Investigators used dual-energy X-ray absorptiometry, or DEXA, to assess bone mineral density at the lumbar spine, femoral neck and hip. Measurements were taken at baseline, after participants had received estrogen therapy alone for at least one year, and after they had received estrogen plus testosterone for at least one year. The mean duration of estrogen-only therapy was 3.5 years, while the mean duration of combined estrogen and testosterone therapy was 3.1 years.

Across the study, participants were followed for an average of 4.1 years. The analysis compared T-scores at the three skeletal locations across these sequential treatment periods. Estrogen therapy alone did not produce a statistically significant increase in T-scores at the lumbar spine, femoral neck or hip.

In contrast, estrogen plus testosterone was associated with a significant increase in the lumbar spine T-score. The femoral neck and hip T-scores remained stable across both treatment periods, making the spine the only measured site where the researchers reported a significant increase after combined therapy. The release did not provide the numerical T-score changes, DEXA values, confidence intervals or other effect estimates, so the magnitude and precision of the observed association cannot be determined from the information supplied.

Based on the site-specific pattern, Davis and colleagues suggested that testosterone may have a synergistic effect with estrogen on trabecular bone, with the clearest measured association occurring at the spine. This was the investigators’ interpretation of the results rather than a separately demonstrated biological mechanism. The observational design and the sequence of estrogen-only and combined treatment mean that the findings establish an observed association, not a causal effect of adding testosterone.

Information about participant characteristics, adverse events and adherence was not included in the release. Bone density can decrease substantially during and after menopause as estrogen levels fall, and the release notes that women may lose 10% to 20% of their bone density in the first five to seven years after menopause. This rapid thinning raises the risk of osteopenia, described as low bone mass, and osteoporosis, characterized by weak, brittle bones that are prone to fracture.

Estrogen therapy has historically been prescribed to lower the risk of spine and hip fractures, while weight-bearing and resistance exercise, adequate calcium and vitamin D intake and hormone therapy are described as proven methods for protecting bone health. The present findings do not report a fracture outcome, and Davis said further research is needed to determine how testosterone could be used safely and effectively in individualized menopausal care. Stephanie Faubion, medical director of The Menopause Society, similarly emphasized the need for more studies exploring options that may help protect women’s bones during and after menopause.

Subject of Research: Bone mineral density during sequential estrogen and combined estrogen-testosterone therapy in postmenopausal women

Article Title: Combined estrogen and testosterone therapy increases lumbar spine bone mineral density

Article References: Combined estrogen and testosterone therapy increases lumbar spine bone mineral density. Original publication (Bibliographic details unavailable.)

Image Credits: AI Generated

DOI: Not provided

Keywords: postmenopausal women, bone mineral density, estrogen therapy, testosterone therapy, lumbar spine, osteoporosis, menopause, DEXA, Combined, estrogen, testosterone, therapy

The study, published in BMC Endocrine Disorders, recruited 102 patients from the endocrinology clinics and wards of Imam Reza and Sina Hospitals in Tabriz. Each participant underwent dual-energy X-ray absorptiometry, the gold-standard imaging technique for measuring bone mineral density, with readings taken at the lumbar spine and the femoral neck, the upper portion of the thigh bone where most hip fractures originate. Following World Health Organization criteria, osteoporosis was defined as a T-score of -2.5 or lower at either site. When degenerative changes in the spine, common in older adults, threatened to distort lumbar measurements, the researchers gave priority to the femoral neck values, a methodological safeguard designed to avoid falsely inflating or deflating the true burden of disease.

The resulting prevalence estimate, 32.4 percent with a 95 percent confidence interval of 23.4 to 42.3 percent, carries a wide margin of uncertainty, reflecting the modest sample size. Even at the lower bound, however, the numbers suggest that nearly a quarter of older diabetic patients in this setting have bones fragile enough to fracture under everyday stresses. That matters because diabetes-related fractures are not ordinary fractures. Studies across multiple populations have shown that people with type 2 diabetes can break hips and vertebrae at bone mineral density levels that would be considered safe in non-diabetic individuals, meaning standard screening thresholds may systematically underestimate their true skeletal risk.

The biological explanation lies partly in a process that has fascinated bone biologists for years: the accumulation of advanced glycation end products, or AGEs. Chronic high blood sugar drives glucose molecules to bind irreversibly to proteins throughout the body, including collagen, the structural scaffold of bone. Glycated collagen becomes stiffer and more brittle, and the normal microscopic repair process, in which bone cells remove and replace damaged tissue, slows down. The result is a bone that may look adequately dense on a scan but behaves mechanically like aged plastic rather than resilient composite material. Diabetes also disrupts the delicate coupling between osteoblasts, the cells that build bone, and osteoclasts, the cells that dismantle it, tilting the balance toward loss.

Against this backdrop, the Tabriz team used logistic regression to identify which characteristics of their patients were actually associated with osteoporosis. Two factors emerged clearly and independently. The first was female sex: women in the cohort had roughly five times the odds of osteoporosis compared with men, an unadjusted odds ratio of 4.84 with a confidence interval of 1.67 to 14.01 and a P value of 0.004. After adjusting for other variables, the association persisted, with an adjusted odds ratio of 3.34 and a P value of 0.035. The finding aligns with decades of bone biology, since the sharp decline in estrogen at menopause removes a powerful protective signal that normally restrains bone resorption, and it suggests that postmenopausal women with diabetes face a compounding of two skeletal threats at once.

The second independent predictor was more surprising to many observers: kidney function. The researchers measured the estimated glomerular filtration rate, or eGFR, a standard laboratory index of how efficiently the kidneys filter blood, expressed in milliliters per minute per 1.73 square meters of body surface area. Lower eGFR was significantly associated with osteoporosis, with an odds ratio of 0.96 per unit increase, a confidence interval of 0.94 to 0.98, and a P value of 0.004. In the multivariable model the relationship held, with an adjusted odds ratio of 0.97 and a P value of 0.037. In practical terms, each incremental decline in filtration capacity nudged patients measurably closer to the osteoporotic range.

The kidney-bone connection is well grounded in physiology. The kidneys are not passive bystanders in skeletal metabolism; they activate vitamin D, regulate calcium and phosphate balance, and orchestrate the hormonal signals that keep bone remodeling on schedule. As filtration declines, phosphate retention and hormonal disturbances trigger a cascade known as chronic kidney disease-mineral and bone disorder, in which parathyroid hormone levels rise and bone turnover becomes disordered. Because diabetic kidney disease is itself one of the most common complications of long-standing type 2 diabetes, the study’s finding effectively identifies a subgroup, older diabetic women with waning renal function, whose bones are being attacked from multiple directions simultaneously.

What the study did not find is equally instructive. Glycemic control, measured through fasting blood sugar and glycated hemoglobin, body mass index, physical activity levels assessed with the International Physical Activity Questionnaire, and medication histories did not emerge as statistically significant independent predictors in this cohort. That may reflect the limited statistical power of a 102-patient sample, or genuine homogeneity among patients recruited from specialized endocrinology services, where most participants receive broadly similar care. The authors are careful on this point, and their conclusion emphasizes that the two robust signals, female sex and reduced eGFR, should guide screening priorities rather than serving as an exhaustive risk map.

The clinical implications are straightforward but consequential. Current guidance in many health systems does not routinely recommend bone density screening for patients with type 2 diabetes until they reach ages well beyond the range of this cohort, partly because diabetes modestly raises body weight, which is traditionally protective against bone loss, and partly because the fracture risk of diabetic patients was underappreciated for years. This study, conducted in a real-world hospital population in northwestern Iran, argues that waiting is a mistake. Integrating a simple DEXA scan and a kidney function check into the routine management of diabetic patients over 55, with heightened vigilance for women, could identify high-risk individuals years before a first fragility fracture, which is often the moment the disease announces itself.

The researchers, led by Yalda Taati Alamdari and corresponding author Mahsa Malekian, with support from the Research Vice-Chancellor of Tabriz University of Medical Sciences, acknowledge the limits of a single-center, cross-sectional design, which captures a snapshot in time and cannot establish whether low kidney function causes bone loss or merely travels alongside it. They call for prospective multicenter studies to sharpen risk stratification and inform screening strategies. With more than half a billion people worldwide now living with diabetes, and populations aging fastest in exactly the regions where diabetes is expanding most rapidly, the study’s central message travels far beyond Tabriz: in older patients with type 2 diabetes, the skeleton is a silent organ of the disease, and the tools to catch its decline already sit in every endocrinology clinic.

Subject of Research: Prevalence and risk factors of osteoporosis among older patients with type 2 diabetes mellitus

Article Title: Prevalence and associated factors of osteoporosis in type 2 diabetes mellitus patients: a cross-sectional study

Article References: Taati Alamdari, Y., Lotfi Yagin, N., Gilani, N., Sadra, V., Najafipour, F., Gaffarzadeh Rad, S., & Malekian, M. (2026). Prevalence and associated factors of osteoporosis in type 2 diabetes mellitus patients: a cross-sectional study. BMC Endocrine Disorders. https://doi.org/10.1186/s12902-026-02525-2

Image Credits: AI Generated

DOI: 10.1186/s12902-026-02525-2

Keywords: type 2 diabetes, osteoporosis, bone mineral density, DEXA, eGFR, kidney function, postmenopausal women, fragility fractures, advanced glycation end products, cross-sectional study, Iran, endocrinology

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