Metabolic Determinants of DXA-Measured Bone Mineral Density

Background: Bone mineral density measured at the lumbar spine and femoral neck may differ because these regions have different bone structures and may be affected differently by aging, metabolic factors, and degenerative changes. These differences may influence the diagnosis of osteoporosis and the assessment of fracture risk.

Objective: This study aims to investigate the metabolic and clinical factors associated with bone mineral density parameters measured by DXA. It will also evaluate lumbar spine-femoral neck T-score differences, bone mineral density discordance, fragility fractures, and FRAX fracture risk.

Method: This retrospective observational study will include adults aged 40 years and older who underwent DXA examination of the lumbar spine and femoral neck. Existing hospital records, DXA results, laboratory findings, and clinical information will be reviewed. The study will examine lumbar vertebral and femoral neck T-scores, the T-score difference between these regions, and concordant or discordant bone mineral density categories. Available metabolic and clinical variables will be analyzed. Previous and newly recorded fragility fractures and FRAX risk estimates will also be evaluated. No new tests or interventions will be performed.

Primary outcomes

• Lumbar Spine-Femoral Neck T-Score Gradient [Baseline]: The lumbar spine-femoral neck T-score gradient will be calculated by subtracting the femoral neck T-score from the mean lumbar spine T-score obtained from eligible L1-L4 vertebrae. T-scores represent the number of standard deviations by which bone mineral density differs from the young-adult reference mean. T-scores and the calculated gradient do not have predefined minimum or maximum values. Higher positive gradient values indicate a relatively higher lumbar spine T-score compared with the femoral neck, while more negative values indicate a relatively lower lumbar spine T-score. The relationships between the gradient and metabolic and clinical variables will be evaluated.

Secondary outcomes

• Lumbar Spine-Femoral Neck Bone Mineral Density Discordance [Baseline]: Lumbar spine and femoral neck T-scores will be classified as normal (T-score ≥ -1.0), osteopenic (T-score < -1.0 and > -2.5), or osteoporotic (T-score ≤ -2.5). Participants will be classified as concordant when the lumbar spine and femoral neck are in the same diagnostic category and discordant when they are in different diagnostic categories. This is a categorical outcome reported as concordant or discordant and is not a numerical scale; therefore, it has no minimum or maximum score, and higher values do not represent a better or worse outcome.
• Prevalent Fragility Fracture [Before or at the index DXA examination]: The presence of a fragility fracture before or at the time of the index DXA examination will be identified from medical records, radiology reports, and available imaging. Vertebral, hip, distal radius, and proximal humerus fractures caused by low-energy trauma will be included.
• Incident Fragility Fracture [From the index DXA examination to the date of record review, up to 10 years]: New fragility fractures occurring after the index DXA examination will be identified from medical records, radiology reports, and available imaging. Vertebral, hip, distal radius, and proximal humerus fractures caused by low-energy trauma will be included.
• FRAX 10-Year Major Osteoporotic Fracture Probability [Baseline]: The 10-year probability of a major osteoporotic fracture will be calculated using the Turkey-specific Fracture Risk Assessment Tool model, with femoral neck bone mineral density and available clinical risk factors. Major osteoporotic fracture includes clinical vertebral, hip, forearm, or proximal humerus fracture. The probability is reported from 0% to 100%, with higher percentages indicating a greater 10-year risk of major osteoporotic fracture.
• FRAX 10-Year Hip Fracture Probability [Baseline]: The 10-year probability of hip fracture will be calculated using the Turkey-specific Fracture Risk Assessment Tool model, with femoral neck bone mineral density and available clinical risk factors. The probability is reported from 0% to 100%, with higher percentages indicating a greater 10-year risk of hip fracture.

Sex: All, ages: 40 Years to any

Inclusion Criteria:

* Adults aged 40 years or older
* Lumbar spine (L1-L4) and femoral neck DXA measurements performed during the same assessment
* Available T-score and bone mineral density data from the DXA examination
* Available clinical and laboratory data required for the study analyses

Exclusion Criteria:

* Metal implant or prosthesis affecting lumbar spine or femoral neck DXA measurements
* Unreliable lumbar spine measurement due to marked artifact, surgical material, vertebral compression fracture, or extensive degenerative changes
* Fewer than two lumbar vertebrae suitable for analysis
* Active malignancy
* Stage 4 or higher chronic kidney disease
* Metabolic bone disease that may substantially affect bone mineral density
* Long-term systemic glucocorticoid use
* Missing or uninterpretable DXA data

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• Leslie WD, Kovacs CS, Olszynski WP, Towheed T, Kaiser SM, Prior JC, Josse RG, Jamal SA, Kreiger N, Goltzman D; CaMos Research Group. Spine-hip T-score difference predicts major osteoporotic fracture risk independent of FRAX((R)): a population-based report from CAMOS. J Clin Densitom. 2011 Jul-Sep;14(3):286-93. doi: 10.1016/j.jocd.2011.04.011. Epub 2011 Jul 1. PMID 21723768
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