Lower leg arterial calcification assessed by high-resolution peripheral quantitative computed tomography is associated with bone microstructure abnormalities in women.

In older women, the presence of lower leg arterial calcification assessed by high-resolution peripheral quantitative computed tomography is associated with relevant bone microstructure abnormalities at the distal tibia and distal radius. INTRODUCTION: Here, we report the relationships of bone geometry, volumetric bone mineral density (BMD) and bone microarchitecture with lower leg arterial calcification (LLAC) as assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: We utilized the Hertfordshire Cohort Study (HCS), where we were able to study associations between measures obtained from HR-pQCT of the distal radius and distal tibia in 341 participants with or without LLAC. Statistical analyses were performed separately for women and men. We used linear regression models to investigate the cross-sectional relationships between LLAC and bone parameters. RESULTS: The mean (SD) age of participants was 76.4 (2.6) and 76.1 (2.5) years in women and men, respectively. One hundred and eleven of 341 participants (32.6 %) had LLAC that were visible and quantifiable by HR-pQCT. The prevalence of LLAC was higher in men than in women (46.4 % (n = 83) vs. 17.3 % (n = 28), p < 0.001). After adjustment for confounding factors, we found that women with LLAC had substantially lower Ct.area (ß = -0.33, p = 0.016), lower Tb.N (ß = -0.54, p = 0.013) and higher Tb.Sp (ß = 0.54, p = 0.012) at the distal tibia and lower Tb.Th (ß = -0.49, p = 0.027) at the distal radius compared with participants without LLAC. Distal radial or tibial bone parameter analyses in men according to their LLAC status revealed no significant differences with the exception of Tb.N (ß = 0.27, p = 0.035) at the distal tibia. CONCLUSION: In the HCS, the presence of LLAC assessed by HR-pQCT was associated with relevant bone microstructure abnormalities in women. These findings need to be replicated and further research should study possible pathophysiological links between vascular calcification and osteoporosis.

Cortical bone laminar analysis reveals increased midcortical and periosteal porosity in type 2 diabetic postmenopausal women with history of fragility fractures compared to fracture-free diabetics.

UNLABELLED: We investigated the characteristics and spatial distribution of cortical bone pores in postmenopausal women with type 2 diabetes (T2D). High porosity in the midcortical and periosteal layers in T2D subjects with fragility fractures suggests that these cortical zones might be particularly susceptible to T2D-induced toxicity and may reflect cortical microangiopathy. INTRODUCTION: Elevated cortical porosity is regarded as one of the main contributors to the high skeletal fragility in T2D. However, to date, it remains unclear if diabetic cortical porosity results from vascular cortical changes or from an expansion in bone marrow space. Here, we used a novel cortical laminar analysis technique to investigate the characteristics and spatial radial distribution of cortical pores in a T2D group with prior history of fragility fractures (DMFx, assigned high-risk group) and a fracture-free T2D group (DM, assigned low-risk group) and to compare their results to non-diabetic controls with (Fx) and without fragility fractures (Co). METHODS: Eighty postmenopausal women (n = 20/group) underwent high-resolution peripheral quantitative computed tomography (HR-pQCT) of the distal tibia and radius. Cortical bone was divided into three layers of equal width including an endosteal, midcortical, and periosteal layer. Within each layer, total pore area (TPA), total pore number (TPN), and average pore area (APA) were calculated. Statistical analysis employed Mann-Whitney tests and ANOVA with post hoc tests. RESULTS: Compared to the DM group, DMFx subjects exhibited +90 to +365 % elevated global porosity (p = 0.001). Cortical laminar analysis revealed that this increased porosity was for both skeletal sites confined to the midcortical layer, followed by the periosteal layer (midcortical +1327 % TPA, p ≤ 0.001, periosteal +634 % TPA, p = 0.002), and was associated in both layers and skeletal sites with high TPN (+430 % TPN, p < 0.001) and high APA (+71.5 % APA, p < 0.001). CONCLUSION: High porosity in the midcortical and periosteal layers in the high-risk T2D group suggests that these cortical zones might be particularly susceptible to T2D-induced toxicity and may reflect cortical microangiopathy.

Volumetric femoral BMD, bone geometry, and serum sclerostin levels differ between type 2 diabetic postmenopausal women with and without fragility fractures.

UNLABELLED: While type 2 diabetes (T2D) is associated with higher skeletal fragility, specific risk stratification remains incompletely understood. We found volumetric bone mineral density, geometry, and serum sclerostin differences between low-fracture risk and high-fracture risk T2D women. These features might help identify T2D individuals at high fracture risk in the future. INTRODUCTION: Diabetic bone disease, an increasingly recognized complication of type 2 diabetes mellitus (T2D), is associated with high skeletal fragility. Exactly which T2D individuals are at higher risk for fracture, however, remains incompletely understood. Here, we analyzed volumetric bone mineral density (vBMD), geometry, and serum sclerostin levels in two specific T2D subsets with different fracture risk profiles. We examined a T2D group with prior history of fragility fractures (DMFx, assigned high-risk group) and a fracture-free T2D group (DM, assigned low-risk group) and compared their results to nondiabetic controls with (Fx) and without fragility fractures (Co). METHODS: Eighty postmenopausal women (n = 20 per group) underwent quantitative computed tomography (QCT) to compute vBMD and bone geometry of the proximal femur. Additionally, serum sclerostin, vitamin D, parathyroid hormone (PTH), HbA1c, and glomerular filtration rate (GFR) levels were measured. Statistical analyses employed linear regression models. RESULTS: DMFx subjects exhibited up to 33 % lower femoral neck vBMD than DM subjects across all femoral sites (-19 % ≤ ΔvBMD ≤ -33 %, 0.008 ≤ p ≤0.021). Additionally, DMFx subjects showed significantly thinner cortices (-6 %, p = 0.046) and a trend toward larger bone volume (+10 %, p = 0.055) relative to DM women and higher serum sclerostin levels when compared to DM (+31.4 %, p = 0.013), Fx (+25.2 %, p = 0.033), and control (+22.4 %, p = 0.028) subjects. CONCLUSION: Our data suggest that volumetric bone parameters by QCT and serum sclerostin levels can identify T2D individuals at high risk of fracture and might therefore show promise as clinical tools for fracture risk assessment in T2D. However, future research is needed to establish diabetes-specific QCT- and sclerostin-reference databases.

Diabetes and bone.

Traditionally, patients with type 1 diabetes were regarded to be at an increased risk of fractures whereas type 2 diabetics were assumed to be protected from fractures since many of them have high bone mineral density. Nevertheless, several clinical studies consistently demonstrated that type 2 diabetes is a paradigm of a disease with an increased risk of fractures in the presence of high bone mass. The pathophysiology of decreased bone strength in diabetes mellitus is multifactorial: insulin deficiency, insulin resistance, osteoblast insufficiency, vitamin D deficiency, formation of advanced glycation end-products in bone, and microvascular complications appear to contribute. Drugs used for the treatment of type 2 diabetes also may influence bone fragility: thiazolidinedione use has been associated with an increased risk of fractures.