXA (Dual-energy X-ray Absorptiometry) image texture and the provision of complementary DXA analysis. TBS iNsight V4 and the predicate compute TBS from DXA image textures and provide complementary DXA analysis, ensuring continuity in the primary operational utility of the technology.

Differences:

Algorithm for Tissue Thickness: Unlike the predicate device which uses BMI to estimate tissue thickness in its TBS computation algorithm, the subject device directly measures tissue thickness (TT) using the DXA system. This direct measurement potentially increases the accuracy of TBS calculations.
System Architecture: The system architecture of the subject device represents an evolution from the standalone software model used in the predicate. The subject device includes a two-component system comprising a TBS Agent (client) installed on each DXA device and a centralized server that manages results and facilitates DICOM communication with PACS. This advancement supports enhanced scalability and integration within clinical settings.
Data Security: TBS iNsight V4 introduces robust encryption protocols by incorporating encryption or role-based access control, aligning the new device with current best practices in data security.

Table 1. Substantial equivalence of TBS iNsight v4 to predicate device

Elements ofComparison	Subject device	Predicate Device	Comparisonto predicatedevice
Device Name	TBS iNsight	TBS iNsight	Unchanged
Software Version	4	3	Updated
Manufacturer	Medimaps	Medimaps	Unchanged
510(k) #	K243218	K152299	N/A
Class	Class II	Class II	Unchanged
Elements ofComparison	Subject device	Predicate Device	Comparisonto predicatedevice
Classification Rule /Name	21 CFR 892.1170 Bone Densitometer	21 CFR 892.1170 Bone Densitometer	Unchanged
Product Code	KGI	KGI	Unchanged
Level of Concern	Basic Documentation	Moderate	Unchanged
Intended Use	TBS is indicated as an aid, in conjunction with otherclinical factors, for the diagnosis of primary andsecondary osteoporosis. Primary osteoporosis can occurin both sexes with ageing, and in women due to themenopause and associated estrogen deficiency.Secondary osteoporosis occurs as a result of anunderlying disease or condition, which alters bonemetabolism leading to a net loss of bone and degradationof bone quality, for example, diabetes,hyperparathyroidism, chronic kidney disease andrheumatological conditions.	TBS is indicated as an aid, in conjunction with otherclinical factors, for the diagnosis of primary andsecondary osteoporosis. Primary osteoporosis can occurin both sexes with ageing, and in women due to themenopause and associated estrogen deficiency.Secondary osteoporosis occurs as a result of anunderlying disease or condition, which alters bonemetabolism leading to a net loss of bone and degradationof bone quality, for example, diabetes,hyperparathyroidism, chronic kidney disease andrheumatological conditions.	Unchanged
Indications for Use	TBS iNsight is a software provided for use as acomplement to both DXA analysis and clinicalexamination. It computes the antero-posterior spine DXAexamination file and calculates a score (Trabecular BoneScore - TBS) that is compared to those of the agematched controls. The TBS is derived from the texture ofthe DXA image and has been shown to be related to bonemicroarchitecture.TBS iNsight provides as an option an assessment of 10-year fracture risk. It provides an estimate of 10-yearprobability of hip fracture and 10-year probability of amajor osteoporotic fracture (clinical spine, forearm, hipor shoulder fracture). This estimate is based on theWHO'S FRAX® Fracture Risk Assessment Tool, afteradjustment for the TBS. The tool has been validated forCaucasian and Asian men and post-menopausal womenbetween 40 and 90 years old.TBS provides information independent of BMD value; it isused as a complement to the data obtained from the DXAanalysis and the clinical examination (questioning by theclinician about patient history, bioassay of boneresorption markers...).The results can be used by a physician in conjunction withother clinical risk factors as an aid in the diagnosis ofosteoporosis and other medical conditions leading toaltered trabecular bone microarchitecture, and ultimatelyin the assessment of fracture risk.The TBS score can assist the health care professional inmonitoring the effect of treatments on patients acrosstime.Overall fracture risk will depend on many additionalfactors that should be considered before makingdiagnostic or therapeutic recommendations. Thesoftware does not diagnose disease or recommendtreatment regimens. Only the health care professionalcan make these judgments.	TBS iNsight is a software provided for use as acomplement to both DXA analysis and clinicalexamination. It computes the antero-posterior spine DXAexamination file and calculates a score (Trabecular BoneScore - TBS) that is compared to those of the agematched controls. The TBS is derived from the texture ofthe DXA image and has been shown to be related to bonemicroarchitecture.TBS iNsight provides as an option an assessment of 10-year fracture risk. It provides an estimate of 10-yearprobability of hip fracture and 10-year probability of amajor osteoporotic fracture (clinical spine, forearm, hipor shoulder fracture). This estimate is based on theWHO'S FRAX® Fracture Risk Assessment Tool, afteradjustment for the TBS. The tool has been validated forCaucasian and Asian men and post-menopausal womenbetween 40 and 90 years old.TBS provides information independent of BMD value; it isused as a complement to the data obtained from the DXAanalysis and the clinical examination (questioning by theclinician about patient history, bioassay of boneresorption markers...).The results can be used by a physician in conjunction withother clinical risk factors as an aid in the diagnosis ofosteoporosis and other medical conditions leading toaltered trabecular bone microarchitecture, and ultimatelyin the assessment of fracture risk.The TBS score can assist the health care professional inmonitoring the effect of treatments on patients acrosstime.Overall fracture risk will depend on many additionalfactors that should be considered before makingdiagnostic or therapeutic recommendations. Thesoftware does not diagnose disease or recommendtreatment regimens. Only the health care professionalcan make these judgements.	Unchanged
Technological Characteristics
Mode of operation	Dual Energy X-ray Absorptiometry	Dual Energy X-ray Absorptiometry	Unchanged
Input data	Raw DXA images and patient data	Raw DXA images and patient data	Unchanged
Measurementsprovided	Lumbar Spine TBS	Lumbar Spine TBS	Unchanged
Elements ofComparison	Subject device	Predicate Device	Comparisonto predicatedevice
	TBS T-Score and Z-scoreTBS Category of fracture risk: normal, medium,or lowFRAX® Adjusted for TBS Estimate of 10-YearFracture Risk based on clinical risk factors, BMDand TBS; indication of % probability of a hipfracture in the next 10 years and % probabilityof a major osteoporotic fracture (clinical spine,forearm, hip or shoulder fracture) in the next 10years.	TBS T-Score and Z-scoreTBS Category of fracture risk: normal, medium,or lowFRAX® Adjusted for TBS Estimate of 10-YearFracture Risk based on clinical risk factors, BMDand TBS; indication of % probability of a hipfracture in the next 10 years and % probabilityof a major osteoporotic fracture (clinical spine,forearm, hip or shoulder fracture) in the next 10years.
Target population	The intended patient population for TBS iNsightcomprises both men and women, with its purpose for theassessment of bone health and fracture risk. Currently,TBS has not been validated for individuals younger than20 years of age.The intended patient population for FRAX-adjusted byTBS are Caucasian and Asian men and women between40 and 90 years old, for 10-year fracture risk assessment.	The intended patient population for TBS iNsightcomprises both men and women, with its purpose for theassessment of bone health and fracture risk. Currently,TBS has not been validated for individuals younger than20 years of age.The intended patient population for FRAX-adjusted byTBS are Caucasian and Asian men and women between40 and 90 years old, for 10-year fracture risk assessment.	Unchanged
Users	DXA technologists, Physicians, Radiologists	DXA technologists, Physicians, Radiologists	Unchanged
DXA manufacturersupported	GE HC, Hologic	GE HC, Hologic	Unchanged
Segmentation	Automatic ROI segmentation, possibly correctedmanually	Automatic ROI segmentation, possibly correctedmanually	Unchanged
Functionality	Computes TBS from DXA image texture.Outputs complement DXA analysis.	Computes TBS from DXA image texture.Outputs complement DXA analysis.	Unchanged
-Algorithm for TissueThickness	Directly uses tissue thickness (TT) measured by the DXA,in the TBS computation algorithm.	Uses BMI to estimate tissue thickness (TT) in the TBScomputation algorithm.	Updated
-System Architecture	-Two components: TBS Agent (client) installed on eachDXA and a centralized server that manages results andDICOM communication with PACS.	Standalone software installed on the DXA system,capable of communicating with PACS.	Updated
Data security	Implements encryption for data at rest and in transit, aswell as role-based access control to enhancecybersecurity.	No encryption or role-based access control.	Updated

Substantial Equivalence

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Performance Testing Summary & Conclusions

Standalone Performance Testing Summary

The primary advancement in TBS version 4.0 is the replacement of BMI-based adjustments with direct measurement of tissue thickness from DXA scan images. A series of validation studies confirm the performance, accuracy, and reproducibility of TBS version 4.0 compared to the predicate device.

Software Verification and Validation demonstrate specified requirements are met and the software functions as intended. Cybersecurity controls and processes have been implemented to ensure the software and related systems are cybersecurity documentation and testing demonstrates the software, and related systems are in alignment with the recommendations in the "Cybersecurity in Medical Devices: Quality System Considerations and Content of Premarket Submissions" guidance as well as the requirements of Section 524B of the FD&C Act.

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Clinical Association

Two pivotal studies validated the ability of TBS version 4.0 to accurately reflect bone microarchitecture. The first study evaluated the correlation between TBS values and bone microarchitecture parameters using 30 human cadaver lumbar vertebrae. Micro-computed tomography (microCT) measurements were compared to TBS values, revealing strong and statistically significant correlations with parameters such as trabecular number and separation. The results demonstrated that TBS version 4.0 maintained or exceeded the correlations established with the predicate, ensuring its validity in reflecting bone microarchitecture.

The second study examined the agreement between TBS version 4.0 and the predicate software using 15 human cadaver vertebrae. Measurements were performed on multiple DXA systems, and the analysis showed excellent agreement, with correlation coefficients exceeding 0.99. Bland-Altman statistics confirmed negligible differences between versions, supporting the consistency and reliability of TBS version 4.0 across different DXA platforms.

Analytical Reproducibility

The reproducibility of TBS measurements with version 4.0 was evaluated in both ex vivo and in vivo settings. In the ex vivo study, measurements from dried human lumbar vertebrae demonstrated that TBS version 4.0 provides precision and least significant change (LSC) values that are comparable to or slightly improved over those of the predicate. These results were consistent across various DXA systems.

In vivo testing involved 132 participants scanned on four different DXA systems. The analysis included repositioning between scans to assess precision and reproducibility under clinical conditions. Results showed that TBS version 4.0 met or exceeded precision standards established by the International Society for Clinical Densitometry (ISCD), with LSC values within acceptable thresholds. This level of precision helps to support the utility of TBS version 4.0 to assist physicians in monitoring bone health over time.

Performance and Utility

The performance and utility of TBS version 4.0 were evaluated across diverse scenarios, including fracture risk assessment, population-specific reference curves, and monitoring treatment responses. A key advancement of the software is the transition from BMI-based adjustments to direct measurements of tissue thickness. This was validated in-vivo, establishing a valid tissue thickness range of 7-30 cm, which aligns with the physiological parameters relevant to TBS calculations.

The generation of population-specific reference curves for age, sex, and ethnicity demonstrated the applicability of TBS version 4.0 across diverse demographic groups, including multi-ethnic populations in the United States. Comparisons with the predicate software confirmed statistical equivalence, reinforcing the reliability of the subject device in representing bone health across different populations.

For fracture risk assessment, data from over 17,000 individuals across 14 international cohorts were analyzed to compare the performance of TBS-adjusted FRAX and BMD T-scores using the updated software. TBS version 4.0 demonstrated similar TBS-adjusted FRAX and BMD T-scores for major osteoporotic and hip fractures than the predicate.

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Additionally, data from a large cohort of postmenopausal women with osteoporosis, demonstrated the effectiveness of TBS version 4.0 for accurately outputting TBS-adjusted FRAX and BMD T-scores for major osteoporotic and hip fractures over time in order to assist physicians with treatment monitoring, with substantial equivalence to the predicate.

Conclusion

TBS version 4.0 demonstrates substantially equivalent performance in the assessment of bone quality and TBS-adjusted FRAX and BMD T-scores. Standalone validation studies confirm the performance, reliability, and utility of the updated software across diverse populations and DXA systems

Regulation Number and Section

§ 892.1170 Bone densitometer.

(a)
Identification. A bone densitometer is a device intended for medical purposes to measure bone density and mineral content by x-ray or gamma ray transmission measurements through the bone and adjacent tissues. This generic type of device may include signal analysis and display equipment, patient and equipment supports, component parts, and accessories.(b)
Classification. Class II.