Fractures in women with type 2 diabetes are associated with marked deficits in cortical parameters and trabecular plates.

The basis for increased fracture risk in type 2 diabetes (T2DM) is not well understood. In this multi-ethnic, population-based study (n = 565), we investigated bone microstructure, trabecular plate/rod morphology and mineralization in women with T2DM (n = 175) with and without fracture using a second-generation HRpQCT and individual trabecula segmentation and mineralization (ITS; ITM). Covariate-adjusted aBMD was 3.0-6.5% higher at all sites (all p < 0.005) in T2DM versus controls. By HRpQCT, T2DM had higher covariate-adjusted trabecular vBMD (5.3-6.4%) and number (3.8-5.1%) and greater cortical area at the radius and tibia. Covariate-adjusted cortical porosity was 10.0% higher at the tibia only in T2DM versus controls, but failure load did not differ. Among women with T2DM, those with adult atraumatic fracture (n = 59) had 5.2-8.5% lower adjusted aBMD at all sites by DXA compared to those without fracture (n = 103). By HRpQCT, those with fracture had lower adjusted total vBMD and smaller cortical area (10.2-16.1%), lower cortical thickness (10.5-15.8%) and lower cortical vBMD associated with 18.1% and 17.2% lower failure load at the radius and tibia respectively (all p < 0.05); plate volume and thickness were 5.7% and 4.7% lower respectively (p < 0.05) while rod volume fraction was 12.8% higher in the fracture group at the tibia only. Sodium glucose cotransporter 2 inhibitor users (SGLT2i; n = 19), tended to have lower radial rod tissue mineral density by ITS (p = 0.06). GLP1 agonist users (n = 19) had trabecular deficits at both sites and higher cortical porosity and larger pores at the distal tibia. In summary, T2DM is associated with increased cortical porosity while those with T2DM and fracture have more marked cortical deficits and fewer trabecular plates associated with lower failure load.

Reasons for increased fracture risk in type 2 diabetes (T2DM) are not well-understood. We used a multi-ethnic, population-based cohort (n = 565), to study bone structure in women with T2DM (n = 175) using advanced imaging and analysis techniques. Participants with T2DM tended to have higher bone density and better structure by dual energy x-ray absorptiometry and high resolution peripheral quantitative computed tomography respectively at the radius and tibia; only cortical porosity was higher (worse) in participants with diabetes compared to those without diabetes but there was no difference in bone strength. Participants with T2DM and fracture had lower cortical parameters and bone strength compared with participants with T2DM without fracture at both sites. In summary, T2DM is associated with increased cortical porosity while those with T2DM and fracture have more marked cortical deficits associated with lower failure load.

Skeletal Microstructure in Caribbean Hispanic Women.

Hispanic individuals are underrepresented in skeletal research. Bone mineral density (BMD) and fracture data are conflicting. We investigated skeletal health in elderly Caribbean Hispanic (HW), non-Hispanic white (NHW), and non-Hispanic black (NHB) women in a population-based study in New York City. We utilized high-resolution peripheral quantitative CT (HRpQCT), dual-energy X-ray absorptiometry (DXA), and finite element analysis (FEA). Of 442, 48.4% were HW, 21.3% NHW, and 30.3% NHB. Adjusted analyses are shown. Compared to NHW, HW had 8.5% (p < 0.01) lower spine areal BMD (aBMD) and 5.1% lower trabecular bone score (TBS). The frequency of morphometric vertebral fractures did not differ between HW and NHW. By HRpQCT, HW had 2.9% higher cortical (Ct) volumetric BMD (vBMD), 7.9% greater Ct area (Ct.Ar) and 9.4% greater Ct thickness (Ct.Th) at the radius compared to NHW. Results were similar at the tibia but trabecular microstructure tended to be worse. Ultimately, failure load (FL) did not differ between HW and NHW at either site. aBMD was 3.8% to 11.1% lower at the spine, femoral neck, and radius in HW compared to NHB (all p < 0.001) and vertebral fractures were twice as common. Compared to NHB, HW had 7.7% to 10.3% lower Ct.Ar at both the radius and tibia as well as 8.4% lower total vBMD, 6.3% lower trabecular number, and 10.3% lower Ct.Th at the tibia associated with 18.2% and 12.5% lower FL at both sites, respectively. In conclusion, HW had lower spine aBMD and TBS versus NHW women, whereas microstructural differences at the radius and tibia were small and not associated with differences in FL. In contrast, HW had lower aBMD, as well as deteriorated radial and tibial microstructure associated with worse FL compared to NHB women. Our results provide insight into racial/ethnic differences in skeletal health, adding to data that may be used to improve osteoporosis screening and treatment in HW. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Bone microstructure in proton pump inhibitor users.

OBJECTIVES: We assessed skeletal microstructure and stiffness in proton pump inhibitor (PPI) users compared to non-users with high resolution peripheral quantitative computed tomography (HRpQCT) and microfinite element analysis (µFEA) and other modalities. Relationships between PPI dose/frequency and bone parameters were evaluated. METHODS: We cross-sectionally assessed skeletal health in 601 older (≥age 65 years) adults (130 PPI users and 471 non-users) participating in a multi-ethnic population-based study of aging. RESULTS: PPI users tended to have more comorbidities and take more medications than non-users. Female PPI users (n = 100) were more likely to be non-Caucasian, shorter with higher BMI, and more likely to have diabetes, lower physical activity and be using anti-depressants and thiazide diuretics compared to non-users (n = 302). Male PPI users (n = 30) were more likely to have liver disease than non-users (n = 169). In women, historical fractures (53.0 % vs. 43.4 %, p = 0.05) and falls (38 % vs. 26.8 %, p = 0.04) tended to be more frequent in PPI users compared to non-users. Number of falls was higher in women reporting daily rather than intermittent PPI use (1.8/year vs. 1.0/year, p < 0.001). In women, there were no differences in any HRpQCT or µFEA parameter. By HRpQCT, covariate-adjusted cortical volumetric bone density (Ct.vBMD) was 4.2 % lower in male PPI users vs. non-users at the tibia (p = 0.04), but this did not result in reduced stiffness. There were no other differences by HRpQCT at the tibia or radius. CONCLUSIONS: PPI use was not associated with altered skeletal microstructure or stiffness in elderly men and women. The results do not support a relationship between PPI use and microstructure.

Thiazide use and skeletal microstructure: Results from a multi-ethnic study.

Background: Thiazide diuretics, a commonly used class of anti-hypertensives, have been associated with increased areal bone mineral density (aBMD). Data regarding effects on fracture are conflicting and no information is available regarding effects on skeletal microstructure and mechanical competence. Methods: We compared skeletal microstructure, volumetric BMD (vBMD), stiffness and prevalent fractures in current thiazide diuretic users and non-users from a population-based multiethnic cohort of elderly adults age ≥ 65 years (N = 599) with high resolution peripheral quantitative computed tomography (HR-pQCT) and micro-finite element analysis. Results: Female current thiazide diuretic users had higher weight and BMI and were more likely to be non-Caucasian compared to non-users. There were no differences in age, historical fractures or falls between female users and non-users. Female thiazide users tended to have lower calcium and vitamin d intake compared to non-users. After adjusting for age, weight, race and other covariates, 1/3-radius mean aBMD by dual energy x-ray absorptiometry (DXA) was 3.2% (p = 0.03) higher in female users vs. non-users. By HRpQCT, adjusted mean cortical vBMD was 2.4% (p = 0.03) higher at the radius in female users vs. non-users, but there was no difference in stiffness. DXA results were similar in the subset of Black females. There was no difference in any adjusted aBMD or cortical skeletal parameters by DXA or HRpQCT respectively in males. Conclusions: Thiazide use was associated with a modestly higher aBMD at the predominantly cortical 1/3-radius site and radial cortical vBMD by HRpQCT in females. The effect on cortical bone may offer skeletal benefits in women taking thiazides for other indications such as hypertension, hypercalciuria or recurrent nephrolithiasis.

Smoking Is Associated with Sex-Specific Effects on Bone Microstructure in Older Men and Women.

BACKGROUND: Smoking is a risk factor for fracture, but the mechanism by which smoking increases fracture risk is unclear. METHODS: Musculoskeletal health was compared with dual energy X-ray absorptiometry (DXA), high resolution peripheral quantitative computed tomography (HR-pQCT), trabecular bone score, and vertebral fracture assessment in current and past smokers and nonsmokers from a multiethnic study of adults ≥ age 65. Skeletal indices were adjusted for age and weight. RESULTS: Participants (n = 311) were mean age (±SD) 76.1 ± 6.5 years, mostly female (66.0%) and non-white (32.7% black/39.4% mixed race/26.3% white). Mean pack-years was 34.6 ± 20.4. In men (n = 106), weight and BMI were lower (both p < 0.05) in current vs past smokers. Male smokers consumed half the calcium of never and past smokers. BMD by DXA did not differ by smoking status at any skeletal site in either sex. Current male smokers had 13.5%-15.3% lower trabecular bone score vs never and past smokers (both p < 0.05). By HR-pQCT, trabecular volumetric BMD was 26.6%-30.3% lower and trabeculae were fewer, thinner and more widely spaced in male current vs past and never smokers at the radius (all p < 0.05). Cortical indices did not differ. Tibial results were similar, but stiffness was also 17.5%-22.2% lower in male current vs past and never smokers (both p< 0.05). In women, HR-pQCT trabecular indices did not differ, but cortical porosity was almost twice as high in current vs never smokers at the radius and 50% higher at the tibia (both p < 0.05). CONCLUSIONS: In summary, current smoking is associated with trabecular deterioration at the spine and peripheral skeleton in men, while women have cortical deficits. Smoking may have sex-specific skeletal effects. The consistent association with current, but not past smoking, suggests the effects of tobacco use may be reversible with smoking cessation.

Current anti-depressant use is associated with cortical bone deficits and reduced physical function in elderly women.

BACKGROUND: Anti-depressants, particularly selective serotonin reuptake inhibitors (SSRIs), are associated with an increased risk of fracture. The mechanism is unclear and may be due to effects on bone metabolism, muscle strength, falls or other factors. It is unknown if serotonin norepinephrine reuptake inhibitors (SNRIs) have similar effects. METHODS: We compared musculoskeletal health in current female anti-depressant users and non-users from a population-based multiethnic (35.6% black, 22.3% white and 42.1% mixed) cohort study of adults ≥65 years old in New York (N = 195) using dual x-ray absorptiometry (DXA), trabecular bone score (TBS), vertebral fracture assessment (VFA), high resolution peripheral quantitative computed tomography (HR-pQCT), body composition, and grip strength. RESULTS: Current anti-depressant users were more likely to be white than non-white (OR 1.9, 95% CI 1.2-2.9) and were shorter than non-users, but there were no differences in age, weight, BMI, physical activity, calcium/vitamin D intake, falls or self-rated health. There were more pelvic fractures in current vs. non-users (7.1% vs. 0%, p = 0.04). Age- and weight-adjusted T-score by DXA was lower in current users at the 1/3-radius (-1.6 ± 1.1 vs. -1.0 ± 1.4, p = 0.04) site only. There was no difference in TBS, vertebral fractures or fat/lean mass by DXA. Age- and weight-adjusted grip strength was 13.3% lower in current users vs. non-users (p = 0.04). By HR-pQCT, age- and weight-adjusted cortical volumetric BMD (Ct. vBMD) was 4.8% lower in users vs. non-users at the 4% radius site (p = 0.007). A similar cortical pattern was seen at the proximal (30%) tibia. When assessed by anti-depressant class, deteriorated cortical microstructure was present only in SSRI users at the radius and only in SNRI users at the proximal tibia. CONCLUSIONS: Anti-depressant use is associated with cortical deterioration and reduced physical function, but effects may be class-specific. These findings provide insight into the mechanism by which anti-depressants may contribute to the increased fracture risk in older women.