The stakes are enormous. Osteoporosis is a systemic metabolic bone disease in which both bone density and the fine internal architecture of the skeleton deteriorate, and it remains one of the leading causes of fractures in old age. In Russia, the study’s authors note, osteoporosis is diagnosed in 34 percent of women and 27 percent of men aged 50 and older, and the burden of fragility fractures after age 50 has been described as a public health threat comparable to dyslipidemia and hypertension. Secondary osteoporosis also shadows many common conditions of aging, including type 2 diabetes, chronic kidney disease, and long-term glucocorticoid use. Under World Health Organization criteria, the diagnosis rests on three pillars: a pathological low-energy fracture of a large bone, a high 10-year fracture probability on the FRAX risk tool, or a bone mineral density deficit of 2.5 or more standard deviations below the young adult mean, the famous T-score, measured by DXA at the lumbar spine or proximal femur.

DXA earned its status as the clinical standard through elegant physics. A detector measures the differential attenuation of two X-ray energies passing through bone and soft tissue, allowing the machine to calculate areal bone mineral density in grams per square centimeter and to separate out body composition. The patient’s result is then compared with reference values from a young healthy population, expressed as the standard-deviation difference from that reference mean. But the technology has practical drawbacks. Access and affordability remain limited in many regions, including Russia, and although the radiation dose is very low, it is not zero. Those constraints have driven a search for alternatives, and REMS has emerged as one of the most intriguing candidates.

REMS works on an entirely different physical principle. Instead of measuring how X-rays are absorbed, it records how ultrasound vibrations scatter as they pass through bone. A convex transducer, operating at a nominal frequency of 3.5 megahertz, scans the lumbar vertebrae or the femoral neck, and the raw radiofrequency data are compared against an extensive database of reference ultrasound spectral models. From that comparison, the software calculates bone mineral density, T-scores, Z-scores, and even a 10-year fracture risk estimate, all without ionizing radiation. Scanning a single region takes roughly 80 to 90 seconds, guided by on-screen instructions and audio signals. The method’s proponents argue it could be a cost-effective, straightforward alternative to DXA, particularly for primary screening, and a 2026 meta-analysis by R.Y. Liu and E. Liu reported a strong correlation between the two techniques overall. That same meta-analysis, however, flagged substantial heterogeneity across studies and warned that the correlation may be considerably weaker in certain clinical settings and populations.

To find out where REMS stands in the Russian population, researchers at the Russian Gerontology Clinical Research Centre and Pirogov Russian National Research Medical University in Moscow conducted a single-center longitudinal study. They recruited 40 patients, of whom 32 met clinical indications for bone densitometry and 25 completed the full protocol: women aged 49 to 88, with a mean age of about 72 years and body mass index ranging from 22 to 41.9 kilograms per square meter. Each participant underwent both DXA, using a GE HealthCare Lunar Prodigy Advance system, and REMS, using an Echo Station ultrasound machine from EchoLight in Italy, at two visits separated by one year. Measurements targeted the lumbar spine from L1 to L4 and the femoral neck, the two sites where fracture risk is assessed most reliably. Between visits, all participants received standardized anti-osteoporotic therapy under Russian Ministry of Health guidelines, including therapeutic exercise, dietary correction, cholecalciferol at 2,000 to 7,000 international units daily, calcium supplements, and antiresorptive treatment with either annual intravenous zoledronic acid or twice-yearly subcutaneous denosumab. Fourteen patients received zoledronic acid and eleven received denosumab, and adherence was high across the cohort.

The baseline results revealed a picture of moderate, not stellar, diagnostic performance. Mean lumbar T-scores at the first visit were -1.89 by DXA and -2.33 by REMS; at the femoral neck, they were -1.95 and -2.20 respectively. Diagnostic agreement for osteoporosis between the two methods across both bone sites was 64 percent, with a Cohen’s kappa of just 0.28, a statistic indicating that much of that agreement could be attributed to chance. Sensitivity of REMS relative to DXA was 0.63, with a 95 percent confidence interval stretching from 0.33 to 0.94, and specificity was 0.64, with an interval from 0.39 to 0.89. The positive predictive value was 0.58 and the negative predictive value 0.69. In practical terms, REMS caught only about two-thirds of the women whom DXA classified as osteoporotic, and it misclassified roughly a third of those DXA cleared. The correlation between T-scores was moderate at the lumbar spine, 0.65 with a p-value below 0.001, but weak and statistically insignificant at the femoral neck, where the correlation was 0.35 with a p-value of 0.089.

Agreement analysis deepened the concern. Bland-Altman plots, which directly assess how closely two measurement methods track each other across a range of values, showed poor agreement for both bone regions, with wide 95 percent limits. For the lumbar spine, the limits ran from -1.543 to 1.919 T-score units; for the femoral neck, from -1.516 to 2.116. Although the mean bias was close to zero, 0.188 and 0.299 respectively, meaning the methods did not systematically overestimate or underestimate on average, the enormous spread meant that for any individual patient, REMS could deviate from DXA by nearly two full standard deviations in either direction. That is a clinically meaningful margin, given that the diagnostic threshold itself sits at -2.5.

The most striking finding emerged at the one-year follow-up, after antiresorptive therapy had begun. Correlations between REMS and DXA dropped to 0.47 for the lumbar spine, with a p-value of 0.022, and to 0.22 for the femoral neck, with a p-value of 0.307, rendering the femoral neck comparison statistically insignificant. In other words, once patients started receiving zoledronic acid or denosumab, the two methods diverged even further. The authors suggest this may reflect differences in the physical basis of the two techniques: after a year of therapy, the drugs may have altered the amount of hydroxyapatite in bone without yet significantly changing the microarchitecture that ultrasound spectra capture, or vice versa. Whatever the mechanism, the implication is clear: REMS cannot yet be trusted to tell clinicians whether a specific patient’s bone density is responding to treatment.

The authors are careful to contextualize their findings. Many large multicenter studies have demonstrated high agreement between REMS and DXA, and a Russian comparability study of 50 patients published in 2025 also reported a high correlation. But smaller studies have produced results similar to those seen here; in a study by Caffarelli and colleagues with 77 participants, correlations were 0.35 and 0.54 for the lumbar spine and femoral neck respectively. Even in the largest trials, sensitivity and specificity for osteoporosis detection by REMS were comparable to the values seen in this cohort. The structure of the study population may have played a role: elevated body mass index, prior pathological fractures, type 2 diabetes, and other conditions have all been shown to reduce agreement between the two methods, and no trial data exist for REMS devices in patients with a BMI above 40 kilograms per square meter. The femoral neck has consistently shown lower agreement than the lumbar spine across many studies, partly because REMS’s claimed advantage, the automatic exclusion of bone osteophytes and soft tissue calcifications, applies most cleanly to the lumbar region, where degenerative changes often inflate DXA readings.

The study’s limitations are acknowledged candidly: only 25 women completed the protocol, all participants were female, and the sample size could not be expanded within the initial administrative and diagnostic capabilities of the center. The authors conclude that REMS demonstrated statistically significant diagnostic value for osteoporosis, but that the comparability and agreement of its bone mineral density data with DXA was near low, varied widely by bone region, and decreased further during active antiresorptive therapy. The results, they write, are not sufficiently precise or statistically robust to validate REMS unequivocally for bone mineral density monitoring in Russia, but they provide a basis for further research. A larger follow-up study is already underway, with plans to expand the demographic spectrum, analyze inter-rater and test-retest reliability, stratify subgroups by obesity, pathological fractures, and diabetes, and record the device’s fragility score. For now, the message for patients and clinicians is measured: ultrasound-based bone assessment is a promising screening tool with real diagnostic value, but the gold standard for diagnosis and treatment monitoring remains DXA, and REMS must earn its place through larger, more diverse trials before it can claim parity.

Subject of Research: Diagnostic capabilities and monitoring the effectiveness of osteoporosis therapy using radiofrequency echographic multispectrometry in comparison with dual-energy x-ray absorptiometry

Article Title: Diagnostic capabilities and monitoring the effectiveness of osteoporosis therapy using radiofrequency echographic multispectrometry in comparison with dual-energy x-ray absorptiometry

Article References: Sharashkina, N. V., Rodionov, D. V., Runikhina, N. K., & Tkacheva, O. N. (2026). Diagnostic capabilities and monitoring the effectiveness of osteoporosis therapy using radiofrequency echographic multispectrometry in comparison with dual-energy x-ray absorptiometry. Frontiers in Endocrinology, 17, Article 1889333. https://doi.org/10.3389/fendo.2026.1889333

Image Credits: AI Generated

DOI: 10.3389/fendo.2026.1889333

Keywords: osteoporosis, REMS, DXA, bone mineral density, ultrasound imaging, antiresorptive therapy, T-score, fragility fractures, geriatric medicine, diagnostic agreement, Bland-Altman analysis, Russian population

The research, led by Muhammet Fatih Şahin of the Department of Internal Medicine at Kestel State Hospital in Bursa and colleagues at collaborating institutions, was published in BMC Endocrine Disorders as an open-access research article. The team set out to answer a deceptively simple question: among people with type 2 diabetes who undergo clinically indicated dual-energy X-ray absorptiometry, do those taking SGLT2 inhibitors show worse bone health than those who do not? To address it, the investigators assembled a primary analytical cohort of 56 patients with type 2 diabetes who were referred for DEXA scanning between June 2025 and February 2026. Of these, 31 patients were not using SGLT2 inhibitors and 25 were. A separate group of 44 participants without diabetes was recruited purely for secondary, descriptive comparisons, providing a reference point for how bone health parameters distribute in people free of the metabolic disease.

The choice of measurement technique matters enormously in this field, and the study leaned on the gold standard. Dual-energy X-ray absorptiometry, or DEXA, works by firing two X-ray beams of different energies through the body and measuring how much each is attenuated by bone tissue. Because calcium in bone absorbs X-rays far more efficiently than soft tissue, the differential attenuation allows clinicians to calculate bone mineral density with remarkable precision at clinically relevant sites. The researchers focused on the lumbar spine and the femoral neck, the narrow segment of the thigh bone just below the hip joint where fractures are both common and devastating. Each participant received a T-score at these sites, a number that expresses bone density as a comparison against the average peak bone mass of a healthy young adult. A T-score of minus 2.5 or lower at either site defines osteoporosis, while values between minus 1.0 and minus 2.5 fall into the intermediate territory of osteopenia.

The headline result was a statistical null. Osteoporosis, defined as a T-score of minus 2.5 or below at the lumbar spine or femoral neck, was present in 32.3 percent of the patients with type 2 diabetes who were not taking SGLT2 inhibitors and in 36.0 percent of those who were, a difference that was statistically indistinguishable with a p-value of 0.769. When the investigators moved beyond raw prevalence and applied logistic regression, adjusting for age, sex, and body mass index, the odds ratio for osteoporosis associated with SGLT2 inhibitor exposure came out at 1.169 with a 95 percent confidence interval stretching from 0.328 to 4.170, and a p-value of 0.810. An odds ratio of 1.0 would indicate no effect at all; the observed value of 1.169 hints at a modestly elevated risk, but the confidence interval is so wide that it comfortably spans everything from a strong protective effect to a more than fourfold increase in risk. In plain terms, the data cannot tell readers which direction, if any, the true effect points.

The null findings extended across every secondary outcome the team examined. There was no significant association between SGLT2 inhibitor use and the worst T-score recorded for each patient, nor with the site-specific T-scores at the lumbar spine or femoral neck. Actual bone mineral density measurements at both anatomical sites likewise showed no meaningful differences between users and non-users of the drug class. Even when patients were sorted into broader bone mineral density risk categories, normal, osteopenic, or osteoporotic, based on the worse of their two T-scores, the distribution did not differ significantly between the groups. A supplementary analysis incorporating the non-diabetic comparison group, evaluated with a Fisher–Freeman–Halton exact test, found no significant difference in bone mineral density category distribution across all three groups, with a p-value of 0.809. For a drug class that has been shadowed by skeletal concerns, the consistency of the null results across so many related endpoints is itself informative.

Why, then, did the skeletal question arise in the first place? The biological plausibility of harm has never been trivial. SGLT2 inhibitors induce a mild state of glucosuria, and the resulting caloric and fluid shifts alter phosphate handling, insulin secretion, and parathyroid hormone dynamics, all of which participate in the delicate regulation of bone remodeling. Some earlier observational studies and post-marketing analyses raised flags about fracture risk, particularly with canagliflozin, prompting regulators to add warnings to drug labels. At the same time, type 2 diabetes itself complicates the picture in a way that standard DEXA measurements can underappreciate. People with diabetes can sustain fragility fractures at bone densities that would be considered safe in the general population, a phenomenon thought to reflect impaired bone quality, altered collagen cross-linking, and the added danger of hypoglycemia-related falls. Any study of diabetes drugs and bone health therefore has to contend with a disease process that already distorts the relationship between measured density and actual fracture risk.

The authors of the new study are careful, and appropriately so, about what their results can and cannot support. In their conclusion they state that no statistically significant association was detected between SGLT2 inhibitor use and DEXA-derived bone health outcomes in patients with type 2 diabetes, but they immediately qualify this by noting that the limited sample size and the wide confidence intervals preclude excluding clinically meaningful associations. They call for larger prospective studies to settle the question. This is the honest language of exploratory research: a study of 56 patients simply lacks the statistical power to detect anything but a very large effect. With confidence intervals as broad as those reported here, a true doubling of osteoporosis risk could hide within the data undetected. Readers and clinicians should therefore interpret the findings as absence of evidence rather than evidence of absence, a distinction that matters when treatment decisions hang in the balance.

The study’s design also carries limitations worth understanding. As an observational, cross-sectional analysis conducted at a single hospital department, it captured patients at one moment in time rather than following them as bone density evolved. Patients were not randomized to receive SGLT2 inhibitors, so the possibility of confounding by indication, where the reasons a clinician chose a particular drug correlate with other health factors, cannot be fully excluded even with adjustment for age, sex, and body mass index. The duration of SGLT2 inhibitor exposure among users was not a central variable in the reported analysis, yet skeletal effects of any drug typically accumulate over years. The inclusion of a non-diabetic comparison group adds descriptive context, but the core inference rests on the 56 patients with diabetes divided into two modest groups. Ethics approval was granted by the Institutional Ethics Committee of Bursa Yüksek İhtisas Training and Research Hospital, and written informed consent was obtained from all participants in accordance with the Declaration of Helsinki, underscoring that the study met standard procedural safeguards even within its constrained scope.

For the millions of people taking SGLT2 inhibitors worldwide, the practical message is one of cautious reassurance rather than definitive clearance. The study found osteoporosis to be strikingly common in this population regardless of medication, affecting roughly a third of patients in both groups, which reinforces the importance of bone health screening for people with type 2 diabetes independent of their glucose-lowering regimen. Clinicians already weigh fracture risk when selecting diabetes therapies, and these findings do not demand a change in that calculus. What the research does provide is a template for the kind of work that must come next: large, prospective cohorts with longitudinal DEXA monitoring, careful documentation of drug duration and dose, and ideally fracture outcomes rather than surrogate density measures alone. Until such studies arrive, the skeleton’s verdict on SGLT2 inhibitors remains open, but the scales have tilted slightly, and measurably, toward the reassuring side.

Subject of Research: The association between SGLT2 inhibitor use and DEXA-derived bone health parameters in patients with type 2 diabetes mellitus

Article Title: SGLT2 inhibitor use and DEXA-derived bone health in type 2 diabetes mellitus

Article References: Şahin, M. F., Şahin, A., Dinar, A. B. K., Avul, S., İzeet, S. N., & Erol, A. (2026). SGLT2 inhibitor use and DEXA-derived bone health in type 2 diabetes mellitus. BMC Endocrine Disorders. https://doi.org/10.1186/s12902-026-02633-z

Image Credits: AI Generated

DOI: 10.1186/s12902-026-02633-z

Keywords: SGLT2 inhibitors, type 2 diabetes, osteoporosis, bone mineral density, DEXA, T-score, BMC Endocrine Disorders, observational study, endocrinology, fragility fractures, glucosuria, bone health